Article

Magnetic resonance image (MRI) contrast agents can induce profound complications, including gadolinium encephalopathy, kidney injury, gadolinium-associated plaques, and progressive systemic fibrosis, which can be fatal.^1-10 About 50% of MRIs use gadolinium-based contrast (Gd³⁺), a toxic rare earth metal ion that enhances imaging but requires binding with pharmaceutical ligands to reduce toxicity and promote renal elimination (Figure 1). Despite these measures, Gd³⁺ can persist in the body, including the brain.^11,12 Wastewater treatment fails to remove these agents, making Gd³⁺ a growing pollutant in water and the food chain.^13-15 Because Gd³⁺ is a rare earth metal ion in the milieu intérieur, there is an urgent need to study its biological and long-term effects (Appendix 1). 

Case Presentation

A 65-year-old Vietnam-era veteran presented to nephrology at the Raymond G. Murphy Veterans Affairs Medical Center (RGMVAMC) in Albuquerque, New Mexico, for evaluation of gadolinium-induced symptoms. His medical history included metabolic syndrome, hypertension, hyperlipidemia, hypogonadism, cervical spondylosis, and an elevated prostate-specific antigen, previously assessed with a contrast-enhanced MRI in 2019 (Gadobenic acid, 19 mL). Surgical history included cervical fusion and ankle hardware.

The patient had a scheduled MRI 25 days earlier, following an elevated prostate specific antigen test result, prompting urologic surveillance and concern for malignancy. In preparation for the contrast-enhanced MRI, his right arm was cannulated with a line primed with gadobenic acid contrast. Though the technician stated the infusion had not started, the patient’s symptoms began shortly after entry into the scanner, before any programmed pulse sequences. The patient experienced claustrophobia, diaphoresis, palpitations, xerostomia, dysgeusia, shortness of breath, and a sensation of heat in his groin, chest, “kidneys,” and lower back. The MRI was terminated prematurely in response to the patient’s acute symptomatology. The patient continued experiencing new symptoms intermittently during the following week, including lightheadedness, headaches, right clavicular pain, raspy voice, edema, and a sense of doom.

The patient presented to the RGMVAMC emergency department (ED) 8 days after the MRI with worsening symptoms and was hospitalized for 10 days. During this time, he was referred to nephrology for outpatient evaluation. While awaiting his nephrology appointment, the patient presented to the RGMVAMC ED 20 days after the initial episode with ongoing symptoms. “I thought I was dying,” he said. Laboratory results and a 12-lead electrocardiogram showed a finely static background, wide P waves (> 80 ms) with notching in lead II, sinusoidal P waves in V1, R transition in V2, RR’ in V2, ST flat in lead III, and sinus bradycardia (Table 1 and Appendix 2).

The patient’s medical and surgical histories were reviewed at the nephrology evaluation 25 days following the MRI. He reported that household water was sourced from a well and that he filtered his drinking water with a reverse osmosis system. He served in the US Army for 10 years as an engineer specializing in mechanical systems, power generation, and vehicles. Following Army retirement, the patient served in the US Air Force Reserves for 15 years, working as a crew chief in pneudraulics. The patient reported stopping tobacco use 1 year before and also reported regular use of a broad array of prescription medications and dietary supplements, including dexamethasone (4 mg twice daily), fluticasone nasal spray (50 mcg per nostril, twice daily), ibuprofen (400 mg twice daily, as needed), loratadine (10 mg daily), aspirin (81 mg daily), and metoprolol succinate (50 mg nightly). In addition, he reported consistent use of cholecalciferol (3000 IU daily), another supplemental vitamin D preparation, chelated magnesium glycinate (3 tablets daily for bone issues), turmeric (1 tablet daily), a multivitamin (Living Green Liquid Gel, daily), and a mega-B complex.

Physical examination revealed a well-nourished, tall man with hypertension (145/87 mmHg) and bilateral lower extremity edema. Oral examination showed poor dentition, including missing molars (#1-3, #14-16, #17-19, #30-31), with the anterior teeth replaced by bridges supported by dental implants. The review of systems was otherwise unremarkable, with nocturia noted before the consultation.

Serum and urine gadolinium testing, (Mayo Clinic Laboratories) revealed gadolinium levels of 0.3 mcg/24 h in the urine and 0.1 ng/mL in the serum. Nonzero values indicated detectable gadolinium, suggesting retention. The patient had a prior gadolinium exposure during a 2019 MRI (about 1340 days before) and suspected a repeat exposure on day 0, although the MRI technician stated that no contrast was administered. Given his elevated vitamin D levels, the patient was advised to minimize dietary supplements, particularly vitamin D, to avoid confounding symptoms. The plan included monitoring symptoms and a follow-up evaluation with repeat laboratory tests on day 116.

At the nephrology follow-up 4 months postexposure, the patient's symptoms had primarily abated, with a marked reduction in the previously noted metallic dysgeusia. Physical examination remained consistent with prior findings. He was afebrile (97.7 °F) with a blood pressure of 111/72 mmHg, a pulse of 63 beats per minute, and an oxygen saturation of 98% on ambient air. Laboratory analysis revealed serum and urine gadolinium levels below detectable thresholds (< 0.1 ng/mL and < 0.1 mcg/24 h). A 24-hour creatinine clearance, calculated from a urine volume of 1300 mL, measured at an optimal 106 mL/min, indicating preserved renal function (Tables 2 and 3). Of note, his 24-hour oxalate was above the reference range, with a urine pH below the reference range and a high supersaturation index for calcium oxalate.

Discussion

Use of enhanced MRI has increased in the Veterans Health Administration (Figure 2). A growing range of indications for enhanced procedures (eg, cardiac MRI) has contributed to this rise. The market has grown with new gadolinium-based contrast agents, such as gadopiclenol. However, reliance on untested assumptions about the safety of newer agents and need for robust clinical trials pose potential risks to patient safety.

Without prospective evidence, the American College of Radiology (ACR) classifies gadolinium-based contrast agents into 3 groups: Group 1, associated with the highest number of nephrogenic systemic fibrosis cases; Group 2, linked to few, if any, unconfounded cases; and Group 3, where data on nephrogenic systemic fibrosis risk have been limited. As of April 2024, the ACR reclassified Group 3 agents (Ablavar/Vasovist/Angiomark and Primovist/Eovist) into Group 2. Curiously, Vueway and Elucirem were approved in late 2022 and should clearly be categorized as Group 3 (Table 4).There were 19 cases of nephrogenic systemic fibrosis or similar manifestations, 8 of which were unconfounded by other factors. These patients had been exposed to gadobutrol, often combined with other agents. Gadobutrol—like other Group 2 agents—has been associated with nephrogenic systemic fibrosis.^16,17 Despite US Food and Drug Administration (FDA) documentation of rising reports, many clinicians remain unaware that nephrogenic systemic fibrosis is increasingly linked to Group 2 agents classified by the ACR.¹⁸ While declines in reported cases of nephrogenic systemic fibrosis may suggest reduced incidence, this trend may reflect diminished clinical vigilance and underreporting, particularly given emerging evidence implicating even Group 2 gadolinium-based contrast agents in delayed and underrecognized presentations. This information has yet to permeate the medical community, particularly among nephrologists. Considering these cases, revisiting the ACR guidelines may be prudent. 

To address this growing concern, clinicians must adopt stricter vigilance and actively pursue updated information to mitigate patient risks tied to these contrast agents. 

There exists an illusion of knowledge in disregarding the confounded exposures of MRI contrast agents. Ten distinct brands of contrast agents have been approved for clinical use. With repeated imaging, patients are often exposed to varying formulations of gadolinium-based agents. Yet investigators commonly discard these data points when assessing risk. By doing so, they assume—without evidence—that some formulations are inherently less likely to provoke adverse effects (AEs) than others. This untested presumption becomes perilous, especially given the limited understanding of the mechanisms underlying gadolinium-induced pathologies. As Aldous Huxley warned, “Facts do not cease to exist because they are ignored.”¹⁹

Gadolinium Persistence

Contrary to expectations, gadolinium persists in the body far longer than initially presumed. Symptoms associated with gadolinium exposure (SAGE) encapsulate the chronic, often enigmatic maladies tied to MRI contrast agents.²⁰ The prolonged retention of this rare earth metal offers a compelling hypothesis for the etiology of SAGE. It has been hypothesized that Lewis base-rich metabolites increase susceptibility to gadolinium-based contrast agent complications.²¹

The blood and urine concentration elimination curves of gadolinium are exponential and categorized as fast, intermediate, and long-term.¹ For urinary elimination, the function of the curves is exponential. The quantity of gadolinium in the urine at a time (t) after exposure (D_[Gd](t)) is equal to the product of the amount of gadolinium in the sample (urine or blood) at the end of the fast elimination period (D_[Gd](t₀)) and the exponential decay with k being a rate constant.

To the authors’ knowledge, we are the only research team currently investigating the rate constant for the intermediate- and long-term phase gadolinium elimination. The Retention and Toxicity of Gadolinium-based Contrast Agents study was approved by the University of New Mexico Health Sciences Center Institutional Review Board on May 27, 2020 (IRB ID 19-660). The data for the patient in this case were compared with preliminary results for patients with exposure-to-measurement intervals < 100 days. 

The patient in this case presented with detectable gadolinium levels in urine and serum shortly after an attempted contrast-enhanced MRI procedure (Figure 3). The presence of detectable gadolinium levels in the patient’s urine and serum suggests a likely exposure to a contrast agent about 27 days before his consultation. While the technician reported that no contrast was administered during the attempted MRI, it remains possible that a small amount was introduced during cannulation, potentially triggering the patient’s symptoms. Linear modeling of semilogarithmic plots for participants exposed to contrast agents within 100 days (urine: P = 1.8 × 10^ˉ8, adjusted r² = 0.62; blood: P = .005, adjusted r² = 0.21) provided clearance rates (k values) for urine and blood. Extrapolating from these models to the presumed exposure date, the intercepts estimate that the patient received between 0.5% and 8% of a standard contrast dose.

MRI contrast agents can cause skin disease. Systemic fibrosis is considered one of the most severe AEs. Skin pathophysiology involving myeloid cells is driven by elevated levels of monocyte chemoattractant protein-1, which recruits circulating fibroblasts via the C-C chemokine receptor 2.^22,23 This occurs alongside activation of NADPH oxidase Nox4.^4,24,25 Intracellular gadolinium-rich nanoparticles likely serve as catalysts for this reactive cascade.^{2,18,22,26,27} These particles assemble around intracellular lipid droplets and ferrule them in spiculated rare earth-rich shells that compromise cellular architecture.^{2,18,21,22,26,27} Frequently sequestered within endosomal compartments, they disrupt vesicular integrity and threaten cellular homeostasis. Interference with degradative systems such as the endolysosomal axis perturbs energy-recycling pathways—an insidious disturbance, particularly in cells with high metabolic demand. Skin-related symptoms are among the most frequently reported AEs, according to the FDA AE reporting system.¹⁸ 

Studies indicate repeated exposure to MRI contrast agents can lead to permanent gadolinium retention in the brain and other vital organs. Intravenous (IV) contrast agents cross the blood-brain barrier rapidly, while intrathecal administration has been linked to significant and lasting neurologic effects.¹⁸ 

Gadolinium is chemically bound to pharmaceutical ligands to enhance renal clearance and reduce toxicity. However, available data from human samples suggest potential ligand exchanges with undefined physiologic substances. This exchange may facilitate gadolinium precipitation and accumulation within cells into spiculated nanoparticles. Transmission electron microscopy reveals the formation of unilamellar bodies associated with mitochondriopathy and cellular damage, particularly in renal proximal tubules.^{2,18,22,26,27} It is proposed that intracellular nanoparticle formation represents a key mechanism driving the systemic symptoms observed in patients.^{1,2,18, 22,26,27} 

Any hypothesis based on free soluble gadolinium—or concept derived from it—should be discarded. The high affinity of pharmaceutical ligands for gadolinium suggests that the cationic rare earth metal remains predominantly in a ligand-bound, soluble form. It is hypothesized that gadolinium undergoes ligand exchange with physiologic substances, directly leading to nanoparticle formation. Current data demonstrate gadolinium precipitation according to the Le Chatelier’s principle. Since precipitated gadolinium does not readily re-equilibrate with pharmaceutical ligands, repeated administration of different contrast agent brands may contribute to nanoparticle growth.²⁶

Meanwhile, a growing number of patients are turning to chelation therapy, a largely untested treatment. The premise of chelation therapy is rooted in several unproven assumptions.^18,21 First, it assumes that clinically significant amounts of gadolinium persist in compartments such as the extracellular space, where they can be effectively chelated and cleared. Second, it presumes that free gadolinium is the primary driver of chronic symptoms, an assertion that remains scientifically unsubstantiated. Finally, chelation proponents overlook the potential harm caused by depleting essential physiological metals during the process, assuming without evidence that the scant removal of gadolinium outweighs the risk of physiological mineral depletion. 

These assumptions underpin an unproven remedy that demands critical scrutiny. Recent findings reveal that gadolinium deposits in the skin and kidney often take the form of intracellular nanoparticles, directly challenging the foundation of chelation therapy. Chelation advocates must demonstrate that these intracellular gadolinium deposits neither trigger cellular toxicity nor initiate a cytokine cascade. Chelation supporters must prove that the systemic response to these foreign particles is unrelated to the symptoms reported by patients. Until then, the validity of chelation therapy remains highly questionable.

The causality of the symptoms, mainly whether IV gadolinium was administered, was examined. The null hypothesis stated that the patient was not exposed to gadolinium. However, this hypothesis was contradicted by the detection of gadolinium in the serum and urine 27 days after the potential exposure. 

Two plausible explanations exist for the nonzero gadolinium levels detected in the serum and urine. The first possibility is that minute quantities of gadolinium were introduced during cannulation, with the amount being sufficient to persist in measurable concentrations 27 days postexposure. The second possibility is that the gadolinium originated from an MRI contrast agent administered 4 years earlier. In this scenario, gadolinium stored in organ reservoirs such as bone, liver, or kidneys may have been mobilized into the extracellular fluid compartment due to the administration of high-dose steroids 20 days after the recent contrast-enhanced MRI procedure attempt. Coyte et al reported elevated gadolinium levels in the serum, cord blood, breast milk, and placenta of pregnant women with prior exposure to MRI contrast agents.²⁸ These findings suggest that gadolinium, stored in organs such as bone may be remobilized by variables affecting bone remodeling (eg, high-dose steroids). 

Significantly, the patient exhibited elevated urinary oxalate levels. Previous research has found that oxalic acid reacts rapidly with MRI contrast agents, forming digadolinium trioxalate. While the gadolinium-rich nanoparticles identified in tissues such as the skin and kidney (including the human kidney) are amorphous, these in vitro findings establish a proof-of-concept: the intracellular environment facilitates gadolinium dissociation from pharmaceutical chelates. 

Furthermore, in vitro experiments show that proteins and lysosomal pH promote this dissociation, underscoring how human metabolic conditions—particularly oxalic acid concentration—may drive intracellular gadolinium deposition.

Patient Perspective

“They put something into my body that they cannot get out.” This stark realization underpins the patient’s profound concern about gadolinium-based contrast agents and their potential long-term effects. Reflecting on his experience, the patient expressed deep fears about the unknown future impacts: “I’m concerned about my kidneys, I’m concerned about my heart, and I’m concerned about my brain. I don’t know how this stuff is going to affect me in the future.”

He drew an unsettling parallel between gadolinium and heavy metals: “Heavy metal is poison. The body does not produce this kind of stuff on its own.” His reaction to the procedure left a lasting impression, prompting him to question the logic of using a substance that cannot be purged: “Why would you put something into someone’s body that you cannot extract? Nobody—nobody—should experience what I went through.”

The patient emphasized the lack of clear research on long-term outcomes, which compounds his anxiety: “If there was research that said, ‘Well, this is only going to affect these organs for this long,’ OK, I might be able to accept that. But there is no research like that. Nobody can tell me what’s going to happen in 5 years.”

Strengths and Limitations

A significant strength of this approach is the ability to track gadolinium elimination and symptom resolution over time, supported by unique access to intermediate and long-term clearance data from our ongoing research protocol. The investigators were equipped to back-extrapolate the exposure, which provided a rare opportunity to correlate gadolinium levels with clinical outcomes. The primary limitation is the lack of a defined clinical case definition for gadolinium toxicity and limited mechanistic understanding of SAGE, which hinders diagnosis and management.

Metabolites, proteins, and lipids rich in Lewis bases could initiate this process as substrates for intracellular gadolinium sedimentation. Future studies should investigate whether metabolic conditions such as oxalate burden or altered parathyroid hormone levels modulate gadolinium compartmentalization and tissue retention. If gadolinium-rich nanoparticle formation and accumulation disrupt cellular equilibrium, it underscores an urgent need to understand the implications of long-term gadolinium retention. The research team continues to gather evidence that the gadolinium cation remains chelated from the moment MRI contrast agents are administered through to the formation of intracellular nanoparticles. Retained gadolinium nanoparticles may act as a nidus, triggering cellular signaling cascades that lead to multisymptomatic illnesses. Intracellular and insoluble retained gadolinium challenges proponents of untested chelation therapies.

Conclusions

This case highlights emerging clinical and ethical concerns surrounding gadolinium-based contrast agent use. Clinicians may benefit from considering gadolinium retention as a contributor to persistent, unexplained symptoms—particularly in patients with recent imaging exposure. As contrast use continues to rise within federal health systems, regulatory and administrative stakeholders would do well to re-examine current safety frameworks. Informed consent should reflect what is known: gadolinium can remain in the body long after administration, potentially indefinitely. The long-term consequences of cumulative exposure remain poorly defined, but the presence of a lanthanide element in human tissue warrants greater attention from researchers and regulators alike. Interest in alternative imaging modalities and long-term safety monitoring would mark progress toward more transparent, accountable care.

Magnetic resonance image (MRI) contrast agents can induce profound complications, including gadolinium encephalopathy, kidney injury, gadolinium-associated plaques, and progressive systemic fibrosis, which can be fatal.^1-10 About 50% of MRIs use gadolinium-based contrast (Gd³⁺), a toxic rare earth metal ion that enhances imaging but requires binding with pharmaceutical ligands to reduce toxicity and promote renal elimination (Figure 1). Despite these measures, Gd³⁺ can persist in the body, including the brain.^11,12 Wastewater treatment fails to remove these agents, making Gd³⁺ a growing pollutant in water and the food chain.^13-15 Because Gd³⁺ is a rare earth metal ion in the milieu intérieur, there is an urgent need to study its biological and long-term effects (Appendix 1). 

Case Presentation

A 65-year-old Vietnam-era veteran presented to nephrology at the Raymond G. Murphy Veterans Affairs Medical Center (RGMVAMC) in Albuquerque, New Mexico, for evaluation of gadolinium-induced symptoms. His medical history included metabolic syndrome, hypertension, hyperlipidemia, hypogonadism, cervical spondylosis, and an elevated prostate-specific antigen, previously assessed with a contrast-enhanced MRI in 2019 (Gadobenic acid, 19 mL). Surgical history included cervical fusion and ankle hardware.

The patient had a scheduled MRI 25 days earlier, following an elevated prostate specific antigen test result, prompting urologic surveillance and concern for malignancy. In preparation for the contrast-enhanced MRI, his right arm was cannulated with a line primed with gadobenic acid contrast. Though the technician stated the infusion had not started, the patient’s symptoms began shortly after entry into the scanner, before any programmed pulse sequences. The patient experienced claustrophobia, diaphoresis, palpitations, xerostomia, dysgeusia, shortness of breath, and a sensation of heat in his groin, chest, “kidneys,” and lower back. The MRI was terminated prematurely in response to the patient’s acute symptomatology. The patient continued experiencing new symptoms intermittently during the following week, including lightheadedness, headaches, right clavicular pain, raspy voice, edema, and a sense of doom.

The patient presented to the RGMVAMC emergency department (ED) 8 days after the MRI with worsening symptoms and was hospitalized for 10 days. During this time, he was referred to nephrology for outpatient evaluation. While awaiting his nephrology appointment, the patient presented to the RGMVAMC ED 20 days after the initial episode with ongoing symptoms. “I thought I was dying,” he said. Laboratory results and a 12-lead electrocardiogram showed a finely static background, wide P waves (> 80 ms) with notching in lead II, sinusoidal P waves in V1, R transition in V2, RR’ in V2, ST flat in lead III, and sinus bradycardia (Table 1 and Appendix 2).

The patient’s medical and surgical histories were reviewed at the nephrology evaluation 25 days following the MRI. He reported that household water was sourced from a well and that he filtered his drinking water with a reverse osmosis system. He served in the US Army for 10 years as an engineer specializing in mechanical systems, power generation, and vehicles. Following Army retirement, the patient served in the US Air Force Reserves for 15 years, working as a crew chief in pneudraulics. The patient reported stopping tobacco use 1 year before and also reported regular use of a broad array of prescription medications and dietary supplements, including dexamethasone (4 mg twice daily), fluticasone nasal spray (50 mcg per nostril, twice daily), ibuprofen (400 mg twice daily, as needed), loratadine (10 mg daily), aspirin (81 mg daily), and metoprolol succinate (50 mg nightly). In addition, he reported consistent use of cholecalciferol (3000 IU daily), another supplemental vitamin D preparation, chelated magnesium glycinate (3 tablets daily for bone issues), turmeric (1 tablet daily), a multivitamin (Living Green Liquid Gel, daily), and a mega-B complex.

Physical examination revealed a well-nourished, tall man with hypertension (145/87 mmHg) and bilateral lower extremity edema. Oral examination showed poor dentition, including missing molars (#1-3, #14-16, #17-19, #30-31), with the anterior teeth replaced by bridges supported by dental implants. The review of systems was otherwise unremarkable, with nocturia noted before the consultation.

Serum and urine gadolinium testing, (Mayo Clinic Laboratories) revealed gadolinium levels of 0.3 mcg/24 h in the urine and 0.1 ng/mL in the serum. Nonzero values indicated detectable gadolinium, suggesting retention. The patient had a prior gadolinium exposure during a 2019 MRI (about 1340 days before) and suspected a repeat exposure on day 0, although the MRI technician stated that no contrast was administered. Given his elevated vitamin D levels, the patient was advised to minimize dietary supplements, particularly vitamin D, to avoid confounding symptoms. The plan included monitoring symptoms and a follow-up evaluation with repeat laboratory tests on day 116.

At the nephrology follow-up 4 months postexposure, the patient's symptoms had primarily abated, with a marked reduction in the previously noted metallic dysgeusia. Physical examination remained consistent with prior findings. He was afebrile (97.7 °F) with a blood pressure of 111/72 mmHg, a pulse of 63 beats per minute, and an oxygen saturation of 98% on ambient air. Laboratory analysis revealed serum and urine gadolinium levels below detectable thresholds (< 0.1 ng/mL and < 0.1 mcg/24 h). A 24-hour creatinine clearance, calculated from a urine volume of 1300 mL, measured at an optimal 106 mL/min, indicating preserved renal function (Tables 2 and 3). Of note, his 24-hour oxalate was above the reference range, with a urine pH below the reference range and a high supersaturation index for calcium oxalate.

Discussion

Use of enhanced MRI has increased in the Veterans Health Administration (Figure 2). A growing range of indications for enhanced procedures (eg, cardiac MRI) has contributed to this rise. The market has grown with new gadolinium-based contrast agents, such as gadopiclenol. However, reliance on untested assumptions about the safety of newer agents and need for robust clinical trials pose potential risks to patient safety.

Without prospective evidence, the American College of Radiology (ACR) classifies gadolinium-based contrast agents into 3 groups: Group 1, associated with the highest number of nephrogenic systemic fibrosis cases; Group 2, linked to few, if any, unconfounded cases; and Group 3, where data on nephrogenic systemic fibrosis risk have been limited. As of April 2024, the ACR reclassified Group 3 agents (Ablavar/Vasovist/Angiomark and Primovist/Eovist) into Group 2. Curiously, Vueway and Elucirem were approved in late 2022 and should clearly be categorized as Group 3 (Table 4).There were 19 cases of nephrogenic systemic fibrosis or similar manifestations, 8 of which were unconfounded by other factors. These patients had been exposed to gadobutrol, often combined with other agents. Gadobutrol—like other Group 2 agents—has been associated with nephrogenic systemic fibrosis.^16,17 Despite US Food and Drug Administration (FDA) documentation of rising reports, many clinicians remain unaware that nephrogenic systemic fibrosis is increasingly linked to Group 2 agents classified by the ACR.¹⁸ While declines in reported cases of nephrogenic systemic fibrosis may suggest reduced incidence, this trend may reflect diminished clinical vigilance and underreporting, particularly given emerging evidence implicating even Group 2 gadolinium-based contrast agents in delayed and underrecognized presentations. This information has yet to permeate the medical community, particularly among nephrologists. Considering these cases, revisiting the ACR guidelines may be prudent. 

