MDedge Dermatology

Have you ever heard of the American Dermatological Association (ADA)? While many residents may not yet be familiar with this group, its members are among the most respected leaders in dermatology. They serve as current and past presidents of influential organizations including the American Academy of Dermatology (Susan C. Taylor, MD [Philadelphia, Pennsylvania]), the American Society for Dermatologic Surgery (M. Laurin Council, MD, MBA [Creve Coeur, Missouri]), and the Association of Professors of Dermatology (Sewon Kang, MD [Baltimore, Maryland]). Others lead certification boards or serve as editors of key journals like the Journal of the American Academy of Dermatology (Dirk Elston, MD [Charleston, South Carolina]), JAMA Dermatology (Kanade Shinkai, MD [San Francisco, California], and Cutis (Vincent A. DeLeo, MD [Los Angeles, California]).

The ADA is celebrating its 150th anniversary in 2026. What makes the organization so enduring is not just its history, but its culture. The members of the ADA foster deep, long-lasting relationships, and its meetings are purposefully designed to balance structured scientific sessions with unscheduled time for reflection, conversation, and connection. That intentional design cultivates learning, innovation, and wellness.

Steven Covey’s The 7 Habits of Highly Effective People¹ highlights the importance of renewal and relationship building, as does the Harvard Study of Adult Development, one of the longest-running research projects on well-being.^2-4 The key conclusion? Relationships are the strongest predictors of long, healthy, and fulfilling lives, not wealth or achievement. Medical training is intense, and the emphasis often falls squarely on achievement. But the friendships you form in medical school, residency, and early career are just as formative. Membership with the ADA continues this spirit of connection throughout one’s professional life, with meetings that welcome spouses and partners and encourage engagement across generations.

A hallmark of ADA culture is its commitment to mentoring and mutual support. Need advice about transitioning from private practice to academia? Navigating department leadership? Applying for a grant? Considering industry, editorial, or global health roles? Within the ADA, there’s someone who has done it and is eager to help. Recent meetings have addressed future-facing topics such as artificial intelligence, bedside diagnostics, workforce advocacy, and global health while also carving out time for rejuvenating activities: book clubs with best-selling authors, sessions on the arts, storytelling, wellness, and travel. This holistic programming reflects the ADA’s belief in supporting the whole physician.³ Members understand the value of relationships and appreciate these opportunities to learn about the passions and interests of their colleagues (Table).

Candidates are nominated by current members and must be board certified and at least 10 years beyond completion of their training. Members vote upon candidates in a rank voting system each year. If someone is nominated and not selected, they did not fail—they may be nominated again. The idea behind this membership process is to keep the organization small enough that members can get to know one another—there are currently 552 active members. Importantly, the ADA has embraced diversity and inclusion. While historically male- and White-dominated, recent inductee classes now reflect gender parity and a broader range of backgrounds, enriching the organization with fresh perspectives.^5-8

For residents and fellows, the lesson is clear: friendships, mentorship, and time for reflection are not luxuries—they are essential. Burnout stems from relentless output in isolation; however, in cultures that prioritize renewal, authenticity, and community, physicians can flourish.⁹ Membership in small professional organizations is an important step towards avoiding isolation. We encourage you to be active in your local, state, and national organizations.

The ADA stands as a powerful example of how professional societies can help you build the kind of life and career you want, not just a résumé. From informal beachside conversations to high-level scientific discussions, its enduring strength is this: leaders helping others lead.

Have you ever heard of the American Dermatological Association (ADA)? While many residents may not yet be familiar with this group, its members are among the most respected leaders in dermatology. They serve as current and past presidents of influential organizations including the American Academy of Dermatology (Susan C. Taylor, MD [Philadelphia, Pennsylvania]), the American Society for Dermatologic Surgery (M. Laurin Council, MD, MBA [Creve Coeur, Missouri]), and the Association of Professors of Dermatology (Sewon Kang, MD [Baltimore, Maryland]). Others lead certification boards or serve as editors of key journals like the Journal of the American Academy of Dermatology (Dirk Elston, MD [Charleston, South Carolina]), JAMA Dermatology (Kanade Shinkai, MD [San Francisco, California], and Cutis (Vincent A. DeLeo, MD [Los Angeles, California]).

