User login
Topical anticholinergic for axillary hyperhidrosis shows fewer side effects
according to 48-week safety and outcome data.
A structural analogue of glycopyrrolate working through the same mechanism, sofpironium bromide was developed as a retrometabolic agent. This means it is rapidly transformed into an inactive metabolite after application, reducing risk of systemic effects, study investigator Stacy Smith, MD, explained in the late-breaking research session at the American Academy of Dermatology Virtual Meeting Experience.
The anticholinergic glycopyrrolate, which currently is the most commonly used therapy for hyperhidrosis, is absorbed through the skin and excreted through the urine. The systemic exposure to the active agent after topical application explains the substantial risk of adverse effects, said Dr. Smith, a clinician and researcher affiliated with the California Dermatology and Clinical Research Institute, Encinitas.
In contrast,“sofpironium bromide is the ideal topical medication, because it has strong activity at the application site but then reduced systemic activity due to the retrometabolism,” Dr. Smith said.
The 52-week data from the open-label, phase 3 trial supports the premise. In this study of 299 patients randomized to the 5% (102 patients) or 15% (197 patients) topical sofpironium bromide gel formulations, most anticholinergic adverse events were mild or moderate and transient, with complaints concentrated in the first 3 months of the trial.
“The retrometabolic pathway seems to work,” Dr. Smith said. He acknowledged that the treatment-naive patients who entered the study “had to get used to the drug over time,” but the data “show they did.”
The phase 3 trial of sofpironium bromide, which is already approved to treat axillary hyperhidrosis in Japan, did not have a placebo control. It was focused primarily on safety, but outcomes were assessed with the Hyperhidrosis Disease Severity Measure–Axillary (HDSM-Ax).
At least a 1-point improvement in the 7-point HDSM-Ax scale, which is considered clinically meaningful, was achieved by 86.1% and 85.8% of those treated with the 5% and 15% gels, respectively. A 2-point or greater improvement at the end of the study was observed in 69.4% and 61.9%, respectively.
“The medication works well and there was improved efficacy over time. About two-thirds of the patients had at least a 2-point improvement in the HDSM-Ax score at the end of 48 weeks,” Dr. Smith reported.
While response rates climbed over the course of the study, rates of adverse events fell markedly.
After 2 weeks of treatment, the proportions of patients with a treatment-related adverse event were 6% and just under 15% for the 5% and 15% topical-gel groups, respectively. At each 2-week interval when reassessed, the rates fell. By week 12, the rates were less than 2% and about 4% in the two groups, respectively.
The discontinuation rates overall for anticholinergic side effects were 3% and 8.1% for the lower and higher doses. Blurred vision accounted for the vast majority of these discontinuations in both groups. The other discontinuations, which included those for dry mouth, urinary retention, and mydriasis, occurred in one patient each. Again, discontinuations were most common in the first few months of the study.
For the total study population, mild (10.8% vs. 24%) and moderate (10.8% vs. 20.3%) side effects accounted for almost all side effects with the lower and higher doses of the topical drug. Only one patient in the low-dose group had a severe adverse event. At 6.1%, the proportion of the high-dose group with a severe adverse event was higher, but none of the adverse events were considered serious. All were transient.
These rates of adverse events are lower than those reported historically with effective doses of glycopyrrolate, Dr. Smith said.
The data presented by Dr. Smith are part of a phase 3 pivotal trials program designed to gain FDA approval. Going forward, these trials, which are enrolling patients as young as 9 years old, are expected to focus on clinical development of the 15% gel, he added.
The gel is delivered with a metered-dose pump that has an applicator, according to Brickell Biotech, the company developing the treatment in the United States. The 5% formulation was approved in Japan in September 2020, for the treatment of primary axillary hyperhidrosis.
In an interview, David M. Pariser, MD, professor of dermatology, Eastern Virginia Medical School, Norfolk, said that he believes that this drug has could be helpful if the pivotal studies confirm efficacy with a lower risk of adverse events relative to glycopyrrolate. “If it is true that, in phase 3, placebo-controlled trials, there are fewer systemic anticholinergic effects, then this drug will be very useful,” said Dr. Pariser, cofounder of the International Hyperhidrosis Society and an investigator on a previously published dose-ranging, phase 2 study of sofpironium bromide.
The trial was sponsored by Brickell Biotech, which compensated Dr. Smith and other coauthors for their participation. Dr. Pariser has financial relationships with multiple pharmaceutical companies with dermatologic products, including Brickell Biotech.
This article was updated 4/26/21.
according to 48-week safety and outcome data.
A structural analogue of glycopyrrolate working through the same mechanism, sofpironium bromide was developed as a retrometabolic agent. This means it is rapidly transformed into an inactive metabolite after application, reducing risk of systemic effects, study investigator Stacy Smith, MD, explained in the late-breaking research session at the American Academy of Dermatology Virtual Meeting Experience.
The anticholinergic glycopyrrolate, which currently is the most commonly used therapy for hyperhidrosis, is absorbed through the skin and excreted through the urine. The systemic exposure to the active agent after topical application explains the substantial risk of adverse effects, said Dr. Smith, a clinician and researcher affiliated with the California Dermatology and Clinical Research Institute, Encinitas.
In contrast,“sofpironium bromide is the ideal topical medication, because it has strong activity at the application site but then reduced systemic activity due to the retrometabolism,” Dr. Smith said.
The 52-week data from the open-label, phase 3 trial supports the premise. In this study of 299 patients randomized to the 5% (102 patients) or 15% (197 patients) topical sofpironium bromide gel formulations, most anticholinergic adverse events were mild or moderate and transient, with complaints concentrated in the first 3 months of the trial.
“The retrometabolic pathway seems to work,” Dr. Smith said. He acknowledged that the treatment-naive patients who entered the study “had to get used to the drug over time,” but the data “show they did.”
The phase 3 trial of sofpironium bromide, which is already approved to treat axillary hyperhidrosis in Japan, did not have a placebo control. It was focused primarily on safety, but outcomes were assessed with the Hyperhidrosis Disease Severity Measure–Axillary (HDSM-Ax).
At least a 1-point improvement in the 7-point HDSM-Ax scale, which is considered clinically meaningful, was achieved by 86.1% and 85.8% of those treated with the 5% and 15% gels, respectively. A 2-point or greater improvement at the end of the study was observed in 69.4% and 61.9%, respectively.
“The medication works well and there was improved efficacy over time. About two-thirds of the patients had at least a 2-point improvement in the HDSM-Ax score at the end of 48 weeks,” Dr. Smith reported.
While response rates climbed over the course of the study, rates of adverse events fell markedly.
After 2 weeks of treatment, the proportions of patients with a treatment-related adverse event were 6% and just under 15% for the 5% and 15% topical-gel groups, respectively. At each 2-week interval when reassessed, the rates fell. By week 12, the rates were less than 2% and about 4% in the two groups, respectively.
The discontinuation rates overall for anticholinergic side effects were 3% and 8.1% for the lower and higher doses. Blurred vision accounted for the vast majority of these discontinuations in both groups. The other discontinuations, which included those for dry mouth, urinary retention, and mydriasis, occurred in one patient each. Again, discontinuations were most common in the first few months of the study.
For the total study population, mild (10.8% vs. 24%) and moderate (10.8% vs. 20.3%) side effects accounted for almost all side effects with the lower and higher doses of the topical drug. Only one patient in the low-dose group had a severe adverse event. At 6.1%, the proportion of the high-dose group with a severe adverse event was higher, but none of the adverse events were considered serious. All were transient.
These rates of adverse events are lower than those reported historically with effective doses of glycopyrrolate, Dr. Smith said.
The data presented by Dr. Smith are part of a phase 3 pivotal trials program designed to gain FDA approval. Going forward, these trials, which are enrolling patients as young as 9 years old, are expected to focus on clinical development of the 15% gel, he added.
The gel is delivered with a metered-dose pump that has an applicator, according to Brickell Biotech, the company developing the treatment in the United States. The 5% formulation was approved in Japan in September 2020, for the treatment of primary axillary hyperhidrosis.
In an interview, David M. Pariser, MD, professor of dermatology, Eastern Virginia Medical School, Norfolk, said that he believes that this drug has could be helpful if the pivotal studies confirm efficacy with a lower risk of adverse events relative to glycopyrrolate. “If it is true that, in phase 3, placebo-controlled trials, there are fewer systemic anticholinergic effects, then this drug will be very useful,” said Dr. Pariser, cofounder of the International Hyperhidrosis Society and an investigator on a previously published dose-ranging, phase 2 study of sofpironium bromide.
The trial was sponsored by Brickell Biotech, which compensated Dr. Smith and other coauthors for their participation. Dr. Pariser has financial relationships with multiple pharmaceutical companies with dermatologic products, including Brickell Biotech.
This article was updated 4/26/21.
according to 48-week safety and outcome data.
A structural analogue of glycopyrrolate working through the same mechanism, sofpironium bromide was developed as a retrometabolic agent. This means it is rapidly transformed into an inactive metabolite after application, reducing risk of systemic effects, study investigator Stacy Smith, MD, explained in the late-breaking research session at the American Academy of Dermatology Virtual Meeting Experience.
The anticholinergic glycopyrrolate, which currently is the most commonly used therapy for hyperhidrosis, is absorbed through the skin and excreted through the urine. The systemic exposure to the active agent after topical application explains the substantial risk of adverse effects, said Dr. Smith, a clinician and researcher affiliated with the California Dermatology and Clinical Research Institute, Encinitas.
In contrast,“sofpironium bromide is the ideal topical medication, because it has strong activity at the application site but then reduced systemic activity due to the retrometabolism,” Dr. Smith said.
The 52-week data from the open-label, phase 3 trial supports the premise. In this study of 299 patients randomized to the 5% (102 patients) or 15% (197 patients) topical sofpironium bromide gel formulations, most anticholinergic adverse events were mild or moderate and transient, with complaints concentrated in the first 3 months of the trial.
“The retrometabolic pathway seems to work,” Dr. Smith said. He acknowledged that the treatment-naive patients who entered the study “had to get used to the drug over time,” but the data “show they did.”
The phase 3 trial of sofpironium bromide, which is already approved to treat axillary hyperhidrosis in Japan, did not have a placebo control. It was focused primarily on safety, but outcomes were assessed with the Hyperhidrosis Disease Severity Measure–Axillary (HDSM-Ax).
At least a 1-point improvement in the 7-point HDSM-Ax scale, which is considered clinically meaningful, was achieved by 86.1% and 85.8% of those treated with the 5% and 15% gels, respectively. A 2-point or greater improvement at the end of the study was observed in 69.4% and 61.9%, respectively.
“The medication works well and there was improved efficacy over time. About two-thirds of the patients had at least a 2-point improvement in the HDSM-Ax score at the end of 48 weeks,” Dr. Smith reported.
While response rates climbed over the course of the study, rates of adverse events fell markedly.
After 2 weeks of treatment, the proportions of patients with a treatment-related adverse event were 6% and just under 15% for the 5% and 15% topical-gel groups, respectively. At each 2-week interval when reassessed, the rates fell. By week 12, the rates were less than 2% and about 4% in the two groups, respectively.
The discontinuation rates overall for anticholinergic side effects were 3% and 8.1% for the lower and higher doses. Blurred vision accounted for the vast majority of these discontinuations in both groups. The other discontinuations, which included those for dry mouth, urinary retention, and mydriasis, occurred in one patient each. Again, discontinuations were most common in the first few months of the study.
For the total study population, mild (10.8% vs. 24%) and moderate (10.8% vs. 20.3%) side effects accounted for almost all side effects with the lower and higher doses of the topical drug. Only one patient in the low-dose group had a severe adverse event. At 6.1%, the proportion of the high-dose group with a severe adverse event was higher, but none of the adverse events were considered serious. All were transient.
These rates of adverse events are lower than those reported historically with effective doses of glycopyrrolate, Dr. Smith said.
The data presented by Dr. Smith are part of a phase 3 pivotal trials program designed to gain FDA approval. Going forward, these trials, which are enrolling patients as young as 9 years old, are expected to focus on clinical development of the 15% gel, he added.
The gel is delivered with a metered-dose pump that has an applicator, according to Brickell Biotech, the company developing the treatment in the United States. The 5% formulation was approved in Japan in September 2020, for the treatment of primary axillary hyperhidrosis.
In an interview, David M. Pariser, MD, professor of dermatology, Eastern Virginia Medical School, Norfolk, said that he believes that this drug has could be helpful if the pivotal studies confirm efficacy with a lower risk of adverse events relative to glycopyrrolate. “If it is true that, in phase 3, placebo-controlled trials, there are fewer systemic anticholinergic effects, then this drug will be very useful,” said Dr. Pariser, cofounder of the International Hyperhidrosis Society and an investigator on a previously published dose-ranging, phase 2 study of sofpironium bromide.
The trial was sponsored by Brickell Biotech, which compensated Dr. Smith and other coauthors for their participation. Dr. Pariser has financial relationships with multiple pharmaceutical companies with dermatologic products, including Brickell Biotech.
This article was updated 4/26/21.
FROM AAD VMX 2021
Pigmented palmar lesions
Fortunately, the dermoscopy images of these 2 small palmar lesions showed a pattern of pigmentation that aligned in the furrows and was consistent with benign palmar nevi.
It is not uncommon to have nevi on the palms or soles of the feet, so it is important to distinguish between acral lentiginous melanoma (ALM) and benign nevi. ALM is the least common form of melanoma. In contrast to other types of melanoma, it is not considered secondary to excessive sun exposure. Clinically, ALM presents with irregular, enlarging pigmentation that follows, or crosses, the raised ridges of the palms or soles.1 The pigmented areas can progress to ulcerated or bleeding lesions. As with other melanomas, early diagnosis and removal is important to optimize prognosis.
Removal of lesions suspicious for ALM can be achieved in several ways: deep shave biopsy, punch excision if the lesion is small, excision with narrow margins, or, if the lesion is large, by a selective punch biopsy of the most suspicious portion of the lesion (typically the thickest and most irregular area). Larger diameter lesions that are raised and irregular are more worrisome than this patient’s 2-mm macular lesions.
In this case, the patient was reassured that the lesions did not require excision. She was advised to continue to monitor her lesions for growth or changes over time and to return for evaluation, as needed. She was also counseled regarding the American Cancer Society’s ABCDE rules (Asymmetry, Border irregularity, Color, Diameter, Elevation or Evolving) regarding melanomas.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque
1. Hall KH, Rapini RP. Acral lentiginous melanoma. In: StatPearls [Internet]. StatPearls Publishing; 2020. Accessed April 5, 2021. https://www.ncbi.nlm.nih.gov/books/NBK559113/
Fortunately, the dermoscopy images of these 2 small palmar lesions showed a pattern of pigmentation that aligned in the furrows and was consistent with benign palmar nevi.
It is not uncommon to have nevi on the palms or soles of the feet, so it is important to distinguish between acral lentiginous melanoma (ALM) and benign nevi. ALM is the least common form of melanoma. In contrast to other types of melanoma, it is not considered secondary to excessive sun exposure. Clinically, ALM presents with irregular, enlarging pigmentation that follows, or crosses, the raised ridges of the palms or soles.1 The pigmented areas can progress to ulcerated or bleeding lesions. As with other melanomas, early diagnosis and removal is important to optimize prognosis.