To address this growing concern, clinicians must adopt stricter vigilance and actively pursue updated information to mitigate patient risks tied to these contrast agents. 

There exists an illusion of knowledge in disregarding the confounded exposures of MRI contrast agents. Ten distinct brands of contrast agents have been approved for clinical use. With repeated imaging, patients are often exposed to varying formulations of gadolinium-based agents. Yet investigators commonly discard these data points when assessing risk. By doing so, they assume—without evidence—that some formulations are inherently less likely to provoke adverse effects (AEs) than others. This untested presumption becomes perilous, especially given the limited understanding of the mechanisms underlying gadolinium-induced pathologies. As Aldous Huxley warned, “Facts do not cease to exist because they are ignored.”¹⁹

Gadolinium Persistence

Contrary to expectations, gadolinium persists in the body far longer than initially presumed. Symptoms associated with gadolinium exposure (SAGE) encapsulate the chronic, often enigmatic maladies tied to MRI contrast agents.²⁰ The prolonged retention of this rare earth metal offers a compelling hypothesis for the etiology of SAGE. It has been hypothesized that Lewis base-rich metabolites increase susceptibility to gadolinium-based contrast agent complications.²¹

The blood and urine concentration elimination curves of gadolinium are exponential and categorized as fast, intermediate, and long-term.¹ For urinary elimination, the function of the curves is exponential. The quantity of gadolinium in the urine at a time (t) after exposure (D_[Gd](t)) is equal to the product of the amount of gadolinium in the sample (urine or blood) at the end of the fast elimination period (D_[Gd](t₀)) and the exponential decay with k being a rate constant.

To the authors’ knowledge, we are the only research team currently investigating the rate constant for the intermediate- and long-term phase gadolinium elimination. The Retention and Toxicity of Gadolinium-based Contrast Agents study was approved by the University of New Mexico Health Sciences Center Institutional Review Board on May 27, 2020 (IRB ID 19-660). The data for the patient in this case were compared with preliminary results for patients with exposure-to-measurement intervals < 100 days. 

The patient in this case presented with detectable gadolinium levels in urine and serum shortly after an attempted contrast-enhanced MRI procedure (Figure 3). The presence of detectable gadolinium levels in the patient’s urine and serum suggests a likely exposure to a contrast agent about 27 days before his consultation. While the technician reported that no contrast was administered during the attempted MRI, it remains possible that a small amount was introduced during cannulation, potentially triggering the patient’s symptoms. Linear modeling of semilogarithmic plots for participants exposed to contrast agents within 100 days (urine: P = 1.8 × 10^ˉ8, adjusted r² = 0.62; blood: P = .005, adjusted r² = 0.21) provided clearance rates (k values) for urine and blood. Extrapolating from these models to the presumed exposure date, the intercepts estimate that the patient received between 0.5% and 8% of a standard contrast dose.

MRI contrast agents can cause skin disease. Systemic fibrosis is considered one of the most severe AEs. Skin pathophysiology involving myeloid cells is driven by elevated levels of monocyte chemoattractant protein-1, which recruits circulating fibroblasts via the C-C chemokine receptor 2.^22,23 This occurs alongside activation of NADPH oxidase Nox4.^4,24,25 Intracellular gadolinium-rich nanoparticles likely serve as catalysts for this reactive cascade.^{2,18,22,26,27} These particles assemble around intracellular lipid droplets and ferrule them in spiculated rare earth-rich shells that compromise cellular architecture.^{2,18,21,22,26,27} Frequently sequestered within endosomal compartments, they disrupt vesicular integrity and threaten cellular homeostasis. Interference with degradative systems such as the endolysosomal axis perturbs energy-recycling pathways—an insidious disturbance, particularly in cells with high metabolic demand. Skin-related symptoms are among the most frequently reported AEs, according to the FDA AE reporting system.¹⁸ 

Studies indicate repeated exposure to MRI contrast agents can lead to permanent gadolinium retention in the brain and other vital organs. Intravenous (IV) contrast agents cross the blood-brain barrier rapidly, while intrathecal administration has been linked to significant and lasting neurologic effects.¹⁸ 

Gadolinium is chemically bound to pharmaceutical ligands to enhance renal clearance and reduce toxicity. However, available data from human samples suggest potential ligand exchanges with undefined physiologic substances. This exchange may facilitate gadolinium precipitation and accumulation within cells into spiculated nanoparticles. Transmission electron microscopy reveals the formation of unilamellar bodies associated with mitochondriopathy and cellular damage, particularly in renal proximal tubules.^{2,18,22,26,27} It is proposed that intracellular nanoparticle formation represents a key mechanism driving the systemic symptoms observed in patients.^{1,2,18, 22,26,27} 

Any hypothesis based on free soluble gadolinium—or concept derived from it—should be discarded. The high affinity of pharmaceutical ligands for gadolinium suggests that the cationic rare earth metal remains predominantly in a ligand-bound, soluble form. It is hypothesized that gadolinium undergoes ligand exchange with physiologic substances, directly leading to nanoparticle formation. Current data demonstrate gadolinium precipitation according to the Le Chatelier’s principle. Since precipitated gadolinium does not readily re-equilibrate with pharmaceutical ligands, repeated administration of different contrast agent brands may contribute to nanoparticle growth.²⁶

Meanwhile, a growing number of patients are turning to chelation therapy, a largely untested treatment. The premise of chelation therapy is rooted in several unproven assumptions.^18,21 First, it assumes that clinically significant amounts of gadolinium persist in compartments such as the extracellular space, where they can be effectively chelated and cleared. Second, it presumes that free gadolinium is the primary driver of chronic symptoms, an assertion that remains scientifically unsubstantiated. Finally, chelation proponents overlook the potential harm caused by depleting essential physiological metals during the process, assuming without evidence that the scant removal of gadolinium outweighs the risk of physiological mineral depletion. 

These assumptions underpin an unproven remedy that demands critical scrutiny. Recent findings reveal that gadolinium deposits in the skin and kidney often take the form of intracellular nanoparticles, directly challenging the foundation of chelation therapy. Chelation advocates must demonstrate that these intracellular gadolinium deposits neither trigger cellular toxicity nor initiate a cytokine cascade. Chelation supporters must prove that the systemic response to these foreign particles is unrelated to the symptoms reported by patients. Until then, the validity of chelation therapy remains highly questionable.

The causality of the symptoms, mainly whether IV gadolinium was administered, was examined. The null hypothesis stated that the patient was not exposed to gadolinium. However, this hypothesis was contradicted by the detection of gadolinium in the serum and urine 27 days after the potential exposure. 

Two plausible explanations exist for the nonzero gadolinium levels detected in the serum and urine. The first possibility is that minute quantities of gadolinium were introduced during cannulation, with the amount being sufficient to persist in measurable concentrations 27 days postexposure. The second possibility is that the gadolinium originated from an MRI contrast agent administered 4 years earlier. In this scenario, gadolinium stored in organ reservoirs such as bone, liver, or kidneys may have been mobilized into the extracellular fluid compartment due to the administration of high-dose steroids 20 days after the recent contrast-enhanced MRI procedure attempt. Coyte et al reported elevated gadolinium levels in the serum, cord blood, breast milk, and placenta of pregnant women with prior exposure to MRI contrast agents.²⁸ These findings suggest that gadolinium, stored in organs such as bone may be remobilized by variables affecting bone remodeling (eg, high-dose steroids). 

Significantly, the patient exhibited elevated urinary oxalate levels. Previous research has found that oxalic acid reacts rapidly with MRI contrast agents, forming digadolinium trioxalate. While the gadolinium-rich nanoparticles identified in tissues such as the skin and kidney (including the human kidney) are amorphous, these in vitro findings establish a proof-of-concept: the intracellular environment facilitates gadolinium dissociation from pharmaceutical chelates. 

Furthermore, in vitro experiments show that proteins and lysosomal pH promote this dissociation, underscoring how human metabolic conditions—particularly oxalic acid concentration—may drive intracellular gadolinium deposition.

Patient Perspective

“They put something into my body that they cannot get out.” This stark realization underpins the patient’s profound concern about gadolinium-based contrast agents and their potential long-term effects. Reflecting on his experience, the patient expressed deep fears about the unknown future impacts: “I’m concerned about my kidneys, I’m concerned about my heart, and I’m concerned about my brain. I don’t know how this stuff is going to affect me in the future.”

He drew an unsettling parallel between gadolinium and heavy metals: “Heavy metal is poison. The body does not produce this kind of stuff on its own.” His reaction to the procedure left a lasting impression, prompting him to question the logic of using a substance that cannot be purged: “Why would you put something into someone’s body that you cannot extract? Nobody—nobody—should experience what I went through.”

The patient emphasized the lack of clear research on long-term outcomes, which compounds his anxiety: “If there was research that said, ‘Well, this is only going to affect these organs for this long,’ OK, I might be able to accept that. But there is no research like that. Nobody can tell me what’s going to happen in 5 years.”

Strengths and Limitations

A significant strength of this approach is the ability to track gadolinium elimination and symptom resolution over time, supported by unique access to intermediate and long-term clearance data from our ongoing research protocol. The investigators were equipped to back-extrapolate the exposure, which provided a rare opportunity to correlate gadolinium levels with clinical outcomes. The primary limitation is the lack of a defined clinical case definition for gadolinium toxicity and limited mechanistic understanding of SAGE, which hinders diagnosis and management.

Metabolites, proteins, and lipids rich in Lewis bases could initiate this process as substrates for intracellular gadolinium sedimentation. Future studies should investigate whether metabolic conditions such as oxalate burden or altered parathyroid hormone levels modulate gadolinium compartmentalization and tissue retention. If gadolinium-rich nanoparticle formation and accumulation disrupt cellular equilibrium, it underscores an urgent need to understand the implications of long-term gadolinium retention. The research team continues to gather evidence that the gadolinium cation remains chelated from the moment MRI contrast agents are administered through to the formation of intracellular nanoparticles. Retained gadolinium nanoparticles may act as a nidus, triggering cellular signaling cascades that lead to multisymptomatic illnesses. Intracellular and insoluble retained gadolinium challenges proponents of untested chelation therapies.

Conclusions

This case highlights emerging clinical and ethical concerns surrounding gadolinium-based contrast agent use. Clinicians may benefit from considering gadolinium retention as a contributor to persistent, unexplained symptoms—particularly in patients with recent imaging exposure. As contrast use continues to rise within federal health systems, regulatory and administrative stakeholders would do well to re-examine current safety frameworks. Informed consent should reflect what is known: gadolinium can remain in the body long after administration, potentially indefinitely. The long-term consequences of cumulative exposure remain poorly defined, but the presence of a lanthanide element in human tissue warrants greater attention from researchers and regulators alike. Interest in alternative imaging modalities and long-term safety monitoring would mark progress toward more transparent, accountable care.

Magnetic resonance image (MRI) contrast agents can induce profound complications, including gadolinium encephalopathy, kidney injury, gadolinium-associated plaques, and progressive systemic fibrosis, which can be fatal.^1-10 About 50% of MRIs use gadolinium-based contrast (Gd³⁺), a toxic rare earth metal ion that enhances imaging but requires binding with pharmaceutical ligands to reduce toxicity and promote renal elimination (Figure 1). Despite these measures, Gd³⁺ can persist in the body, including the brain.^11,12 Wastewater treatment fails to remove these agents, making Gd³⁺ a growing pollutant in water and the food chain.^13-15 Because Gd³⁺ is a rare earth metal ion in the milieu intérieur, there is an urgent need to study its biological and long-term effects (Appendix 1). 

Case Presentation

A 65-year-old Vietnam-era veteran presented to nephrology at the Raymond G. Murphy Veterans Affairs Medical Center (RGMVAMC) in Albuquerque, New Mexico, for evaluation of gadolinium-induced symptoms. His medical history included metabolic syndrome, hypertension, hyperlipidemia, hypogonadism, cervical spondylosis, and an elevated prostate-specific antigen, previously assessed with a contrast-enhanced MRI in 2019 (Gadobenic acid, 19 mL). Surgical history included cervical fusion and ankle hardware.

The patient had a scheduled MRI 25 days earlier, following an elevated prostate specific antigen test result, prompting urologic surveillance and concern for malignancy. In preparation for the contrast-enhanced MRI, his right arm was cannulated with a line primed with gadobenic acid contrast. Though the technician stated the infusion had not started, the patient’s symptoms began shortly after entry into the scanner, before any programmed pulse sequences. The patient experienced claustrophobia, diaphoresis, palpitations, xerostomia, dysgeusia, shortness of breath, and a sensation of heat in his groin, chest, “kidneys,” and lower back. The MRI was terminated prematurely in response to the patient’s acute symptomatology. The patient continued experiencing new symptoms intermittently during the following week, including lightheadedness, headaches, right clavicular pain, raspy voice, edema, and a sense of doom.

The patient presented to the RGMVAMC emergency department (ED) 8 days after the MRI with worsening symptoms and was hospitalized for 10 days. During this time, he was referred to nephrology for outpatient evaluation. While awaiting his nephrology appointment, the patient presented to the RGMVAMC ED 20 days after the initial episode with ongoing symptoms. “I thought I was dying,” he said. Laboratory results and a 12-lead electrocardiogram showed a finely static background, wide P waves (> 80 ms) with notching in lead II, sinusoidal P waves in V1, R transition in V2, RR’ in V2, ST flat in lead III, and sinus bradycardia (Table 1 and Appendix 2).

The patient’s medical and surgical histories were reviewed at the nephrology evaluation 25 days following the MRI. He reported that household water was sourced from a well and that he filtered his drinking water with a reverse osmosis system. He served in the US Army for 10 years as an engineer specializing in mechanical systems, power generation, and vehicles. Following Army retirement, the patient served in the US Air Force Reserves for 15 years, working as a crew chief in pneudraulics. The patient reported stopping tobacco use 1 year before and also reported regular use of a broad array of prescription medications and dietary supplements, including dexamethasone (4 mg twice daily), fluticasone nasal spray (50 mcg per nostril, twice daily), ibuprofen (400 mg twice daily, as needed), loratadine (10 mg daily), aspirin (81 mg daily), and metoprolol succinate (50 mg nightly). In addition, he reported consistent use of cholecalciferol (3000 IU daily), another supplemental vitamin D preparation, chelated magnesium glycinate (3 tablets daily for bone issues), turmeric (1 tablet daily), a multivitamin (Living Green Liquid Gel, daily), and a mega-B complex.

Physical examination revealed a well-nourished, tall man with hypertension (145/87 mmHg) and bilateral lower extremity edema. Oral examination showed poor dentition, including missing molars (#1-3, #14-16, #17-19, #30-31), with the anterior teeth replaced by bridges supported by dental implants. The review of systems was otherwise unremarkable, with nocturia noted before the consultation.

Serum and urine gadolinium testing, (Mayo Clinic Laboratories) revealed gadolinium levels of 0.3 mcg/24 h in the urine and 0.1 ng/mL in the serum. Nonzero values indicated detectable gadolinium, suggesting retention. The patient had a prior gadolinium exposure during a 2019 MRI (about 1340 days before) and suspected a repeat exposure on day 0, although the MRI technician stated that no contrast was administered. Given his elevated vitamin D levels, the patient was advised to minimize dietary supplements, particularly vitamin D, to avoid confounding symptoms. The plan included monitoring symptoms and a follow-up evaluation with repeat laboratory tests on day 116.

At the nephrology follow-up 4 months postexposure, the patient's symptoms had primarily abated, with a marked reduction in the previously noted metallic dysgeusia. Physical examination remained consistent with prior findings. He was afebrile (97.7 °F) with a blood pressure of 111/72 mmHg, a pulse of 63 beats per minute, and an oxygen saturation of 98% on ambient air. Laboratory analysis revealed serum and urine gadolinium levels below detectable thresholds (< 0.1 ng/mL and < 0.1 mcg/24 h). A 24-hour creatinine clearance, calculated from a urine volume of 1300 mL, measured at an optimal 106 mL/min, indicating preserved renal function (Tables 2 and 3). Of note, his 24-hour oxalate was above the reference range, with a urine pH below the reference range and a high supersaturation index for calcium oxalate.

Discussion

Use of enhanced MRI has increased in the Veterans Health Administration (Figure 2). A growing range of indications for enhanced procedures (eg, cardiac MRI) has contributed to this rise. The market has grown with new gadolinium-based contrast agents, such as gadopiclenol. However, reliance on untested assumptions about the safety of newer agents and need for robust clinical trials pose potential risks to patient safety.

Without prospective evidence, the American College of Radiology (ACR) classifies gadolinium-based contrast agents into 3 groups: Group 1, associated with the highest number of nephrogenic systemic fibrosis cases; Group 2, linked to few, if any, unconfounded cases; and Group 3, where data on nephrogenic systemic fibrosis risk have been limited. As of April 2024, the ACR reclassified Group 3 agents (Ablavar/Vasovist/Angiomark and Primovist/Eovist) into Group 2. Curiously, Vueway and Elucirem were approved in late 2022 and should clearly be categorized as Group 3 (Table 4).There were 19 cases of nephrogenic systemic fibrosis or similar manifestations, 8 of which were unconfounded by other factors. These patients had been exposed to gadobutrol, often combined with other agents. Gadobutrol—like other Group 2 agents—has been associated with nephrogenic systemic fibrosis.^16,17 Despite US Food and Drug Administration (FDA) documentation of rising reports, many clinicians remain unaware that nephrogenic systemic fibrosis is increasingly linked to Group 2 agents classified by the ACR.¹⁸ While declines in reported cases of nephrogenic systemic fibrosis may suggest reduced incidence, this trend may reflect diminished clinical vigilance and underreporting, particularly given emerging evidence implicating even Group 2 gadolinium-based contrast agents in delayed and underrecognized presentations. This information has yet to permeate the medical community, particularly among nephrologists. Considering these cases, revisiting the ACR guidelines may be prudent. 

To address this growing concern, clinicians must adopt stricter vigilance and actively pursue updated information to mitigate patient risks tied to these contrast agents. 

There exists an illusion of knowledge in disregarding the confounded exposures of MRI contrast agents. Ten distinct brands of contrast agents have been approved for clinical use. With repeated imaging, patients are often exposed to varying formulations of gadolinium-based agents. Yet investigators commonly discard these data points when assessing risk. By doing so, they assume—without evidence—that some formulations are inherently less likely to provoke adverse effects (AEs) than others. This untested presumption becomes perilous, especially given the limited understanding of the mechanisms underlying gadolinium-induced pathologies. As Aldous Huxley warned, “Facts do not cease to exist because they are ignored.”¹⁹

Gadolinium Persistence

Contrary to expectations, gadolinium persists in the body far longer than initially presumed. Symptoms associated with gadolinium exposure (SAGE) encapsulate the chronic, often enigmatic maladies tied to MRI contrast agents.²⁰ The prolonged retention of this rare earth metal offers a compelling hypothesis for the etiology of SAGE. It has been hypothesized that Lewis base-rich metabolites increase susceptibility to gadolinium-based contrast agent complications.²¹

The blood and urine concentration elimination curves of gadolinium are exponential and categorized as fast, intermediate, and long-term.¹ For urinary elimination, the function of the curves is exponential. The quantity of gadolinium in the urine at a time (t) after exposure (D_[Gd](t)) is equal to the product of the amount of gadolinium in the sample (urine or blood) at the end of the fast elimination period (D_[Gd](t₀)) and the exponential decay with k being a rate constant.

To the authors’ knowledge, we are the only research team currently investigating the rate constant for the intermediate- and long-term phase gadolinium elimination. The Retention and Toxicity of Gadolinium-based Contrast Agents study was approved by the University of New Mexico Health Sciences Center Institutional Review Board on May 27, 2020 (IRB ID 19-660). The data for the patient in this case were compared with preliminary results for patients with exposure-to-measurement intervals < 100 days. 

The patient in this case presented with detectable gadolinium levels in urine and serum shortly after an attempted contrast-enhanced MRI procedure (Figure 3). The presence of detectable gadolinium levels in the patient’s urine and serum suggests a likely exposure to a contrast agent about 27 days before his consultation. While the technician reported that no contrast was administered during the attempted MRI, it remains possible that a small amount was introduced during cannulation, potentially triggering the patient’s symptoms. Linear modeling of semilogarithmic plots for participants exposed to contrast agents within 100 days (urine: P = 1.8 × 10^ˉ8, adjusted r² = 0.62; blood: P = .005, adjusted r² = 0.21) provided clearance rates (k values) for urine and blood. Extrapolating from these models to the presumed exposure date, the intercepts estimate that the patient received between 0.5% and 8% of a standard contrast dose.

MRI contrast agents can cause skin disease. Systemic fibrosis is considered one of the most severe AEs. Skin pathophysiology involving myeloid cells is driven by elevated levels of monocyte chemoattractant protein-1, which recruits circulating fibroblasts via the C-C chemokine receptor 2.^22,23 This occurs alongside activation of NADPH oxidase Nox4.^4,24,25 Intracellular gadolinium-rich nanoparticles likely serve as catalysts for this reactive cascade.^{2,18,22,26,27} These particles assemble around intracellular lipid droplets and ferrule them in spiculated rare earth-rich shells that compromise cellular architecture.^{2,18,21,22,26,27} Frequently sequestered within endosomal compartments, they disrupt vesicular integrity and threaten cellular homeostasis. Interference with degradative systems such as the endolysosomal axis perturbs energy-recycling pathways—an insidious disturbance, particularly in cells with high metabolic demand. Skin-related symptoms are among the most frequently reported AEs, according to the FDA AE reporting system.¹⁸ 

Studies indicate repeated exposure to MRI contrast agents can lead to permanent gadolinium retention in the brain and other vital organs. Intravenous (IV) contrast agents cross the blood-brain barrier rapidly, while intrathecal administration has been linked to significant and lasting neurologic effects.¹⁸ 

Gadolinium is chemically bound to pharmaceutical ligands to enhance renal clearance and reduce toxicity. However, available data from human samples suggest potential ligand exchanges with undefined physiologic substances. This exchange may facilitate gadolinium precipitation and accumulation within cells into spiculated nanoparticles. Transmission electron microscopy reveals the formation of unilamellar bodies associated with mitochondriopathy and cellular damage, particularly in renal proximal tubules.^{2,18,22,26,27} It is proposed that intracellular nanoparticle formation represents a key mechanism driving the systemic symptoms observed in patients.^{1,2,18, 22,26,27} 

Any hypothesis based on free soluble gadolinium—or concept derived from it—should be discarded. The high affinity of pharmaceutical ligands for gadolinium suggests that the cationic rare earth metal remains predominantly in a ligand-bound, soluble form. It is hypothesized that gadolinium undergoes ligand exchange with physiologic substances, directly leading to nanoparticle formation. Current data demonstrate gadolinium precipitation according to the Le Chatelier’s principle. Since precipitated gadolinium does not readily re-equilibrate with pharmaceutical ligands, repeated administration of different contrast agent brands may contribute to nanoparticle growth.²⁶

Meanwhile, a growing number of patients are turning to chelation therapy, a largely untested treatment. The premise of chelation therapy is rooted in several unproven assumptions.^18,21 First, it assumes that clinically significant amounts of gadolinium persist in compartments such as the extracellular space, where they can be effectively chelated and cleared. Second, it presumes that free gadolinium is the primary driver of chronic symptoms, an assertion that remains scientifically unsubstantiated. Finally, chelation proponents overlook the potential harm caused by depleting essential physiological metals during the process, assuming without evidence that the scant removal of gadolinium outweighs the risk of physiological mineral depletion. 

These assumptions underpin an unproven remedy that demands critical scrutiny. Recent findings reveal that gadolinium deposits in the skin and kidney often take the form of intracellular nanoparticles, directly challenging the foundation of chelation therapy. Chelation advocates must demonstrate that these intracellular gadolinium deposits neither trigger cellular toxicity nor initiate a cytokine cascade. Chelation supporters must prove that the systemic response to these foreign particles is unrelated to the symptoms reported by patients. Until then, the validity of chelation therapy remains highly questionable.