The ADA is celebrating its 150th anniversary in 2026. What makes the organization so enduring is not just its history, but its culture. The members of the ADA foster deep, long-lasting relationships, and its meetings are purposefully designed to balance structured scientific sessions with unscheduled time for reflection, conversation, and connection. That intentional design cultivates learning, innovation, and wellness.

Steven Covey’s The 7 Habits of Highly Effective People¹ highlights the importance of renewal and relationship building, as does the Harvard Study of Adult Development, one of the longest-running research projects on well-being.^2-4 The key conclusion? Relationships are the strongest predictors of long, healthy, and fulfilling lives, not wealth or achievement. Medical training is intense, and the emphasis often falls squarely on achievement. But the friendships you form in medical school, residency, and early career are just as formative. Membership with the ADA continues this spirit of connection throughout one’s professional life, with meetings that welcome spouses and partners and encourage engagement across generations.

A hallmark of ADA culture is its commitment to mentoring and mutual support. Need advice about transitioning from private practice to academia? Navigating department leadership? Applying for a grant? Considering industry, editorial, or global health roles? Within the ADA, there’s someone who has done it and is eager to help. Recent meetings have addressed future-facing topics such as artificial intelligence, bedside diagnostics, workforce advocacy, and global health while also carving out time for rejuvenating activities: book clubs with best-selling authors, sessions on the arts, storytelling, wellness, and travel. This holistic programming reflects the ADA’s belief in supporting the whole physician.³ Members understand the value of relationships and appreciate these opportunities to learn about the passions and interests of their colleagues (Table).

Candidates are nominated by current members and must be board certified and at least 10 years beyond completion of their training. Members vote upon candidates in a rank voting system each year. If someone is nominated and not selected, they did not fail—they may be nominated again. The idea behind this membership process is to keep the organization small enough that members can get to know one another—there are currently 552 active members. Importantly, the ADA has embraced diversity and inclusion. While historically male- and White-dominated, recent inductee classes now reflect gender parity and a broader range of backgrounds, enriching the organization with fresh perspectives.^5-8

For residents and fellows, the lesson is clear: friendships, mentorship, and time for reflection are not luxuries—they are essential. Burnout stems from relentless output in isolation; however, in cultures that prioritize renewal, authenticity, and community, physicians can flourish.⁹ Membership in small professional organizations is an important step towards avoiding isolation. We encourage you to be active in your local, state, and national organizations.

The ADA stands as a powerful example of how professional societies can help you build the kind of life and career you want, not just a résumé. From informal beachside conversations to high-level scientific discussions, its enduring strength is this: leaders helping others lead.

Have you ever heard of the American Dermatological Association (ADA)? While many residents may not yet be familiar with this group, its members are among the most respected leaders in dermatology. They serve as current and past presidents of influential organizations including the American Academy of Dermatology (Susan C. Taylor, MD [Philadelphia, Pennsylvania]), the American Society for Dermatologic Surgery (M. Laurin Council, MD, MBA [Creve Coeur, Missouri]), and the Association of Professors of Dermatology (Sewon Kang, MD [Baltimore, Maryland]). Others lead certification boards or serve as editors of key journals like the Journal of the American Academy of Dermatology (Dirk Elston, MD [Charleston, South Carolina]), JAMA Dermatology (Kanade Shinkai, MD [San Francisco, California], and Cutis (Vincent A. DeLeo, MD [Los Angeles, California]).

The ADA is celebrating its 150th anniversary in 2026. What makes the organization so enduring is not just its history, but its culture. The members of the ADA foster deep, long-lasting relationships, and its meetings are purposefully designed to balance structured scientific sessions with unscheduled time for reflection, conversation, and connection. That intentional design cultivates learning, innovation, and wellness.