Removal of lesions suspicious for ALM can be achieved in several ways: deep shave biopsy, punch excision if the lesion is small, excision with narrow margins, or, if the lesion is large, by a selective punch biopsy of the most suspicious portion of the lesion (typically the thickest and most irregular area). Larger diameter lesions that are raised and irregular are more worrisome than this patient’s 2-mm macular lesions.
In this case, the patient was reassured that the lesions did not require excision. She was advised to continue to monitor her lesions for growth or changes over time and to return for evaluation, as needed. She was also counseled regarding the American Cancer Society’s ABCDE rules (Asymmetry, Border irregularity, Color, Diameter, Elevation or Evolving) regarding melanomas.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque
Fortunately, the dermoscopy images of these 2 small palmar lesions showed a pattern of pigmentation that aligned in the furrows and was consistent with benign palmar nevi.
It is not uncommon to have nevi on the palms or soles of the feet, so it is important to distinguish between acral lentiginous melanoma (ALM) and benign nevi. ALM is the least common form of melanoma. In contrast to other types of melanoma, it is not considered secondary to excessive sun exposure. Clinically, ALM presents with irregular, enlarging pigmentation that follows, or crosses, the raised ridges of the palms or soles.1 The pigmented areas can progress to ulcerated or bleeding lesions. As with other melanomas, early diagnosis and removal is important to optimize prognosis.
Removal of lesions suspicious for ALM can be achieved in several ways: deep shave biopsy, punch excision if the lesion is small, excision with narrow margins, or, if the lesion is large, by a selective punch biopsy of the most suspicious portion of the lesion (typically the thickest and most irregular area). Larger diameter lesions that are raised and irregular are more worrisome than this patient’s 2-mm macular lesions.
In this case, the patient was reassured that the lesions did not require excision. She was advised to continue to monitor her lesions for growth or changes over time and to return for evaluation, as needed. She was also counseled regarding the American Cancer Society’s ABCDE rules (Asymmetry, Border irregularity, Color, Diameter, Elevation or Evolving) regarding melanomas.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque
1. Hall KH, Rapini RP. Acral lentiginous melanoma. In: StatPearls [Internet]. StatPearls Publishing; 2020. Accessed April 5, 2021. https://www.ncbi.nlm.nih.gov/books/NBK559113/
1. Hall KH, Rapini RP. Acral lentiginous melanoma. In: StatPearls [Internet]. StatPearls Publishing; 2020. Accessed April 5, 2021. https://www.ncbi.nlm.nih.gov/books/NBK559113/
Boosting the presence of darker skin in rheumatology education
Studies are flagging racial and ethnic disparities in rheumatology training materials, pointing to a need to boost representation of darker skin tones and better educate physicians in evaluating this cohort.
Not enough is known about these disparities in rheumatology education, despite the fact that minorities make up 40% of the population in the United States.
The problem starts with books and references used in medical schools, Lynn McKinley-Grant, MD, immediate past president of the Skin of Color Society and associate professor of dermatology at Howard University, Washington, said in an interview. “In the medical literature there has been a dearth of images in skin of color in all specialties,” she said. With an increased diversity in the U.S. population, there is a need for health care providers to be able to recognize disease patterns in all skin types.” If a physician is training at an institution where there are not many patients of color in the community, the rheumatologists are even more limited in terms of their clinical experience.
This lack of training in diagnosis of disease has serious clinical repercussions, as seen in COVID cases, Dr. McKinley-Grant noted. “You end up not being able to recognize early erythema, jaundice, anemia, or hypoxemia because those conditions are a different color or pattern in the darker skin types. This can lead to errors in treatment, diagnosis, and medical care, resulting in increased morbidity and mortality.”
Studies point to education gaps
A team of researchers from Washington University in St. Louis called attention to this issue at the American College of Rhematology’s Convergence 2020 conference.
“Patients of color with lupus are especially vulnerable as they often carry a greater disease burden, yet studies show that individuals with darker skin tones are underrepresented in medical educational materials,” Vijay Kannuthurai, MD, and colleagues wrote in their study abstract. The team surveyed 132 providers in St. Louis, Mo., on their confidence in evaluating any rash, and rashes in patients with lupus and varied skin tones.
Participating clinicians, mostly rheumatologists, dermatologists, or internists, had a higher confidence level in diagnosing any rash versus lupus rashes, but were considerably less confident in diagnosing lupus rash on darker skin, compared with those on fair skin. This represents “a disparity between provider confidence and the patient population lupus traditionally affects,” the investigators concluded.
Another recent study found evidence of disparities in clinical education resources. “The lack of dark skin representation among rheumatology educational materials contributes to the implicit bias and structural racism present in medical education by promoting White-only models of disease,” lead author Adrienne Strait, a medical student at the University of California, San Francisco, said in an interview. “Given that rheumatic diseases disproportionately impact racial and ethnic minorities, we felt it was important to examine the representation of these groups within rheumatology training resources.”
She and her colleagues gathered images of rheumatic diseases from four major databases: the American College of Rheumatology’s Image Library, UpToDate, the New England Journal of Medicine Images in Clinical Medicine and Clinical Cases filtered by “Rheumatology,” and the 9th edition of Kelley’s Textbook of Rheumatology. They used Fitzpatrick’s skin phototypes to independently code images depicting skin as “light” (skin types I-IV), “dark” (skin types V-VI), or “indeterminate,” focusing on systemic lupus erythematosus (SLE) and rheumatoid arthritis, two conditions with a known connection to racial and ethnic health disparities.
Taking into account the high incidence of sarcoidosis and SLE in Black patients when compared with White patients, the investigators did a secondary analysis that excluded these cases.
Among 1,043 patient images studied, just 13.4% represented dark skin, compared with 84% that represented light skin. More than 2% represented an indeterminate skin color. Comparing dark-skin representation in the clinical images and SLE images with the representation of Asian, Native American, and Black individuals in the United States and within lupus cases nationally, the investigators found significant underrepresentation of dark skin.
Only 4.2% of RA images had dark-skin representation, making RA one of the diseases with the lowest representation in the study, along with juvenile idiopathic arthritis, the spondyloarthropathies, and Kawasaki disease. “Representation of dark skin in SLE was also lower than the proportion of Black individuals in SLE studies,” the investigators noted. Overall, representation of dark skin in SLE images was just 22.6%. Sarcoidosis comparatively had the largest representation of dark-skin images (69.6%, n = 32).
“Excluding sarcoidosis and SLE images, the overall representation of dark skin was 9.4% (n = 84), which was significantly lower than the proportion of Asian, Native American, and Black individuals within the U.S. Census population,” according to Ms. Strait and her associates. UpToDate contained the largest proportion of images of dark skin respective to other databases, whereas Kelley’s Textbook had the smallest.
Actionable steps
Many physicians are willing to improve upon their skills in identifying conditions on darker skin, as the study by Dr. Kannuthurai and associates suggests. Overall, 93% of the survey’s participants wanted to learn more about rashes in patients of color. “Future educational interventions may help practitioners improve their confidence when diagnosing rashes in lupus patients” with darker skin, they suggested.
Ms. Strait and her colleagues recommended a series of actionable steps to improve diversity and equity of dark skin tone representation in rheumatology curricula.
Editors of educational resources, for example, should make image diversity a priority for those diseases that are most commonly associated with cutaneous manifestations, such as SLE, vasculitis, inflammatory myopathies, systemic sclerosis, sarcoidosis, and psoriasis. They also called for educators in academic rheumatology programs to collaborate to improve diversity in resources used at the undergraduate and graduate medical education level.
Efforts should take place at the local, regional, and national level to publicly discuss and educate clinicians about rheumatic diseases in individuals of color. Speakers at rheumatology conferences should strive to educate learners about presentations of rheumatic diseases in individuals of color. The ACR in the meantime could establish a task force to enhance racial and ethnic diversity in their image library and other published resources.
“These steps may improve provider recognition and diagnosis of rheumatic disease manifestations in skin of color, which may in turn reduce health disparities among racial and ethnic minority groups,” Ms. Strait said.
Beth L. Jonas, MD, chair of the ACR’s Committee on Rheumatology Training and Workforce Issues, called the findings of this study “timely and important.” The researchers highlighted a deficiency in rheumatology training materials that needs addressing, she said in an interview. “I definitely agree that ACR needs to be mindful of this. There’s no doubt that we need to take these recommendations and move along these lines.”
The ACR took a first step in 2020 with the creation of a diversity, equity, and inclusion committee. “We are undergoing a college-wide look at what we do, with an eye toward inclusion. There is a strong interest in addressing health disparities and being an equitable and inclusive community of rheumatology health care professionals,” said Dr. Jonas, chief of the University of North Carolina at Chapel Hill’s division of rheumatology, allergy, and immunology.
The American Academy of Dermatology is also working to improve the image library with images of disease in skin of color. “Everyone’s jumping on this now,” Dr. McKinley-Grant observed. The medical profession can’t afford not to. It’s a life-threatening issue when rheumatoid arthritis and other diseases in people of color aren’t diagnosed early and correctly, she added.
Technologies seek to reduce bias
While many organizations are taking steps to improve representation of darker skin images, VisualDx has taken the lead on this, she said. “They’ve been doing this for years now. There are over 14,000 images of disease in skin of color, including all the rheumatologic diseases. There’s a mobile app and desktop decision support system, and it is very popular. A majority of medical schools have this as a library resource, and hospital systems license it for EHR integration.” Doctors can also get it individually. This enables them to share images and handouts of a diagnosis and select images of patients of color, said Dr. McKinley-Grant, who uses the VisualDx smartphone app DermExpert, which is an app for nondermatologists that features an image library of skin lesions, including darker-skin images.
ProjectIMPACT, powered by VisualDx, is another effort to support reducing health care bias in darker skin. The project is a collaboration between the New England Journal of Medicine Group and the Skin Of Color Society. According to Dr. McKinley-Grant, the organizers are building awareness of the importance of reducing the educational and clinical gaps in diagnosing patients of color and trying to get students and educators to pledge to take meaningful steps and to have real-world impact.
This isn’t just exclusive to dermatology and rheumatology – it involves all medical specialties, she stressed.
ProjectIMPACT isn’t just a resource for physicians, she continued. Librarians can also use it to develop more resources on skin of color.
The Skin Of Color Society and VisualDx have also partnered with the NEJM Group to develop a comprehensive virtual series on the impact of skin color and ethnicity on clinical research. The four-part series addresses structural racism and racial bias in medicine, hair disorders in people of color, pigmentary disorders, keloids, COVID-19 comorbidities, and cutaneous manifestations of systemic diseases in children and adults.
Nuances of recognizing disease
As a medical student, Dr. McKinley-Grant said she was fortunate to attend the Albert Schweitzer Hospital in Lambarene, Gabon, on a fellowship. For 3 months, she gained a wealth of experience examining only African patients with brown skin.
In her other training in medicine, “I’ve been at institutions with diverse populations, in Boston, New York, and Washington,” learning more about all different skin pigments.
This type of training should be more widely available, especially now, with COVID-19 producing new manifestations of skin lesions, she emphasized. Such efforts involve a diversification of images physicians are being trained on so that they can recognize the same disease in a person of color.
“Doctors have to be able to recognize different colors, different shades of brown and shades of white. Not all white skin is the same color,” she noted. In looking at a rash or lesion, “you have to learn how to discern differences in the background color of the skin, which is determined by melanin in the skin (Fitzpatrick skin types I-VI) and by what’s going on in the blood, such as how much oxygen and hemoglobin the patient has in their blood.” Inflammation and infection (erythema) will appear more violaceous in IV-VI skin types, for example.
At the University of North Carolina at Chapel Hill, a group of students and faculty have created a dermatology image library to address the deficiency in the availability of images for teaching purposes. “Our medical students recognized the gap and started this,” Dr. Jonas said. Julie Mervak, MD, assistant professor of dermatology, is spearheading this effort, with students Linnea Westerkam and Anuj Pranav Sanghvi.
“I understand that others around the country are working on similar initiatives,” Dr. Jonas said.
None of the sources for this story had any relevant disclosures.
Studies are flagging racial and ethnic disparities in rheumatology training materials, pointing to a need to boost representation of darker skin tones and better educate physicians in evaluating this cohort.
Not enough is known about these disparities in rheumatology education, despite the fact that minorities make up 40% of the population in the United States.
The problem starts with books and references used in medical schools, Lynn McKinley-Grant, MD, immediate past president of the Skin of Color Society and associate professor of dermatology at Howard University, Washington, said in an interview. “In the medical literature there has been a dearth of images in skin of color in all specialties,” she said. With an increased diversity in the U.S. population, there is a need for health care providers to be able to recognize disease patterns in all skin types.” If a physician is training at an institution where there are not many patients of color in the community, the rheumatologists are even more limited in terms of their clinical experience.
This lack of training in diagnosis of disease has serious clinical repercussions, as seen in COVID cases, Dr. McKinley-Grant noted. “You end up not being able to recognize early erythema, jaundice, anemia, or hypoxemia because those conditions are a different color or pattern in the darker skin types. This can lead to errors in treatment, diagnosis, and medical care, resulting in increased morbidity and mortality.”
Studies point to education gaps
A team of researchers from Washington University in St. Louis called attention to this issue at the American College of Rhematology’s Convergence 2020 conference.
“Patients of color with lupus are especially vulnerable as they often carry a greater disease burden, yet studies show that individuals with darker skin tones are underrepresented in medical educational materials,” Vijay Kannuthurai, MD, and colleagues wrote in their study abstract. The team surveyed 132 providers in St. Louis, Mo., on their confidence in evaluating any rash, and rashes in patients with lupus and varied skin tones.
Participating clinicians, mostly rheumatologists, dermatologists, or internists, had a higher confidence level in diagnosing any rash versus lupus rashes, but were considerably less confident in diagnosing lupus rash on darker skin, compared with those on fair skin. This represents “a disparity between provider confidence and the patient population lupus traditionally affects,” the investigators concluded.
Another recent study found evidence of disparities in clinical education resources. “The lack of dark skin representation among rheumatology educational materials contributes to the implicit bias and structural racism present in medical education by promoting White-only models of disease,” lead author Adrienne Strait, a medical student at the University of California, San Francisco, said in an interview. “Given that rheumatic diseases disproportionately impact racial and ethnic minorities, we felt it was important to examine the representation of these groups within rheumatology training resources.”
She and her colleagues gathered images of rheumatic diseases from four major databases: the American College of Rheumatology’s Image Library, UpToDate, the New England Journal of Medicine Images in Clinical Medicine and Clinical Cases filtered by “Rheumatology,” and the 9th edition of Kelley’s Textbook of Rheumatology. They used Fitzpatrick’s skin phototypes to independently code images depicting skin as “light” (skin types I-IV), “dark” (skin types V-VI), or “indeterminate,” focusing on systemic lupus erythematosus (SLE) and rheumatoid arthritis, two conditions with a known connection to racial and ethnic health disparities.
Taking into account the high incidence of sarcoidosis and SLE in Black patients when compared with White patients, the investigators did a secondary analysis that excluded these cases.
Among 1,043 patient images studied, just 13.4% represented dark skin, compared with 84% that represented light skin. More than 2% represented an indeterminate skin color. Comparing dark-skin representation in the clinical images and SLE images with the representation of Asian, Native American, and Black individuals in the United States and within lupus cases nationally, the investigators found significant underrepresentation of dark skin.