The causality of the symptoms, mainly whether IV gadolinium was administered, was examined. The null hypothesis stated that the patient was not exposed to gadolinium. However, this hypothesis was contradicted by the detection of gadolinium in the serum and urine 27 days after the potential exposure. 

Two plausible explanations exist for the nonzero gadolinium levels detected in the serum and urine. The first possibility is that minute quantities of gadolinium were introduced during cannulation, with the amount being sufficient to persist in measurable concentrations 27 days postexposure. The second possibility is that the gadolinium originated from an MRI contrast agent administered 4 years earlier. In this scenario, gadolinium stored in organ reservoirs such as bone, liver, or kidneys may have been mobilized into the extracellular fluid compartment due to the administration of high-dose steroids 20 days after the recent contrast-enhanced MRI procedure attempt. Coyte et al reported elevated gadolinium levels in the serum, cord blood, breast milk, and placenta of pregnant women with prior exposure to MRI contrast agents.²⁸ These findings suggest that gadolinium, stored in organs such as bone may be remobilized by variables affecting bone remodeling (eg, high-dose steroids). 

Significantly, the patient exhibited elevated urinary oxalate levels. Previous research has found that oxalic acid reacts rapidly with MRI contrast agents, forming digadolinium trioxalate. While the gadolinium-rich nanoparticles identified in tissues such as the skin and kidney (including the human kidney) are amorphous, these in vitro findings establish a proof-of-concept: the intracellular environment facilitates gadolinium dissociation from pharmaceutical chelates. 

Furthermore, in vitro experiments show that proteins and lysosomal pH promote this dissociation, underscoring how human metabolic conditions—particularly oxalic acid concentration—may drive intracellular gadolinium deposition.

Patient Perspective

“They put something into my body that they cannot get out.” This stark realization underpins the patient’s profound concern about gadolinium-based contrast agents and their potential long-term effects. Reflecting on his experience, the patient expressed deep fears about the unknown future impacts: “I’m concerned about my kidneys, I’m concerned about my heart, and I’m concerned about my brain. I don’t know how this stuff is going to affect me in the future.”

He drew an unsettling parallel between gadolinium and heavy metals: “Heavy metal is poison. The body does not produce this kind of stuff on its own.” His reaction to the procedure left a lasting impression, prompting him to question the logic of using a substance that cannot be purged: “Why would you put something into someone’s body that you cannot extract? Nobody—nobody—should experience what I went through.”

The patient emphasized the lack of clear research on long-term outcomes, which compounds his anxiety: “If there was research that said, ‘Well, this is only going to affect these organs for this long,’ OK, I might be able to accept that. But there is no research like that. Nobody can tell me what’s going to happen in 5 years.”

Strengths and Limitations

A significant strength of this approach is the ability to track gadolinium elimination and symptom resolution over time, supported by unique access to intermediate and long-term clearance data from our ongoing research protocol. The investigators were equipped to back-extrapolate the exposure, which provided a rare opportunity to correlate gadolinium levels with clinical outcomes. The primary limitation is the lack of a defined clinical case definition for gadolinium toxicity and limited mechanistic understanding of SAGE, which hinders diagnosis and management.

Metabolites, proteins, and lipids rich in Lewis bases could initiate this process as substrates for intracellular gadolinium sedimentation. Future studies should investigate whether metabolic conditions such as oxalate burden or altered parathyroid hormone levels modulate gadolinium compartmentalization and tissue retention. If gadolinium-rich nanoparticle formation and accumulation disrupt cellular equilibrium, it underscores an urgent need to understand the implications of long-term gadolinium retention. The research team continues to gather evidence that the gadolinium cation remains chelated from the moment MRI contrast agents are administered through to the formation of intracellular nanoparticles. Retained gadolinium nanoparticles may act as a nidus, triggering cellular signaling cascades that lead to multisymptomatic illnesses. Intracellular and insoluble retained gadolinium challenges proponents of untested chelation therapies.

Conclusions

This case highlights emerging clinical and ethical concerns surrounding gadolinium-based contrast agent use. Clinicians may benefit from considering gadolinium retention as a contributor to persistent, unexplained symptoms—particularly in patients with recent imaging exposure. As contrast use continues to rise within federal health systems, regulatory and administrative stakeholders would do well to re-examine current safety frameworks. Informed consent should reflect what is known: gadolinium can remain in the body long after administration, potentially indefinitely. The long-term consequences of cumulative exposure remain poorly defined, but the presence of a lanthanide element in human tissue warrants greater attention from researchers and regulators alike. Interest in alternative imaging modalities and long-term safety monitoring would mark progress toward more transparent, accountable care.

The patient was diagnosed with erythema ab igne based on characteristic skin findings on physical examination along with a convincing history of chronic localized heat exposure. Erythema ab igne manifests as a persistent reticulated, erythematous, or hyperpigmented rash at sites of chronic heat exposure.¹ Commonplace items that emit heat such as electric heaters, car heaters, heating pads, hot water bottles, and, in our case, laptops also emit infrared radiation, which can lead to changes in the skin with long-term exposure.² Because exposure to these sources often is limited to one area of the body, erythema ab igne usually manifests locally, as exemplified in this case. Chronic heat exposure and infrared radiation from these sources are thought to induce hyperthermia below the threshold for a thermal burn, and the cutaneous findings correspond with the dermal venous plexus.³

Diagnosis of erythema ab igne primarily is made clinically based on characteristic skin findings and exposure history. Relevant history may include occupations with prolonged heat exposure, such as baking, silversmithing, or foundry work. Heat exposure also may result from cultural practices such as cupping with moxibustion.⁴ Additionally, repeated use of heating pads or hot water bottles for pain relief by patients diagnosed with chronic pain or an underlying illness may contribute to development of erythema ab igne.^1,4

Biopsy was not needed for diagnosis of this patient, but if the presentation is equivocal and history of potential exposures is unclear, a biopsy may be taken. A hematoxylin and eosin stain would reveal dilation of small vascular channels in the superficial dermis, contributing to the classic reticulated appearance. Biopsy findings also would reveal either an interface dermatitis or pigment incontinence containing melanin-laden macrophages correlating to either the erythema or hyperpigmentation, respectively.⁴

The prognosis for erythema ab igne is excellent, especially if diagnosed early. Treatment involves removal of the inciting heat source.¹ The discoloration may resolve within a few months to years or may persist. If the hyperpigmentation is persistent, patients may consider laser treatments or lightening agents such as topical hydroquinone or topical tretinoin.⁴ However, if undiagnosed, patients may be at risk for development of a cutaneous malignancy, such as squamous cell carcinoma, Merkel cell carcinoma, poorly differentiated carcinoma, or cutaneous marginal zone lymphoma.^2,4 Malignant transformation has been reported to occur decades after the initial skin eruption, although the risk is rare⁵; however, due to this risk, patients with erythema ab igne should be followed regularly and screened for new lesions in the affected areas.

The patient was diagnosed with erythema ab igne based on characteristic skin findings on physical examination along with a convincing history of chronic localized heat exposure. Erythema ab igne manifests as a persistent reticulated, erythematous, or hyperpigmented rash at sites of chronic heat exposure.¹ Commonplace items that emit heat such as electric heaters, car heaters, heating pads, hot water bottles, and, in our case, laptops also emit infrared radiation, which can lead to changes in the skin with long-term exposure.² Because exposure to these sources often is limited to one area of the body, erythema ab igne usually manifests locally, as exemplified in this case. Chronic heat exposure and infrared radiation from these sources are thought to induce hyperthermia below the threshold for a thermal burn, and the cutaneous findings correspond with the dermal venous plexus.³

Diagnosis of erythema ab igne primarily is made clinically based on characteristic skin findings and exposure history. Relevant history may include occupations with prolonged heat exposure, such as baking, silversmithing, or foundry work. Heat exposure also may result from cultural practices such as cupping with moxibustion.⁴ Additionally, repeated use of heating pads or hot water bottles for pain relief by patients diagnosed with chronic pain or an underlying illness may contribute to development of erythema ab igne.^1,4

Biopsy was not needed for diagnosis of this patient, but if the presentation is equivocal and history of potential exposures is unclear, a biopsy may be taken. A hematoxylin and eosin stain would reveal dilation of small vascular channels in the superficial dermis, contributing to the classic reticulated appearance. Biopsy findings also would reveal either an interface dermatitis or pigment incontinence containing melanin-laden macrophages correlating to either the erythema or hyperpigmentation, respectively.⁴

The prognosis for erythema ab igne is excellent, especially if diagnosed early. Treatment involves removal of the inciting heat source.¹ The discoloration may resolve within a few months to years or may persist. If the hyperpigmentation is persistent, patients may consider laser treatments or lightening agents such as topical hydroquinone or topical tretinoin.⁴ However, if undiagnosed, patients may be at risk for development of a cutaneous malignancy, such as squamous cell carcinoma, Merkel cell carcinoma, poorly differentiated carcinoma, or cutaneous marginal zone lymphoma.^2,4 Malignant transformation has been reported to occur decades after the initial skin eruption, although the risk is rare⁵; however, due to this risk, patients with erythema ab igne should be followed regularly and screened for new lesions in the affected areas.

The patient was diagnosed with erythema ab igne based on characteristic skin findings on physical examination along with a convincing history of chronic localized heat exposure. Erythema ab igne manifests as a persistent reticulated, erythematous, or hyperpigmented rash at sites of chronic heat exposure.¹ Commonplace items that emit heat such as electric heaters, car heaters, heating pads, hot water bottles, and, in our case, laptops also emit infrared radiation, which can lead to changes in the skin with long-term exposure.² Because exposure to these sources often is limited to one area of the body, erythema ab igne usually manifests locally, as exemplified in this case. Chronic heat exposure and infrared radiation from these sources are thought to induce hyperthermia below the threshold for a thermal burn, and the cutaneous findings correspond with the dermal venous plexus.³

Diagnosis of erythema ab igne primarily is made clinically based on characteristic skin findings and exposure history. Relevant history may include occupations with prolonged heat exposure, such as baking, silversmithing, or foundry work. Heat exposure also may result from cultural practices such as cupping with moxibustion.⁴ Additionally, repeated use of heating pads or hot water bottles for pain relief by patients diagnosed with chronic pain or an underlying illness may contribute to development of erythema ab igne.^1,4

Biopsy was not needed for diagnosis of this patient, but if the presentation is equivocal and history of potential exposures is unclear, a biopsy may be taken. A hematoxylin and eosin stain would reveal dilation of small vascular channels in the superficial dermis, contributing to the classic reticulated appearance. Biopsy findings also would reveal either an interface dermatitis or pigment incontinence containing melanin-laden macrophages correlating to either the erythema or hyperpigmentation, respectively.⁴

The prognosis for erythema ab igne is excellent, especially if diagnosed early. Treatment involves removal of the inciting heat source.¹ The discoloration may resolve within a few months to years or may persist. If the hyperpigmentation is persistent, patients may consider laser treatments or lightening agents such as topical hydroquinone or topical tretinoin.⁴ However, if undiagnosed, patients may be at risk for development of a cutaneous malignancy, such as squamous cell carcinoma, Merkel cell carcinoma, poorly differentiated carcinoma, or cutaneous marginal zone lymphoma.^2,4 Malignant transformation has been reported to occur decades after the initial skin eruption, although the risk is rare⁵; however, due to this risk, patients with erythema ab igne should be followed regularly and screened for new lesions in the affected areas.

TOPLINE: Large Language Models (LLMs) achieve more than 95% accuracy in extracting colorectal cancer and dysplasia diagnoses from Veterans Health Administration (VHA) pathology reports, including patients with Million Veteran Program (MVP) genomic data. The validated approach using publicly available LLMs demonstrates excellent performance across both Inflammatory Bowel Disease (IBD) and non-IBD populations.

METHODOLOGY: 

Researchers analyzed 116,373 pathology reports generated in the VHA between 1999 and 2024, utilizing search term filtering followed by simple yes/no question prompts for identifying colorectal dysplasia, high-grade dysplasia and/or colorectal adenocarcinoma, and invasive colorectal cancer.

• Results were compared to blinded manual chart review of 200 to 300 pathology reports for each patient cohort and diagnostic task, totaling 3,816 reviewed reports, to validate the LLM approach.

• Validation was performed independently in IBD and non-IBD populations using Gemma-2 and Llama-3 LLMs without any task-specific training or fine-tuning.

• Performance metrics included F1 scores, positive predictive value, negative predictive value, sensitivity, specificity, and Matthew's correlation coefficient to evaluate accuracy across different tasks.

TAKEAWAY:

• In patients with IBD in the MVP, the LLM achieved (F1-score, 96.9%; 95% confidence interval [CI], 94.0%-99.6%) for identifying dysplasia, (F1-score, 93.7%; 95% CI, 88.2%-98.4%) for identifying high-grade dysplasia/colorectal cancer, and (F1-score, 98%; 95% CI, 96.3%-99.4%) for identifying colorectal cancer.

• In non-IBD MVP patients, the LLM demonstrated (F1-score, 99.2%; 95% CI, 98.2%-100%) for identifying colorectal dysplasia, (F1-score, 96.5%; 95% CI, 93.0%-99.2%) for high-grade dysplasia/colorectal cancer, and (F1-score, 95%; 95% CI, 92.8%-97.2%) for identifying colorectal cancer.

• Agreement between reviewers was excellent across tasks, with (Cohen's kappa, 89%-97%) for main tasks, and (Cohen's kappa, 78.1%-93.1%) for indefinite for dysplasia in IBD cohort.

• The LLM approach maintained high accuracy when applied to full pathology reports, with (F1-score, 97.1%; 95% CI, 93.5%-100%) for dysplasia detection in IBD patients.

IN PRACTICE: “We have shown that LLMs are powerful, potentially generalizable tools for accurately extracting important information from clinical semistructured and unstructured text and which require little human-led development.” the authors of the study wrote

SOURCE: The study was based on data from the Million Veteran Program and supported by the Office of Research and Development, Veterans Health Administration, and the US Department of Veterans Affairs Biomedical Laboratory. It was published online in BMJ Open Gastroenterology.

LIMITATIONS:  According to the authors, this research may be specific to the VHA system and the LLM models used. The authors did not test larger models. The authors acknowledge that without long-term access to graphics processing units, they could not feasibly test larger models, which may overcome some of the shortcomings seen in smaller models. Additionally, the researchers could not rule out overlap between Million Veteran Program and Corporate Data Warehouse reports, though they state that results in either cohort alone are sufficient validation compared with previously published work.

DISCLOSURES: The study was supported by Merit Review Award from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, AGA Research Foundation, National Institutes of Health grants, and the National Library of Medicine Training Grant. Kit Curtius reported receiving an investigator-led research grant from Phathom Pharmaceuticals. Shailja C Shah disclosed being a paid consultant for RedHill Biopharma and Phathom Pharmaceuticals, and an unpaid scientific advisory board member for Ilico Genetics, Inc.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: Large Language Models (LLMs) achieve more than 95% accuracy in extracting colorectal cancer and dysplasia diagnoses from Veterans Health Administration (VHA) pathology reports, including patients with Million Veteran Program (MVP) genomic data. The validated approach using publicly available LLMs demonstrates excellent performance across both Inflammatory Bowel Disease (IBD) and non-IBD populations.

METHODOLOGY: 

Researchers analyzed 116,373 pathology reports generated in the VHA between 1999 and 2024, utilizing search term filtering followed by simple yes/no question prompts for identifying colorectal dysplasia, high-grade dysplasia and/or colorectal adenocarcinoma, and invasive colorectal cancer.

• Results were compared to blinded manual chart review of 200 to 300 pathology reports for each patient cohort and diagnostic task, totaling 3,816 reviewed reports, to validate the LLM approach.

• Validation was performed independently in IBD and non-IBD populations using Gemma-2 and Llama-3 LLMs without any task-specific training or fine-tuning.

• Performance metrics included F1 scores, positive predictive value, negative predictive value, sensitivity, specificity, and Matthew's correlation coefficient to evaluate accuracy across different tasks.

TAKEAWAY:

• In patients with IBD in the MVP, the LLM achieved (F1-score, 96.9%; 95% confidence interval [CI], 94.0%-99.6%) for identifying dysplasia, (F1-score, 93.7%; 95% CI, 88.2%-98.4%) for identifying high-grade dysplasia/colorectal cancer, and (F1-score, 98%; 95% CI, 96.3%-99.4%) for identifying colorectal cancer.

• In non-IBD MVP patients, the LLM demonstrated (F1-score, 99.2%; 95% CI, 98.2%-100%) for identifying colorectal dysplasia, (F1-score, 96.5%; 95% CI, 93.0%-99.2%) for high-grade dysplasia/colorectal cancer, and (F1-score, 95%; 95% CI, 92.8%-97.2%) for identifying colorectal cancer.

• Agreement between reviewers was excellent across tasks, with (Cohen's kappa, 89%-97%) for main tasks, and (Cohen's kappa, 78.1%-93.1%) for indefinite for dysplasia in IBD cohort.

• The LLM approach maintained high accuracy when applied to full pathology reports, with (F1-score, 97.1%; 95% CI, 93.5%-100%) for dysplasia detection in IBD patients.

IN PRACTICE: “We have shown that LLMs are powerful, potentially generalizable tools for accurately extracting important information from clinical semistructured and unstructured text and which require little human-led development.” the authors of the study wrote

SOURCE: The study was based on data from the Million Veteran Program and supported by the Office of Research and Development, Veterans Health Administration, and the US Department of Veterans Affairs Biomedical Laboratory. It was published online in BMJ Open Gastroenterology.

LIMITATIONS:  According to the authors, this research may be specific to the VHA system and the LLM models used. The authors did not test larger models. The authors acknowledge that without long-term access to graphics processing units, they could not feasibly test larger models, which may overcome some of the shortcomings seen in smaller models. Additionally, the researchers could not rule out overlap between Million Veteran Program and Corporate Data Warehouse reports, though they state that results in either cohort alone are sufficient validation compared with previously published work.

DISCLOSURES: The study was supported by Merit Review Award from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, AGA Research Foundation, National Institutes of Health grants, and the National Library of Medicine Training Grant. Kit Curtius reported receiving an investigator-led research grant from Phathom Pharmaceuticals. Shailja C Shah disclosed being a paid consultant for RedHill Biopharma and Phathom Pharmaceuticals, and an unpaid scientific advisory board member for Ilico Genetics, Inc.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: Large Language Models (LLMs) achieve more than 95% accuracy in extracting colorectal cancer and dysplasia diagnoses from Veterans Health Administration (VHA) pathology reports, including patients with Million Veteran Program (MVP) genomic data. The validated approach using publicly available LLMs demonstrates excellent performance across both Inflammatory Bowel Disease (IBD) and non-IBD populations.

METHODOLOGY: 

Researchers analyzed 116,373 pathology reports generated in the VHA between 1999 and 2024, utilizing search term filtering followed by simple yes/no question prompts for identifying colorectal dysplasia, high-grade dysplasia and/or colorectal adenocarcinoma, and invasive colorectal cancer.

• Results were compared to blinded manual chart review of 200 to 300 pathology reports for each patient cohort and diagnostic task, totaling 3,816 reviewed reports, to validate the LLM approach.

• Validation was performed independently in IBD and non-IBD populations using Gemma-2 and Llama-3 LLMs without any task-specific training or fine-tuning.

• Performance metrics included F1 scores, positive predictive value, negative predictive value, sensitivity, specificity, and Matthew's correlation coefficient to evaluate accuracy across different tasks.

TAKEAWAY:

• In patients with IBD in the MVP, the LLM achieved (F1-score, 96.9%; 95% confidence interval [CI], 94.0%-99.6%) for identifying dysplasia, (F1-score, 93.7%; 95% CI, 88.2%-98.4%) for identifying high-grade dysplasia/colorectal cancer, and (F1-score, 98%; 95% CI, 96.3%-99.4%) for identifying colorectal cancer.

• In non-IBD MVP patients, the LLM demonstrated (F1-score, 99.2%; 95% CI, 98.2%-100%) for identifying colorectal dysplasia, (F1-score, 96.5%; 95% CI, 93.0%-99.2%) for high-grade dysplasia/colorectal cancer, and (F1-score, 95%; 95% CI, 92.8%-97.2%) for identifying colorectal cancer.

• Agreement between reviewers was excellent across tasks, with (Cohen's kappa, 89%-97%) for main tasks, and (Cohen's kappa, 78.1%-93.1%) for indefinite for dysplasia in IBD cohort.

• The LLM approach maintained high accuracy when applied to full pathology reports, with (F1-score, 97.1%; 95% CI, 93.5%-100%) for dysplasia detection in IBD patients.

IN PRACTICE: “We have shown that LLMs are powerful, potentially generalizable tools for accurately extracting important information from clinical semistructured and unstructured text and which require little human-led development.” the authors of the study wrote

SOURCE: The study was based on data from the Million Veteran Program and supported by the Office of Research and Development, Veterans Health Administration, and the US Department of Veterans Affairs Biomedical Laboratory. It was published online in BMJ Open Gastroenterology.

LIMITATIONS:  According to the authors, this research may be specific to the VHA system and the LLM models used. The authors did not test larger models. The authors acknowledge that without long-term access to graphics processing units, they could not feasibly test larger models, which may overcome some of the shortcomings seen in smaller models. Additionally, the researchers could not rule out overlap between Million Veteran Program and Corporate Data Warehouse reports, though they state that results in either cohort alone are sufficient validation compared with previously published work.

DISCLOSURES: The study was supported by Merit Review Award from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, AGA Research Foundation, National Institutes of Health grants, and the National Library of Medicine Training Grant. Kit Curtius reported receiving an investigator-led research grant from Phathom Pharmaceuticals. Shailja C Shah disclosed being a paid consultant for RedHill Biopharma and Phathom Pharmaceuticals, and an unpaid scientific advisory board member for Ilico Genetics, Inc.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Discussion

A diagnosis of lichen sclerosus (LS) was made based on clinical and dermoscopic features, followed by confirmation with histology. The patient’s presentation included typical signs and symptoms of LS: itching, burning, intermittent bleeding, perianal hemorrhage, fusion of the clitoral head, and fissures. Other presentations can include dyspareunia, erosions, and excoriations; however, these symptoms and signs were not reported or seen in this patient.

LS typically affects the anogenital region and has 2 peak incidences: in preadolescent teens and during the fifth to sixth decade of life.¹ This patient presented with a case of extragenital LS, which is less common than the classic presentation of LS that affects the genitals. This variant’s epidemiology differs, as it is less common in children and more common in postmenopausal women.² Extragenital LS presents as white, atrophic plaques with a predilection for sites including the trunk, breasts, upper arms, and sites of physical trauma, with symptoms of dryness and pruritus. Over time, the papules can coalesce and form ivory, scar-like papules or plaques with a wrinkled surface. In advanced stages, telangiectasia or follicular plugging can be present, along with flattening of the dermal-epidermal junction. This flat interface is fragile and can result in bullae that may become hemorrhagic.

Cutaneous squamous cell carcinoma (SCC) may infrequently arise from LS, similar to other chronic inflammatory dermatoses.³ Lichen planus is typically not associated with an increased risk of SCC, except in the oral and hypertrophic variants. However, LS may be considered a premalignant process, and many vulvar SCC cases are noted to have adjacent LS lesions.³

Autoimmune and genetic factors contribute to the pathogenesis of LS. Extracellular matrix protein 1 (ECM1) binds molecules of the basement membrane zone and dermis, contributing to the structure and integrity of skin. Autoantibodies against ECM1 and other antigens of the basement membrane zone, including BP180 and BP320, were found in LS.² HLA-DQ7 major histocompatibility complex class II antigens have been associated with LS.¹

On histologic examination, the epidermis of LS is atrophic with hyperkeratosis. The dermis shows homogenization and sclerosis of superficial collagen with a band-like lymphocytic infiltrate below the sclerosis. The basal layer is thickened, showing basal cell vacuolization and hydropic degeneration.⁴

First-line treatment for genital and extragenital variants of LS is high-potency topical steroids for 3 months or until the skin texture and color resolve (ie, clobetasol 0.05% cream or ointment). The second-line treatment is a topical calcineurin inhibitor. These treatments are used for management. They are not cures for LS, as relapse is possible after the initial treatment course is completed. Adverse effects of high potency topical steroids are skin burning, skin atrophy, and fragility, telangiectasia. The adverse effects of topical calcineurin inhibitors are stinging and burning on application.