Steven Covey’s The 7 Habits of Highly Effective People¹ highlights the importance of renewal and relationship building, as does the Harvard Study of Adult Development, one of the longest-running research projects on well-being.^2-4 The key conclusion? Relationships are the strongest predictors of long, healthy, and fulfilling lives, not wealth or achievement. Medical training is intense, and the emphasis often falls squarely on achievement. But the friendships you form in medical school, residency, and early career are just as formative. Membership with the ADA continues this spirit of connection throughout one’s professional life, with meetings that welcome spouses and partners and encourage engagement across generations.

A hallmark of ADA culture is its commitment to mentoring and mutual support. Need advice about transitioning from private practice to academia? Navigating department leadership? Applying for a grant? Considering industry, editorial, or global health roles? Within the ADA, there’s someone who has done it and is eager to help. Recent meetings have addressed future-facing topics such as artificial intelligence, bedside diagnostics, workforce advocacy, and global health while also carving out time for rejuvenating activities: book clubs with best-selling authors, sessions on the arts, storytelling, wellness, and travel. This holistic programming reflects the ADA’s belief in supporting the whole physician.³ Members understand the value of relationships and appreciate these opportunities to learn about the passions and interests of their colleagues (Table).

Candidates are nominated by current members and must be board certified and at least 10 years beyond completion of their training. Members vote upon candidates in a rank voting system each year. If someone is nominated and not selected, they did not fail—they may be nominated again. The idea behind this membership process is to keep the organization small enough that members can get to know one another—there are currently 552 active members. Importantly, the ADA has embraced diversity and inclusion. While historically male- and White-dominated, recent inductee classes now reflect gender parity and a broader range of backgrounds, enriching the organization with fresh perspectives.^5-8

For residents and fellows, the lesson is clear: friendships, mentorship, and time for reflection are not luxuries—they are essential. Burnout stems from relentless output in isolation; however, in cultures that prioritize renewal, authenticity, and community, physicians can flourish.⁹ Membership in small professional organizations is an important step towards avoiding isolation. We encourage you to be active in your local, state, and national organizations.

The ADA stands as a powerful example of how professional societies can help you build the kind of life and career you want, not just a résumé. From informal beachside conversations to high-level scientific discussions, its enduring strength is this: leaders helping others lead.

Dermatologists play a central role in the care of hospitalized patients with skin disease. This review summarizes research from January 2024 to December 2025 on severe cutaneous adverse drug reactions, emerging infectious diseases, hidradenitis suppurativa (HS), and inpatient dermatology workforce issues. Key developments include improved recognition and management of drug reactions; updated diagnostic and prognostic tools for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN); and guidance for emerging infections such as measles, dengue, mpox, orthopoxviruses, and resistant dermatophytes. Evidence-based strategies for HS aim to reduce unnecessary admissions and optimize care. Workforce challenges, including limited access, high call burden, and potential for artificial intelligence (AI)–assisted diagnosis, are also highlighted. These findings emphasize the critical contributions of dermatologists to hospital-based care and provide emerging evidence to guide clinical practice.

Dermatologists play a critical role in the care of hospitalized patients. Herein, we review the research developments between January 2024 and December 2025 most relevant to the care of hospitalized patients with skin disease, including severe cutaneous adverse reactions (SCARs), emerging and re-emerging infectious diseases, hidradenitis suppurativa (HS), and access to inpatient dermatology services.