Only 4.2% of RA images had dark-skin representation, making RA one of the diseases with the lowest representation in the study, along with juvenile idiopathic arthritis, the spondyloarthropathies, and Kawasaki disease. “Representation of dark skin in SLE was also lower than the proportion of Black individuals in SLE studies,” the investigators noted. Overall, representation of dark skin in SLE images was just 22.6%. Sarcoidosis comparatively had the largest representation of dark-skin images (69.6%, n = 32).
“Excluding sarcoidosis and SLE images, the overall representation of dark skin was 9.4% (n = 84), which was significantly lower than the proportion of Asian, Native American, and Black individuals within the U.S. Census population,” according to Ms. Strait and her associates. UpToDate contained the largest proportion of images of dark skin respective to other databases, whereas Kelley’s Textbook had the smallest.
Actionable steps
Many physicians are willing to improve upon their skills in identifying conditions on darker skin, as the study by Dr. Kannuthurai and associates suggests. Overall, 93% of the survey’s participants wanted to learn more about rashes in patients of color. “Future educational interventions may help practitioners improve their confidence when diagnosing rashes in lupus patients” with darker skin, they suggested.
Ms. Strait and her colleagues recommended a series of actionable steps to improve diversity and equity of dark skin tone representation in rheumatology curricula.
Editors of educational resources, for example, should make image diversity a priority for those diseases that are most commonly associated with cutaneous manifestations, such as SLE, vasculitis, inflammatory myopathies, systemic sclerosis, sarcoidosis, and psoriasis. They also called for educators in academic rheumatology programs to collaborate to improve diversity in resources used at the undergraduate and graduate medical education level.
Efforts should take place at the local, regional, and national level to publicly discuss and educate clinicians about rheumatic diseases in individuals of color. Speakers at rheumatology conferences should strive to educate learners about presentations of rheumatic diseases in individuals of color. The ACR in the meantime could establish a task force to enhance racial and ethnic diversity in their image library and other published resources.
“These steps may improve provider recognition and diagnosis of rheumatic disease manifestations in skin of color, which may in turn reduce health disparities among racial and ethnic minority groups,” Ms. Strait said.
Beth L. Jonas, MD, chair of the ACR’s Committee on Rheumatology Training and Workforce Issues, called the findings of this study “timely and important.” The researchers highlighted a deficiency in rheumatology training materials that needs addressing, she said in an interview. “I definitely agree that ACR needs to be mindful of this. There’s no doubt that we need to take these recommendations and move along these lines.”
The ACR took a first step in 2020 with the creation of a diversity, equity, and inclusion committee. “We are undergoing a college-wide look at what we do, with an eye toward inclusion. There is a strong interest in addressing health disparities and being an equitable and inclusive community of rheumatology health care professionals,” said Dr. Jonas, chief of the University of North Carolina at Chapel Hill’s division of rheumatology, allergy, and immunology.
The American Academy of Dermatology is also working to improve the image library with images of disease in skin of color. “Everyone’s jumping on this now,” Dr. McKinley-Grant observed. The medical profession can’t afford not to. It’s a life-threatening issue when rheumatoid arthritis and other diseases in people of color aren’t diagnosed early and correctly, she added.
Technologies seek to reduce bias
While many organizations are taking steps to improve representation of darker skin images, VisualDx has taken the lead on this, she said. “They’ve been doing this for years now. There are over 14,000 images of disease in skin of color, including all the rheumatologic diseases. There’s a mobile app and desktop decision support system, and it is very popular. A majority of medical schools have this as a library resource, and hospital systems license it for EHR integration.” Doctors can also get it individually. This enables them to share images and handouts of a diagnosis and select images of patients of color, said Dr. McKinley-Grant, who uses the VisualDx smartphone app DermExpert, which is an app for nondermatologists that features an image library of skin lesions, including darker-skin images.
ProjectIMPACT, powered by VisualDx, is another effort to support reducing health care bias in darker skin. The project is a collaboration between the New England Journal of Medicine Group and the Skin Of Color Society. According to Dr. McKinley-Grant, the organizers are building awareness of the importance of reducing the educational and clinical gaps in diagnosing patients of color and trying to get students and educators to pledge to take meaningful steps and to have real-world impact.
This isn’t just exclusive to dermatology and rheumatology – it involves all medical specialties, she stressed.
ProjectIMPACT isn’t just a resource for physicians, she continued. Librarians can also use it to develop more resources on skin of color.
The Skin Of Color Society and VisualDx have also partnered with the NEJM Group to develop a comprehensive virtual series on the impact of skin color and ethnicity on clinical research. The four-part series addresses structural racism and racial bias in medicine, hair disorders in people of color, pigmentary disorders, keloids, COVID-19 comorbidities, and cutaneous manifestations of systemic diseases in children and adults.
Nuances of recognizing disease
As a medical student, Dr. McKinley-Grant said she was fortunate to attend the Albert Schweitzer Hospital in Lambarene, Gabon, on a fellowship. For 3 months, she gained a wealth of experience examining only African patients with brown skin.
In her other training in medicine, “I’ve been at institutions with diverse populations, in Boston, New York, and Washington,” learning more about all different skin pigments.
This type of training should be more widely available, especially now, with COVID-19 producing new manifestations of skin lesions, she emphasized. Such efforts involve a diversification of images physicians are being trained on so that they can recognize the same disease in a person of color.
“Doctors have to be able to recognize different colors, different shades of brown and shades of white. Not all white skin is the same color,” she noted. In looking at a rash or lesion, “you have to learn how to discern differences in the background color of the skin, which is determined by melanin in the skin (Fitzpatrick skin types I-VI) and by what’s going on in the blood, such as how much oxygen and hemoglobin the patient has in their blood.” Inflammation and infection (erythema) will appear more violaceous in IV-VI skin types, for example.
At the University of North Carolina at Chapel Hill, a group of students and faculty have created a dermatology image library to address the deficiency in the availability of images for teaching purposes. “Our medical students recognized the gap and started this,” Dr. Jonas said. Julie Mervak, MD, assistant professor of dermatology, is spearheading this effort, with students Linnea Westerkam and Anuj Pranav Sanghvi.
“I understand that others around the country are working on similar initiatives,” Dr. Jonas said.
None of the sources for this story had any relevant disclosures.
Studies are flagging racial and ethnic disparities in rheumatology training materials, pointing to a need to boost representation of darker skin tones and better educate physicians in evaluating this cohort.
Not enough is known about these disparities in rheumatology education, despite the fact that minorities make up 40% of the population in the United States.
The problem starts with books and references used in medical schools, Lynn McKinley-Grant, MD, immediate past president of the Skin of Color Society and associate professor of dermatology at Howard University, Washington, said in an interview. “In the medical literature there has been a dearth of images in skin of color in all specialties,” she said. With an increased diversity in the U.S. population, there is a need for health care providers to be able to recognize disease patterns in all skin types.” If a physician is training at an institution where there are not many patients of color in the community, the rheumatologists are even more limited in terms of their clinical experience.
This lack of training in diagnosis of disease has serious clinical repercussions, as seen in COVID cases, Dr. McKinley-Grant noted. “You end up not being able to recognize early erythema, jaundice, anemia, or hypoxemia because those conditions are a different color or pattern in the darker skin types. This can lead to errors in treatment, diagnosis, and medical care, resulting in increased morbidity and mortality.”
Studies point to education gaps
A team of researchers from Washington University in St. Louis called attention to this issue at the American College of Rhematology’s Convergence 2020 conference.
“Patients of color with lupus are especially vulnerable as they often carry a greater disease burden, yet studies show that individuals with darker skin tones are underrepresented in medical educational materials,” Vijay Kannuthurai, MD, and colleagues wrote in their study abstract. The team surveyed 132 providers in St. Louis, Mo., on their confidence in evaluating any rash, and rashes in patients with lupus and varied skin tones.
Participating clinicians, mostly rheumatologists, dermatologists, or internists, had a higher confidence level in diagnosing any rash versus lupus rashes, but were considerably less confident in diagnosing lupus rash on darker skin, compared with those on fair skin. This represents “a disparity between provider confidence and the patient population lupus traditionally affects,” the investigators concluded.
Another recent study found evidence of disparities in clinical education resources. “The lack of dark skin representation among rheumatology educational materials contributes to the implicit bias and structural racism present in medical education by promoting White-only models of disease,” lead author Adrienne Strait, a medical student at the University of California, San Francisco, said in an interview. “Given that rheumatic diseases disproportionately impact racial and ethnic minorities, we felt it was important to examine the representation of these groups within rheumatology training resources.”
She and her colleagues gathered images of rheumatic diseases from four major databases: the American College of Rheumatology’s Image Library, UpToDate, the New England Journal of Medicine Images in Clinical Medicine and Clinical Cases filtered by “Rheumatology,” and the 9th edition of Kelley’s Textbook of Rheumatology. They used Fitzpatrick’s skin phototypes to independently code images depicting skin as “light” (skin types I-IV), “dark” (skin types V-VI), or “indeterminate,” focusing on systemic lupus erythematosus (SLE) and rheumatoid arthritis, two conditions with a known connection to racial and ethnic health disparities.
Taking into account the high incidence of sarcoidosis and SLE in Black patients when compared with White patients, the investigators did a secondary analysis that excluded these cases.
Among 1,043 patient images studied, just 13.4% represented dark skin, compared with 84% that represented light skin. More than 2% represented an indeterminate skin color. Comparing dark-skin representation in the clinical images and SLE images with the representation of Asian, Native American, and Black individuals in the United States and within lupus cases nationally, the investigators found significant underrepresentation of dark skin.
Only 4.2% of RA images had dark-skin representation, making RA one of the diseases with the lowest representation in the study, along with juvenile idiopathic arthritis, the spondyloarthropathies, and Kawasaki disease. “Representation of dark skin in SLE was also lower than the proportion of Black individuals in SLE studies,” the investigators noted. Overall, representation of dark skin in SLE images was just 22.6%. Sarcoidosis comparatively had the largest representation of dark-skin images (69.6%, n = 32).
“Excluding sarcoidosis and SLE images, the overall representation of dark skin was 9.4% (n = 84), which was significantly lower than the proportion of Asian, Native American, and Black individuals within the U.S. Census population,” according to Ms. Strait and her associates. UpToDate contained the largest proportion of images of dark skin respective to other databases, whereas Kelley’s Textbook had the smallest.
Actionable steps
Many physicians are willing to improve upon their skills in identifying conditions on darker skin, as the study by Dr. Kannuthurai and associates suggests. Overall, 93% of the survey’s participants wanted to learn more about rashes in patients of color. “Future educational interventions may help practitioners improve their confidence when diagnosing rashes in lupus patients” with darker skin, they suggested.
Ms. Strait and her colleagues recommended a series of actionable steps to improve diversity and equity of dark skin tone representation in rheumatology curricula.
Editors of educational resources, for example, should make image diversity a priority for those diseases that are most commonly associated with cutaneous manifestations, such as SLE, vasculitis, inflammatory myopathies, systemic sclerosis, sarcoidosis, and psoriasis. They also called for educators in academic rheumatology programs to collaborate to improve diversity in resources used at the undergraduate and graduate medical education level.
Efforts should take place at the local, regional, and national level to publicly discuss and educate clinicians about rheumatic diseases in individuals of color. Speakers at rheumatology conferences should strive to educate learners about presentations of rheumatic diseases in individuals of color. The ACR in the meantime could establish a task force to enhance racial and ethnic diversity in their image library and other published resources.
“These steps may improve provider recognition and diagnosis of rheumatic disease manifestations in skin of color, which may in turn reduce health disparities among racial and ethnic minority groups,” Ms. Strait said.
Beth L. Jonas, MD, chair of the ACR’s Committee on Rheumatology Training and Workforce Issues, called the findings of this study “timely and important.” The researchers highlighted a deficiency in rheumatology training materials that needs addressing, she said in an interview. “I definitely agree that ACR needs to be mindful of this. There’s no doubt that we need to take these recommendations and move along these lines.”
The ACR took a first step in 2020 with the creation of a diversity, equity, and inclusion committee. “We are undergoing a college-wide look at what we do, with an eye toward inclusion. There is a strong interest in addressing health disparities and being an equitable and inclusive community of rheumatology health care professionals,” said Dr. Jonas, chief of the University of North Carolina at Chapel Hill’s division of rheumatology, allergy, and immunology.
The American Academy of Dermatology is also working to improve the image library with images of disease in skin of color. “Everyone’s jumping on this now,” Dr. McKinley-Grant observed. The medical profession can’t afford not to. It’s a life-threatening issue when rheumatoid arthritis and other diseases in people of color aren’t diagnosed early and correctly, she added.
Technologies seek to reduce bias
While many organizations are taking steps to improve representation of darker skin images, VisualDx has taken the lead on this, she said. “They’ve been doing this for years now. There are over 14,000 images of disease in skin of color, including all the rheumatologic diseases. There’s a mobile app and desktop decision support system, and it is very popular. A majority of medical schools have this as a library resource, and hospital systems license it for EHR integration.” Doctors can also get it individually. This enables them to share images and handouts of a diagnosis and select images of patients of color, said Dr. McKinley-Grant, who uses the VisualDx smartphone app DermExpert, which is an app for nondermatologists that features an image library of skin lesions, including darker-skin images.
ProjectIMPACT, powered by VisualDx, is another effort to support reducing health care bias in darker skin. The project is a collaboration between the New England Journal of Medicine Group and the Skin Of Color Society. According to Dr. McKinley-Grant, the organizers are building awareness of the importance of reducing the educational and clinical gaps in diagnosing patients of color and trying to get students and educators to pledge to take meaningful steps and to have real-world impact.
This isn’t just exclusive to dermatology and rheumatology – it involves all medical specialties, she stressed.
ProjectIMPACT isn’t just a resource for physicians, she continued. Librarians can also use it to develop more resources on skin of color.
The Skin Of Color Society and VisualDx have also partnered with the NEJM Group to develop a comprehensive virtual series on the impact of skin color and ethnicity on clinical research. The four-part series addresses structural racism and racial bias in medicine, hair disorders in people of color, pigmentary disorders, keloids, COVID-19 comorbidities, and cutaneous manifestations of systemic diseases in children and adults.
Nuances of recognizing disease
As a medical student, Dr. McKinley-Grant said she was fortunate to attend the Albert Schweitzer Hospital in Lambarene, Gabon, on a fellowship. For 3 months, she gained a wealth of experience examining only African patients with brown skin.
In her other training in medicine, “I’ve been at institutions with diverse populations, in Boston, New York, and Washington,” learning more about all different skin pigments.
This type of training should be more widely available, especially now, with COVID-19 producing new manifestations of skin lesions, she emphasized. Such efforts involve a diversification of images physicians are being trained on so that they can recognize the same disease in a person of color.
“Doctors have to be able to recognize different colors, different shades of brown and shades of white. Not all white skin is the same color,” she noted. In looking at a rash or lesion, “you have to learn how to discern differences in the background color of the skin, which is determined by melanin in the skin (Fitzpatrick skin types I-VI) and by what’s going on in the blood, such as how much oxygen and hemoglobin the patient has in their blood.” Inflammation and infection (erythema) will appear more violaceous in IV-VI skin types, for example.