Other Diagnostic Considerations

Inverse psoriasis (IP) is a variant of psoriasis that presents as erythematous, well-demarcated plaques with minimal scale in intertriginous areas and flexural surfaces. Localized dermatophyte, candidal, or bacterial infections can trigger IP.⁵ It occurs in about 3% to 7% of patients with plaque psoriasis and is thought to form due to koebnerization via mechanical friction of flexural zones.⁶ The patient described in this case did not have IP because IP would be more likely to present as a well-demarcated erythematous plaque rather than a patch.

Histologically, IP shows regular psoriasiform acanthosis and hypogranulosis of the epidermis, Munro microabscess, spongiform pustules of Kogoj, dilated tortuous dermal vessels, and thinning of the suprapapillary plates.⁵

Lichen planus pigmentosus-inversus (LPPI) is also known as lichen planus pigmentosus—intertriginous variant. This variant of lichen planus pigmentosus presents as multiple gray to dark brown macules and patches with poorly defined borders in a linear distribution limited to intertriginous areas, flexural surfaces, or following the lines of Blaschko.⁷ About 20% of cases present with frontal fibrosing alopecia. It is most common in individuals with intermediate and darker skin pigmentation, has a higher prevalence in females, and typically occurs within the third and fifth decades of life. Friction is a common trigger of LPPI.⁷ A diagnosis of LPPI is incorrect because the lesions would present as gray to dark brown macules, as opposed to the shiny white atrophic thin papules with surrounding pink and purple patches seen in this case.

Histologically, while both LS and LPPI share band-like lymphocytic infiltrate and basal cell vacuolization, findings in the dermis differ. LPPI shows melanophages and prominent melanin incontinence, while LS shows homogenization and sclerosis of superficial collagen.^1,8 LPPI also shows absence of compensatory keratinocyte proliferation.

Morphea is an inflammatory disease that affects the dermis and subcutaneous fat, resulting in sclerosis that appears scarlike. Its prevalence increases with age and has a 4:1 prevalence in females, with the plaque type being the most common variant. ⁹ The typical presentation of plaque-type morphea is an insidious onset of asymptomatic, slightly elevated, erythematous or violaceous, slightly edematous plaques with centrifugal expansion. The center of the plaque may become sclerotic and indurated, acquiring a shiny white color with a peripheral “lilac” ring. Trunk and upper extremity involvement is common. Morphea is associated with increased antisingle-stranded DNA, antitopoisomerase IIa, antiphospholipid, antifibrillin-1, and antihistone antibodies. Triggers of morphea are believed to be localized insults to the skin, including mechanical trauma, injections, vaccinations, and irradiation.⁹ This answer is incorrect because the patient’s lesions were pruritic and had genital involvement, which are not typical of morphea. Morphea can be differentiated with based on symptoms (lack of pruritus, pain, burning), morphology of lesions (induration versus atrophy), dermoscopy (fibrotic beams with less scale and hemorrhage vs keratotic follicular plugs), and histopathology (depth of inflammation in superficial and deep dermis).

Histology of morphea can differ based on the stage, whether the lesion is sampled in the inflammatory margin or central sclerosis, and the depth of affected skin. At the inflammatory margin, vascular changes, including endothelial swelling and edema, are present, as well as CD4+ T cells, eosinophils, plasma cells, and mast cells surrounding smaller blood vessels. In late stages, the inflammatory infiltrate is no longer present, the epidermis appears regular, and there is a flattened dermal-epidermal junction. Distinct features include homogenous collagen bundles that replace many dermal structures, with atrophic eccrine glands that appear “trapped” in the thickened dermis, and homogenized and hyalinized subcutis.⁹

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma and presents as annular, erythematous or hypopigmented patches and plaques with fine scale and tumors on the buttocks and sun-protected areas of the limbs and trunk. Lesions can appear with prominent poikiloderma or atrophic or lichenified skin.¹⁰ It is most common in males of African descent aged 50 to 55 years. The etiology is largely unknown but believed to be multifactorial. This answer is incorrect because the lesions in this patient appeared more atrophic, were less well demarcated, and lacked the scale that would be present in MF.

On histology, both LS and MF show band-like lymphocytic infiltrate, however MF lacks the homogenization and sclerosis of superficial collagen that is present in the dermis of LS. Also, MF demonstrates epidermotropism of atypical lymphocytes forming Pautrier microabscess.¹⁰

Primary Care Role

Primary care physicians can diagnose and treat LS. Referral to dermatology is not mandatory. Note that topical steroids can be used daily for up to 12 weeks. In LS, early treatment is associated with improved outcomes and minimizes the risk of irreversible skin changes.¹¹ Follow-up during the treatment period is recommended to monitor subjective and objective response to treatment. Follow-up after the initial treatment is recommended since LS is typically chronic, can relapse, and SCC can infrequently arise from LS lesions.¹¹

Discussion

A diagnosis of lichen sclerosus (LS) was made based on clinical and dermoscopic features, followed by confirmation with histology. The patient’s presentation included typical signs and symptoms of LS: itching, burning, intermittent bleeding, perianal hemorrhage, fusion of the clitoral head, and fissures. Other presentations can include dyspareunia, erosions, and excoriations; however, these symptoms and signs were not reported or seen in this patient.

LS typically affects the anogenital region and has 2 peak incidences: in preadolescent teens and during the fifth to sixth decade of life.¹ This patient presented with a case of extragenital LS, which is less common than the classic presentation of LS that affects the genitals. This variant’s epidemiology differs, as it is less common in children and more common in postmenopausal women.² Extragenital LS presents as white, atrophic plaques with a predilection for sites including the trunk, breasts, upper arms, and sites of physical trauma, with symptoms of dryness and pruritus. Over time, the papules can coalesce and form ivory, scar-like papules or plaques with a wrinkled surface. In advanced stages, telangiectasia or follicular plugging can be present, along with flattening of the dermal-epidermal junction. This flat interface is fragile and can result in bullae that may become hemorrhagic.

Cutaneous squamous cell carcinoma (SCC) may infrequently arise from LS, similar to other chronic inflammatory dermatoses.³ Lichen planus is typically not associated with an increased risk of SCC, except in the oral and hypertrophic variants. However, LS may be considered a premalignant process, and many vulvar SCC cases are noted to have adjacent LS lesions.³

Autoimmune and genetic factors contribute to the pathogenesis of LS. Extracellular matrix protein 1 (ECM1) binds molecules of the basement membrane zone and dermis, contributing to the structure and integrity of skin. Autoantibodies against ECM1 and other antigens of the basement membrane zone, including BP180 and BP320, were found in LS.² HLA-DQ7 major histocompatibility complex class II antigens have been associated with LS.¹

On histologic examination, the epidermis of LS is atrophic with hyperkeratosis. The dermis shows homogenization and sclerosis of superficial collagen with a band-like lymphocytic infiltrate below the sclerosis. The basal layer is thickened, showing basal cell vacuolization and hydropic degeneration.⁴

First-line treatment for genital and extragenital variants of LS is high-potency topical steroids for 3 months or until the skin texture and color resolve (ie, clobetasol 0.05% cream or ointment). The second-line treatment is a topical calcineurin inhibitor. These treatments are used for management. They are not cures for LS, as relapse is possible after the initial treatment course is completed. Adverse effects of high potency topical steroids are skin burning, skin atrophy, and fragility, telangiectasia. The adverse effects of topical calcineurin inhibitors are stinging and burning on application.

Other Diagnostic Considerations

Inverse psoriasis (IP) is a variant of psoriasis that presents as erythematous, well-demarcated plaques with minimal scale in intertriginous areas and flexural surfaces. Localized dermatophyte, candidal, or bacterial infections can trigger IP.⁵ It occurs in about 3% to 7% of patients with plaque psoriasis and is thought to form due to koebnerization via mechanical friction of flexural zones.⁶ The patient described in this case did not have IP because IP would be more likely to present as a well-demarcated erythematous plaque rather than a patch.

Histologically, IP shows regular psoriasiform acanthosis and hypogranulosis of the epidermis, Munro microabscess, spongiform pustules of Kogoj, dilated tortuous dermal vessels, and thinning of the suprapapillary plates.⁵

Lichen planus pigmentosus-inversus (LPPI) is also known as lichen planus pigmentosus—intertriginous variant. This variant of lichen planus pigmentosus presents as multiple gray to dark brown macules and patches with poorly defined borders in a linear distribution limited to intertriginous areas, flexural surfaces, or following the lines of Blaschko.⁷ About 20% of cases present with frontal fibrosing alopecia. It is most common in individuals with intermediate and darker skin pigmentation, has a higher prevalence in females, and typically occurs within the third and fifth decades of life. Friction is a common trigger of LPPI.⁷ A diagnosis of LPPI is incorrect because the lesions would present as gray to dark brown macules, as opposed to the shiny white atrophic thin papules with surrounding pink and purple patches seen in this case.

Histologically, while both LS and LPPI share band-like lymphocytic infiltrate and basal cell vacuolization, findings in the dermis differ. LPPI shows melanophages and prominent melanin incontinence, while LS shows homogenization and sclerosis of superficial collagen.^1,8 LPPI also shows absence of compensatory keratinocyte proliferation.

Morphea is an inflammatory disease that affects the dermis and subcutaneous fat, resulting in sclerosis that appears scarlike. Its prevalence increases with age and has a 4:1 prevalence in females, with the plaque type being the most common variant. ⁹ The typical presentation of plaque-type morphea is an insidious onset of asymptomatic, slightly elevated, erythematous or violaceous, slightly edematous plaques with centrifugal expansion. The center of the plaque may become sclerotic and indurated, acquiring a shiny white color with a peripheral “lilac” ring. Trunk and upper extremity involvement is common. Morphea is associated with increased antisingle-stranded DNA, antitopoisomerase IIa, antiphospholipid, antifibrillin-1, and antihistone antibodies. Triggers of morphea are believed to be localized insults to the skin, including mechanical trauma, injections, vaccinations, and irradiation.⁹ This answer is incorrect because the patient’s lesions were pruritic and had genital involvement, which are not typical of morphea. Morphea can be differentiated with based on symptoms (lack of pruritus, pain, burning), morphology of lesions (induration versus atrophy), dermoscopy (fibrotic beams with less scale and hemorrhage vs keratotic follicular plugs), and histopathology (depth of inflammation in superficial and deep dermis).

Histology of morphea can differ based on the stage, whether the lesion is sampled in the inflammatory margin or central sclerosis, and the depth of affected skin. At the inflammatory margin, vascular changes, including endothelial swelling and edema, are present, as well as CD4+ T cells, eosinophils, plasma cells, and mast cells surrounding smaller blood vessels. In late stages, the inflammatory infiltrate is no longer present, the epidermis appears regular, and there is a flattened dermal-epidermal junction. Distinct features include homogenous collagen bundles that replace many dermal structures, with atrophic eccrine glands that appear “trapped” in the thickened dermis, and homogenized and hyalinized subcutis.⁹

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma and presents as annular, erythematous or hypopigmented patches and plaques with fine scale and tumors on the buttocks and sun-protected areas of the limbs and trunk. Lesions can appear with prominent poikiloderma or atrophic or lichenified skin.¹⁰ It is most common in males of African descent aged 50 to 55 years. The etiology is largely unknown but believed to be multifactorial. This answer is incorrect because the lesions in this patient appeared more atrophic, were less well demarcated, and lacked the scale that would be present in MF.

On histology, both LS and MF show band-like lymphocytic infiltrate, however MF lacks the homogenization and sclerosis of superficial collagen that is present in the dermis of LS. Also, MF demonstrates epidermotropism of atypical lymphocytes forming Pautrier microabscess.¹⁰

Primary Care Role

Primary care physicians can diagnose and treat LS. Referral to dermatology is not mandatory. Note that topical steroids can be used daily for up to 12 weeks. In LS, early treatment is associated with improved outcomes and minimizes the risk of irreversible skin changes.¹¹ Follow-up during the treatment period is recommended to monitor subjective and objective response to treatment. Follow-up after the initial treatment is recommended since LS is typically chronic, can relapse, and SCC can infrequently arise from LS lesions.¹¹

Discussion

A diagnosis of lichen sclerosus (LS) was made based on clinical and dermoscopic features, followed by confirmation with histology. The patient’s presentation included typical signs and symptoms of LS: itching, burning, intermittent bleeding, perianal hemorrhage, fusion of the clitoral head, and fissures. Other presentations can include dyspareunia, erosions, and excoriations; however, these symptoms and signs were not reported or seen in this patient.

LS typically affects the anogenital region and has 2 peak incidences: in preadolescent teens and during the fifth to sixth decade of life.¹ This patient presented with a case of extragenital LS, which is less common than the classic presentation of LS that affects the genitals. This variant’s epidemiology differs, as it is less common in children and more common in postmenopausal women.² Extragenital LS presents as white, atrophic plaques with a predilection for sites including the trunk, breasts, upper arms, and sites of physical trauma, with symptoms of dryness and pruritus. Over time, the papules can coalesce and form ivory, scar-like papules or plaques with a wrinkled surface. In advanced stages, telangiectasia or follicular plugging can be present, along with flattening of the dermal-epidermal junction. This flat interface is fragile and can result in bullae that may become hemorrhagic.

Cutaneous squamous cell carcinoma (SCC) may infrequently arise from LS, similar to other chronic inflammatory dermatoses.³ Lichen planus is typically not associated with an increased risk of SCC, except in the oral and hypertrophic variants. However, LS may be considered a premalignant process, and many vulvar SCC cases are noted to have adjacent LS lesions.³

Autoimmune and genetic factors contribute to the pathogenesis of LS. Extracellular matrix protein 1 (ECM1) binds molecules of the basement membrane zone and dermis, contributing to the structure and integrity of skin. Autoantibodies against ECM1 and other antigens of the basement membrane zone, including BP180 and BP320, were found in LS.² HLA-DQ7 major histocompatibility complex class II antigens have been associated with LS.¹

On histologic examination, the epidermis of LS is atrophic with hyperkeratosis. The dermis shows homogenization and sclerosis of superficial collagen with a band-like lymphocytic infiltrate below the sclerosis. The basal layer is thickened, showing basal cell vacuolization and hydropic degeneration.⁴

First-line treatment for genital and extragenital variants of LS is high-potency topical steroids for 3 months or until the skin texture and color resolve (ie, clobetasol 0.05% cream or ointment). The second-line treatment is a topical calcineurin inhibitor. These treatments are used for management. They are not cures for LS, as relapse is possible after the initial treatment course is completed. Adverse effects of high potency topical steroids are skin burning, skin atrophy, and fragility, telangiectasia. The adverse effects of topical calcineurin inhibitors are stinging and burning on application.

Other Diagnostic Considerations

Inverse psoriasis (IP) is a variant of psoriasis that presents as erythematous, well-demarcated plaques with minimal scale in intertriginous areas and flexural surfaces. Localized dermatophyte, candidal, or bacterial infections can trigger IP.⁵ It occurs in about 3% to 7% of patients with plaque psoriasis and is thought to form due to koebnerization via mechanical friction of flexural zones.⁶ The patient described in this case did not have IP because IP would be more likely to present as a well-demarcated erythematous plaque rather than a patch.

Histologically, IP shows regular psoriasiform acanthosis and hypogranulosis of the epidermis, Munro microabscess, spongiform pustules of Kogoj, dilated tortuous dermal vessels, and thinning of the suprapapillary plates.⁵

Lichen planus pigmentosus-inversus (LPPI) is also known as lichen planus pigmentosus—intertriginous variant. This variant of lichen planus pigmentosus presents as multiple gray to dark brown macules and patches with poorly defined borders in a linear distribution limited to intertriginous areas, flexural surfaces, or following the lines of Blaschko.⁷ About 20% of cases present with frontal fibrosing alopecia. It is most common in individuals with intermediate and darker skin pigmentation, has a higher prevalence in females, and typically occurs within the third and fifth decades of life. Friction is a common trigger of LPPI.⁷ A diagnosis of LPPI is incorrect because the lesions would present as gray to dark brown macules, as opposed to the shiny white atrophic thin papules with surrounding pink and purple patches seen in this case.

Histologically, while both LS and LPPI share band-like lymphocytic infiltrate and basal cell vacuolization, findings in the dermis differ. LPPI shows melanophages and prominent melanin incontinence, while LS shows homogenization and sclerosis of superficial collagen.^1,8 LPPI also shows absence of compensatory keratinocyte proliferation.

Morphea is an inflammatory disease that affects the dermis and subcutaneous fat, resulting in sclerosis that appears scarlike. Its prevalence increases with age and has a 4:1 prevalence in females, with the plaque type being the most common variant. ⁹ The typical presentation of plaque-type morphea is an insidious onset of asymptomatic, slightly elevated, erythematous or violaceous, slightly edematous plaques with centrifugal expansion. The center of the plaque may become sclerotic and indurated, acquiring a shiny white color with a peripheral “lilac” ring. Trunk and upper extremity involvement is common. Morphea is associated with increased antisingle-stranded DNA, antitopoisomerase IIa, antiphospholipid, antifibrillin-1, and antihistone antibodies. Triggers of morphea are believed to be localized insults to the skin, including mechanical trauma, injections, vaccinations, and irradiation.⁹ This answer is incorrect because the patient’s lesions were pruritic and had genital involvement, which are not typical of morphea. Morphea can be differentiated with based on symptoms (lack of pruritus, pain, burning), morphology of lesions (induration versus atrophy), dermoscopy (fibrotic beams with less scale and hemorrhage vs keratotic follicular plugs), and histopathology (depth of inflammation in superficial and deep dermis).

Histology of morphea can differ based on the stage, whether the lesion is sampled in the inflammatory margin or central sclerosis, and the depth of affected skin. At the inflammatory margin, vascular changes, including endothelial swelling and edema, are present, as well as CD4+ T cells, eosinophils, plasma cells, and mast cells surrounding smaller blood vessels. In late stages, the inflammatory infiltrate is no longer present, the epidermis appears regular, and there is a flattened dermal-epidermal junction. Distinct features include homogenous collagen bundles that replace many dermal structures, with atrophic eccrine glands that appear “trapped” in the thickened dermis, and homogenized and hyalinized subcutis.⁹

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma and presents as annular, erythematous or hypopigmented patches and plaques with fine scale and tumors on the buttocks and sun-protected areas of the limbs and trunk. Lesions can appear with prominent poikiloderma or atrophic or lichenified skin.¹⁰ It is most common in males of African descent aged 50 to 55 years. The etiology is largely unknown but believed to be multifactorial. This answer is incorrect because the lesions in this patient appeared more atrophic, were less well demarcated, and lacked the scale that would be present in MF.

On histology, both LS and MF show band-like lymphocytic infiltrate, however MF lacks the homogenization and sclerosis of superficial collagen that is present in the dermis of LS. Also, MF demonstrates epidermotropism of atypical lymphocytes forming Pautrier microabscess.¹⁰

Primary Care Role

Primary care physicians can diagnose and treat LS. Referral to dermatology is not mandatory. Note that topical steroids can be used daily for up to 12 weeks. In LS, early treatment is associated with improved outcomes and minimizes the risk of irreversible skin changes.¹¹ Follow-up during the treatment period is recommended to monitor subjective and objective response to treatment. Follow-up after the initial treatment is recommended since LS is typically chronic, can relapse, and SCC can infrequently arise from LS lesions.¹¹

Clinical simulation is a technique, not a technology, used to replace or amplify real experiences with guided experiences that evoke or replicate substantial aspects of the real world in a fully interactive fashion.¹ Simulation is widely used in medical education and spans a spectrum of sophistication, from simple reproduction of isolated body parts to high-fidelity human patient simulators that replicate whole body appearance and variable physiological parameters.^2,3

Simulation-based medical education can be a valuable tool for safe health care delivery.⁴Simulation-based education is typically provided via 5 modalities: mannequins, computer-based mannequins, standardized patients, computer-based simulators, and software-based simulations. Simulation technology increases procedural skill by allowing for deliberate practice in a safe environment.⁵ Mastery learning is a stringent form of competency-based education that requires trainees to acquire clinical skill measured against a fixed achievement standard.⁶ In mastery learning, educational practice time varies but results are uniform. This approach improves patient outcomes and is more effective than clinical training alone.^7-9

Advanced simulation models are helpful tools for neurologic education and training, especially for emergency department encounters.¹⁰ In recent years, advanced simulation models have been applied in various fields of medicine, especially emergency medicine and anesthesia.^11-14

Acute neurology

In acute neurologic conditions (eg, stroke, intracerebral hemorrhage, status epilepticus, and neuromuscular respiratory failure) clinical outcomes are highly time dependent; consequently, a reduction in treatment delays can improve patient care. The application of simulation methodology allows trainees to address acute and potentially life-threatening emergencies in a safe, controlled, and reproducible environment. In addition to improving trainees’ knowledge base, simulation also helps to enhance team skills, communication, multidisciplinary collaboration, and leadership. Research has shown that deliberate practice leads to a decrease in clinical errors and improved procedural performance in the operating room.^8,15 These results can be extrapolated to acute neurology settings to improve adherence to set protocols, thus streamlining management in acute settings.

Scenarios can be built to teach skills such as eliciting an appropriate history, establishing inclusion or exclusion criteria for the use of certain medications, evaluating neuroimaging and laboratory studies (while avoiding related common pitfalls), and managing treatment complications. Simulation also provides an opportunity for interprofessional education by training nurses and collaborative staff. It can be used to enhance nontechnical skills (eg, communication, situation awareness, decision making, and leadership) that further contribute to patient safety. 

Simulation can be performed with the help of mannequins such as the SimMan 3G(Laerdal), which can display neurologic symptoms and physiological findings, or live actors who portray a patient by mimicking focal neurologic deficits.^16,17 A briefing familiarizes the trainees with the equipment and explains the simulation process. The documentation and equipment are the same as that which is used in emergency departments or intensive care units. 

Once the simulation is completed, a trainee’s performance is checked against a critical action checklist before a debriefing process during which the scenario is reviewed and learning goals are assessed. Immediate feedback is given to trainees to identify weaknesses and the simulation is repeated if multiple critical action items are missed. (Figure).¹⁷

RESIDENCY TRAINING

Simulation training in stroke is mandatory in some residency programs for neurology postgraduate year (PGY) 2 residents.¹⁸ These simulations are a part of a boot camp for incoming neurology residents after completing an internal medicine internship. The simulation program is not standardized across various training programs. The European Stroke Organization Simulation Committee has published an opinion paper with a consensus of experts about the implementation of simulation techniques in the stroke field.^19,20 Residents participating in these mandatory programs are required to complete certification in the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale, including a pretest that assesses their knowledge of acute stroke protocols prior to live simulation.¹⁷ A stepwise algorithm that incorporates faculty specialized in the field is used to evaluate and debrief the simulation.

Stroke vignettes are typically selected by the vascular neurology attending physician to cover thrombolytic therapy (indications and contraindications), mechanical thrombectomy, early arterial blood pressure management, anticoagulant reversal protocols, and management of thrombolytic complications (eg, neurologic worsening). Nursing staff is educated on the acute stroke protocol. Computed tomography (CT) and CT angiography scans are retrieved from teaching files. These are provided as live responses along with pertinent laboratory work, vital signs, and electrocardiogram tracings. Trainee performance is based on adherence to a critical action checklist, which includes (but is not limited to) identification of relative and absolute contraindications of thrombolytic treatments, estimation of NIHSS within 5 minutes of arrival, and consideration of candidacy for endovascular intervention.¹⁷

EVIDENCE FOR SIMULATION TRAINING

Simulations for acute ischemic stroke also improve cohesive teamwork to improve the door-to-needle and door-to-puncture time. A retrospective analysis involving first-year neurology residents at a comprehensive stroke center that compared patient cohort data before and after implementation of simulation training found that there was an improvement in door-to-needle time after implementation of stroke simulation training program by nearly 10 minutes.¹⁷ This was likely due to improvement in the comfort of the flow of management across multidisciplinary teams.