Severe Cutaneous Adverse Drug Reactions

Severe cutaneous adverse drug reactions are among the most frequent reasons for inpatient dermatology consultation. A National Inpatient Sample study identified more than 160,000 cases of drug rash with eosinophilia and systemic symptoms (DRESS syndrome) between January 2016 and December 2020.¹ The overall mortality rate was 2.0%, substantially lower than the rates of up to 10% reported in earlier studies.² Case burden and mortality peaked during the fall months, possibly due to either increased use of antibiotics or increased viral infection or reactivation during these months.¹

A retrospective cohort study of patients with probable or definite DRESS syndrome showed that, among 93 patients with at least 1 viral marker tested, human herpesvirus (HHV) reactivation was found in 42% (39/93), including HHV-6 (28%)(24/85), Epstein-Barr virus (17%)(15/87), and cytomegalovirus (20%)(18/89); furthermore, viral reactivation was associated with higher 1-year mortality (odds ratio, 3.9), dialysis initiation, flares of disease, and longer hospital stay (all P<.05).¹ Multiple reactivations were associated with higher inpatient mortality and 1-year mortality; however, despite apparent prognostic importance, the role of screening for viral reactivation in DRESS syndrome is undefined.³ A 2024 effort using the Delphi technique found consensus for obtaining HHV-6, Epstein-Barr virus, and cytomegalovirus viral load in all patients with suspected DRESS syndrome, but this topic was the subject of greatest uncertainty.⁴

A systematic review of 610 studies including 2122 patients with DRESS syndrome demonstrated that, among 193 causal agents identified, 14 drugs accounted for more than 1% of cases each and therefore were considered high risk. Seventy-eight percent of cases were attributed to these 14 drugs (Table).⁵ A TriNetX Query study analyzed antibiotic exposures across SCARs and reported that sulfonamides (hazard ratio [HR], 7.5), aminoglycosides (HR, 3.7), and tetracyclines (HR, 1.7) were associated with an elevated risk for SCARs. Sulfonamides had the highest absolute incidence of SCARs, followed by cephalosporins and penicillins.⁶

A multicenter randomized clinical trial⁷ compared high-potency topical corticosteroids (clobetasol 30 g/d) to systemic corticosteroids (prednisone 0.5 mg/kg/d) for treatment of moderate DRESS syndrome. On day 30, 53.8% (14/26) of patients in the topical group had achieved remission of visceral involvement, compared to 72.0% (18/25) in the systemic group. Before day 30, 23.1% (6/26) of patients in the topical group worsened, necessitating transition to high-dose systemic steroids. When inpatient monitoring is available, low-dose systemic corticosteroids or high-potency topical steroids may be reasonable management strategies for moderate DRESS syndrome⁷; however, the frequent need for treatment intensification suggests limitations to this strategy.

Since prolonged courses of systemic steroids generally are necessary for management of DRESS syndrome, steroid-sparing options are needed. A retrospective case series examined interleukin 5 inhibition in patients with possible DRESS syndrome (Registry of Severe Cutaneous Adverse Reactions score ≥3). All patients demonstrated rapid eosinophil reduction within 1 to 3 days (mean [SD] time to resolution, 1.4 [0.9] days) after treatment with mepolizumab or benralizumab, with clinical improvement occurring at a mean (SD) of 16 (3.7) days (range, 13-21 days).⁸

A French cohort study of 1221 adult patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) reported in-hospital mortality of 19% and a total mortality of 34% at 1 year.⁹ Risk factors contributing to in-hospital mortality included age, history of/current diagnosis of cancer, dementia, and liver disease, while postdischarge mortality was associated with acute kidney injury and sepsis. Long-term complications included ophthalmologic and mood disorders.⁹

A new set of diagnostic criteria for SJS/TEN, known as the Niigata criteria,¹⁰ includes 3 main items: severe mucosal lesions in cutaneous-mucosal transition zones (eg, eyes, lips, vulva) or generalized erythema with necrotic lesions; fever of 38.5 °C or higher; and necrosis of the epidermis seen on histopathology. Because epidermal detachment involving 10% of the body surface area (BSA) is an important mortality risk predicter, SJS is defined as less than 10% BSA involvement, and TEN has been redefined as 10% or more BSA involvement (not ≥30%). A new prognostic score—clinical risk score for TEN (CRISTEN)—can be tabulated at the point of care without laboratory values. It was developed based on the 10 most important risk factors for death in a retrospective study of 382 patients, which included age 65 years or older; epidermal detachment involving 10% BSA or higher; an antibiotic as causative agent; systemic corticosteroid therapy before the onset of SJS/TEN; involvement of all 3 mucosal surfaces; and medical comorbidities such as renal impairment, diabetes, cardiac disease, active cancer, and bacterial infection.¹¹