At the University of North Carolina at Chapel Hill, a group of students and faculty have created a dermatology image library to address the deficiency in the availability of images for teaching purposes. “Our medical students recognized the gap and started this,” Dr. Jonas said. Julie Mervak, MD, assistant professor of dermatology, is spearheading this effort, with students Linnea Westerkam and Anuj Pranav Sanghvi.
“I understand that others around the country are working on similar initiatives,” Dr. Jonas said.
None of the sources for this story had any relevant disclosures.
Most patients with chronic inflammatory diseases have sufficient response to COVID-19 vaccination
Glucocorticoids and B-cell–depleting therapies are trouble spots
Although most patients with chronic inflammatory diseases mounted immune responses after two doses of mRNA-based COVID-19 vaccines, glucocorticoids and B-cell–depleting therapies markedly reduced the response, according to a recently published preprint of a new study.
The study, published on MedRxiv and not yet peer reviewed, involved a prospective look at 133 patients with chronic inflammatory disease (CID) and 53 patients with healthy immune systems at Washington University, St. Louis, and the University of California, San Francisco. It is regarded as the largest and most detailed study yet in how vaccines perform in people with immune-mediated inflammatory disease. The patients were enrolled between December 2020 and March 2021, and the most common diseases were inflammatory bowel disease (32%), rheumatoid arthritis (29%), spondyloarthritis (15%), and systemic lupus erythematosus (11%).
A ‘modest’ reduction in antibody response
Senior author Alfred Kim, MD, PhD, of the department of medicine at Washington University, said the overall results so far are encouraging.
“Most patients with an autoimmune disease that are on immunosuppression can mount antibody responses,” he said. “We’re seeing the majority of our subjects respond.”
The immune-healthy controls and most of the patients with CID had a robust immune response against the spike protein, although the CID group had a mean reduction in antibody titers that was three times lower than the controls (P = .0092). The CID group similarly had a 2.7-fold reduction in preventing neutralization, or halting the virus’ ability to infect (P < .0001), researchers reported.
This reduction in response is “modest,” he said.
“Is the level of reduction going to be detrimental for protection? Time will tell,” he said, adding that researchers anticipate that it won’t have a critical effect on protection because responses tended to be within the range of the immunocompetent controls, who themselves had wildly varied antibody titers across a 20-fold range. “ ‘Optimal’ isn’t necessarily the same as ‘sufficient.’ ”
Type of medication has big impact on antibody titers
But there was a wide variety of effects on the immune response depending on the medication. Glucorticoids resulted in a response that was 10 times lower than the immune-healthy controls, as well as fewer circulating plasmablasts after vaccination. Researchers found that 98% of controls were seropositive for antibody, compared with 92% of those with CID who were not taking prednisone, and 65% of CID patients on prednisone (P = .0006 and .0115, respectively). Prevention of neutralization of the virus was similarly reduced in those groups, compared with the controls. Dr. Kim noted this was a small sample size, with about 15 patients. These effects were seen regardless of the dose.
“We would’ve anticipated this would have been dose dependent, so this was a little bit surprising,” Dr. Kim said.
B-cell–depleting therapies, such as rituximab (Rituxan) and ocrelizumab (Ocrevus), reduced antibody titers by 36 times, compared with controls (P < .0001), with a similar reduction in preventing infection (P = .0066), the researchers found. The reduction in antibody titers was the most pronounced among those who had received B-cell–depleting therapies within the previous 6 months. Dr. Kim noted this was a small sample size, with about 10 patients.
CID study subjects taking an antimetabolite, including methotrexate, had an average of a two- to threefold reduction in antibody titers and in neutralization (P = .0006). This reduction was greatest with methotrexate, researchers found (P = .0027).
JAK inhibitors also significantly reduced antibody titers (P = .0066), but the reduction in neutralization of the virus was not significant. In addition, researchers found a reduction in antibody titers, the prevention of viral infection, and circulating plasmablasts among those on tumor necrosis factor (TNF) inhibitors, compared with controls, but these were insignificant statistically except for virus neutralization.
Dr. Kim said he hopes the glucocorticoid data spur physicians to try harder to wean patients off the drugs, when possible, in keeping with recommendations already in place.
“The general culture in rheumatology has been very lax about the need to reduce glucocorticoids,” he said. “This reinvigorates that call.” Questions about possible drug holidays from glucocorticoids remain, regarding how long a holiday would be needed, he said. He noted that many patients on glucocorticoids nonetheless mounted responses.
Those on B-cell–depleting therapies present a “much more difficult” question, he said. Some patients possibly could wait a bit longer than their normal, every-6-month schedule, but it’s an individual decision, he said. Since a booster of influenza vaccine has been found to enhance the response even within the 6-month window among ocrelizumab patients, a booster of COVID-19 vaccine might also help, although this remains to be studied.
The study group has already increased its sample size and is looking at adverse reactions and long-term immune responses, Dr. Kim said.
Encouraging, rather than discouraging, results
Leonard Calabrese, DO, professor of medicine at the Cleveland Clinic in Ohio, said the findings shouldn’t discourage clinicians from encouraging vaccination.
“There’s still a preponderance of people who will develop a robust antibody vaccine response,” he said.
He cautioned that the findings look only at antibodies to the spike protein and at plasmablasts. The reduction in these titers is “of concern,” he said, but “we don’t really know with certainty what are the effects of these drugs, and these data are on the overall biologic protective effect of the vaccine. There’s much more to a vaccine response than anti–spike protein and plasmablasts,” including cell-mediated immune response.
For an individual patient, the findings “mean a lot,” he said.
“I think that people who are on significant prednisone and B-cell–depleting agents, I think you have to share with them that there’s a reasonable chance that you’re not going to be making a response similar to healthy people,” he said. “Thus, even with your vaccine, we’re not going to cut you loose to do things that are violating social distancing and group settings. … Should you be hugging your grandchildren if you’re a rituximab vaccine recipient? I think I would wait until we have a little bit more data.”
Kevin Winthrop, MD, MPH, professor of ophthalmology at Oregon Health & Science University, Portland, where he studies vaccinations in the immunocompromised, said that glucocorticoids tend to have little effect on vaccinations generally at low doses.
When effects are seen they can be difficult to interpret, he said.
“It’s hard to extricate that from the effect of the underlying disease,” he said. The drug can be a proxy for worse disease control.
Although it’s a small study, it’s reassuring that overall the responses were similar to healthy controls.
For B-cell–depleting therapies, his usual guidance is to not give vaccine until a patient is at least 3 months out from their last dose, and not to restart until at least 2 weeks after vaccination.
“It’s not surprising that some of these DMARDs [disease-modifying antirheumatic drugs] do negatively affect vaccine response, particularly B-cell–depletion therapy. We need to do some studies to find a way to overcome that, or optimize delivery of the vaccine.”
Dr. Kim reported participating in consulting, advisory board, or speaker’s bureau for Alexion, Aurinia, Annexon Biosciences, Exagen Diagnostics, and GlaxoSmithKline, and receiving funding under a sponsored research agreement unrelated to the data in the paper from GlaxoSmithKline. Dr. Winthrop reported receiving consulting fees from Pfizer, AbbVie, UCB, Eli Lilly, Galapagos, GlaxoSmithKline, Roche, Gilead, Bristol-Myers Squibb, Regeneron, Sanofi, AstraZeneca, Novartis, and research grants from Bristol-Myers Squibb and Pfizer. Dr. Calabrese reported no relevant disclosures.
Glucocorticoids and B-cell–depleting therapies are trouble spots
Glucocorticoids and B-cell–depleting therapies are trouble spots
Although most patients with chronic inflammatory diseases mounted immune responses after two doses of mRNA-based COVID-19 vaccines, glucocorticoids and B-cell–depleting therapies markedly reduced the response, according to a recently published preprint of a new study.
The study, published on MedRxiv and not yet peer reviewed, involved a prospective look at 133 patients with chronic inflammatory disease (CID) and 53 patients with healthy immune systems at Washington University, St. Louis, and the University of California, San Francisco. It is regarded as the largest and most detailed study yet in how vaccines perform in people with immune-mediated inflammatory disease. The patients were enrolled between December 2020 and March 2021, and the most common diseases were inflammatory bowel disease (32%), rheumatoid arthritis (29%), spondyloarthritis (15%), and systemic lupus erythematosus (11%).
A ‘modest’ reduction in antibody response
Senior author Alfred Kim, MD, PhD, of the department of medicine at Washington University, said the overall results so far are encouraging.
“Most patients with an autoimmune disease that are on immunosuppression can mount antibody responses,” he said. “We’re seeing the majority of our subjects respond.”
The immune-healthy controls and most of the patients with CID had a robust immune response against the spike protein, although the CID group had a mean reduction in antibody titers that was three times lower than the controls (P = .0092). The CID group similarly had a 2.7-fold reduction in preventing neutralization, or halting the virus’ ability to infect (P < .0001), researchers reported.
This reduction in response is “modest,” he said.
“Is the level of reduction going to be detrimental for protection? Time will tell,” he said, adding that researchers anticipate that it won’t have a critical effect on protection because responses tended to be within the range of the immunocompetent controls, who themselves had wildly varied antibody titers across a 20-fold range. “ ‘Optimal’ isn’t necessarily the same as ‘sufficient.’ ”
Type of medication has big impact on antibody titers
But there was a wide variety of effects on the immune response depending on the medication. Glucorticoids resulted in a response that was 10 times lower than the immune-healthy controls, as well as fewer circulating plasmablasts after vaccination. Researchers found that 98% of controls were seropositive for antibody, compared with 92% of those with CID who were not taking prednisone, and 65% of CID patients on prednisone (P = .0006 and .0115, respectively). Prevention of neutralization of the virus was similarly reduced in those groups, compared with the controls. Dr. Kim noted this was a small sample size, with about 15 patients. These effects were seen regardless of the dose.
“We would’ve anticipated this would have been dose dependent, so this was a little bit surprising,” Dr. Kim said.
B-cell–depleting therapies, such as rituximab (Rituxan) and ocrelizumab (Ocrevus), reduced antibody titers by 36 times, compared with controls (P < .0001), with a similar reduction in preventing infection (P = .0066), the researchers found. The reduction in antibody titers was the most pronounced among those who had received B-cell–depleting therapies within the previous 6 months. Dr. Kim noted this was a small sample size, with about 10 patients.
CID study subjects taking an antimetabolite, including methotrexate, had an average of a two- to threefold reduction in antibody titers and in neutralization (P = .0006). This reduction was greatest with methotrexate, researchers found (P = .0027).
JAK inhibitors also significantly reduced antibody titers (P = .0066), but the reduction in neutralization of the virus was not significant. In addition, researchers found a reduction in antibody titers, the prevention of viral infection, and circulating plasmablasts among those on tumor necrosis factor (TNF) inhibitors, compared with controls, but these were insignificant statistically except for virus neutralization.
Dr. Kim said he hopes the glucocorticoid data spur physicians to try harder to wean patients off the drugs, when possible, in keeping with recommendations already in place.
“The general culture in rheumatology has been very lax about the need to reduce glucocorticoids,” he said. “This reinvigorates that call.” Questions about possible drug holidays from glucocorticoids remain, regarding how long a holiday would be needed, he said. He noted that many patients on glucocorticoids nonetheless mounted responses.
Those on B-cell–depleting therapies present a “much more difficult” question, he said. Some patients possibly could wait a bit longer than their normal, every-6-month schedule, but it’s an individual decision, he said. Since a booster of influenza vaccine has been found to enhance the response even within the 6-month window among ocrelizumab patients, a booster of COVID-19 vaccine might also help, although this remains to be studied.
The study group has already increased its sample size and is looking at adverse reactions and long-term immune responses, Dr. Kim said.
Encouraging, rather than discouraging, results
Leonard Calabrese, DO, professor of medicine at the Cleveland Clinic in Ohio, said the findings shouldn’t discourage clinicians from encouraging vaccination.
“There’s still a preponderance of people who will develop a robust antibody vaccine response,” he said.
He cautioned that the findings look only at antibodies to the spike protein and at plasmablasts. The reduction in these titers is “of concern,” he said, but “we don’t really know with certainty what are the effects of these drugs, and these data are on the overall biologic protective effect of the vaccine. There’s much more to a vaccine response than anti–spike protein and plasmablasts,” including cell-mediated immune response.
For an individual patient, the findings “mean a lot,” he said.
“I think that people who are on significant prednisone and B-cell–depleting agents, I think you have to share with them that there’s a reasonable chance that you’re not going to be making a response similar to healthy people,” he said. “Thus, even with your vaccine, we’re not going to cut you loose to do things that are violating social distancing and group settings. … Should you be hugging your grandchildren if you’re a rituximab vaccine recipient? I think I would wait until we have a little bit more data.”
Kevin Winthrop, MD, MPH, professor of ophthalmology at Oregon Health & Science University, Portland, where he studies vaccinations in the immunocompromised, said that glucocorticoids tend to have little effect on vaccinations generally at low doses.
When effects are seen they can be difficult to interpret, he said.
“It’s hard to extricate that from the effect of the underlying disease,” he said. The drug can be a proxy for worse disease control.
Although it’s a small study, it’s reassuring that overall the responses were similar to healthy controls.
For B-cell–depleting therapies, his usual guidance is to not give vaccine until a patient is at least 3 months out from their last dose, and not to restart until at least 2 weeks after vaccination.
“It’s not surprising that some of these DMARDs [disease-modifying antirheumatic drugs] do negatively affect vaccine response, particularly B-cell–depletion therapy. We need to do some studies to find a way to overcome that, or optimize delivery of the vaccine.”
Dr. Kim reported participating in consulting, advisory board, or speaker’s bureau for Alexion, Aurinia, Annexon Biosciences, Exagen Diagnostics, and GlaxoSmithKline, and receiving funding under a sponsored research agreement unrelated to the data in the paper from GlaxoSmithKline. Dr. Winthrop reported receiving consulting fees from Pfizer, AbbVie, UCB, Eli Lilly, Galapagos, GlaxoSmithKline, Roche, Gilead, Bristol-Myers Squibb, Regeneron, Sanofi, AstraZeneca, Novartis, and research grants from Bristol-Myers Squibb and Pfizer. Dr. Calabrese reported no relevant disclosures.
Although most patients with chronic inflammatory diseases mounted immune responses after two doses of mRNA-based COVID-19 vaccines, glucocorticoids and B-cell–depleting therapies markedly reduced the response, according to a recently published preprint of a new study.
The study, published on MedRxiv and not yet peer reviewed, involved a prospective look at 133 patients with chronic inflammatory disease (CID) and 53 patients with healthy immune systems at Washington University, St. Louis, and the University of California, San Francisco. It is regarded as the largest and most detailed study yet in how vaccines perform in people with immune-mediated inflammatory disease. The patients were enrolled between December 2020 and March 2021, and the most common diseases were inflammatory bowel disease (32%), rheumatoid arthritis (29%), spondyloarthritis (15%), and systemic lupus erythematosus (11%).
A ‘modest’ reduction in antibody response
Senior author Alfred Kim, MD, PhD, of the department of medicine at Washington University, said the overall results so far are encouraging.
“Most patients with an autoimmune disease that are on immunosuppression can mount antibody responses,” he said. “We’re seeing the majority of our subjects respond.”
The immune-healthy controls and most of the patients with CID had a robust immune response against the spike protein, although the CID group had a mean reduction in antibody titers that was three times lower than the controls (P = .0092). The CID group similarly had a 2.7-fold reduction in preventing neutralization, or halting the virus’ ability to infect (P < .0001), researchers reported.