Discussing goals of care, communicating poor prognosis or complex decisions with distraught family members or patients requires practice. Simulation programs with video playback help focus on trainee’s body language, avoiding medical jargon and handling ethical dilemmas while adjusting the communication style to the patient’s personality.²⁰ Enhanced communication skills improve patient satisfaction, trust, and adherence to treatments, all of which lead to better outcomes.²¹

Simulation has been effectively used as a training tool for recognizing and managing acute neuromuscular respiratory failure. These scenarios emphasize the importance of obtaining a focused clinical history, performing key neurological assessments (such as neck flexion strength and breath counting), evaluating pulmonary function tests, and identifying when to initiate ventilatory support.²² In a study designed as a simulation-based learning curriculum for status epilepticus, there was an improvement in the performance of PGY-2 residents after completing the curriculum from a median of 44.2% at pretest to 94.2% at posttest.²³ In this curriculum, an emphasis was placed on the following: recognizing the delay in identification and treatment of status epilepticus; evaluating contraindications of certain antiseizure medication (ASM) based on history or laboratory work; giving first-line ASM within 5 minutes of seizure onset; airway and blood pressure assessment; suctioning the patient; use of second-line ASMs after first-line has failed; ordering a head CT and re-evaluating the case with postload ASM level; ordering a stat electroencephalography (EEG); and communicating the decision regarding patient disposition/level of care.²⁴

There is a growing need for well designed simulation education programs targeted at the management of disorders requiring acute neurologic care, including not only stroke and status epilepticus, but also traumatic brain injury, subarachnoid hemorrhage, neuromuscular respiratory failure, flare of multiple sclerosis, acutely elevated intracranial pressure, malignant cerebral infarction, deterioration of Parkinson disease, and brain death evaluation with family counseling.²⁵ This novel approach to teaching provides an opportunity to learn in addition to remediation with repetition of scenario and might be used for maintenance of recertification programs.

PROCEDURAL SKILLs

Perhaps one of the most studied uses for simulation in neurology is in procedural skills. This extends beyond neurology trainees and can include pulmonary critical care fellows, pediatric residents, and internal medicine residents receiving training in neurology-based procedures such as lumbar punctures (LPs). Other examples of neurology procedures and protocols in which simulation has been studied include fundoscopy, brain death evaluation, EEG interpretation in context of status epilepticus, and simulated stroke code responses. Additional procedures that lack research but may benefit from simulation-based training include the use of Doppler ultrasound and botulinum toxin injections practiced on mannequins.

Proficiency in LP procedural skills has been extensively studied by multiple institutions, with trainee levels ranging from medical students to fellows. One study in France enrolled 115 medical students without prior LP experience and randomized them to either a simulation or a control group.²⁶ Those in the simulation group received instruction using a mannequin, and those in the control group received clinical training through hospital rotations. Both groups received an email containing literature-based information on the procedure as well as a self-assessment questionnaire before participating in either educational program. 

The study showed that those students who received simulation training had a success rate of 67% on their first LP on a live patient compared with a success rate of 14% in those with traditional training. Students receiving simulation training required less assistance during the procedure from a supervisor and had higher satisfaction rates and confidence in their procedural skills.²⁶

Another study of 128 medical students at the University of Pittsburgh found that a hybrid LP simulation significantly improved students’ confidence and perceived skill in performing LPs, obtaining informed consent, and electronic order entry. For example, confidence with LP increased from 5.95% presimulation to 90% postsimulation, with 58.24% of students reporting an improvement from minimal or no confidence to average or better (P < .001). Similarly, the proportion of students who felt able to perform LP with minimal or no assistance rose from 0% to 38.57% (P < .001). Confidence and perceived skill in obtaining informed consent and electronic order entry also saw significant gains. Although real-world skill assessments were limited by low survey response rates, preceptor evaluations and follow-up surveys suggested that students who participated in the simulation were more likely to perform these tasks independently or with minimal supervision during clinical rotations.²⁷

Research on simulation training involving nonneurology residents is also encouraging. One study compared the LP skills of traditionally trained neurology residents (PGY-2 to PGY-4) to internal medicine residents (PGY-1) who underwent simulation on a mannequin.²⁸ The internal medicine residents first underwent a pretest on LP performance, watched an educational video, underwent an LP demonstration, and practiced on a mannequin with feedback. The neurology residents completed the checklist-style pretest and performed an LP on a mannequin. Internal medicine residents were found to increase their pretest scores from a mean of 46.3% to 95.7% following training, whereas neurology residents scored a mean of 65.4%. More than half of neurology residents were unable to identify the correct anatomic location or standard cerebrospinal fluid (CSF) tests to be ordered on a routine LP.²⁸

A pediatric resident study in Canada found that following simulation-based training, LP procedural skill improved in 15 of 16 residents tested, and PGY-1 residents showed a reduction in anxiety related to performing the procedure.²⁹

Virtual Reality

An additional tool for simulation is the use of virtual reality (VR) in combination with mannequins. A French study used videos of LPs on actual patients, from equipment set up to final CSF collection and termination of the procedure.³⁰ These videos included a 360-degree view of the procedure. The short video was administered through a VR device (the Oculus Go headset by Microsoft) or by a YouTube video (if VR was not desired).

Participants in the study watched the video then performed an LP on a mannequin. Those who used the VR option had minimal adverse effects (eg, low rates of cybersickness, blurred vision, nausea) and high satisfaction regarding their training environment.³⁰Another VR-based program is the vascular intervention system trainer, which allows clinicians to use endovascular devices and simulate procedures such as thrombectomies. VR simulation is used for trainees and to retrain experienced physicians in performance of high-risk procedures.³¹

Fundoscopic and Ultrasound Simulations

The AR403 eye stimulator device for fundoscopic examinations is a mannequin-based simulation.³² In a single-center, prospective, single-blind study of neurology and pediatric neurology residents, trainees were split into control and intervention groups, with the intervention group receiving simulator training. Both groups received video lectures on fundoscopy techniques. Pre- and postintervention measurements included knowledge, skill, and total scores on the skills assessment. Of the 48 trainees who participated, the intervention group demonstrated significantly higher increases in skills (P = .01) and total (P = .02) scores, although knowledge scores did not improve. The intervention group also reported higher comfort levels, higher confidence, and higher success rates.

Areas that would benefit from simulation training and development include ultrasound training, such as transcranial Doppler evaluation. In a national survey of residents in anesthesia and critical care, trainees reported that simulation was not frequently used in ultrasound training and that bedside teaching was more common. Interestingly, there was a discrepancy between the opinions of residents and program directors. The program directors felt simulation was in fact used (18.2% of program directors reported this vs 5.3% of trainees).³³

A new program, the NewroSim (Gaumard), is a computer-based model of cerebral perfusion that may be a useful tool in this setting. It can simulate blood flow velocities, including pathologic ones, both with a mannequin or without.³⁴

Another potential area for development is the use of mannequins to teach botulinum toxin injections for migraine, dystonia and spasticity in a training environment This is typically led by pharmaceutical representatives who are not necessarily clinicians. Residents and fellows may benefit instead from clinician-led education during their training programs.

Simulation in Patient Communication

Simulation provides a realistic environment for teaching rapid decision-making, leadership, and appropriate management of acutely ill neurologic patients; this includes the communication skills needed in response to neurologic injury.³⁵ Simulation can be particularly useful in situations involving brain death determination, where the communication techniques differ significantly from those used in shared decision-making. Simulation provides a low-stakes setting for clinicians to practice the process of brain death determination and communication, leading to improved confidence and knowledge.³⁶

In the context of acute neurologic emergencies, simulation exercises have been used to investigate the consistency of prognostication across a spectrum of neurology physicians. These exercises revealed that acute neuroprognostication is highly variable and often inaccurate among neurology clinicians, suggesting a potential area for improvement through further simulation training.³⁷

FUTURE DIRECTIONS

Simulation education in neurology can be directed towards learners at all levels, including medical students, residents, fellows, nurses, and medical technologists. In addition, simulation has great value to different disciplines, including emergency medicine, intensive care, and psychiatry. In our view simulation is not being used to full potential in neurology.

Simulation can be used to expose clinicians to rare pathology, play an integral role in competency-based evaluations, and serve as the foundation for simulation-based neurology curriculums, teleneurology simulation training programs, and team training for neurologic emergencies.³⁸Another under-recognized aspect of neurology education is teaching interpersonal communication and professionalism. A survey conducted at a neurology department (20 residents and 73 faculty respondents) asked about residents’ comfort level in performing a number of interpersonal communication and professionalism tasks.³⁸ While none of the residents said they were “very uncomfortable” with these tasks, only 1 resident reported being “very comfortable.” In addition, fewer than 50% noted that they had been directly observed by a faculty member while performing these tasks. The results prompted the facility to develop a simulation curriculum that including observation and feedback from 8 objective structured clinical examinations at a simulation center. A standardized professional simulated the role of a patient, caregiver, medical student, or a faculty member. Residents indicated in postsimulation surveys that it was very useful, and a majority voted for the activity to be repeated for future classes.³⁸

Simulation models may also provide a more objective method to evaluate neurology residents. Accreditation Council for Graduate Medical Education has provided Milestones that are used for assessment of neurology residents. Most of the programs rely on end-of-rotation faculty evaluations. These are subjective evaluations, rely on chance evaluations and may not reflect the exact caliber of a trainee in different clinical situations. Simulation models can serve as alternatives to provide an objective and accurate assessment of resident’s competency in different neurologic scenarios. 

In a study of PGY-4 neurology residents from 3 tertiary care academic medical centers were evaluated using simulation-based assessment. Their skills in identifying and managing status epilepticus were assessed via a simulation-based model and compared with clinical experience. No graduating neurology residents were able to meet or exceed the minimum passing score during the testing. It was suggested that end-of-rotation evaluations are inadequate for assigning level of Milestones.²⁴ To move forward with use of simulation-based assessments, these models need to be trialed more extensively and validated. 

Morris et al developed simulations for assessment in neurocritical care.³⁹ Ten evaluative simulation cases were developed. Researchers reported on 64 trainee participants in 274 evaluative simulation scenarios. The participants were very satisfied with the cases, found them to be very realistic and appropriately difficult. Interrater reliability was acceptable for both checklist action items and global rating scales. The researchers concluded that they were able to demonstrate validity evidence via the 10 simulation cases for assessment in neurologic emergencies.³⁹ It is the authors’ belief that the future of residents’ competency assessment should include more widespread use of similar simulation models. 

Finally, VR and augmented reality (AR) have shown promise in various fields, including neurology. In neurology, these technologies are being explored for applications in rehabilitation, therapy, and medical training. Ongoing research aims to leverage these technologies for improved patient outcomes and medical education. Virtual simulations can recreate neurologic scenarios, allowing learners to interact with 3-dimensional (3D) models of the brain or experience virtual patient cases. AR can enhance traditional learning materials by overlaying digital information onto real-world objects, aiding in the understanding of complex neuroanatomy and medical concepts. These technologies contribute to more engaging and effective neurology education.³⁹In a study of 84 graduate medical students divided into 3 groups, the first group attended a traditional lecture on neuroanatomy, the second group was shown VR-based 3D images, and the third group had a VR-based, interactive and stereoscopic session.⁴⁰ Groups 2 and 3 showed the highest mean scores in evaluations and differed significantly from Group 1 (P < .05). Groups 2 and 3 did not differ significantly from each other. The researchers concluded that VR-based resources for teaching neuroanatomy fostered significantly higher learning when compared to the traditional methods.⁴⁰

Clinical simulation is a technique, not a technology, used to replace or amplify real experiences with guided experiences that evoke or replicate substantial aspects of the real world in a fully interactive fashion.¹ Simulation is widely used in medical education and spans a spectrum of sophistication, from simple reproduction of isolated body parts to high-fidelity human patient simulators that replicate whole body appearance and variable physiological parameters.^2,3

Simulation-based medical education can be a valuable tool for safe health care delivery.⁴Simulation-based education is typically provided via 5 modalities: mannequins, computer-based mannequins, standardized patients, computer-based simulators, and software-based simulations. Simulation technology increases procedural skill by allowing for deliberate practice in a safe environment.⁵ Mastery learning is a stringent form of competency-based education that requires trainees to acquire clinical skill measured against a fixed achievement standard.⁶ In mastery learning, educational practice time varies but results are uniform. This approach improves patient outcomes and is more effective than clinical training alone.^7-9

Advanced simulation models are helpful tools for neurologic education and training, especially for emergency department encounters.¹⁰ In recent years, advanced simulation models have been applied in various fields of medicine, especially emergency medicine and anesthesia.^11-14

Acute neurology

In acute neurologic conditions (eg, stroke, intracerebral hemorrhage, status epilepticus, and neuromuscular respiratory failure) clinical outcomes are highly time dependent; consequently, a reduction in treatment delays can improve patient care. The application of simulation methodology allows trainees to address acute and potentially life-threatening emergencies in a safe, controlled, and reproducible environment. In addition to improving trainees’ knowledge base, simulation also helps to enhance team skills, communication, multidisciplinary collaboration, and leadership. Research has shown that deliberate practice leads to a decrease in clinical errors and improved procedural performance in the operating room.^8,15 These results can be extrapolated to acute neurology settings to improve adherence to set protocols, thus streamlining management in acute settings.

Scenarios can be built to teach skills such as eliciting an appropriate history, establishing inclusion or exclusion criteria for the use of certain medications, evaluating neuroimaging and laboratory studies (while avoiding related common pitfalls), and managing treatment complications. Simulation also provides an opportunity for interprofessional education by training nurses and collaborative staff. It can be used to enhance nontechnical skills (eg, communication, situation awareness, decision making, and leadership) that further contribute to patient safety. 

Simulation can be performed with the help of mannequins such as the SimMan 3G(Laerdal), which can display neurologic symptoms and physiological findings, or live actors who portray a patient by mimicking focal neurologic deficits.^16,17 A briefing familiarizes the trainees with the equipment and explains the simulation process. The documentation and equipment are the same as that which is used in emergency departments or intensive care units. 

Once the simulation is completed, a trainee’s performance is checked against a critical action checklist before a debriefing process during which the scenario is reviewed and learning goals are assessed. Immediate feedback is given to trainees to identify weaknesses and the simulation is repeated if multiple critical action items are missed. (Figure).¹⁷

RESIDENCY TRAINING

Simulation training in stroke is mandatory in some residency programs for neurology postgraduate year (PGY) 2 residents.¹⁸ These simulations are a part of a boot camp for incoming neurology residents after completing an internal medicine internship. The simulation program is not standardized across various training programs. The European Stroke Organization Simulation Committee has published an opinion paper with a consensus of experts about the implementation of simulation techniques in the stroke field.^19,20 Residents participating in these mandatory programs are required to complete certification in the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale, including a pretest that assesses their knowledge of acute stroke protocols prior to live simulation.¹⁷ A stepwise algorithm that incorporates faculty specialized in the field is used to evaluate and debrief the simulation.

Stroke vignettes are typically selected by the vascular neurology attending physician to cover thrombolytic therapy (indications and contraindications), mechanical thrombectomy, early arterial blood pressure management, anticoagulant reversal protocols, and management of thrombolytic complications (eg, neurologic worsening). Nursing staff is educated on the acute stroke protocol. Computed tomography (CT) and CT angiography scans are retrieved from teaching files. These are provided as live responses along with pertinent laboratory work, vital signs, and electrocardiogram tracings. Trainee performance is based on adherence to a critical action checklist, which includes (but is not limited to) identification of relative and absolute contraindications of thrombolytic treatments, estimation of NIHSS within 5 minutes of arrival, and consideration of candidacy for endovascular intervention.¹⁷

EVIDENCE FOR SIMULATION TRAINING

Simulations for acute ischemic stroke also improve cohesive teamwork to improve the door-to-needle and door-to-puncture time. A retrospective analysis involving first-year neurology residents at a comprehensive stroke center that compared patient cohort data before and after implementation of simulation training found that there was an improvement in door-to-needle time after implementation of stroke simulation training program by nearly 10 minutes.¹⁷ This was likely due to improvement in the comfort of the flow of management across multidisciplinary teams.

Discussing goals of care, communicating poor prognosis or complex decisions with distraught family members or patients requires practice. Simulation programs with video playback help focus on trainee’s body language, avoiding medical jargon and handling ethical dilemmas while adjusting the communication style to the patient’s personality.²⁰ Enhanced communication skills improve patient satisfaction, trust, and adherence to treatments, all of which lead to better outcomes.²¹

Simulation has been effectively used as a training tool for recognizing and managing acute neuromuscular respiratory failure. These scenarios emphasize the importance of obtaining a focused clinical history, performing key neurological assessments (such as neck flexion strength and breath counting), evaluating pulmonary function tests, and identifying when to initiate ventilatory support.²² In a study designed as a simulation-based learning curriculum for status epilepticus, there was an improvement in the performance of PGY-2 residents after completing the curriculum from a median of 44.2% at pretest to 94.2% at posttest.²³ In this curriculum, an emphasis was placed on the following: recognizing the delay in identification and treatment of status epilepticus; evaluating contraindications of certain antiseizure medication (ASM) based on history or laboratory work; giving first-line ASM within 5 minutes of seizure onset; airway and blood pressure assessment; suctioning the patient; use of second-line ASMs after first-line has failed; ordering a head CT and re-evaluating the case with postload ASM level; ordering a stat electroencephalography (EEG); and communicating the decision regarding patient disposition/level of care.²⁴

There is a growing need for well designed simulation education programs targeted at the management of disorders requiring acute neurologic care, including not only stroke and status epilepticus, but also traumatic brain injury, subarachnoid hemorrhage, neuromuscular respiratory failure, flare of multiple sclerosis, acutely elevated intracranial pressure, malignant cerebral infarction, deterioration of Parkinson disease, and brain death evaluation with family counseling.²⁵ This novel approach to teaching provides an opportunity to learn in addition to remediation with repetition of scenario and might be used for maintenance of recertification programs.

PROCEDURAL SKILLs

Perhaps one of the most studied uses for simulation in neurology is in procedural skills. This extends beyond neurology trainees and can include pulmonary critical care fellows, pediatric residents, and internal medicine residents receiving training in neurology-based procedures such as lumbar punctures (LPs). Other examples of neurology procedures and protocols in which simulation has been studied include fundoscopy, brain death evaluation, EEG interpretation in context of status epilepticus, and simulated stroke code responses. Additional procedures that lack research but may benefit from simulation-based training include the use of Doppler ultrasound and botulinum toxin injections practiced on mannequins.

Proficiency in LP procedural skills has been extensively studied by multiple institutions, with trainee levels ranging from medical students to fellows. One study in France enrolled 115 medical students without prior LP experience and randomized them to either a simulation or a control group.²⁶ Those in the simulation group received instruction using a mannequin, and those in the control group received clinical training through hospital rotations. Both groups received an email containing literature-based information on the procedure as well as a self-assessment questionnaire before participating in either educational program. 

The study showed that those students who received simulation training had a success rate of 67% on their first LP on a live patient compared with a success rate of 14% in those with traditional training. Students receiving simulation training required less assistance during the procedure from a supervisor and had higher satisfaction rates and confidence in their procedural skills.²⁶

Another study of 128 medical students at the University of Pittsburgh found that a hybrid LP simulation significantly improved students’ confidence and perceived skill in performing LPs, obtaining informed consent, and electronic order entry. For example, confidence with LP increased from 5.95% presimulation to 90% postsimulation, with 58.24% of students reporting an improvement from minimal or no confidence to average or better (P < .001). Similarly, the proportion of students who felt able to perform LP with minimal or no assistance rose from 0% to 38.57% (P < .001). Confidence and perceived skill in obtaining informed consent and electronic order entry also saw significant gains. Although real-world skill assessments were limited by low survey response rates, preceptor evaluations and follow-up surveys suggested that students who participated in the simulation were more likely to perform these tasks independently or with minimal supervision during clinical rotations.²⁷

Research on simulation training involving nonneurology residents is also encouraging. One study compared the LP skills of traditionally trained neurology residents (PGY-2 to PGY-4) to internal medicine residents (PGY-1) who underwent simulation on a mannequin.²⁸ The internal medicine residents first underwent a pretest on LP performance, watched an educational video, underwent an LP demonstration, and practiced on a mannequin with feedback. The neurology residents completed the checklist-style pretest and performed an LP on a mannequin. Internal medicine residents were found to increase their pretest scores from a mean of 46.3% to 95.7% following training, whereas neurology residents scored a mean of 65.4%. More than half of neurology residents were unable to identify the correct anatomic location or standard cerebrospinal fluid (CSF) tests to be ordered on a routine LP.²⁸

A pediatric resident study in Canada found that following simulation-based training, LP procedural skill improved in 15 of 16 residents tested, and PGY-1 residents showed a reduction in anxiety related to performing the procedure.²⁹

Virtual Reality

An additional tool for simulation is the use of virtual reality (VR) in combination with mannequins. A French study used videos of LPs on actual patients, from equipment set up to final CSF collection and termination of the procedure.³⁰ These videos included a 360-degree view of the procedure. The short video was administered through a VR device (the Oculus Go headset by Microsoft) or by a YouTube video (if VR was not desired).

Participants in the study watched the video then performed an LP on a mannequin. Those who used the VR option had minimal adverse effects (eg, low rates of cybersickness, blurred vision, nausea) and high satisfaction regarding their training environment.³⁰Another VR-based program is the vascular intervention system trainer, which allows clinicians to use endovascular devices and simulate procedures such as thrombectomies. VR simulation is used for trainees and to retrain experienced physicians in performance of high-risk procedures.³¹

Fundoscopic and Ultrasound Simulations

The AR403 eye stimulator device for fundoscopic examinations is a mannequin-based simulation.³² In a single-center, prospective, single-blind study of neurology and pediatric neurology residents, trainees were split into control and intervention groups, with the intervention group receiving simulator training. Both groups received video lectures on fundoscopy techniques. Pre- and postintervention measurements included knowledge, skill, and total scores on the skills assessment. Of the 48 trainees who participated, the intervention group demonstrated significantly higher increases in skills (P = .01) and total (P = .02) scores, although knowledge scores did not improve. The intervention group also reported higher comfort levels, higher confidence, and higher success rates.

Areas that would benefit from simulation training and development include ultrasound training, such as transcranial Doppler evaluation. In a national survey of residents in anesthesia and critical care, trainees reported that simulation was not frequently used in ultrasound training and that bedside teaching was more common. Interestingly, there was a discrepancy between the opinions of residents and program directors. The program directors felt simulation was in fact used (18.2% of program directors reported this vs 5.3% of trainees).³³

A new program, the NewroSim (Gaumard), is a computer-based model of cerebral perfusion that may be a useful tool in this setting. It can simulate blood flow velocities, including pathologic ones, both with a mannequin or without.³⁴

Another potential area for development is the use of mannequins to teach botulinum toxin injections for migraine, dystonia and spasticity in a training environment This is typically led by pharmaceutical representatives who are not necessarily clinicians. Residents and fellows may benefit instead from clinician-led education during their training programs.

Simulation in Patient Communication

Simulation provides a realistic environment for teaching rapid decision-making, leadership, and appropriate management of acutely ill neurologic patients; this includes the communication skills needed in response to neurologic injury.³⁵ Simulation can be particularly useful in situations involving brain death determination, where the communication techniques differ significantly from those used in shared decision-making. Simulation provides a low-stakes setting for clinicians to practice the process of brain death determination and communication, leading to improved confidence and knowledge.³⁶

In the context of acute neurologic emergencies, simulation exercises have been used to investigate the consistency of prognostication across a spectrum of neurology physicians. These exercises revealed that acute neuroprognostication is highly variable and often inaccurate among neurology clinicians, suggesting a potential area for improvement through further simulation training.³⁷

FUTURE DIRECTIONS

Simulation education in neurology can be directed towards learners at all levels, including medical students, residents, fellows, nurses, and medical technologists. In addition, simulation has great value to different disciplines, including emergency medicine, intensive care, and psychiatry. In our view simulation is not being used to full potential in neurology.

Simulation can be used to expose clinicians to rare pathology, play an integral role in competency-based evaluations, and serve as the foundation for simulation-based neurology curriculums, teleneurology simulation training programs, and team training for neurologic emergencies.³⁸Another under-recognized aspect of neurology education is teaching interpersonal communication and professionalism. A survey conducted at a neurology department (20 residents and 73 faculty respondents) asked about residents’ comfort level in performing a number of interpersonal communication and professionalism tasks.³⁸ While none of the residents said they were “very uncomfortable” with these tasks, only 1 resident reported being “very comfortable.” In addition, fewer than 50% noted that they had been directly observed by a faculty member while performing these tasks. The results prompted the facility to develop a simulation curriculum that including observation and feedback from 8 objective structured clinical examinations at a simulation center. A standardized professional simulated the role of a patient, caregiver, medical student, or a faculty member. Residents indicated in postsimulation surveys that it was very useful, and a majority voted for the activity to be repeated for future classes.³⁸

Simulation models may also provide a more objective method to evaluate neurology residents. Accreditation Council for Graduate Medical Education has provided Milestones that are used for assessment of neurology residents. Most of the programs rely on end-of-rotation faculty evaluations. These are subjective evaluations, rely on chance evaluations and may not reflect the exact caliber of a trainee in different clinical situations. Simulation models can serve as alternatives to provide an objective and accurate assessment of resident’s competency in different neurologic scenarios. 

In a study of PGY-4 neurology residents from 3 tertiary care academic medical centers were evaluated using simulation-based assessment. Their skills in identifying and managing status epilepticus were assessed via a simulation-based model and compared with clinical experience. No graduating neurology residents were able to meet or exceed the minimum passing score during the testing. It was suggested that end-of-rotation evaluations are inadequate for assigning level of Milestones.²⁴ To move forward with use of simulation-based assessments, these models need to be trialed more extensively and validated. 

Morris et al developed simulations for assessment in neurocritical care.³⁹ Ten evaluative simulation cases were developed. Researchers reported on 64 trainee participants in 274 evaluative simulation scenarios. The participants were very satisfied with the cases, found them to be very realistic and appropriately difficult. Interrater reliability was acceptable for both checklist action items and global rating scales. The researchers concluded that they were able to demonstrate validity evidence via the 10 simulation cases for assessment in neurologic emergencies.³⁹ It is the authors’ belief that the future of residents’ competency assessment should include more widespread use of similar simulation models. 

Finally, VR and augmented reality (AR) have shown promise in various fields, including neurology. In neurology, these technologies are being explored for applications in rehabilitation, therapy, and medical training. Ongoing research aims to leverage these technologies for improved patient outcomes and medical education. Virtual simulations can recreate neurologic scenarios, allowing learners to interact with 3-dimensional (3D) models of the brain or experience virtual patient cases. AR can enhance traditional learning materials by overlaying digital information onto real-world objects, aiding in the understanding of complex neuroanatomy and medical concepts. These technologies contribute to more engaging and effective neurology education.³⁹In a study of 84 graduate medical students divided into 3 groups, the first group attended a traditional lecture on neuroanatomy, the second group was shown VR-based 3D images, and the third group had a VR-based, interactive and stereoscopic session.⁴⁰ Groups 2 and 3 showed the highest mean scores in evaluations and differed significantly from Group 1 (P < .05). Groups 2 and 3 did not differ significantly from each other. The researchers concluded that VR-based resources for teaching neuroanatomy fostered significantly higher learning when compared to the traditional methods.⁴⁰

Clinical simulation is a technique, not a technology, used to replace or amplify real experiences with guided experiences that evoke or replicate substantial aspects of the real world in a fully interactive fashion.¹ Simulation is widely used in medical education and spans a spectrum of sophistication, from simple reproduction of isolated body parts to high-fidelity human patient simulators that replicate whole body appearance and variable physiological parameters.^2,3

Simulation-based medical education can be a valuable tool for safe health care delivery.⁴Simulation-based education is typically provided via 5 modalities: mannequins, computer-based mannequins, standardized patients, computer-based simulators, and software-based simulations. Simulation technology increases procedural skill by allowing for deliberate practice in a safe environment.⁵ Mastery learning is a stringent form of competency-based education that requires trainees to acquire clinical skill measured against a fixed achievement standard.⁶ In mastery learning, educational practice time varies but results are uniform. This approach improves patient outcomes and is more effective than clinical training alone.^7-9

Advanced simulation models are helpful tools for neurologic education and training, especially for emergency department encounters.¹⁰ In recent years, advanced simulation models have been applied in various fields of medicine, especially emergency medicine and anesthesia.^11-14

Acute neurology

In acute neurologic conditions (eg, stroke, intracerebral hemorrhage, status epilepticus, and neuromuscular respiratory failure) clinical outcomes are highly time dependent; consequently, a reduction in treatment delays can improve patient care. The application of simulation methodology allows trainees to address acute and potentially life-threatening emergencies in a safe, controlled, and reproducible environment. In addition to improving trainees’ knowledge base, simulation also helps to enhance team skills, communication, multidisciplinary collaboration, and leadership. Research has shown that deliberate practice leads to a decrease in clinical errors and improved procedural performance in the operating room.^8,15 These results can be extrapolated to acute neurology settings to improve adherence to set protocols, thus streamlining management in acute settings.

Scenarios can be built to teach skills such as eliciting an appropriate history, establishing inclusion or exclusion criteria for the use of certain medications, evaluating neuroimaging and laboratory studies (while avoiding related common pitfalls), and managing treatment complications. Simulation also provides an opportunity for interprofessional education by training nurses and collaborative staff. It can be used to enhance nontechnical skills (eg, communication, situation awareness, decision making, and leadership) that further contribute to patient safety. 

Simulation can be performed with the help of mannequins such as the SimMan 3G(Laerdal), which can display neurologic symptoms and physiological findings, or live actors who portray a patient by mimicking focal neurologic deficits.^16,17 A briefing familiarizes the trainees with the equipment and explains the simulation process. The documentation and equipment are the same as that which is used in emergency departments or intensive care units. 

Once the simulation is completed, a trainee’s performance is checked against a critical action checklist before a debriefing process during which the scenario is reviewed and learning goals are assessed. Immediate feedback is given to trainees to identify weaknesses and the simulation is repeated if multiple critical action items are missed. (Figure).¹⁷

RESIDENCY TRAINING

Simulation training in stroke is mandatory in some residency programs for neurology postgraduate year (PGY) 2 residents.¹⁸ These simulations are a part of a boot camp for incoming neurology residents after completing an internal medicine internship. The simulation program is not standardized across various training programs. The European Stroke Organization Simulation Committee has published an opinion paper with a consensus of experts about the implementation of simulation techniques in the stroke field.^19,20 Residents participating in these mandatory programs are required to complete certification in the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale, including a pretest that assesses their knowledge of acute stroke protocols prior to live simulation.¹⁷ A stepwise algorithm that incorporates faculty specialized in the field is used to evaluate and debrief the simulation.

Stroke vignettes are typically selected by the vascular neurology attending physician to cover thrombolytic therapy (indications and contraindications), mechanical thrombectomy, early arterial blood pressure management, anticoagulant reversal protocols, and management of thrombolytic complications (eg, neurologic worsening). Nursing staff is educated on the acute stroke protocol. Computed tomography (CT) and CT angiography scans are retrieved from teaching files. These are provided as live responses along with pertinent laboratory work, vital signs, and electrocardiogram tracings. Trainee performance is based on adherence to a critical action checklist, which includes (but is not limited to) identification of relative and absolute contraindications of thrombolytic treatments, estimation of NIHSS within 5 minutes of arrival, and consideration of candidacy for endovascular intervention.¹⁷

EVIDENCE FOR SIMULATION TRAINING

Simulations for acute ischemic stroke also improve cohesive teamwork to improve the door-to-needle and door-to-puncture time. A retrospective analysis involving first-year neurology residents at a comprehensive stroke center that compared patient cohort data before and after implementation of simulation training found that there was an improvement in door-to-needle time after implementation of stroke simulation training program by nearly 10 minutes.¹⁷ This was likely due to improvement in the comfort of the flow of management across multidisciplinary teams.

Discussing goals of care, communicating poor prognosis or complex decisions with distraught family members or patients requires practice. Simulation programs with video playback help focus on trainee’s body language, avoiding medical jargon and handling ethical dilemmas while adjusting the communication style to the patient’s personality.²⁰ Enhanced communication skills improve patient satisfaction, trust, and adherence to treatments, all of which lead to better outcomes.²¹

Simulation has been effectively used as a training tool for recognizing and managing acute neuromuscular respiratory failure. These scenarios emphasize the importance of obtaining a focused clinical history, performing key neurological assessments (such as neck flexion strength and breath counting), evaluating pulmonary function tests, and identifying when to initiate ventilatory support.²² In a study designed as a simulation-based learning curriculum for status epilepticus, there was an improvement in the performance of PGY-2 residents after completing the curriculum from a median of 44.2% at pretest to 94.2% at posttest.²³ In this curriculum, an emphasis was placed on the following: recognizing the delay in identification and treatment of status epilepticus; evaluating contraindications of certain antiseizure medication (ASM) based on history or laboratory work; giving first-line ASM within 5 minutes of seizure onset; airway and blood pressure assessment; suctioning the patient; use of second-line ASMs after first-line has failed; ordering a head CT and re-evaluating the case with postload ASM level; ordering a stat electroencephalography (EEG); and communicating the decision regarding patient disposition/level of care.²⁴

There is a growing need for well designed simulation education programs targeted at the management of disorders requiring acute neurologic care, including not only stroke and status epilepticus, but also traumatic brain injury, subarachnoid hemorrhage, neuromuscular respiratory failure, flare of multiple sclerosis, acutely elevated intracranial pressure, malignant cerebral infarction, deterioration of Parkinson disease, and brain death evaluation with family counseling.²⁵ This novel approach to teaching provides an opportunity to learn in addition to remediation with repetition of scenario and might be used for maintenance of recertification programs.

PROCEDURAL SKILLs

Perhaps one of the most studied uses for simulation in neurology is in procedural skills. This extends beyond neurology trainees and can include pulmonary critical care fellows, pediatric residents, and internal medicine residents receiving training in neurology-based procedures such as lumbar punctures (LPs). Other examples of neurology procedures and protocols in which simulation has been studied include fundoscopy, brain death evaluation, EEG interpretation in context of status epilepticus, and simulated stroke code responses. Additional procedures that lack research but may benefit from simulation-based training include the use of Doppler ultrasound and botulinum toxin injections practiced on mannequins.

Proficiency in LP procedural skills has been extensively studied by multiple institutions, with trainee levels ranging from medical students to fellows. One study in France enrolled 115 medical students without prior LP experience and randomized them to either a simulation or a control group.²⁶ Those in the simulation group received instruction using a mannequin, and those in the control group received clinical training through hospital rotations. Both groups received an email containing literature-based information on the procedure as well as a self-assessment questionnaire before participating in either educational program. 

The study showed that those students who received simulation training had a success rate of 67% on their first LP on a live patient compared with a success rate of 14% in those with traditional training. Students receiving simulation training required less assistance during the procedure from a supervisor and had higher satisfaction rates and confidence in their procedural skills.²⁶

Another study of 128 medical students at the University of Pittsburgh found that a hybrid LP simulation significantly improved students’ confidence and perceived skill in performing LPs, obtaining informed consent, and electronic order entry. For example, confidence with LP increased from 5.95% presimulation to 90% postsimulation, with 58.24% of students reporting an improvement from minimal or no confidence to average or better (P < .001). Similarly, the proportion of students who felt able to perform LP with minimal or no assistance rose from 0% to 38.57% (P < .001). Confidence and perceived skill in obtaining informed consent and electronic order entry also saw significant gains. Although real-world skill assessments were limited by low survey response rates, preceptor evaluations and follow-up surveys suggested that students who participated in the simulation were more likely to perform these tasks independently or with minimal supervision during clinical rotations.²⁷

Research on simulation training involving nonneurology residents is also encouraging. One study compared the LP skills of traditionally trained neurology residents (PGY-2 to PGY-4) to internal medicine residents (PGY-1) who underwent simulation on a mannequin.²⁸ The internal medicine residents first underwent a pretest on LP performance, watched an educational video, underwent an LP demonstration, and practiced on a mannequin with feedback. The neurology residents completed the checklist-style pretest and performed an LP on a mannequin. Internal medicine residents were found to increase their pretest scores from a mean of 46.3% to 95.7% following training, whereas neurology residents scored a mean of 65.4%. More than half of neurology residents were unable to identify the correct anatomic location or standard cerebrospinal fluid (CSF) tests to be ordered on a routine LP.²⁸

A pediatric resident study in Canada found that following simulation-based training, LP procedural skill improved in 15 of 16 residents tested, and PGY-1 residents showed a reduction in anxiety related to performing the procedure.²⁹

Virtual Reality

An additional tool for simulation is the use of virtual reality (VR) in combination with mannequins. A French study used videos of LPs on actual patients, from equipment set up to final CSF collection and termination of the procedure.³⁰ These videos included a 360-degree view of the procedure. The short video was administered through a VR device (the Oculus Go headset by Microsoft) or by a YouTube video (if VR was not desired).

Participants in the study watched the video then performed an LP on a mannequin. Those who used the VR option had minimal adverse effects (eg, low rates of cybersickness, blurred vision, nausea) and high satisfaction regarding their training environment.³⁰Another VR-based program is the vascular intervention system trainer, which allows clinicians to use endovascular devices and simulate procedures such as thrombectomies. VR simulation is used for trainees and to retrain experienced physicians in performance of high-risk procedures.³¹

Fundoscopic and Ultrasound Simulations

The AR403 eye stimulator device for fundoscopic examinations is a mannequin-based simulation.³² In a single-center, prospective, single-blind study of neurology and pediatric neurology residents, trainees were split into control and intervention groups, with the intervention group receiving simulator training. Both groups received video lectures on fundoscopy techniques. Pre- and postintervention measurements included knowledge, skill, and total scores on the skills assessment. Of the 48 trainees who participated, the intervention group demonstrated significantly higher increases in skills (P = .01) and total (P = .02) scores, although knowledge scores did not improve. The intervention group also reported higher comfort levels, higher confidence, and higher success rates.

Areas that would benefit from simulation training and development include ultrasound training, such as transcranial Doppler evaluation. In a national survey of residents in anesthesia and critical care, trainees reported that simulation was not frequently used in ultrasound training and that bedside teaching was more common. Interestingly, there was a discrepancy between the opinions of residents and program directors. The program directors felt simulation was in fact used (18.2% of program directors reported this vs 5.3% of trainees).³³

A new program, the NewroSim (Gaumard), is a computer-based model of cerebral perfusion that may be a useful tool in this setting. It can simulate blood flow velocities, including pathologic ones, both with a mannequin or without.³⁴

Another potential area for development is the use of mannequins to teach botulinum toxin injections for migraine, dystonia and spasticity in a training environment This is typically led by pharmaceutical representatives who are not necessarily clinicians. Residents and fellows may benefit instead from clinician-led education during their training programs.

Simulation in Patient Communication

Simulation provides a realistic environment for teaching rapid decision-making, leadership, and appropriate management of acutely ill neurologic patients; this includes the communication skills needed in response to neurologic injury.³⁵ Simulation can be particularly useful in situations involving brain death determination, where the communication techniques differ significantly from those used in shared decision-making. Simulation provides a low-stakes setting for clinicians to practice the process of brain death determination and communication, leading to improved confidence and knowledge.³⁶

In the context of acute neurologic emergencies, simulation exercises have been used to investigate the consistency of prognostication across a spectrum of neurology physicians. These exercises revealed that acute neuroprognostication is highly variable and often inaccurate among neurology clinicians, suggesting a potential area for improvement through further simulation training.³⁷

FUTURE DIRECTIONS

Simulation education in neurology can be directed towards learners at all levels, including medical students, residents, fellows, nurses, and medical technologists. In addition, simulation has great value to different disciplines, including emergency medicine, intensive care, and psychiatry. In our view simulation is not being used to full potential in neurology.

Simulation can be used to expose clinicians to rare pathology, play an integral role in competency-based evaluations, and serve as the foundation for simulation-based neurology curriculums, teleneurology simulation training programs, and team training for neurologic emergencies.³⁸Another under-recognized aspect of neurology education is teaching interpersonal communication and professionalism. A survey conducted at a neurology department (20 residents and 73 faculty respondents) asked about residents’ comfort level in performing a number of interpersonal communication and professionalism tasks.³⁸ While none of the residents said they were “very uncomfortable” with these tasks, only 1 resident reported being “very comfortable.” In addition, fewer than 50% noted that they had been directly observed by a faculty member while performing these tasks. The results prompted the facility to develop a simulation curriculum that including observation and feedback from 8 objective structured clinical examinations at a simulation center. A standardized professional simulated the role of a patient, caregiver, medical student, or a faculty member. Residents indicated in postsimulation surveys that it was very useful, and a majority voted for the activity to be repeated for future classes.³⁸

Simulation models may also provide a more objective method to evaluate neurology residents. Accreditation Council for Graduate Medical Education has provided Milestones that are used for assessment of neurology residents. Most of the programs rely on end-of-rotation faculty evaluations. These are subjective evaluations, rely on chance evaluations and may not reflect the exact caliber of a trainee in different clinical situations. Simulation models can serve as alternatives to provide an objective and accurate assessment of resident’s competency in different neurologic scenarios. 

In a study of PGY-4 neurology residents from 3 tertiary care academic medical centers were evaluated using simulation-based assessment. Their skills in identifying and managing status epilepticus were assessed via a simulation-based model and compared with clinical experience. No graduating neurology residents were able to meet or exceed the minimum passing score during the testing. It was suggested that end-of-rotation evaluations are inadequate for assigning level of Milestones.²⁴ To move forward with use of simulation-based assessments, these models need to be trialed more extensively and validated. 

Morris et al developed simulations for assessment in neurocritical care.³⁹ Ten evaluative simulation cases were developed. Researchers reported on 64 trainee participants in 274 evaluative simulation scenarios. The participants were very satisfied with the cases, found them to be very realistic and appropriately difficult. Interrater reliability was acceptable for both checklist action items and global rating scales. The researchers concluded that they were able to demonstrate validity evidence via the 10 simulation cases for assessment in neurologic emergencies.³⁹ It is the authors’ belief that the future of residents’ competency assessment should include more widespread use of similar simulation models. 

Finally, VR and augmented reality (AR) have shown promise in various fields, including neurology. In neurology, these technologies are being explored for applications in rehabilitation, therapy, and medical training. Ongoing research aims to leverage these technologies for improved patient outcomes and medical education. Virtual simulations can recreate neurologic scenarios, allowing learners to interact with 3-dimensional (3D) models of the brain or experience virtual patient cases. AR can enhance traditional learning materials by overlaying digital information onto real-world objects, aiding in the understanding of complex neuroanatomy and medical concepts. These technologies contribute to more engaging and effective neurology education.³⁹In a study of 84 graduate medical students divided into 3 groups, the first group attended a traditional lecture on neuroanatomy, the second group was shown VR-based 3D images, and the third group had a VR-based, interactive and stereoscopic session.⁴⁰ Groups 2 and 3 showed the highest mean scores in evaluations and differed significantly from Group 1 (P < .05). Groups 2 and 3 did not differ significantly from each other. The researchers concluded that VR-based resources for teaching neuroanatomy fostered significantly higher learning when compared to the traditional methods.⁴⁰

Are you seeing any increase or trends in cutaneous adverse effects related to the use of GLP-1 agonists in your practice?

DR. SHIELDS: The use of GLP-1 agonists is increasing substantially across numerous populations. Patients are using these medications not only for weight management and diabetes control but also for blood pressure modulation and cardiovascular risk reduction. The market size is expected to grow at a rate of about 6% until 2027. While severe cutaneous adverse effects still are considered relatively rare with GLP-1 agonist use, mild adverse effects are quite common. Dermatologists should be familiar with these effects and how to manage them. Rare but serious cutaneous reactions include morbilliform drug eruptions, dermal hypersensitivity reactions, panniculitis, and bullous pemphigoid. It is thought that some GLP-1 agonists may cause more skin reactions than others; for example, exenatide extended-release has been associated with cutaneous adverse events more frequently than other GLP-1 agonists in a recent comprehensive literature review.

Do you see a role for dermatologists in monitoring or managing the downstream dermatologic effects of GLP-1 agonists over the next few years?

DR. SHIELDS: Absolutely. When patients develop a drug eruption, bullous pemphigoid, or eosinophilic panniculitis, dermatologists are going to be the ones to diagnose and manage therapy. Awareness of these adverse effects is crucial to timely and thoughtful discussions surrounding medication discontinuation vs a “treat through” approach.

Do you recommend coordinating with endocrinologists or obesity medicine specialists when managing shared patients on GLP-1s (particularly if skin concerns arise)?

DR. SHIELDS: Yes. This is crucial to patient success. Co-management can provide clarity around the indication for therapy and allow for a thoughtful risk-benefit discussion with the patient, primary care physician, endocrinologist, cardiologist, etc. In my practice, I have found that many patients do not want to stop therapy even when they develop cutaneous adverse effects. There are options to transition therapy or treat through in some cases, but having a comprehensive monitoring and therapy plan is critical.

Have you encountered cases in which rapid weight loss from GLP-1s worsened conditions such as loose skin, cellulite, or facial lipoatrophy, leading to new aesthetic concerns? How would you recommend counseling and/or treating affected patients?

DR. SHIELDS: Accelerated facial aging is a noticeable adverse effect in patients who undergo treatment with GLP-1 agonists, especially when used off-label for weight loss. Localized loss of facial fat can result in altered facial proportions and excess skin. There are multiple additional mechanisms that may underlie accelerated facial aging in patients on GLP-1s, and really we are just beginning to scratch the surface of why and how this happens. Understanding these mechanisms will open the door to downstream preventive and therapeutic options. If patients experience new aesthetic concerns, I currently work with them to adjust their medication to slow weight loss, recommend improved nutrition and hydration, encourage exercise and weight training to maintain muscle mass, and engage my cosmetic dermatology colleagues to discuss procedures such as dermal fillers.

All patients starting GLP-1 agonists should be thoroughly counseled on risks and adverse effects of their medication. These are well reported and should be considered carefully. Starting with lower medication dosing in conjunction with slow escalation and careful monitoring can be helpful in combatting these adverse effects.

Are you seeing any increase or trends in cutaneous adverse effects related to the use of GLP-1 agonists in your practice?

DR. SHIELDS: The use of GLP-1 agonists is increasing substantially across numerous populations. Patients are using these medications not only for weight management and diabetes control but also for blood pressure modulation and cardiovascular risk reduction. The market size is expected to grow at a rate of about 6% until 2027. While severe cutaneous adverse effects still are considered relatively rare with GLP-1 agonist use, mild adverse effects are quite common. Dermatologists should be familiar with these effects and how to manage them. Rare but serious cutaneous reactions include morbilliform drug eruptions, dermal hypersensitivity reactions, panniculitis, and bullous pemphigoid. It is thought that some GLP-1 agonists may cause more skin reactions than others; for example, exenatide extended-release has been associated with cutaneous adverse events more frequently than other GLP-1 agonists in a recent comprehensive literature review.

Do you see a role for dermatologists in monitoring or managing the downstream dermatologic effects of GLP-1 agonists over the next few years?

DR. SHIELDS: Absolutely. When patients develop a drug eruption, bullous pemphigoid, or eosinophilic panniculitis, dermatologists are going to be the ones to diagnose and manage therapy. Awareness of these adverse effects is crucial to timely and thoughtful discussions surrounding medication discontinuation vs a “treat through” approach.

Do you recommend coordinating with endocrinologists or obesity medicine specialists when managing shared patients on GLP-1s (particularly if skin concerns arise)?

DR. SHIELDS: Yes. This is crucial to patient success. Co-management can provide clarity around the indication for therapy and allow for a thoughtful risk-benefit discussion with the patient, primary care physician, endocrinologist, cardiologist, etc. In my practice, I have found that many patients do not want to stop therapy even when they develop cutaneous adverse effects. There are options to transition therapy or treat through in some cases, but having a comprehensive monitoring and therapy plan is critical.

Have you encountered cases in which rapid weight loss from GLP-1s worsened conditions such as loose skin, cellulite, or facial lipoatrophy, leading to new aesthetic concerns? How would you recommend counseling and/or treating affected patients?

DR. SHIELDS: Accelerated facial aging is a noticeable adverse effect in patients who undergo treatment with GLP-1 agonists, especially when used off-label for weight loss. Localized loss of facial fat can result in altered facial proportions and excess skin. There are multiple additional mechanisms that may underlie accelerated facial aging in patients on GLP-1s, and really we are just beginning to scratch the surface of why and how this happens. Understanding these mechanisms will open the door to downstream preventive and therapeutic options. If patients experience new aesthetic concerns, I currently work with them to adjust their medication to slow weight loss, recommend improved nutrition and hydration, encourage exercise and weight training to maintain muscle mass, and engage my cosmetic dermatology colleagues to discuss procedures such as dermal fillers.