This reduction in response is “modest,” he said.
“Is the level of reduction going to be detrimental for protection? Time will tell,” he said, adding that researchers anticipate that it won’t have a critical effect on protection because responses tended to be within the range of the immunocompetent controls, who themselves had wildly varied antibody titers across a 20-fold range. “ ‘Optimal’ isn’t necessarily the same as ‘sufficient.’ ”
Type of medication has big impact on antibody titers
But there was a wide variety of effects on the immune response depending on the medication. Glucorticoids resulted in a response that was 10 times lower than the immune-healthy controls, as well as fewer circulating plasmablasts after vaccination. Researchers found that 98% of controls were seropositive for antibody, compared with 92% of those with CID who were not taking prednisone, and 65% of CID patients on prednisone (P = .0006 and .0115, respectively). Prevention of neutralization of the virus was similarly reduced in those groups, compared with the controls. Dr. Kim noted this was a small sample size, with about 15 patients. These effects were seen regardless of the dose.
“We would’ve anticipated this would have been dose dependent, so this was a little bit surprising,” Dr. Kim said.
B-cell–depleting therapies, such as rituximab (Rituxan) and ocrelizumab (Ocrevus), reduced antibody titers by 36 times, compared with controls (P < .0001), with a similar reduction in preventing infection (P = .0066), the researchers found. The reduction in antibody titers was the most pronounced among those who had received B-cell–depleting therapies within the previous 6 months. Dr. Kim noted this was a small sample size, with about 10 patients.
CID study subjects taking an antimetabolite, including methotrexate, had an average of a two- to threefold reduction in antibody titers and in neutralization (P = .0006). This reduction was greatest with methotrexate, researchers found (P = .0027).
JAK inhibitors also significantly reduced antibody titers (P = .0066), but the reduction in neutralization of the virus was not significant. In addition, researchers found a reduction in antibody titers, the prevention of viral infection, and circulating plasmablasts among those on tumor necrosis factor (TNF) inhibitors, compared with controls, but these were insignificant statistically except for virus neutralization.
Dr. Kim said he hopes the glucocorticoid data spur physicians to try harder to wean patients off the drugs, when possible, in keeping with recommendations already in place.
“The general culture in rheumatology has been very lax about the need to reduce glucocorticoids,” he said. “This reinvigorates that call.” Questions about possible drug holidays from glucocorticoids remain, regarding how long a holiday would be needed, he said. He noted that many patients on glucocorticoids nonetheless mounted responses.
Those on B-cell–depleting therapies present a “much more difficult” question, he said. Some patients possibly could wait a bit longer than their normal, every-6-month schedule, but it’s an individual decision, he said. Since a booster of influenza vaccine has been found to enhance the response even within the 6-month window among ocrelizumab patients, a booster of COVID-19 vaccine might also help, although this remains to be studied.
The study group has already increased its sample size and is looking at adverse reactions and long-term immune responses, Dr. Kim said.
Encouraging, rather than discouraging, results
Leonard Calabrese, DO, professor of medicine at the Cleveland Clinic in Ohio, said the findings shouldn’t discourage clinicians from encouraging vaccination.
“There’s still a preponderance of people who will develop a robust antibody vaccine response,” he said.
He cautioned that the findings look only at antibodies to the spike protein and at plasmablasts. The reduction in these titers is “of concern,” he said, but “we don’t really know with certainty what are the effects of these drugs, and these data are on the overall biologic protective effect of the vaccine. There’s much more to a vaccine response than anti–spike protein and plasmablasts,” including cell-mediated immune response.
For an individual patient, the findings “mean a lot,” he said.
“I think that people who are on significant prednisone and B-cell–depleting agents, I think you have to share with them that there’s a reasonable chance that you’re not going to be making a response similar to healthy people,” he said. “Thus, even with your vaccine, we’re not going to cut you loose to do things that are violating social distancing and group settings. … Should you be hugging your grandchildren if you’re a rituximab vaccine recipient? I think I would wait until we have a little bit more data.”
Kevin Winthrop, MD, MPH, professor of ophthalmology at Oregon Health & Science University, Portland, where he studies vaccinations in the immunocompromised, said that glucocorticoids tend to have little effect on vaccinations generally at low doses.
When effects are seen they can be difficult to interpret, he said.
“It’s hard to extricate that from the effect of the underlying disease,” he said. The drug can be a proxy for worse disease control.
Although it’s a small study, it’s reassuring that overall the responses were similar to healthy controls.
For B-cell–depleting therapies, his usual guidance is to not give vaccine until a patient is at least 3 months out from their last dose, and not to restart until at least 2 weeks after vaccination.
“It’s not surprising that some of these DMARDs [disease-modifying antirheumatic drugs] do negatively affect vaccine response, particularly B-cell–depletion therapy. We need to do some studies to find a way to overcome that, or optimize delivery of the vaccine.”
Dr. Kim reported participating in consulting, advisory board, or speaker’s bureau for Alexion, Aurinia, Annexon Biosciences, Exagen Diagnostics, and GlaxoSmithKline, and receiving funding under a sponsored research agreement unrelated to the data in the paper from GlaxoSmithKline. Dr. Winthrop reported receiving consulting fees from Pfizer, AbbVie, UCB, Eli Lilly, Galapagos, GlaxoSmithKline, Roche, Gilead, Bristol-Myers Squibb, Regeneron, Sanofi, AstraZeneca, Novartis, and research grants from Bristol-Myers Squibb and Pfizer. Dr. Calabrese reported no relevant disclosures.
FROM MEDRXIV
Teen tanning bed ban would prevent more than 15,000 melanoma cases
and cost less than other, well-established public health interventions, according to a microsimulation of that age group’s virtual life course.
“Even with extensive sensitivity analyses on the costs of inspections, noncompliance with a ban, and the risk of developing melanoma in those who have used tanning beds, a ban can be considered highly cost effective,” Antoine Eskander, MD, ScM, of the University of Toronto, and associates said in Cancer.
Compared with no ban, such an intervention could save over $205 million in lifetime health care costs among the 17.1 million young people (based on the 2010 Census population) who would be affected, they said.
The more than 15,000 melanoma cases and 3,300 recurrences prevented would save $12 per average minor after adjusting for societal costs, such as lost productivity, formal and informal health care, economic losses to the tanning bed industry, and the need for monitoring, the investigators reported.
Switching to quality-adjusted life-years shows an improvement of 0.0002 QALYs per child for a ban, based on an overall cost of almost $24.9 per QALY, compared with no ban, they said, which makes it “more cost effective than many well-established public health interventions”:
- Processed meats taxation ($270/QALY).
- Smoking education campaign ($1,337/QALY).
- Cervical cancer screening ($2,166/QALY).
- Breast cancer screening ($29,284/QALY).
- Lung cancer screening ($49,200-$96,700/QALY).
Among the many parameters included in the microsimulation were the odds ratio of developing melanoma from exposure to tanning beds before age 25 (1.35), melanoma stage at presentation, risk of recurrence, and the cost of four annual inspections for each of the nation’s more than 13,000 tanning salons, Dr. Eskander and associates explained.
and cost less than other, well-established public health interventions, according to a microsimulation of that age group’s virtual life course.
“Even with extensive sensitivity analyses on the costs of inspections, noncompliance with a ban, and the risk of developing melanoma in those who have used tanning beds, a ban can be considered highly cost effective,” Antoine Eskander, MD, ScM, of the University of Toronto, and associates said in Cancer.
Compared with no ban, such an intervention could save over $205 million in lifetime health care costs among the 17.1 million young people (based on the 2010 Census population) who would be affected, they said.
The more than 15,000 melanoma cases and 3,300 recurrences prevented would save $12 per average minor after adjusting for societal costs, such as lost productivity, formal and informal health care, economic losses to the tanning bed industry, and the need for monitoring, the investigators reported.
Switching to quality-adjusted life-years shows an improvement of 0.0002 QALYs per child for a ban, based on an overall cost of almost $24.9 per QALY, compared with no ban, they said, which makes it “more cost effective than many well-established public health interventions”:
- Processed meats taxation ($270/QALY).
- Smoking education campaign ($1,337/QALY).
- Cervical cancer screening ($2,166/QALY).
- Breast cancer screening ($29,284/QALY).
- Lung cancer screening ($49,200-$96,700/QALY).
Among the many parameters included in the microsimulation were the odds ratio of developing melanoma from exposure to tanning beds before age 25 (1.35), melanoma stage at presentation, risk of recurrence, and the cost of four annual inspections for each of the nation’s more than 13,000 tanning salons, Dr. Eskander and associates explained.
and cost less than other, well-established public health interventions, according to a microsimulation of that age group’s virtual life course.
“Even with extensive sensitivity analyses on the costs of inspections, noncompliance with a ban, and the risk of developing melanoma in those who have used tanning beds, a ban can be considered highly cost effective,” Antoine Eskander, MD, ScM, of the University of Toronto, and associates said in Cancer.
Compared with no ban, such an intervention could save over $205 million in lifetime health care costs among the 17.1 million young people (based on the 2010 Census population) who would be affected, they said.
The more than 15,000 melanoma cases and 3,300 recurrences prevented would save $12 per average minor after adjusting for societal costs, such as lost productivity, formal and informal health care, economic losses to the tanning bed industry, and the need for monitoring, the investigators reported.
Switching to quality-adjusted life-years shows an improvement of 0.0002 QALYs per child for a ban, based on an overall cost of almost $24.9 per QALY, compared with no ban, they said, which makes it “more cost effective than many well-established public health interventions”:
- Processed meats taxation ($270/QALY).
- Smoking education campaign ($1,337/QALY).
- Cervical cancer screening ($2,166/QALY).
- Breast cancer screening ($29,284/QALY).
- Lung cancer screening ($49,200-$96,700/QALY).
Among the many parameters included in the microsimulation were the odds ratio of developing melanoma from exposure to tanning beds before age 25 (1.35), melanoma stage at presentation, risk of recurrence, and the cost of four annual inspections for each of the nation’s more than 13,000 tanning salons, Dr. Eskander and associates explained.
FROM CANCER
Survey finds Mohs surgeons favor nicotinamide for chemoprevention
, in a survey of members of the American College of Mohs Surgeons.
Although nicotinamide, a vitamin B3 derivative, has been shown to reduce keratinocyte carcinoma (KC) in high-risk patients, it is not approved by the Food and Drug Administration for chemoprevention, and no safe upper limit has been established in clinical trials to date, wrote Sheena Desai of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.
The investigators emailed an anonymous 12-question survey to 1,500 members of the American College of Mohs Surgeons. Of the 170 who responded, 10 were excluded for discordant responses, leaving 160 participants whose replies were included in a multiple logistic regression analysis. The respondents were mainly U.S. board-certified dermatologists and Mohs surgeons (99.4% for both); 86.9% were in clinical practice, including 78.8% in private practice, according to the report of the results, published in Dermatologic Surgery.
Overall, 76.9% of the respondents said they recommended nicotinamide for preventing KC, and 20% said they had recommended nicotinamide to more than 100 patients in the past year. In addition, 45% of respondents reported patients who had been taking nicotinamide for 2 years or more. Overall, 63.8% of the respondents expressed no concerns about long-term safety of nicotinamide, compared with 28.1% who said they were uncertain about long-term safety. Those who expressed concern or uncertainty about long-term safety were significantly less likely to recommend nicotinamide for KC prevention in the past year (odds ratio, 0.30; 95% confidence interval [CI] 0.13-0.71). Clinicians with more than 10 years in practice were significantly less likely to recommend nicotinamide for chemoprevention (OR, 0.20; 95% CI 0.05-0.82).
The study findings were limited by several factors, including the low number of responses and the potential lack of generalizability to clinicians other than Mohs surgeons, the researchers noted. “Additional studies on nicotinamide safety and use patterns, including cost-effectiveness analyses, are needed given the widespread use identified in this study,” they concluded.
Limited safety data highlight research gaps
The study is particularly important at this time because nicotinamide has been increasingly used for KC chemoprevention since a randomized, controlled trial published in 2015 in the New England Journal of Medicine showed benefits, corresponding author Rebecca I. Hartman, MD, of the department of dermatology, Brigham and Women’s Hospital and Harvard University, Boston, said in an interview. That study of high-risk patients found that nicotinamide, 500 mg twice a day, was safe and effective in lowering the rates of new nonmelanoma skin cancers and AKs after 12 months .
“However, because this is not a prescription medication, but rather an OTC vitamin supplement, data on its use are not available,” she said.
Dr. Hartman said she was not surprised that nicotinamide is being used frequently by a majority of the survey respondents. “Most are using this if someone has two KCs over 2 years, which is a quite common occurrence,” she noted. However, “I was a bit surprised that nearly two-thirds had no safety concerns with long-term use, even though this has not been well-studied,” she added.
“Like anything we recommend, we must consider the risks and benefits,” Dr. Hartman said of nicotinamide. “Unfortunately, we don’t know the risks well, since this hasn’t been well-characterized with regular long-term use in these doses,” and more research is needed, she said. “The risks are likely low, as this is a vitamin that has been used for years in various OTC supplements,” she added. “However, there are some data showing slightly increased all-cause mortality with similar doses of a related medicine, niacin, in cardiovascular patients. For this reason, I recommend the medication when a patient’s KCs are really becoming burdensome – several KCs in a year or two – or when they are high-risk due to immunosuppression,” she explained.
“We also must consider the individual patient. For a healthy younger patient who has a public-facing job and as a result is very averse to developing any KCs on his or her face and very motivated to try prevention, it may make sense to try nicotinamide,” Dr. Hartman said. But for an older patient with cardiovascular comorbidities who is not bothered by a KC on his or her back or extremities, “this medication may not have a favorable risk-benefit profile.”
To address safety concerns, “researchers need to examine whether there are any harms in long-term regular nicotinamide use for KC prevention,” Dr. Hartman said. “This is something we hope to do in our patients; however, it is challenging to study in a retrospective way since the harm is likely small and there are so many other features that influence mortality as an outcome,” she noted.
The study received no outside funding. The researchers had no financial conflicts to disclose.
, in a survey of members of the American College of Mohs Surgeons.
Although nicotinamide, a vitamin B3 derivative, has been shown to reduce keratinocyte carcinoma (KC) in high-risk patients, it is not approved by the Food and Drug Administration for chemoprevention, and no safe upper limit has been established in clinical trials to date, wrote Sheena Desai of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.
The investigators emailed an anonymous 12-question survey to 1,500 members of the American College of Mohs Surgeons. Of the 170 who responded, 10 were excluded for discordant responses, leaving 160 participants whose replies were included in a multiple logistic regression analysis. The respondents were mainly U.S. board-certified dermatologists and Mohs surgeons (99.4% for both); 86.9% were in clinical practice, including 78.8% in private practice, according to the report of the results, published in Dermatologic Surgery.
Overall, 76.9% of the respondents said they recommended nicotinamide for preventing KC, and 20% said they had recommended nicotinamide to more than 100 patients in the past year. In addition, 45% of respondents reported patients who had been taking nicotinamide for 2 years or more. Overall, 63.8% of the respondents expressed no concerns about long-term safety of nicotinamide, compared with 28.1% who said they were uncertain about long-term safety. Those who expressed concern or uncertainty about long-term safety were significantly less likely to recommend nicotinamide for KC prevention in the past year (odds ratio, 0.30; 95% confidence interval [CI] 0.13-0.71). Clinicians with more than 10 years in practice were significantly less likely to recommend nicotinamide for chemoprevention (OR, 0.20; 95% CI 0.05-0.82).
The study findings were limited by several factors, including the low number of responses and the potential lack of generalizability to clinicians other than Mohs surgeons, the researchers noted. “Additional studies on nicotinamide safety and use patterns, including cost-effectiveness analyses, are needed given the widespread use identified in this study,” they concluded.
Limited safety data highlight research gaps
The study is particularly important at this time because nicotinamide has been increasingly used for KC chemoprevention since a randomized, controlled trial published in 2015 in the New England Journal of Medicine showed benefits, corresponding author Rebecca I. Hartman, MD, of the department of dermatology, Brigham and Women’s Hospital and Harvard University, Boston, said in an interview. That study of high-risk patients found that nicotinamide, 500 mg twice a day, was safe and effective in lowering the rates of new nonmelanoma skin cancers and AKs after 12 months .
“However, because this is not a prescription medication, but rather an OTC vitamin supplement, data on its use are not available,” she said.
Dr. Hartman said she was not surprised that nicotinamide is being used frequently by a majority of the survey respondents. “Most are using this if someone has two KCs over 2 years, which is a quite common occurrence,” she noted. However, “I was a bit surprised that nearly two-thirds had no safety concerns with long-term use, even though this has not been well-studied,” she added.
“Like anything we recommend, we must consider the risks and benefits,” Dr. Hartman said of nicotinamide. “Unfortunately, we don’t know the risks well, since this hasn’t been well-characterized with regular long-term use in these doses,” and more research is needed, she said. “The risks are likely low, as this is a vitamin that has been used for years in various OTC supplements,” she added. “However, there are some data showing slightly increased all-cause mortality with similar doses of a related medicine, niacin, in cardiovascular patients. For this reason, I recommend the medication when a patient’s KCs are really becoming burdensome – several KCs in a year or two – or when they are high-risk due to immunosuppression,” she explained.
“We also must consider the individual patient. For a healthy younger patient who has a public-facing job and as a result is very averse to developing any KCs on his or her face and very motivated to try prevention, it may make sense to try nicotinamide,” Dr. Hartman said. But for an older patient with cardiovascular comorbidities who is not bothered by a KC on his or her back or extremities, “this medication may not have a favorable risk-benefit profile.”
To address safety concerns, “researchers need to examine whether there are any harms in long-term regular nicotinamide use for KC prevention,” Dr. Hartman said. “This is something we hope to do in our patients; however, it is challenging to study in a retrospective way since the harm is likely small and there are so many other features that influence mortality as an outcome,” she noted.
The study received no outside funding. The researchers had no financial conflicts to disclose.
, in a survey of members of the American College of Mohs Surgeons.
Although nicotinamide, a vitamin B3 derivative, has been shown to reduce keratinocyte carcinoma (KC) in high-risk patients, it is not approved by the Food and Drug Administration for chemoprevention, and no safe upper limit has been established in clinical trials to date, wrote Sheena Desai of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.
The investigators emailed an anonymous 12-question survey to 1,500 members of the American College of Mohs Surgeons. Of the 170 who responded, 10 were excluded for discordant responses, leaving 160 participants whose replies were included in a multiple logistic regression analysis. The respondents were mainly U.S. board-certified dermatologists and Mohs surgeons (99.4% for both); 86.9% were in clinical practice, including 78.8% in private practice, according to the report of the results, published in Dermatologic Surgery.
Overall, 76.9% of the respondents said they recommended nicotinamide for preventing KC, and 20% said they had recommended nicotinamide to more than 100 patients in the past year. In addition, 45% of respondents reported patients who had been taking nicotinamide for 2 years or more. Overall, 63.8% of the respondents expressed no concerns about long-term safety of nicotinamide, compared with 28.1% who said they were uncertain about long-term safety. Those who expressed concern or uncertainty about long-term safety were significantly less likely to recommend nicotinamide for KC prevention in the past year (odds ratio, 0.30; 95% confidence interval [CI] 0.13-0.71). Clinicians with more than 10 years in practice were significantly less likely to recommend nicotinamide for chemoprevention (OR, 0.20; 95% CI 0.05-0.82).
The study findings were limited by several factors, including the low number of responses and the potential lack of generalizability to clinicians other than Mohs surgeons, the researchers noted. “Additional studies on nicotinamide safety and use patterns, including cost-effectiveness analyses, are needed given the widespread use identified in this study,” they concluded.
Limited safety data highlight research gaps
The study is particularly important at this time because nicotinamide has been increasingly used for KC chemoprevention since a randomized, controlled trial published in 2015 in the New England Journal of Medicine showed benefits, corresponding author Rebecca I. Hartman, MD, of the department of dermatology, Brigham and Women’s Hospital and Harvard University, Boston, said in an interview. That study of high-risk patients found that nicotinamide, 500 mg twice a day, was safe and effective in lowering the rates of new nonmelanoma skin cancers and AKs after 12 months .
“However, because this is not a prescription medication, but rather an OTC vitamin supplement, data on its use are not available,” she said.
Dr. Hartman said she was not surprised that nicotinamide is being used frequently by a majority of the survey respondents. “Most are using this if someone has two KCs over 2 years, which is a quite common occurrence,” she noted. However, “I was a bit surprised that nearly two-thirds had no safety concerns with long-term use, even though this has not been well-studied,” she added.
“Like anything we recommend, we must consider the risks and benefits,” Dr. Hartman said of nicotinamide. “Unfortunately, we don’t know the risks well, since this hasn’t been well-characterized with regular long-term use in these doses,” and more research is needed, she said. “The risks are likely low, as this is a vitamin that has been used for years in various OTC supplements,” she added. “However, there are some data showing slightly increased all-cause mortality with similar doses of a related medicine, niacin, in cardiovascular patients. For this reason, I recommend the medication when a patient’s KCs are really becoming burdensome – several KCs in a year or two – or when they are high-risk due to immunosuppression,” she explained.
“We also must consider the individual patient. For a healthy younger patient who has a public-facing job and as a result is very averse to developing any KCs on his or her face and very motivated to try prevention, it may make sense to try nicotinamide,” Dr. Hartman said. But for an older patient with cardiovascular comorbidities who is not bothered by a KC on his or her back or extremities, “this medication may not have a favorable risk-benefit profile.”
To address safety concerns, “researchers need to examine whether there are any harms in long-term regular nicotinamide use for KC prevention,” Dr. Hartman said. “This is something we hope to do in our patients; however, it is challenging to study in a retrospective way since the harm is likely small and there are so many other features that influence mortality as an outcome,” she noted.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM DERMATOLOGIC SURGERY
A Rash Against the Grain
ANSWER
The correct answer is dermatitis herpetiformis (DH; choice “b”).
DISCUSSION
DH is unusual, although not rare, and it is often overlooked in the investigation of itchy rashes—even by dermatologists. As is so often the case, the biopsy was the missing piece of the puzzle, since it clearly showed changes consistent with this condition.
The history of DH has some interesting overlap with that of biopsy. It was Rudolph Virchow, an 18th century Austrian pathologist, who first connected clinical disease to specific arrangements of disordered tissue seen microscopically—at that time, a giant leap for medicine. An American dermatologist, Louis Adolphus Duhring, had the good fortune to study under Virchow and his successors in Vienna and brought this cutting-edge knowledge back to this country, where he began the process of categorizing diseases by their histologic patterns as well as by their presentation and clinical course. This was when he discovered the basis for the condition that became known as Duhring disease, also known as dermatitis herpetiformis.
It was much later (1967) that a connection was made between DH and the ingestion of gluten. Our patient experienced a rapid decline in his itching and rash as soon as he started a gluten-free diet. However, since many patients find such a diet difficult to maintain, there are pharmacologic options as well: dapsone, colchicine, sulfa drugs, drugs from the tetracycline family, and nicotinamide. All have potential adverse effects with which the prescriber needs to become familiar.
With a combination of medication and reduced gluten intake, it’s entirely possible that the patient’s DH will permanently resolve, although he will remain at increased risk for other autoimmune conditions.
ANSWER
The correct answer is dermatitis herpetiformis (DH; choice “b”).
DISCUSSION
DH is unusual, although not rare, and it is often overlooked in the investigation of itchy rashes—even by dermatologists. As is so often the case, the biopsy was the missing piece of the puzzle, since it clearly showed changes consistent with this condition.
The history of DH has some interesting overlap with that of biopsy. It was Rudolph Virchow, an 18th century Austrian pathologist, who first connected clinical disease to specific arrangements of disordered tissue seen microscopically—at that time, a giant leap for medicine. An American dermatologist, Louis Adolphus Duhring, had the good fortune to study under Virchow and his successors in Vienna and brought this cutting-edge knowledge back to this country, where he began the process of categorizing diseases by their histologic patterns as well as by their presentation and clinical course. This was when he discovered the basis for the condition that became known as Duhring disease, also known as dermatitis herpetiformis.
It was much later (1967) that a connection was made between DH and the ingestion of gluten. Our patient experienced a rapid decline in his itching and rash as soon as he started a gluten-free diet. However, since many patients find such a diet difficult to maintain, there are pharmacologic options as well: dapsone, colchicine, sulfa drugs, drugs from the tetracycline family, and nicotinamide. All have potential adverse effects with which the prescriber needs to become familiar.
With a combination of medication and reduced gluten intake, it’s entirely possible that the patient’s DH will permanently resolve, although he will remain at increased risk for other autoimmune conditions.
ANSWER
The correct answer is dermatitis herpetiformis (DH; choice “b”).
DISCUSSION
DH is unusual, although not rare, and it is often overlooked in the investigation of itchy rashes—even by dermatologists. As is so often the case, the biopsy was the missing piece of the puzzle, since it clearly showed changes consistent with this condition.
The history of DH has some interesting overlap with that of biopsy. It was Rudolph Virchow, an 18th century Austrian pathologist, who first connected clinical disease to specific arrangements of disordered tissue seen microscopically—at that time, a giant leap for medicine. An American dermatologist, Louis Adolphus Duhring, had the good fortune to study under Virchow and his successors in Vienna and brought this cutting-edge knowledge back to this country, where he began the process of categorizing diseases by their histologic patterns as well as by their presentation and clinical course. This was when he discovered the basis for the condition that became known as Duhring disease, also known as dermatitis herpetiformis.
It was much later (1967) that a connection was made between DH and the ingestion of gluten. Our patient experienced a rapid decline in his itching and rash as soon as he started a gluten-free diet. However, since many patients find such a diet difficult to maintain, there are pharmacologic options as well: dapsone, colchicine, sulfa drugs, drugs from the tetracycline family, and nicotinamide. All have potential adverse effects with which the prescriber needs to become familiar.
With a combination of medication and reduced gluten intake, it’s entirely possible that the patient’s DH will permanently resolve, although he will remain at increased risk for other autoimmune conditions.
A 56-year-old man began to itch almost 10 years ago, when lesions appeared on his extensor forearms; they later branched out to his knees, scalp, and waistline. He has continued to suffer despite seeing numerous providers, including dermatologists.
An allergist pronounced him free of any significant allergies. Another provider was certain the patient had scabies, although his household was unaffected and the prescribed treatment—permethrin lotion and oral ivermectin—had no impact on the rash or the symptoms. Most of the other consulted providers diagnosed eczema, despite a complete lack of atopy in the patient or his family of origin. Furthermore, treatment with topical, oral, and intramuscular steroids had offered minimal and very short-lived relief. No one took a scraping or performed a biopsy of the rash.
The patient claims to be otherwise healthy, with no gastrointestinal symptoms and no new medications. Examination reveals a slightly overweight man in no distress.
The lesions in question are patches of excoriated papulovesicular lesions. Microscopic examination of a KOH prep shows no scabetic elements. His volar wrists, the sides of his fingers, and his genitals are free of lesions.
A shave biopsy is performed under local anesthetic. The pathology report indicates subepidermal collections of eosinophils.
Study aims to enhance understanding of ‘tremendously understudied’ prurigo nodularis
compared with age-matched controls, as well those with atopic dermatitis and psoriasis.
Those are key findings from a retrospective analysis of claims data that was published online April 3, 2021, in the Journal of Investigative Dermatology.
“Prurigo nodularis is a tremendously understudied inflammatory skin disease,” one of the study’s cosenior authors, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said in an interview. “Prurigo nodularis patients have uncontrolled itch, which leads to reduced quality of life, and the association with many disease comorbidities. We focused on better understanding in this work the unique comorbidities of prurigo nodularis, compared to other inflammatory skin diseases.”
For the study, Dr. Kwatra, cosenior author Yevgeniy R. Semenov, MD, of the department of dermatology, Massachusetts General Hospital, Boston, and colleagues evaluated nationally representative, private insurance claims data from October 2015 to December 2019 to identify prurigo nodularis (PN) patients, who were defined as individuals with two or more medical claims for PN using ICD-10-CM codes. For comparison with patients with inflammatory skin diseases, they used the same claims data to identify patients with atopic dermatitis (AD) and psoriasis as well as to select controls who were age and gender matched to PN patients. Next, they quantified the overall comorbidity burden with the Charlson Comorbidity Index (CCI).
In 2016, the claims database included 2,658 patients with PN, 21,482 patients with AD, 21,073 patients with psoriasis, and 13,290 controls. The number of patients in each category rose each subsequent year, so that by the end of 2019 there were 9,426 patients with PN, 70,298 patients with AD, 59,509 patients with psoriasis, and 47,130 controls. Between 2016 and 2019 the mean age of PN patients increased from 57.5 to 59.8 years and the percent of male patients rose from 44.5% to 46.5%.
Between 2016 and 2019, the overall PN prevalence rates rose from 18 per 100,000 to 58 per 100,000, while the PN prevalence rates among adults increased from 22 per 100,000 to 70 per 100,000, and the rates among children rose grew from 2 per 100,000 to 7 per 100,000. “Our report shows an estimated disease prevalence of around 335,000 cases of PN in the United States,” said Dr. Kwatra, who was among a group of researchers to recently report on systemic Th22-polarized inflammation in PN patients.
The researchers also found that patients with PN had the highest mean CCI in both 2016 and 2019. In 2016, their mean CCI was 1.53, compared with 0.98 among controls, 0.53 among those with AD, and 1.16 among those with psoriasis. In 2019, the mean CCI had increased in all groups of patients, to 2.32 among those with PN, 1.57 among controls, 0.75 among those with AD patients, and 1.71 among those with psoriasis.
The top five medical specialties who cared for PN patients, defined as the estimated number of visits per year per patient, were internal medicine (2.01 visits), dermatology (1.87 visits), family practice (1.60 visits), cardiology or cardiovascular disease (0.85 visits), and orthopedics or orthopedic surgery (0.49 visits).
“If you encounter a patient with prurigo nodularis, it’s important to perform a screening for chronic kidney disease, diabetes, and liver disease,” Dr. Kwatra said. “These comorbidities along with emerging studies on circulating blood biomarkers suggest prurigo nodularis is a systemic inflammatory disorder; thus systemic agents are needed for most patients as part of multimodal therapy in prurigo nodularis.”