All patients starting GLP-1 agonists should be thoroughly counseled on risks and adverse effects of their medication. These are well reported and should be considered carefully. Starting with lower medication dosing in conjunction with slow escalation and careful monitoring can be helpful in combatting these adverse effects.

Are you seeing any increase or trends in cutaneous adverse effects related to the use of GLP-1 agonists in your practice?

DR. SHIELDS: The use of GLP-1 agonists is increasing substantially across numerous populations. Patients are using these medications not only for weight management and diabetes control but also for blood pressure modulation and cardiovascular risk reduction. The market size is expected to grow at a rate of about 6% until 2027. While severe cutaneous adverse effects still are considered relatively rare with GLP-1 agonist use, mild adverse effects are quite common. Dermatologists should be familiar with these effects and how to manage them. Rare but serious cutaneous reactions include morbilliform drug eruptions, dermal hypersensitivity reactions, panniculitis, and bullous pemphigoid. It is thought that some GLP-1 agonists may cause more skin reactions than others; for example, exenatide extended-release has been associated with cutaneous adverse events more frequently than other GLP-1 agonists in a recent comprehensive literature review.

Do you see a role for dermatologists in monitoring or managing the downstream dermatologic effects of GLP-1 agonists over the next few years?

DR. SHIELDS: Absolutely. When patients develop a drug eruption, bullous pemphigoid, or eosinophilic panniculitis, dermatologists are going to be the ones to diagnose and manage therapy. Awareness of these adverse effects is crucial to timely and thoughtful discussions surrounding medication discontinuation vs a “treat through” approach.

Do you recommend coordinating with endocrinologists or obesity medicine specialists when managing shared patients on GLP-1s (particularly if skin concerns arise)?

DR. SHIELDS: Yes. This is crucial to patient success. Co-management can provide clarity around the indication for therapy and allow for a thoughtful risk-benefit discussion with the patient, primary care physician, endocrinologist, cardiologist, etc. In my practice, I have found that many patients do not want to stop therapy even when they develop cutaneous adverse effects. There are options to transition therapy or treat through in some cases, but having a comprehensive monitoring and therapy plan is critical.

Have you encountered cases in which rapid weight loss from GLP-1s worsened conditions such as loose skin, cellulite, or facial lipoatrophy, leading to new aesthetic concerns? How would you recommend counseling and/or treating affected patients?

DR. SHIELDS: Accelerated facial aging is a noticeable adverse effect in patients who undergo treatment with GLP-1 agonists, especially when used off-label for weight loss. Localized loss of facial fat can result in altered facial proportions and excess skin. There are multiple additional mechanisms that may underlie accelerated facial aging in patients on GLP-1s, and really we are just beginning to scratch the surface of why and how this happens. Understanding these mechanisms will open the door to downstream preventive and therapeutic options. If patients experience new aesthetic concerns, I currently work with them to adjust their medication to slow weight loss, recommend improved nutrition and hydration, encourage exercise and weight training to maintain muscle mass, and engage my cosmetic dermatology colleagues to discuss procedures such as dermal fillers.

All patients starting GLP-1 agonists should be thoroughly counseled on risks and adverse effects of their medication. These are well reported and should be considered carefully. Starting with lower medication dosing in conjunction with slow escalation and careful monitoring can be helpful in combatting these adverse effects.

Use of artificial intelligence (AI) in dermatology has increased over the past decade, likely driven by advances in deep learning algorithms, computing hardware, and machine learning.¹ Studies comparing the performance of AI algorithms to dermatologists in classifying skin disorders have shown conflicting results.^2,3 In this study, we aimed to analyze AI tools used for diagnosing and classifying skin disease and evaluate the role of dermatologists in the creation of AI technology. We also investigated the number of clinical images used in datasets to train AI programs and compared tools that were created with dermatologist input to those created without dermatologist/clinician involvement.

Methods

A search of PubMed articles indexed for MEDLINE using the terms machine learning, artificial intelligence, and dermatology was conducted on September 18, 2022. Articles were included if they described full-length trials; used machine learning for diagnosis of or screening for dermatologic conditions; and used dermoscopic or gross image datasets of the skin, hair, or nails. Articles were categorized into 4 groups based on the conditions covered: chronic wounds, inflammatory skin diseases, mixed conditions, and pigmented skin lesions. Algorithms were sorted into 4 categories: convolutional/convoluted neural network, deep learning model/deep neural network, AI/artificial neural network, and other. Details regarding Fitzpatrick skin type and skin of color (SoC) inclusion in the articles or AI algorithm datasets were recorded. Univariate and multivariate analyses were performed using Microsoft Excel and SAS Studio 3.8. Sensitivity and specificity were calculated for all included AI technology. Sensitivity, specificity, and the number of clinical images were compared among the included articles using analysis of variance and t tests (α=0.05; P<.05 indicated statistical significance).

Results

Our search yielded 1016 articles, 58 of which met the inclusion criteria. Overall, 25.9% (15/58) of the articles utilized AI to diagnose or classify mixed skin diseases; 22.4% (13/58) for pigmented skin lesions; 19.0% (11/58) for wounds; 17.2% (10/58) for inflammatory skin diseases; and 5.2% (3/58) each for acne, psoriasis, and onychomycosis. Overall, 24.0% (14/58) of articles provided information about Fitzpatrick skin type, and 58.7% (34/58) included clinical images depicting SoC. Furthermore, we found that only 20.7% (12/58) of articles on deep learning models included descriptions of patient ethnicity or race in at least 1 dataset, and only 10.3% (6/58) of studies included any information about skin tone in the dataset. Studies with a dermatologist as the last author (most likely to be supervising the project) were more likely to include clinical images depicting SoC than those without (82.6% [19/23] and 16.7% [3/18], respectively [P=.0411]).

The mean (SD) number of clinical images in the study articles was 28,422 (84,050). Thirty-seven (63.8%) of the study articles included gross images, 17 (29.3%) used dermoscopic images, and 4 (6.9%) used both. Twenty-seven (46.6%) articles used convolutional/convoluted neural networks, 15 (25.9%) used deep learning model/deep neural networks, 8 (13.8%) used other algorithms, 6 (10.3%) used AI/artificial neural network, and 2 (3.4%) used fuzzy algorithms. Most studies were conducted in China (29.3% [17/58]), Germany (12.1% [7/58]), India (10.3% [6/58]), multiple nations (10.3% [6/58]), and the United States (10.3% [6/58]). Overall, 82.8% (48/58) of articles included at least 1 dermatologist coauthor. Sensitivity of the AI models was 0.85, and specificity was 0.85. The average percentage of images in the dataset correctly identified by a physician was 76.87% vs 81.62% of images correctly identified by AI. Average agreement between AI and physician assessment was 77.98%, defined as AI and physician both having the same diagnosis. 

Articles authored by dermatologists contained more clinical images than those without dermatologists in key authorship roles (P<.0001)(eTable). Psoriasis-related algorithms had the fewest (mean [SD]: 3173 [4203]), and pigmented skin lesions had the most clinical images (mean [SD]: 53,19l [155,579]).

Comment

Our results indicated that AI studies with dermatologist authors had significantly more images in their datasets (ie, the set of clinical images of skin lesions used to train AI algorithms in diagnosing or classifying lesions) than those with nondermatologist authors (P<.0001)(eTable). Similarly, in a study of AI technology for skin cancer diagnosis, AI studies with dermatologist authors (ie, included in the development of the AI algorithm) had more images than studies without dermatologist authors.¹ Deep learning textbooks have suggested that 5000 clinical images or training input per output category are needed to produce acceptable algorithm performance, and more than 10 million are needed to produce results superior to human performance.^4-10 Despite advances in AI for dermatologic image analysis, the creation of these models often has been directed by nondermatologists¹; therefore, dermatologist involvement in AI development is necessary to facilitate collection of larger image datasets and optimal performance for image diagnosis/classification tasks.

We found that 20.7% of articles on deep learning models included descriptions of patient ethnicity or race, and only 10.3% of studies included any information about skin tone in the dataset. Furthermore, American investigators primarily trained models using clinical images of patients with lighter skin tones, whereas Chinese investigators exclusively included images depicting darker skin tones. Similarly, in a study of 52 cutaneous imaging deep learning articles, only 17.3% (9/52) reported race and/or Fitzpatrick skin type, and only 7.7% (4/52) of articles included both.^2,6,8 Therefore, dermatologists are needed to contribute images representing diverse populations and collaborate in AI research studies, as their involvement is necessary to ensure the accuracy of AI models in classifying lesions or diagnosing skin lesions across all skin types.

Our search was limited to PubMed, and real-world applications could not be evaluated.

Conclusion

In summary, we found that AI studies with dermatologist authors used larger numbers of clinical images in their datasets and more images representing diverse skin types than studies without. Therefore, we advocate for greater involvement of dermatologists in AI research, which might result in better patient outcomes by improving diagnostic accuracy.

Use of artificial intelligence (AI) in dermatology has increased over the past decade, likely driven by advances in deep learning algorithms, computing hardware, and machine learning.¹ Studies comparing the performance of AI algorithms to dermatologists in classifying skin disorders have shown conflicting results.^2,3 In this study, we aimed to analyze AI tools used for diagnosing and classifying skin disease and evaluate the role of dermatologists in the creation of AI technology. We also investigated the number of clinical images used in datasets to train AI programs and compared tools that were created with dermatologist input to those created without dermatologist/clinician involvement.

Methods

A search of PubMed articles indexed for MEDLINE using the terms machine learning, artificial intelligence, and dermatology was conducted on September 18, 2022. Articles were included if they described full-length trials; used machine learning for diagnosis of or screening for dermatologic conditions; and used dermoscopic or gross image datasets of the skin, hair, or nails. Articles were categorized into 4 groups based on the conditions covered: chronic wounds, inflammatory skin diseases, mixed conditions, and pigmented skin lesions. Algorithms were sorted into 4 categories: convolutional/convoluted neural network, deep learning model/deep neural network, AI/artificial neural network, and other. Details regarding Fitzpatrick skin type and skin of color (SoC) inclusion in the articles or AI algorithm datasets were recorded. Univariate and multivariate analyses were performed using Microsoft Excel and SAS Studio 3.8. Sensitivity and specificity were calculated for all included AI technology. Sensitivity, specificity, and the number of clinical images were compared among the included articles using analysis of variance and t tests (α=0.05; P<.05 indicated statistical significance).

Results

Our search yielded 1016 articles, 58 of which met the inclusion criteria. Overall, 25.9% (15/58) of the articles utilized AI to diagnose or classify mixed skin diseases; 22.4% (13/58) for pigmented skin lesions; 19.0% (11/58) for wounds; 17.2% (10/58) for inflammatory skin diseases; and 5.2% (3/58) each for acne, psoriasis, and onychomycosis. Overall, 24.0% (14/58) of articles provided information about Fitzpatrick skin type, and 58.7% (34/58) included clinical images depicting SoC. Furthermore, we found that only 20.7% (12/58) of articles on deep learning models included descriptions of patient ethnicity or race in at least 1 dataset, and only 10.3% (6/58) of studies included any information about skin tone in the dataset. Studies with a dermatologist as the last author (most likely to be supervising the project) were more likely to include clinical images depicting SoC than those without (82.6% [19/23] and 16.7% [3/18], respectively [P=.0411]).

The mean (SD) number of clinical images in the study articles was 28,422 (84,050). Thirty-seven (63.8%) of the study articles included gross images, 17 (29.3%) used dermoscopic images, and 4 (6.9%) used both. Twenty-seven (46.6%) articles used convolutional/convoluted neural networks, 15 (25.9%) used deep learning model/deep neural networks, 8 (13.8%) used other algorithms, 6 (10.3%) used AI/artificial neural network, and 2 (3.4%) used fuzzy algorithms. Most studies were conducted in China (29.3% [17/58]), Germany (12.1% [7/58]), India (10.3% [6/58]), multiple nations (10.3% [6/58]), and the United States (10.3% [6/58]). Overall, 82.8% (48/58) of articles included at least 1 dermatologist coauthor. Sensitivity of the AI models was 0.85, and specificity was 0.85. The average percentage of images in the dataset correctly identified by a physician was 76.87% vs 81.62% of images correctly identified by AI. Average agreement between AI and physician assessment was 77.98%, defined as AI and physician both having the same diagnosis. 

Articles authored by dermatologists contained more clinical images than those without dermatologists in key authorship roles (P<.0001)(eTable). Psoriasis-related algorithms had the fewest (mean [SD]: 3173 [4203]), and pigmented skin lesions had the most clinical images (mean [SD]: 53,19l [155,579]).

Comment

Our results indicated that AI studies with dermatologist authors had significantly more images in their datasets (ie, the set of clinical images of skin lesions used to train AI algorithms in diagnosing or classifying lesions) than those with nondermatologist authors (P<.0001)(eTable). Similarly, in a study of AI technology for skin cancer diagnosis, AI studies with dermatologist authors (ie, included in the development of the AI algorithm) had more images than studies without dermatologist authors.¹ Deep learning textbooks have suggested that 5000 clinical images or training input per output category are needed to produce acceptable algorithm performance, and more than 10 million are needed to produce results superior to human performance.^4-10 Despite advances in AI for dermatologic image analysis, the creation of these models often has been directed by nondermatologists¹; therefore, dermatologist involvement in AI development is necessary to facilitate collection of larger image datasets and optimal performance for image diagnosis/classification tasks.

We found that 20.7% of articles on deep learning models included descriptions of patient ethnicity or race, and only 10.3% of studies included any information about skin tone in the dataset. Furthermore, American investigators primarily trained models using clinical images of patients with lighter skin tones, whereas Chinese investigators exclusively included images depicting darker skin tones. Similarly, in a study of 52 cutaneous imaging deep learning articles, only 17.3% (9/52) reported race and/or Fitzpatrick skin type, and only 7.7% (4/52) of articles included both.^2,6,8 Therefore, dermatologists are needed to contribute images representing diverse populations and collaborate in AI research studies, as their involvement is necessary to ensure the accuracy of AI models in classifying lesions or diagnosing skin lesions across all skin types.

Our search was limited to PubMed, and real-world applications could not be evaluated.

Conclusion

In summary, we found that AI studies with dermatologist authors used larger numbers of clinical images in their datasets and more images representing diverse skin types than studies without. Therefore, we advocate for greater involvement of dermatologists in AI research, which might result in better patient outcomes by improving diagnostic accuracy.

Use of artificial intelligence (AI) in dermatology has increased over the past decade, likely driven by advances in deep learning algorithms, computing hardware, and machine learning.¹ Studies comparing the performance of AI algorithms to dermatologists in classifying skin disorders have shown conflicting results.^2,3 In this study, we aimed to analyze AI tools used for diagnosing and classifying skin disease and evaluate the role of dermatologists in the creation of AI technology. We also investigated the number of clinical images used in datasets to train AI programs and compared tools that were created with dermatologist input to those created without dermatologist/clinician involvement.

Methods

A search of PubMed articles indexed for MEDLINE using the terms machine learning, artificial intelligence, and dermatology was conducted on September 18, 2022. Articles were included if they described full-length trials; used machine learning for diagnosis of or screening for dermatologic conditions; and used dermoscopic or gross image datasets of the skin, hair, or nails. Articles were categorized into 4 groups based on the conditions covered: chronic wounds, inflammatory skin diseases, mixed conditions, and pigmented skin lesions. Algorithms were sorted into 4 categories: convolutional/convoluted neural network, deep learning model/deep neural network, AI/artificial neural network, and other. Details regarding Fitzpatrick skin type and skin of color (SoC) inclusion in the articles or AI algorithm datasets were recorded. Univariate and multivariate analyses were performed using Microsoft Excel and SAS Studio 3.8. Sensitivity and specificity were calculated for all included AI technology. Sensitivity, specificity, and the number of clinical images were compared among the included articles using analysis of variance and t tests (α=0.05; P<.05 indicated statistical significance).

Results

Our search yielded 1016 articles, 58 of which met the inclusion criteria. Overall, 25.9% (15/58) of the articles utilized AI to diagnose or classify mixed skin diseases; 22.4% (13/58) for pigmented skin lesions; 19.0% (11/58) for wounds; 17.2% (10/58) for inflammatory skin diseases; and 5.2% (3/58) each for acne, psoriasis, and onychomycosis. Overall, 24.0% (14/58) of articles provided information about Fitzpatrick skin type, and 58.7% (34/58) included clinical images depicting SoC. Furthermore, we found that only 20.7% (12/58) of articles on deep learning models included descriptions of patient ethnicity or race in at least 1 dataset, and only 10.3% (6/58) of studies included any information about skin tone in the dataset. Studies with a dermatologist as the last author (most likely to be supervising the project) were more likely to include clinical images depicting SoC than those without (82.6% [19/23] and 16.7% [3/18], respectively [P=.0411]).

The mean (SD) number of clinical images in the study articles was 28,422 (84,050). Thirty-seven (63.8%) of the study articles included gross images, 17 (29.3%) used dermoscopic images, and 4 (6.9%) used both. Twenty-seven (46.6%) articles used convolutional/convoluted neural networks, 15 (25.9%) used deep learning model/deep neural networks, 8 (13.8%) used other algorithms, 6 (10.3%) used AI/artificial neural network, and 2 (3.4%) used fuzzy algorithms. Most studies were conducted in China (29.3% [17/58]), Germany (12.1% [7/58]), India (10.3% [6/58]), multiple nations (10.3% [6/58]), and the United States (10.3% [6/58]). Overall, 82.8% (48/58) of articles included at least 1 dermatologist coauthor. Sensitivity of the AI models was 0.85, and specificity was 0.85. The average percentage of images in the dataset correctly identified by a physician was 76.87% vs 81.62% of images correctly identified by AI. Average agreement between AI and physician assessment was 77.98%, defined as AI and physician both having the same diagnosis. 

Articles authored by dermatologists contained more clinical images than those without dermatologists in key authorship roles (P<.0001)(eTable). Psoriasis-related algorithms had the fewest (mean [SD]: 3173 [4203]), and pigmented skin lesions had the most clinical images (mean [SD]: 53,19l [155,579]).

Comment

Our results indicated that AI studies with dermatologist authors had significantly more images in their datasets (ie, the set of clinical images of skin lesions used to train AI algorithms in diagnosing or classifying lesions) than those with nondermatologist authors (P<.0001)(eTable). Similarly, in a study of AI technology for skin cancer diagnosis, AI studies with dermatologist authors (ie, included in the development of the AI algorithm) had more images than studies without dermatologist authors.¹ Deep learning textbooks have suggested that 5000 clinical images or training input per output category are needed to produce acceptable algorithm performance, and more than 10 million are needed to produce results superior to human performance.^4-10 Despite advances in AI for dermatologic image analysis, the creation of these models often has been directed by nondermatologists¹; therefore, dermatologist involvement in AI development is necessary to facilitate collection of larger image datasets and optimal performance for image diagnosis/classification tasks.

We found that 20.7% of articles on deep learning models included descriptions of patient ethnicity or race, and only 10.3% of studies included any information about skin tone in the dataset. Furthermore, American investigators primarily trained models using clinical images of patients with lighter skin tones, whereas Chinese investigators exclusively included images depicting darker skin tones. Similarly, in a study of 52 cutaneous imaging deep learning articles, only 17.3% (9/52) reported race and/or Fitzpatrick skin type, and only 7.7% (4/52) of articles included both.^2,6,8 Therefore, dermatologists are needed to contribute images representing diverse populations and collaborate in AI research studies, as their involvement is necessary to ensure the accuracy of AI models in classifying lesions or diagnosing skin lesions across all skin types.

Our search was limited to PubMed, and real-world applications could not be evaluated.

Conclusion

In summary, we found that AI studies with dermatologist authors used larger numbers of clinical images in their datasets and more images representing diverse skin types than studies without. Therefore, we advocate for greater involvement of dermatologists in AI research, which might result in better patient outcomes by improving diagnostic accuracy.

Nurse practitioners (NPs) and physician assistants (PAs) often help provide dermatologic care but lack the same mandatory specialized postgraduate training required of board-certified dermatologists (BCDs), which includes at least 3 years of dermatology-focused education in an accredited residency program in addition to an intern year of general medicine, pediatrics, or surgery. Dermatology residency is followed by a certification examination administered by the American Board of Dermatology (ABD) or the American Osteopathic Board of Dermatology, leading to board certification. Some physicians choose to do a fellowship, which typically involves an additional 1 to 2 years of postresidency subspeciality training.

Optional postgraduate dermatology training programs for advanced practice providers (APPs) have been offered by some academic institutions and private practice groups since at least 2003, including Lahey Hospital and Medical Center (Burlington, Massachusetts) as well as the University of Rochester Medical Center (Rochester, New York). Despite a lack of accreditation or standardization, the programs can be beneficial for NPs and PAs to expand their dermatologic knowledge and skills and help bridge the care gap within the specialty. Didactics often are conducted in parallel with the educational activities of the parent institution’s traditional dermatology residency program (eg, lectures, grand rounds). While these programs often are managed by practicing dermatology NPs and PAs, dermatologists also may be involved in their education with didactic instruction, curriculum development, and clinical preceptorship. 

In this cross-sectional study, we identified and evaluated 10 postgraduate dermatology training programs for APPs across the United States. With the growing number of NPs and PAs in the dermatology workforce—both in academic and private practice—it is important for BCDs to be aware of the differences in the dermatology training received in order to ensure safe and effective care is provided through supervisory or collaborative roles (depending on state independent practice laws for APPs and to be aware of the implications these programs may have on the field of dermatology.

Methods

To identify postgraduate dermatology training programs for APPs in the United States, we conducted a cross-sectional study using data obtained via a Google search of various combinations of the following terms: nurse practitioner, NP, physician assistant, PA, advance practice provider, APP, dermatology, postgraduate training, residency, and fellowship. We excluded postgraduate dermatology training programs for APPs that required tuition and did not provide a stipend, as well as programs that lacked the formal structure and credibility needed to qualify as legitimate postgraduate training. Many of the excluded programs operate in a manner that raises ethical concerns, offering pay-to-play opportunities under the guise of education. Information collected on each program included the program name, location, parent institution, program length, class size, curriculum, and any associated salary and benefits.

Results

Ten academic and private practice organizations across the United States that offer postgraduate dermatologic training programs for APPs were identified (eTable). Four (40%) programs were advertised as fellowships. Six (60%) of the programs were offered at academic medical centers, and 4 (40%) were offered by private practices. Most programs were located east of the Mississippi River, and many institutions offered instruction at 1 or more locations within the same state (eFigure). The Advanced Dermatology and Cosmetic Surgery private practice group offered training opportunities in multiple states.

Six programs required APPs to become board-certified NPs or PAs prior to enrolling. Most programs enrolled both NPs and PAs, while some only enrolled NPs (eTable). Only 1 (10%) program required NPs to be board certified as a family NP, while another (10%) recommended that applicants have experience in urgent care, emergency medicine, or trauma medicine. Lahey Hospital & Medical Center required experience as an NP in a general setting for 1 to 2 years prior to applying. No program required prior experience in the field of dermatology.

Program length varied from 6 to 24 months, and cohort size typically was limited to 1 to 2 providers (eTable). Although the exact numbers could not be ascertained, most curricula focused on medical dermatology, including clinical and didactic components, but many offered electives such as cosmetic and procedural dermatology. Two institutions (20%) required independent research. Work typically was limited to 40 hours per week, and most paid a full-time employee salary and provided benefits such as health insurance, retirement, and paid leave (eTable). Kansas Medical Clinic (Topeka, Kansas) required at least 3 years of employment in an underserved community following program completion. The Oasis Dermatology private practice group in Texas required a 1-year teaching commitment after program completion. The Advanced Dermatology and Cosmetic Surgery group offered a full-time position upon program completion.