The researchers acknowledged certain limitations of the study, including its retrospective design and the identification of patients with PN with the ICD-10-CM code, which require further validation. “Furthermore, the increase in annual prevalence estimates for PN, AD, and psoriasis observed in the study could also be a result of increasing coding of these diagnoses in the claims data along with rising awareness by the medical profession,” they wrote.
Dr. Kwatra disclosed that he is an advisory board member/consultant for AbbVie, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals, and has received grant funding from Galderma, Pfizer, and Kiniksa. He has also received a Dermatology Foundation Medical Dermatology Career Development Award, a research grant from the Skin of Color Society, and is supported by the National Institutes of Health. One coauthor has been funded by NIH grants.
compared with age-matched controls, as well those with atopic dermatitis and psoriasis.
Those are key findings from a retrospective analysis of claims data that was published online April 3, 2021, in the Journal of Investigative Dermatology.
“Prurigo nodularis is a tremendously understudied inflammatory skin disease,” one of the study’s cosenior authors, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said in an interview. “Prurigo nodularis patients have uncontrolled itch, which leads to reduced quality of life, and the association with many disease comorbidities. We focused on better understanding in this work the unique comorbidities of prurigo nodularis, compared to other inflammatory skin diseases.”
For the study, Dr. Kwatra, cosenior author Yevgeniy R. Semenov, MD, of the department of dermatology, Massachusetts General Hospital, Boston, and colleagues evaluated nationally representative, private insurance claims data from October 2015 to December 2019 to identify prurigo nodularis (PN) patients, who were defined as individuals with two or more medical claims for PN using ICD-10-CM codes. For comparison with patients with inflammatory skin diseases, they used the same claims data to identify patients with atopic dermatitis (AD) and psoriasis as well as to select controls who were age and gender matched to PN patients. Next, they quantified the overall comorbidity burden with the Charlson Comorbidity Index (CCI).
In 2016, the claims database included 2,658 patients with PN, 21,482 patients with AD, 21,073 patients with psoriasis, and 13,290 controls. The number of patients in each category rose each subsequent year, so that by the end of 2019 there were 9,426 patients with PN, 70,298 patients with AD, 59,509 patients with psoriasis, and 47,130 controls. Between 2016 and 2019 the mean age of PN patients increased from 57.5 to 59.8 years and the percent of male patients rose from 44.5% to 46.5%.
Between 2016 and 2019, the overall PN prevalence rates rose from 18 per 100,000 to 58 per 100,000, while the PN prevalence rates among adults increased from 22 per 100,000 to 70 per 100,000, and the rates among children rose grew from 2 per 100,000 to 7 per 100,000. “Our report shows an estimated disease prevalence of around 335,000 cases of PN in the United States,” said Dr. Kwatra, who was among a group of researchers to recently report on systemic Th22-polarized inflammation in PN patients.
The researchers also found that patients with PN had the highest mean CCI in both 2016 and 2019. In 2016, their mean CCI was 1.53, compared with 0.98 among controls, 0.53 among those with AD, and 1.16 among those with psoriasis. In 2019, the mean CCI had increased in all groups of patients, to 2.32 among those with PN, 1.57 among controls, 0.75 among those with AD patients, and 1.71 among those with psoriasis.
The top five medical specialties who cared for PN patients, defined as the estimated number of visits per year per patient, were internal medicine (2.01 visits), dermatology (1.87 visits), family practice (1.60 visits), cardiology or cardiovascular disease (0.85 visits), and orthopedics or orthopedic surgery (0.49 visits).
“If you encounter a patient with prurigo nodularis, it’s important to perform a screening for chronic kidney disease, diabetes, and liver disease,” Dr. Kwatra said. “These comorbidities along with emerging studies on circulating blood biomarkers suggest prurigo nodularis is a systemic inflammatory disorder; thus systemic agents are needed for most patients as part of multimodal therapy in prurigo nodularis.”
The researchers acknowledged certain limitations of the study, including its retrospective design and the identification of patients with PN with the ICD-10-CM code, which require further validation. “Furthermore, the increase in annual prevalence estimates for PN, AD, and psoriasis observed in the study could also be a result of increasing coding of these diagnoses in the claims data along with rising awareness by the medical profession,” they wrote.
Dr. Kwatra disclosed that he is an advisory board member/consultant for AbbVie, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals, and has received grant funding from Galderma, Pfizer, and Kiniksa. He has also received a Dermatology Foundation Medical Dermatology Career Development Award, a research grant from the Skin of Color Society, and is supported by the National Institutes of Health. One coauthor has been funded by NIH grants.
compared with age-matched controls, as well those with atopic dermatitis and psoriasis.
Those are key findings from a retrospective analysis of claims data that was published online April 3, 2021, in the Journal of Investigative Dermatology.
“Prurigo nodularis is a tremendously understudied inflammatory skin disease,” one of the study’s cosenior authors, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said in an interview. “Prurigo nodularis patients have uncontrolled itch, which leads to reduced quality of life, and the association with many disease comorbidities. We focused on better understanding in this work the unique comorbidities of prurigo nodularis, compared to other inflammatory skin diseases.”
For the study, Dr. Kwatra, cosenior author Yevgeniy R. Semenov, MD, of the department of dermatology, Massachusetts General Hospital, Boston, and colleagues evaluated nationally representative, private insurance claims data from October 2015 to December 2019 to identify prurigo nodularis (PN) patients, who were defined as individuals with two or more medical claims for PN using ICD-10-CM codes. For comparison with patients with inflammatory skin diseases, they used the same claims data to identify patients with atopic dermatitis (AD) and psoriasis as well as to select controls who were age and gender matched to PN patients. Next, they quantified the overall comorbidity burden with the Charlson Comorbidity Index (CCI).
In 2016, the claims database included 2,658 patients with PN, 21,482 patients with AD, 21,073 patients with psoriasis, and 13,290 controls. The number of patients in each category rose each subsequent year, so that by the end of 2019 there were 9,426 patients with PN, 70,298 patients with AD, 59,509 patients with psoriasis, and 47,130 controls. Between 2016 and 2019 the mean age of PN patients increased from 57.5 to 59.8 years and the percent of male patients rose from 44.5% to 46.5%.
Between 2016 and 2019, the overall PN prevalence rates rose from 18 per 100,000 to 58 per 100,000, while the PN prevalence rates among adults increased from 22 per 100,000 to 70 per 100,000, and the rates among children rose grew from 2 per 100,000 to 7 per 100,000. “Our report shows an estimated disease prevalence of around 335,000 cases of PN in the United States,” said Dr. Kwatra, who was among a group of researchers to recently report on systemic Th22-polarized inflammation in PN patients.
The researchers also found that patients with PN had the highest mean CCI in both 2016 and 2019. In 2016, their mean CCI was 1.53, compared with 0.98 among controls, 0.53 among those with AD, and 1.16 among those with psoriasis. In 2019, the mean CCI had increased in all groups of patients, to 2.32 among those with PN, 1.57 among controls, 0.75 among those with AD patients, and 1.71 among those with psoriasis.
The top five medical specialties who cared for PN patients, defined as the estimated number of visits per year per patient, were internal medicine (2.01 visits), dermatology (1.87 visits), family practice (1.60 visits), cardiology or cardiovascular disease (0.85 visits), and orthopedics or orthopedic surgery (0.49 visits).
“If you encounter a patient with prurigo nodularis, it’s important to perform a screening for chronic kidney disease, diabetes, and liver disease,” Dr. Kwatra said. “These comorbidities along with emerging studies on circulating blood biomarkers suggest prurigo nodularis is a systemic inflammatory disorder; thus systemic agents are needed for most patients as part of multimodal therapy in prurigo nodularis.”
The researchers acknowledged certain limitations of the study, including its retrospective design and the identification of patients with PN with the ICD-10-CM code, which require further validation. “Furthermore, the increase in annual prevalence estimates for PN, AD, and psoriasis observed in the study could also be a result of increasing coding of these diagnoses in the claims data along with rising awareness by the medical profession,” they wrote.
Dr. Kwatra disclosed that he is an advisory board member/consultant for AbbVie, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals, and has received grant funding from Galderma, Pfizer, and Kiniksa. He has also received a Dermatology Foundation Medical Dermatology Career Development Award, a research grant from the Skin of Color Society, and is supported by the National Institutes of Health. One coauthor has been funded by NIH grants.
FROM THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
A 12-year-old male has persistent purple toes and new red lesions on his hands
A punch biopsy from one of the lesions on the feet showed subtle basal vacuolar interface inflammation on the epidermis and rare apoptotic keratinocytes. There was an underlying dermal lymphocytic inflammatory infiltrate around the vascular plexus. Dermal mucin appeared slightly increased. The histologic findings are consistent with pernio. He had a negative direct immunofluorescence study.
Laboratory work-up showed an elevated antinuclear antibody (ANA) of 1:620; positive anticardiolipin IgM was at 15.2. A complete blood count showed no anemia or lymphopenia, he had normal complement C3 and C4 levels, normal urinalysis, negative cryoglobulins and cold agglutinins, and a normal protein electrophoresis.
Given the chronicity of his lesions, the lack of improvement with weather changes, the histopathologic findings of a vacuolar interface dermatitis and the positive ANA titer he was diagnosed with chilblain lupus.
Chilblain lupus erythematosus (CLE) is an uncommon form of chronic cutaneous lupus erythematosus that presents with tender pink to violaceous macules, papules, and/or nodules that sometimes can ulcerate and are present on the fingers, toes, and sometimes the nose and ears. The lesions are usually triggered by cold exposure.1 These patients also have clinical and laboratory findings consistent with lupus erythematosus.
Even though more studies are needed to clarify the clinical and histopathologic features of chilblain lupus, compared with idiopathic pernio, some authors suggest several characteristics: CLE lesions tend to persist in summer months, as occurred in our patient, and histopathologic evaluation usually shows vacuolar and interface inflammation on the basal cell layer and may also have a positive lupus band on direct immunofluorescence.2 About 20% of patient with CLE may later develop systemic lupus erythematosus.3
There is also a familial form of CLE which is usually inherited as an autosomal-dominant trait. Mutations in TREX1, SAMHD1, and STING have been described in these patients.4 Affected children present with skin lesions at a young age and those with TREX1 mutations are at a higher risk to develop systemic lupus erythematosus.
The differential diagnosis of chilblain lupus includes idiopathic pernio or pernio secondary to other conditions. Other conditions that are thought to be associated with pernio, besides lupus erythematosus, include infectious causes (hepatitis B, COVID-19 infection),5 autoimmune conditions, malignancy and hematologic disorders (paraproteinemia).6 In histopathology, pernio lesions present with dermal edema and superficial and deep lymphocytic infiltrate.
The pathogenesis of pernio is not fully understood but is thought be related to vasospasm with secondary poor perfusion and ischemia and type I interferon (INF1) immune response. A recent review of the published studies trying to explain the causality between COVID 19 and pernio-like lesions, from January 2020 to December 2020, speculate several possible mechanisms: an increase in the vasoconstrictive, prothrombotic, and proinflammatory effects of the angiotensin II pathway through activation of the ACE2 by the virus; COVID-19 triggers a robust INF1 immune response in predisposed patients; pernio as a sign of mild disease, may be explained by genetic and hormonal differences in the patients affected.7
Another condition that can be confused with CLE is Raynaud phenomenon, were patients present with white to purple to red patches on the fingers and toes after exposure to cold, but in comparison with pernio, the lesions improve within minutes to hours after rewarming. Secondary Raynaud phenomenon can be seen in patients with systemic lupus erythematosus and in patients with other connective tissue disorders. The skin lesions in our patient were persistent and were not triggered by cold exposure, making Raynaud phenomenon less likely. Children with vasculitis can present with painful red, violaceous, or necrotic lesions on the extremities, which can mimic pernio. Vasculitis lesions tend to be more purpuric and angulated, compared with pernio lesions, though in severe cases of pernio with ulceration it may be difficult to distinguish between the two entities and a skin biopsy may be needed.
Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare skin condition in which children present with edematous tender nodules on the hands and with less frequency in other parts of the body with associated fever, malaise, conjunctivitis, or joint pain and it is usually associated with infection or malignancy. Our patient denied any systemic symptoms and had no conjunctivitis nor arthritis.
Most patients with idiopathic pernio do not require a biopsy or further laboratory evaluation unless the lesions are atypical, chronic, or there is a suspected associated condition. The workup for patients with prolonged or atypical pernio-like lesions include a skin biopsy with direct immunofluorescence, ANA, complete blood count, complement levels, antiphospholipid antibodies, cold agglutinins, and cryoglobulins.
Treatment of mild CLE is with moderate- to high-potency topical corticosteroids. In those patients not responding to topical measures and keeping the extremities warm, the use of hydroxychloroquine has been reported to be beneficial in some patients as well as the use of calcium-channel blockers.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
1. Su WP et al. Cutis. 1994 Dec;54(6):395-9.
2. Boada A et al. Am J Dermatopathol. 2010 Feb;32(1):19-23.
3. Patel et al. SBMJ Case Rep. 2013;2013:bcr2013201165.
4. Genes Yi et al. BMC. 2020 Apr 15;18(1):32.
5. Battesti G et al. J Am Acad Dermatol. 2020;83(4):1219-22.
6. Cappel JA et al. Mayo Clin Proc. 2014 Feb;89(2):207-15.
7. Cappel MA et al. Mayo Clin Proc. 2021;96(4):989-1005.
A punch biopsy from one of the lesions on the feet showed subtle basal vacuolar interface inflammation on the epidermis and rare apoptotic keratinocytes. There was an underlying dermal lymphocytic inflammatory infiltrate around the vascular plexus. Dermal mucin appeared slightly increased. The histologic findings are consistent with pernio. He had a negative direct immunofluorescence study.
Laboratory work-up showed an elevated antinuclear antibody (ANA) of 1:620; positive anticardiolipin IgM was at 15.2. A complete blood count showed no anemia or lymphopenia, he had normal complement C3 and C4 levels, normal urinalysis, negative cryoglobulins and cold agglutinins, and a normal protein electrophoresis.
Given the chronicity of his lesions, the lack of improvement with weather changes, the histopathologic findings of a vacuolar interface dermatitis and the positive ANA titer he was diagnosed with chilblain lupus.
Chilblain lupus erythematosus (CLE) is an uncommon form of chronic cutaneous lupus erythematosus that presents with tender pink to violaceous macules, papules, and/or nodules that sometimes can ulcerate and are present on the fingers, toes, and sometimes the nose and ears. The lesions are usually triggered by cold exposure.1 These patients also have clinical and laboratory findings consistent with lupus erythematosus.
Even though more studies are needed to clarify the clinical and histopathologic features of chilblain lupus, compared with idiopathic pernio, some authors suggest several characteristics: CLE lesions tend to persist in summer months, as occurred in our patient, and histopathologic evaluation usually shows vacuolar and interface inflammation on the basal cell layer and may also have a positive lupus band on direct immunofluorescence.2 About 20% of patient with CLE may later develop systemic lupus erythematosus.3
There is also a familial form of CLE which is usually inherited as an autosomal-dominant trait. Mutations in TREX1, SAMHD1, and STING have been described in these patients.4 Affected children present with skin lesions at a young age and those with TREX1 mutations are at a higher risk to develop systemic lupus erythematosus.
The differential diagnosis of chilblain lupus includes idiopathic pernio or pernio secondary to other conditions. Other conditions that are thought to be associated with pernio, besides lupus erythematosus, include infectious causes (hepatitis B, COVID-19 infection),5 autoimmune conditions, malignancy and hematologic disorders (paraproteinemia).6 In histopathology, pernio lesions present with dermal edema and superficial and deep lymphocytic infiltrate.
The pathogenesis of pernio is not fully understood but is thought be related to vasospasm with secondary poor perfusion and ischemia and type I interferon (INF1) immune response. A recent review of the published studies trying to explain the causality between COVID 19 and pernio-like lesions, from January 2020 to December 2020, speculate several possible mechanisms: an increase in the vasoconstrictive, prothrombotic, and proinflammatory effects of the angiotensin II pathway through activation of the ACE2 by the virus; COVID-19 triggers a robust INF1 immune response in predisposed patients; pernio as a sign of mild disease, may be explained by genetic and hormonal differences in the patients affected.7
Another condition that can be confused with CLE is Raynaud phenomenon, were patients present with white to purple to red patches on the fingers and toes after exposure to cold, but in comparison with pernio, the lesions improve within minutes to hours after rewarming. Secondary Raynaud phenomenon can be seen in patients with systemic lupus erythematosus and in patients with other connective tissue disorders. The skin lesions in our patient were persistent and were not triggered by cold exposure, making Raynaud phenomenon less likely. Children with vasculitis can present with painful red, violaceous, or necrotic lesions on the extremities, which can mimic pernio. Vasculitis lesions tend to be more purpuric and angulated, compared with pernio lesions, though in severe cases of pernio with ulceration it may be difficult to distinguish between the two entities and a skin biopsy may be needed.
Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare skin condition in which children present with edematous tender nodules on the hands and with less frequency in other parts of the body with associated fever, malaise, conjunctivitis, or joint pain and it is usually associated with infection or malignancy. Our patient denied any systemic symptoms and had no conjunctivitis nor arthritis.
Most patients with idiopathic pernio do not require a biopsy or further laboratory evaluation unless the lesions are atypical, chronic, or there is a suspected associated condition. The workup for patients with prolonged or atypical pernio-like lesions include a skin biopsy with direct immunofluorescence, ANA, complete blood count, complement levels, antiphospholipid antibodies, cold agglutinins, and cryoglobulins.
Treatment of mild CLE is with moderate- to high-potency topical corticosteroids. In those patients not responding to topical measures and keeping the extremities warm, the use of hydroxychloroquine has been reported to be beneficial in some patients as well as the use of calcium-channel blockers.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
1. Su WP et al. Cutis. 1994 Dec;54(6):395-9.
2. Boada A et al. Am J Dermatopathol. 2010 Feb;32(1):19-23.
3. Patel et al. SBMJ Case Rep. 2013;2013:bcr2013201165.
4. Genes Yi et al. BMC. 2020 Apr 15;18(1):32.
5. Battesti G et al. J Am Acad Dermatol. 2020;83(4):1219-22.
6. Cappel JA et al. Mayo Clin Proc. 2014 Feb;89(2):207-15.
7. Cappel MA et al. Mayo Clin Proc. 2021;96(4):989-1005.
A punch biopsy from one of the lesions on the feet showed subtle basal vacuolar interface inflammation on the epidermis and rare apoptotic keratinocytes. There was an underlying dermal lymphocytic inflammatory infiltrate around the vascular plexus. Dermal mucin appeared slightly increased. The histologic findings are consistent with pernio. He had a negative direct immunofluorescence study.
Laboratory work-up showed an elevated antinuclear antibody (ANA) of 1:620; positive anticardiolipin IgM was at 15.2. A complete blood count showed no anemia or lymphopenia, he had normal complement C3 and C4 levels, normal urinalysis, negative cryoglobulins and cold agglutinins, and a normal protein electrophoresis.
Given the chronicity of his lesions, the lack of improvement with weather changes, the histopathologic findings of a vacuolar interface dermatitis and the positive ANA titer he was diagnosed with chilblain lupus.
Chilblain lupus erythematosus (CLE) is an uncommon form of chronic cutaneous lupus erythematosus that presents with tender pink to violaceous macules, papules, and/or nodules that sometimes can ulcerate and are present on the fingers, toes, and sometimes the nose and ears. The lesions are usually triggered by cold exposure.1 These patients also have clinical and laboratory findings consistent with lupus erythematosus.
Even though more studies are needed to clarify the clinical and histopathologic features of chilblain lupus, compared with idiopathic pernio, some authors suggest several characteristics: CLE lesions tend to persist in summer months, as occurred in our patient, and histopathologic evaluation usually shows vacuolar and interface inflammation on the basal cell layer and may also have a positive lupus band on direct immunofluorescence.2 About 20% of patient with CLE may later develop systemic lupus erythematosus.3
There is also a familial form of CLE which is usually inherited as an autosomal-dominant trait. Mutations in TREX1, SAMHD1, and STING have been described in these patients.4 Affected children present with skin lesions at a young age and those with TREX1 mutations are at a higher risk to develop systemic lupus erythematosus.
The differential diagnosis of chilblain lupus includes idiopathic pernio or pernio secondary to other conditions. Other conditions that are thought to be associated with pernio, besides lupus erythematosus, include infectious causes (hepatitis B, COVID-19 infection),5 autoimmune conditions, malignancy and hematologic disorders (paraproteinemia).6 In histopathology, pernio lesions present with dermal edema and superficial and deep lymphocytic infiltrate.
The pathogenesis of pernio is not fully understood but is thought be related to vasospasm with secondary poor perfusion and ischemia and type I interferon (INF1) immune response. A recent review of the published studies trying to explain the causality between COVID 19 and pernio-like lesions, from January 2020 to December 2020, speculate several possible mechanisms: an increase in the vasoconstrictive, prothrombotic, and proinflammatory effects of the angiotensin II pathway through activation of the ACE2 by the virus; COVID-19 triggers a robust INF1 immune response in predisposed patients; pernio as a sign of mild disease, may be explained by genetic and hormonal differences in the patients affected.7
Another condition that can be confused with CLE is Raynaud phenomenon, were patients present with white to purple to red patches on the fingers and toes after exposure to cold, but in comparison with pernio, the lesions improve within minutes to hours after rewarming. Secondary Raynaud phenomenon can be seen in patients with systemic lupus erythematosus and in patients with other connective tissue disorders. The skin lesions in our patient were persistent and were not triggered by cold exposure, making Raynaud phenomenon less likely. Children with vasculitis can present with painful red, violaceous, or necrotic lesions on the extremities, which can mimic pernio. Vasculitis lesions tend to be more purpuric and angulated, compared with pernio lesions, though in severe cases of pernio with ulceration it may be difficult to distinguish between the two entities and a skin biopsy may be needed.
Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare skin condition in which children present with edematous tender nodules on the hands and with less frequency in other parts of the body with associated fever, malaise, conjunctivitis, or joint pain and it is usually associated with infection or malignancy. Our patient denied any systemic symptoms and had no conjunctivitis nor arthritis.
Most patients with idiopathic pernio do not require a biopsy or further laboratory evaluation unless the lesions are atypical, chronic, or there is a suspected associated condition. The workup for patients with prolonged or atypical pernio-like lesions include a skin biopsy with direct immunofluorescence, ANA, complete blood count, complement levels, antiphospholipid antibodies, cold agglutinins, and cryoglobulins.
Treatment of mild CLE is with moderate- to high-potency topical corticosteroids. In those patients not responding to topical measures and keeping the extremities warm, the use of hydroxychloroquine has been reported to be beneficial in some patients as well as the use of calcium-channel blockers.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
1. Su WP et al. Cutis. 1994 Dec;54(6):395-9.
2. Boada A et al. Am J Dermatopathol. 2010 Feb;32(1):19-23.
3. Patel et al. SBMJ Case Rep. 2013;2013:bcr2013201165.
4. Genes Yi et al. BMC. 2020 Apr 15;18(1):32.
5. Battesti G et al. J Am Acad Dermatol. 2020;83(4):1219-22.
6. Cappel JA et al. Mayo Clin Proc. 2014 Feb;89(2):207-15.
7. Cappel MA et al. Mayo Clin Proc. 2021;96(4):989-1005.
He denied any hair loss, mouth sores, sun sensitivity, headaches, gastrointestinal complaints, joint pain, or muscle weakness.
He is not taking any medications.
He has been at home doing virtual school and has not traveled. He likes to play the piano. There is no family history of similar lesions, connective tissue disorder, or autoimmunity.
On physical exam he has purple discoloration on the toes with some violaceous and pink papules. On the fingers he has pink to violaceous papules and macules.
There is no joint edema or pain.
A woman with a history of diabetes, and plaques on both shins
. Women are often more affected than men. Patients often present in their 30s and 40s. The cause of NLD is unknown. Twenty percent of patients with NLD will have glucose intolerance or a family history of diabetes.1 The percentage of patients with NLD who have diabetes varies in reports from 11% to 65%.2 NLD may progress despite the diabetes treatment. Only 0.03% of patient with diabetes will have NLD.3
Lesions most commonly occur on the extremities, with shins being affected in most cases. They vary from asymptomatic to painful. Typically, lesions begin as small, firm erythematous papules that evolve into shiny, well-defined plaques. In older plaques, the center will often appear yellow, depressed, and atrophic, with telangiectasias. The periphery appears pink to violaceous to brown. Ulceration may be present, particularly after trauma, and there may be decreased sensation in the plaques. NLD is clinically distinct from diabetic dermopathy, which appear as brown macules, often in older patients with diabetes.
Ideally, biopsy should be taken at the edge of a lesion. Histologically, the epidermis appears normal or atrophic. A diffuse palisaded and interstitial granulomatous dermatitis consisting of histiocytes, multinucleated giant cells, lymphocytes, and plasma cells is seen in the dermis. Granulomas are often oriented parallel to the epidermis. There is no mucin at the center of the granulomas (as seen in granuloma annulare). Inflammation may extend into the subcutaneous fat. Asteroid bodies (as seen in sarcoid) are absent.
Unfortunately, treatment of NLD is often unsuccessful. Treatment includes potent topical corticosteroids for early lesions and intralesional triamcinolone to the leading edge of lesions. Care should be taken to avoid injecting centrally where atrophy and ulceration may result. Systemic steroids may be helpful in some cases, but can elevate glucose levels. Other reported medical treatments include pentoxifylline, cyclosporine, and niacinamide. Some lesions may spontaneously resolve. Ulcerations may require surgical excision with grafting.
This case and photo are provided by Dr. Bilu Martin, who is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.
References
1. James WD et al. Andrews’ Diseases of the Skin: Clinical Dermatology. Philadelphia: Saunders Elsevier, 2006.
2. Hashemi D et al. JAMA Dermatol. 2019 Apr 1;155(4):455-9.
3. Bolognia JL et al. Dermatology. St. Louis, Mo.: Mosby Elsevier, 2008.
. Women are often more affected than men. Patients often present in their 30s and 40s. The cause of NLD is unknown. Twenty percent of patients with NLD will have glucose intolerance or a family history of diabetes.1 The percentage of patients with NLD who have diabetes varies in reports from 11% to 65%.2 NLD may progress despite the diabetes treatment. Only 0.03% of patient with diabetes will have NLD.3
Lesions most commonly occur on the extremities, with shins being affected in most cases. They vary from asymptomatic to painful. Typically, lesions begin as small, firm erythematous papules that evolve into shiny, well-defined plaques. In older plaques, the center will often appear yellow, depressed, and atrophic, with telangiectasias. The periphery appears pink to violaceous to brown. Ulceration may be present, particularly after trauma, and there may be decreased sensation in the plaques. NLD is clinically distinct from diabetic dermopathy, which appear as brown macules, often in older patients with diabetes.
Ideally, biopsy should be taken at the edge of a lesion. Histologically, the epidermis appears normal or atrophic. A diffuse palisaded and interstitial granulomatous dermatitis consisting of histiocytes, multinucleated giant cells, lymphocytes, and plasma cells is seen in the dermis. Granulomas are often oriented parallel to the epidermis. There is no mucin at the center of the granulomas (as seen in granuloma annulare). Inflammation may extend into the subcutaneous fat. Asteroid bodies (as seen in sarcoid) are absent.
Unfortunately, treatment of NLD is often unsuccessful. Treatment includes potent topical corticosteroids for early lesions and intralesional triamcinolone to the leading edge of lesions. Care should be taken to avoid injecting centrally where atrophy and ulceration may result. Systemic steroids may be helpful in some cases, but can elevate glucose levels. Other reported medical treatments include pentoxifylline, cyclosporine, and niacinamide. Some lesions may spontaneously resolve. Ulcerations may require surgical excision with grafting.
This case and photo are provided by Dr. Bilu Martin, who is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.
References
1. James WD et al. Andrews’ Diseases of the Skin: Clinical Dermatology. Philadelphia: Saunders Elsevier, 2006.
2. Hashemi D et al. JAMA Dermatol. 2019 Apr 1;155(4):455-9.
3. Bolognia JL et al. Dermatology. St. Louis, Mo.: Mosby Elsevier, 2008.
. Women are often more affected than men. Patients often present in their 30s and 40s. The cause of NLD is unknown. Twenty percent of patients with NLD will have glucose intolerance or a family history of diabetes.1 The percentage of patients with NLD who have diabetes varies in reports from 11% to 65%.2 NLD may progress despite the diabetes treatment. Only 0.03% of patient with diabetes will have NLD.3
Lesions most commonly occur on the extremities, with shins being affected in most cases. They vary from asymptomatic to painful. Typically, lesions begin as small, firm erythematous papules that evolve into shiny, well-defined plaques. In older plaques, the center will often appear yellow, depressed, and atrophic, with telangiectasias. The periphery appears pink to violaceous to brown. Ulceration may be present, particularly after trauma, and there may be decreased sensation in the plaques. NLD is clinically distinct from diabetic dermopathy, which appear as brown macules, often in older patients with diabetes.
Ideally, biopsy should be taken at the edge of a lesion. Histologically, the epidermis appears normal or atrophic. A diffuse palisaded and interstitial granulomatous dermatitis consisting of histiocytes, multinucleated giant cells, lymphocytes, and plasma cells is seen in the dermis. Granulomas are often oriented parallel to the epidermis. There is no mucin at the center of the granulomas (as seen in granuloma annulare). Inflammation may extend into the subcutaneous fat. Asteroid bodies (as seen in sarcoid) are absent.
Unfortunately, treatment of NLD is often unsuccessful. Treatment includes potent topical corticosteroids for early lesions and intralesional triamcinolone to the leading edge of lesions. Care should be taken to avoid injecting centrally where atrophy and ulceration may result. Systemic steroids may be helpful in some cases, but can elevate glucose levels. Other reported medical treatments include pentoxifylline, cyclosporine, and niacinamide. Some lesions may spontaneously resolve. Ulcerations may require surgical excision with grafting.
This case and photo are provided by Dr. Bilu Martin, who is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.
References
1. James WD et al. Andrews’ Diseases of the Skin: Clinical Dermatology. Philadelphia: Saunders Elsevier, 2006.
2. Hashemi D et al. JAMA Dermatol. 2019 Apr 1;155(4):455-9.
3. Bolognia JL et al. Dermatology. St. Louis, Mo.: Mosby Elsevier, 2008.