Comment

There is a large difference in the total number of training and credentialing hours when comparing graduate school training and postgraduate credentialing of medical and osteopathic physicians compared with APPs. A new graduate physician has at least twice as many clinical hours as a PA and 10 times as many clinical hours as an NP prior to starting residency. Physicians also typically complete at least 6 times the number of hours of certification examinations compared to NPs and PAs.¹

Nurse practitioner students typically complete the 500 hours of prelicensure clinical training required for NP school in 2 to 4 years.^2,3 The amount of time required for completion is dependent on the degree and experience of the student upon program entry (eg, bachelor of science in nursing vs master of science in nursing as a terminal degree). Physician assistant students are required to complete 2000 prelicensure clinical hours, and most PA programs are 3 years in duration.⁴ Many NP and PA programs require some degree of clinical experience prior to beginning graduate education.⁵

When comparing prelicensure examinations, questions assessing dermatologic knowledge comprise approximately 6% to 10% of the total questions on the United States Medical Licensing Examination Steps 1 and 2.⁶ The Comprehensive Osteopathic Medical Licensing Examination of the United States Level 1 and Level 2-Cognitive Evaluation both have at least 5% of questions dedicated to dermatology.⁷ Approximately 5% of the questions on the Physician Assistant National Certifying Examination are dedicated to dermatology.⁸ The dermatology content on either of the NP certification examinations is unclear.^2,3 In the states of California, Indiana, and New York, national certification through the American Association of Nurse Practitioners or American Nurses Credentialing Center is not required for NPs to practice in their respective states.⁹

Regarding dermatologic board certification, a new graduate NP may obtain certification from the Dermatology Nurse Practitioner Certification Board with 3000 hours of general dermatology practice that may occur during normal working hours.¹⁰ These hours do not have to occur in one of the previously identified postgraduate APP training programs. The National Board of Dermatology Physician Assistants was founded in 2018 and has since dissolved. The National Board of Dermatology Physician Assistants was not accredited and required at least 3 years of training in dermatology with the same dermatologist in addition to completing a 125-question multiple-choice examination.¹¹ Of note, this examination was opposed by both the ABD and the Society for Dermatology Physician Associates.¹² A PA also may become a Diplomate Fellow with the Society of Dermatology Physician Associates after completion of 64.5 hours of online continuing education modules.⁴ Some PAs may choose to obtain a Certificate of Added Qualifications, which is a voluntary credential that helps document specialty experience and expertise in dermatology or other specialties.

In contrast, a dermatology resident physician requires nearly 11,000 to 13,000 hours of clinical training hours, which last 3 to 4 years following medical school.¹³ This training involves direct patient care under supervision in various settings, including hospitals, outpatient clinics, and surgical procedures. In addition to this clinical experience, dermatology residents must pass a 3-step certification examination process administered by the ABD.¹³ This process includes approximately 20 hours of examinations designed to assess both knowledge and practical skills. For those who wish to further specialize, additional fellowship training in areas such as pediatric dermatology, dermatopathology, or Mohs surgery may follow residency; such fellowships involve an extra 2500 to 3500 hours of training and culminate in another certification examination, further refining a resident’s expertise in a specific dermatologic field. Osteopathic physicians may opt out of the ABD 3-step pathway and obtain board certification through the American Osteopathic Board of Dermatology.¹⁴

Many of the programs we evaluated integrate APP trainees into resident education, allowing participation in equivalent didactic curricula, clinical rotations, and departmental academic activities. The salary and benefits associated with these programs are somewhat like those of resident physicians.^15,16 While most tuition-based programs were excluded from our study due to their lack of credibility and alignment with our study criteria, we identified 2 specific programs that stood out as credible despite requiring students to pay tuition. These programs demonstrated a structured and rigorous curriculum with a clear focus on comprehensive dermatologic training, meeting our standards for inclusion. These programs offer dermatologic training for graduates of NP and PA programs at a cost to the student.^15,16 The program at the Florida Atlantic University, Boca Raton, is largely online,¹⁵ and the program at the University of Miami, Florida, offers no direct clinical contact.¹⁶ These programs illustrate the variety of postgraduate dermatology curricula available nationally in comparison to resident salaries; however, they were not included in our formal analysis because they do not provide structured, in-person clinical training consistent with our inclusion criteria. Neither of these programs would enable participants to qualify for credentialing with the Dermatology Nurse Practitioner Certification Board after completion. While this study identified postgraduate training programs for APPs in dermatology advertised online, it is possible some were omitted or not advertised online.

While many of the postgraduate programs we evaluated provide unique educational opportunities for APPs, it is unknown if graduating providers are equipped to handle the care of patients with complex dermatologic needs. Regardless, the increased utilization of APPs by BCDs has been well documented over the past 2 decades.^17-20 It has been suggested that a higher ratio of APPs to dermatologists can decrease the time it takes for a patient to be seen in a clinic.^21-23 However, investigators have expressed concerns that APPs lack standardized surgical training and clinical hour requirements in the field of dermatology.²⁴ Despite these concerns, Medicare claims data show that APPs are performing advanced surgical and cosmetic procedures at increasing rates.^17,18 Other authors have questioned the cost-effectiveness of APPs, as multiple studies have shown that the number of biopsies needed to diagnose 1 case of skin cancer is higher for midlevel providers than for dermatologists.^25-27

Conclusion

With the anticipated expansion of private equity in dermatology and the growth of our Medicare-eligible population, we are likely to see increased utilization of APPs to address the shortage of BCDs.^28,29 Understanding the prelicensure and postlicensure clinical training requirements, examination hours, and extent of dermatology-focused education among APPs and BCDs can help dermatologists collaborate more effectively and ensure safe, high-quality patient care. Standardizing, improving, and providing high-quality education and promoting lifelong learning in the field of dermatology should be celebrated, and dermatologists are the skin experts best equipped to lead dermatologic education forward.

Nurse practitioners (NPs) and physician assistants (PAs) often help provide dermatologic care but lack the same mandatory specialized postgraduate training required of board-certified dermatologists (BCDs), which includes at least 3 years of dermatology-focused education in an accredited residency program in addition to an intern year of general medicine, pediatrics, or surgery. Dermatology residency is followed by a certification examination administered by the American Board of Dermatology (ABD) or the American Osteopathic Board of Dermatology, leading to board certification. Some physicians choose to do a fellowship, which typically involves an additional 1 to 2 years of postresidency subspeciality training.

Optional postgraduate dermatology training programs for advanced practice providers (APPs) have been offered by some academic institutions and private practice groups since at least 2003, including Lahey Hospital and Medical Center (Burlington, Massachusetts) as well as the University of Rochester Medical Center (Rochester, New York). Despite a lack of accreditation or standardization, the programs can be beneficial for NPs and PAs to expand their dermatologic knowledge and skills and help bridge the care gap within the specialty. Didactics often are conducted in parallel with the educational activities of the parent institution’s traditional dermatology residency program (eg, lectures, grand rounds). While these programs often are managed by practicing dermatology NPs and PAs, dermatologists also may be involved in their education with didactic instruction, curriculum development, and clinical preceptorship. 

In this cross-sectional study, we identified and evaluated 10 postgraduate dermatology training programs for APPs across the United States. With the growing number of NPs and PAs in the dermatology workforce—both in academic and private practice—it is important for BCDs to be aware of the differences in the dermatology training received in order to ensure safe and effective care is provided through supervisory or collaborative roles (depending on state independent practice laws for APPs and to be aware of the implications these programs may have on the field of dermatology.

Methods

To identify postgraduate dermatology training programs for APPs in the United States, we conducted a cross-sectional study using data obtained via a Google search of various combinations of the following terms: nurse practitioner, NP, physician assistant, PA, advance practice provider, APP, dermatology, postgraduate training, residency, and fellowship. We excluded postgraduate dermatology training programs for APPs that required tuition and did not provide a stipend, as well as programs that lacked the formal structure and credibility needed to qualify as legitimate postgraduate training. Many of the excluded programs operate in a manner that raises ethical concerns, offering pay-to-play opportunities under the guise of education. Information collected on each program included the program name, location, parent institution, program length, class size, curriculum, and any associated salary and benefits.

Results

Ten academic and private practice organizations across the United States that offer postgraduate dermatologic training programs for APPs were identified (eTable). Four (40%) programs were advertised as fellowships. Six (60%) of the programs were offered at academic medical centers, and 4 (40%) were offered by private practices. Most programs were located east of the Mississippi River, and many institutions offered instruction at 1 or more locations within the same state (eFigure). The Advanced Dermatology and Cosmetic Surgery private practice group offered training opportunities in multiple states.

Six programs required APPs to become board-certified NPs or PAs prior to enrolling. Most programs enrolled both NPs and PAs, while some only enrolled NPs (eTable). Only 1 (10%) program required NPs to be board certified as a family NP, while another (10%) recommended that applicants have experience in urgent care, emergency medicine, or trauma medicine. Lahey Hospital & Medical Center required experience as an NP in a general setting for 1 to 2 years prior to applying. No program required prior experience in the field of dermatology.

Program length varied from 6 to 24 months, and cohort size typically was limited to 1 to 2 providers (eTable). Although the exact numbers could not be ascertained, most curricula focused on medical dermatology, including clinical and didactic components, but many offered electives such as cosmetic and procedural dermatology. Two institutions (20%) required independent research. Work typically was limited to 40 hours per week, and most paid a full-time employee salary and provided benefits such as health insurance, retirement, and paid leave (eTable). Kansas Medical Clinic (Topeka, Kansas) required at least 3 years of employment in an underserved community following program completion. The Oasis Dermatology private practice group in Texas required a 1-year teaching commitment after program completion. The Advanced Dermatology and Cosmetic Surgery group offered a full-time position upon program completion.

Comment

There is a large difference in the total number of training and credentialing hours when comparing graduate school training and postgraduate credentialing of medical and osteopathic physicians compared with APPs. A new graduate physician has at least twice as many clinical hours as a PA and 10 times as many clinical hours as an NP prior to starting residency. Physicians also typically complete at least 6 times the number of hours of certification examinations compared to NPs and PAs.¹

Nurse practitioner students typically complete the 500 hours of prelicensure clinical training required for NP school in 2 to 4 years.^2,3 The amount of time required for completion is dependent on the degree and experience of the student upon program entry (eg, bachelor of science in nursing vs master of science in nursing as a terminal degree). Physician assistant students are required to complete 2000 prelicensure clinical hours, and most PA programs are 3 years in duration.⁴ Many NP and PA programs require some degree of clinical experience prior to beginning graduate education.⁵

When comparing prelicensure examinations, questions assessing dermatologic knowledge comprise approximately 6% to 10% of the total questions on the United States Medical Licensing Examination Steps 1 and 2.⁶ The Comprehensive Osteopathic Medical Licensing Examination of the United States Level 1 and Level 2-Cognitive Evaluation both have at least 5% of questions dedicated to dermatology.⁷ Approximately 5% of the questions on the Physician Assistant National Certifying Examination are dedicated to dermatology.⁸ The dermatology content on either of the NP certification examinations is unclear.^2,3 In the states of California, Indiana, and New York, national certification through the American Association of Nurse Practitioners or American Nurses Credentialing Center is not required for NPs to practice in their respective states.⁹

Regarding dermatologic board certification, a new graduate NP may obtain certification from the Dermatology Nurse Practitioner Certification Board with 3000 hours of general dermatology practice that may occur during normal working hours.¹⁰ These hours do not have to occur in one of the previously identified postgraduate APP training programs. The National Board of Dermatology Physician Assistants was founded in 2018 and has since dissolved. The National Board of Dermatology Physician Assistants was not accredited and required at least 3 years of training in dermatology with the same dermatologist in addition to completing a 125-question multiple-choice examination.¹¹ Of note, this examination was opposed by both the ABD and the Society for Dermatology Physician Associates.¹² A PA also may become a Diplomate Fellow with the Society of Dermatology Physician Associates after completion of 64.5 hours of online continuing education modules.⁴ Some PAs may choose to obtain a Certificate of Added Qualifications, which is a voluntary credential that helps document specialty experience and expertise in dermatology or other specialties.

In contrast, a dermatology resident physician requires nearly 11,000 to 13,000 hours of clinical training hours, which last 3 to 4 years following medical school.¹³ This training involves direct patient care under supervision in various settings, including hospitals, outpatient clinics, and surgical procedures. In addition to this clinical experience, dermatology residents must pass a 3-step certification examination process administered by the ABD.¹³ This process includes approximately 20 hours of examinations designed to assess both knowledge and practical skills. For those who wish to further specialize, additional fellowship training in areas such as pediatric dermatology, dermatopathology, or Mohs surgery may follow residency; such fellowships involve an extra 2500 to 3500 hours of training and culminate in another certification examination, further refining a resident’s expertise in a specific dermatologic field. Osteopathic physicians may opt out of the ABD 3-step pathway and obtain board certification through the American Osteopathic Board of Dermatology.¹⁴

Many of the programs we evaluated integrate APP trainees into resident education, allowing participation in equivalent didactic curricula, clinical rotations, and departmental academic activities. The salary and benefits associated with these programs are somewhat like those of resident physicians.^15,16 While most tuition-based programs were excluded from our study due to their lack of credibility and alignment with our study criteria, we identified 2 specific programs that stood out as credible despite requiring students to pay tuition. These programs demonstrated a structured and rigorous curriculum with a clear focus on comprehensive dermatologic training, meeting our standards for inclusion. These programs offer dermatologic training for graduates of NP and PA programs at a cost to the student.^15,16 The program at the Florida Atlantic University, Boca Raton, is largely online,¹⁵ and the program at the University of Miami, Florida, offers no direct clinical contact.¹⁶ These programs illustrate the variety of postgraduate dermatology curricula available nationally in comparison to resident salaries; however, they were not included in our formal analysis because they do not provide structured, in-person clinical training consistent with our inclusion criteria. Neither of these programs would enable participants to qualify for credentialing with the Dermatology Nurse Practitioner Certification Board after completion. While this study identified postgraduate training programs for APPs in dermatology advertised online, it is possible some were omitted or not advertised online.

While many of the postgraduate programs we evaluated provide unique educational opportunities for APPs, it is unknown if graduating providers are equipped to handle the care of patients with complex dermatologic needs. Regardless, the increased utilization of APPs by BCDs has been well documented over the past 2 decades.^17-20 It has been suggested that a higher ratio of APPs to dermatologists can decrease the time it takes for a patient to be seen in a clinic.^21-23 However, investigators have expressed concerns that APPs lack standardized surgical training and clinical hour requirements in the field of dermatology.²⁴ Despite these concerns, Medicare claims data show that APPs are performing advanced surgical and cosmetic procedures at increasing rates.^17,18 Other authors have questioned the cost-effectiveness of APPs, as multiple studies have shown that the number of biopsies needed to diagnose 1 case of skin cancer is higher for midlevel providers than for dermatologists.^25-27

Conclusion

With the anticipated expansion of private equity in dermatology and the growth of our Medicare-eligible population, we are likely to see increased utilization of APPs to address the shortage of BCDs.^28,29 Understanding the prelicensure and postlicensure clinical training requirements, examination hours, and extent of dermatology-focused education among APPs and BCDs can help dermatologists collaborate more effectively and ensure safe, high-quality patient care. Standardizing, improving, and providing high-quality education and promoting lifelong learning in the field of dermatology should be celebrated, and dermatologists are the skin experts best equipped to lead dermatologic education forward.

Nurse practitioners (NPs) and physician assistants (PAs) often help provide dermatologic care but lack the same mandatory specialized postgraduate training required of board-certified dermatologists (BCDs), which includes at least 3 years of dermatology-focused education in an accredited residency program in addition to an intern year of general medicine, pediatrics, or surgery. Dermatology residency is followed by a certification examination administered by the American Board of Dermatology (ABD) or the American Osteopathic Board of Dermatology, leading to board certification. Some physicians choose to do a fellowship, which typically involves an additional 1 to 2 years of postresidency subspeciality training.

Optional postgraduate dermatology training programs for advanced practice providers (APPs) have been offered by some academic institutions and private practice groups since at least 2003, including Lahey Hospital and Medical Center (Burlington, Massachusetts) as well as the University of Rochester Medical Center (Rochester, New York). Despite a lack of accreditation or standardization, the programs can be beneficial for NPs and PAs to expand their dermatologic knowledge and skills and help bridge the care gap within the specialty. Didactics often are conducted in parallel with the educational activities of the parent institution’s traditional dermatology residency program (eg, lectures, grand rounds). While these programs often are managed by practicing dermatology NPs and PAs, dermatologists also may be involved in their education with didactic instruction, curriculum development, and clinical preceptorship. 

In this cross-sectional study, we identified and evaluated 10 postgraduate dermatology training programs for APPs across the United States. With the growing number of NPs and PAs in the dermatology workforce—both in academic and private practice—it is important for BCDs to be aware of the differences in the dermatology training received in order to ensure safe and effective care is provided through supervisory or collaborative roles (depending on state independent practice laws for APPs and to be aware of the implications these programs may have on the field of dermatology.

Methods

To identify postgraduate dermatology training programs for APPs in the United States, we conducted a cross-sectional study using data obtained via a Google search of various combinations of the following terms: nurse practitioner, NP, physician assistant, PA, advance practice provider, APP, dermatology, postgraduate training, residency, and fellowship. We excluded postgraduate dermatology training programs for APPs that required tuition and did not provide a stipend, as well as programs that lacked the formal structure and credibility needed to qualify as legitimate postgraduate training. Many of the excluded programs operate in a manner that raises ethical concerns, offering pay-to-play opportunities under the guise of education. Information collected on each program included the program name, location, parent institution, program length, class size, curriculum, and any associated salary and benefits.

Results

Ten academic and private practice organizations across the United States that offer postgraduate dermatologic training programs for APPs were identified (eTable). Four (40%) programs were advertised as fellowships. Six (60%) of the programs were offered at academic medical centers, and 4 (40%) were offered by private practices. Most programs were located east of the Mississippi River, and many institutions offered instruction at 1 or more locations within the same state (eFigure). The Advanced Dermatology and Cosmetic Surgery private practice group offered training opportunities in multiple states.

Six programs required APPs to become board-certified NPs or PAs prior to enrolling. Most programs enrolled both NPs and PAs, while some only enrolled NPs (eTable). Only 1 (10%) program required NPs to be board certified as a family NP, while another (10%) recommended that applicants have experience in urgent care, emergency medicine, or trauma medicine. Lahey Hospital & Medical Center required experience as an NP in a general setting for 1 to 2 years prior to applying. No program required prior experience in the field of dermatology.

Program length varied from 6 to 24 months, and cohort size typically was limited to 1 to 2 providers (eTable). Although the exact numbers could not be ascertained, most curricula focused on medical dermatology, including clinical and didactic components, but many offered electives such as cosmetic and procedural dermatology. Two institutions (20%) required independent research. Work typically was limited to 40 hours per week, and most paid a full-time employee salary and provided benefits such as health insurance, retirement, and paid leave (eTable). Kansas Medical Clinic (Topeka, Kansas) required at least 3 years of employment in an underserved community following program completion. The Oasis Dermatology private practice group in Texas required a 1-year teaching commitment after program completion. The Advanced Dermatology and Cosmetic Surgery group offered a full-time position upon program completion.

Comment

There is a large difference in the total number of training and credentialing hours when comparing graduate school training and postgraduate credentialing of medical and osteopathic physicians compared with APPs. A new graduate physician has at least twice as many clinical hours as a PA and 10 times as many clinical hours as an NP prior to starting residency. Physicians also typically complete at least 6 times the number of hours of certification examinations compared to NPs and PAs.¹

Nurse practitioner students typically complete the 500 hours of prelicensure clinical training required for NP school in 2 to 4 years.^2,3 The amount of time required for completion is dependent on the degree and experience of the student upon program entry (eg, bachelor of science in nursing vs master of science in nursing as a terminal degree). Physician assistant students are required to complete 2000 prelicensure clinical hours, and most PA programs are 3 years in duration.⁴ Many NP and PA programs require some degree of clinical experience prior to beginning graduate education.⁵

When comparing prelicensure examinations, questions assessing dermatologic knowledge comprise approximately 6% to 10% of the total questions on the United States Medical Licensing Examination Steps 1 and 2.⁶ The Comprehensive Osteopathic Medical Licensing Examination of the United States Level 1 and Level 2-Cognitive Evaluation both have at least 5% of questions dedicated to dermatology.⁷ Approximately 5% of the questions on the Physician Assistant National Certifying Examination are dedicated to dermatology.⁸ The dermatology content on either of the NP certification examinations is unclear.^2,3 In the states of California, Indiana, and New York, national certification through the American Association of Nurse Practitioners or American Nurses Credentialing Center is not required for NPs to practice in their respective states.⁹

Regarding dermatologic board certification, a new graduate NP may obtain certification from the Dermatology Nurse Practitioner Certification Board with 3000 hours of general dermatology practice that may occur during normal working hours.¹⁰ These hours do not have to occur in one of the previously identified postgraduate APP training programs. The National Board of Dermatology Physician Assistants was founded in 2018 and has since dissolved. The National Board of Dermatology Physician Assistants was not accredited and required at least 3 years of training in dermatology with the same dermatologist in addition to completing a 125-question multiple-choice examination.¹¹ Of note, this examination was opposed by both the ABD and the Society for Dermatology Physician Associates.¹² A PA also may become a Diplomate Fellow with the Society of Dermatology Physician Associates after completion of 64.5 hours of online continuing education modules.⁴ Some PAs may choose to obtain a Certificate of Added Qualifications, which is a voluntary credential that helps document specialty experience and expertise in dermatology or other specialties.

In contrast, a dermatology resident physician requires nearly 11,000 to 13,000 hours of clinical training hours, which last 3 to 4 years following medical school.¹³ This training involves direct patient care under supervision in various settings, including hospitals, outpatient clinics, and surgical procedures. In addition to this clinical experience, dermatology residents must pass a 3-step certification examination process administered by the ABD.¹³ This process includes approximately 20 hours of examinations designed to assess both knowledge and practical skills. For those who wish to further specialize, additional fellowship training in areas such as pediatric dermatology, dermatopathology, or Mohs surgery may follow residency; such fellowships involve an extra 2500 to 3500 hours of training and culminate in another certification examination, further refining a resident’s expertise in a specific dermatologic field. Osteopathic physicians may opt out of the ABD 3-step pathway and obtain board certification through the American Osteopathic Board of Dermatology.¹⁴

Many of the programs we evaluated integrate APP trainees into resident education, allowing participation in equivalent didactic curricula, clinical rotations, and departmental academic activities. The salary and benefits associated with these programs are somewhat like those of resident physicians.^15,16 While most tuition-based programs were excluded from our study due to their lack of credibility and alignment with our study criteria, we identified 2 specific programs that stood out as credible despite requiring students to pay tuition. These programs demonstrated a structured and rigorous curriculum with a clear focus on comprehensive dermatologic training, meeting our standards for inclusion. These programs offer dermatologic training for graduates of NP and PA programs at a cost to the student.^15,16 The program at the Florida Atlantic University, Boca Raton, is largely online,¹⁵ and the program at the University of Miami, Florida, offers no direct clinical contact.¹⁶ These programs illustrate the variety of postgraduate dermatology curricula available nationally in comparison to resident salaries; however, they were not included in our formal analysis because they do not provide structured, in-person clinical training consistent with our inclusion criteria. Neither of these programs would enable participants to qualify for credentialing with the Dermatology Nurse Practitioner Certification Board after completion. While this study identified postgraduate training programs for APPs in dermatology advertised online, it is possible some were omitted or not advertised online.

While many of the postgraduate programs we evaluated provide unique educational opportunities for APPs, it is unknown if graduating providers are equipped to handle the care of patients with complex dermatologic needs. Regardless, the increased utilization of APPs by BCDs has been well documented over the past 2 decades.^17-20 It has been suggested that a higher ratio of APPs to dermatologists can decrease the time it takes for a patient to be seen in a clinic.^21-23 However, investigators have expressed concerns that APPs lack standardized surgical training and clinical hour requirements in the field of dermatology.²⁴ Despite these concerns, Medicare claims data show that APPs are performing advanced surgical and cosmetic procedures at increasing rates.^17,18 Other authors have questioned the cost-effectiveness of APPs, as multiple studies have shown that the number of biopsies needed to diagnose 1 case of skin cancer is higher for midlevel providers than for dermatologists.^25-27

Conclusion

With the anticipated expansion of private equity in dermatology and the growth of our Medicare-eligible population, we are likely to see increased utilization of APPs to address the shortage of BCDs.^28,29 Understanding the prelicensure and postlicensure clinical training requirements, examination hours, and extent of dermatology-focused education among APPs and BCDs can help dermatologists collaborate more effectively and ensure safe, high-quality patient care. Standardizing, improving, and providing high-quality education and promoting lifelong learning in the field of dermatology should be celebrated, and dermatologists are the skin experts best equipped to lead dermatologic education forward.