New potential therapeutic targets for SJS/TEN include PC111 (monoclonal antibody to Fas ligand), formyl peptide receptor 1 antagonists (which inhibit necroptosis induced by formyl peptide receptor 1–annexin A1 interaction), daratumumab (which depletes cytotoxic CD8-positive and CD38-positive T cells), and Janus kinase (JAK) inhibitors.¹⁰ Spatial proteomics showed marked enrichment of type I and type II interferon signatures as well as activation of signal transducer and activator of transcription 1. In vitro, tofacitinib reduced keratinocyte-directed cytotoxicity, and in vivo JAK inhibitors ameliorated disease severity in 2 TEN mouse models. Patients with TEN that was refractory to corticosteroid therapy received rescue treatment with JAK inhibitors and had re-epithelization within several days with marked reduction in levels of phosphorylated signal transducer and activator of transcription 1.¹² Controlled studies are needed to assess the potential role of JAK inhibitors for SJS/TEN.

Emerging and Re-emerging Infectious Diseases

Dermatologists may encounter emerging or re-emerging infections, performing an essential public health role in the process. In 2025, a total of 2281 confirmed cases of measles had been reported across 45 of the United States.¹³ During the COVID-19 pandemic, measles vaccine coverage in the United States dropped to 93%—down from 95% to 97% prepandemic. Worldwide, 2022 saw an increase of 1.4 million measles cases (18% increase) and 41,200 excess deaths (43% increase) compared to the previous year. Complications of measles include pneumonia, blindness, otitis media, and encephalitis, with 1 in 5 (20%) unvaccinated people with measles in the United States requiring hospitalization.¹⁴ A vaccine coverage rate higher than 95% is needed to prevent community spread of disease. Since efforts to detect and rapidly isolate cases of measles are critical, dermatologists should consider measles in the differential of morbilliform eruptions with viral symptoms and ask about vaccination status.

Since 2023, dengue infection rates have tripled in the Americas, representing the highest levels recorded since tracking began in 1980. In 2024, there were more than 12 million cases, with approximately 8000 deaths reported. Ninety percent of cases occur in Argentina, Brazil, Colombia, and Mexico, but local transmission has been reported in Arizona, California, Florida, Hawaii, and Texas.¹⁵ The characteristic exanthem of dengue is diffuse erythema with islands of sparing.<

Unlike during the 2022 outbreak of mpox clade II, which predominantly impacted men who have sex with men, there now is an ongoing outbreak of mpox clades 1a and 1b in the Democratic Republic of the Congo and surrounding countries that more commonly affects children and heterosexual adults. It is also more transmissible and virulent. Cases of mpox clade I have been reported in several European countries and across the United States, mostly among travelers from areas of active transmission. Vaccination of at-risk individuals is considered effective; however, tecovirimat is not.¹⁶

Outbreaks of 2 emerging zoonotic orthopoxviruses recently have been reported. Buffalopox virus (BPXV) is transmitted via direct contact with the skin of infected cattle and buffalo as well as fomites and has been responsible for human cases in South Asia. Characteristics of BPXV include macules, umbilicated papules, vesicles, pustules, and eschars that evolve over several weeks, with a predilection for the hands and face. It can manifest with prodromal symptoms of fever, malaise, and lymphadenopathy.¹⁷ Borealpox virus (formerly known as Alaskapox) has similar manifestations. Its reservoir includes small mammals such as voles and shrews, but it also has been found in cats and dogs and has been responsible for at least one human fatality. Cidofovir may be an effective therapy for both BPXV and borealpox virus, and prior smallpox vaccination may provide protection.¹⁸ These outbreaks demonstrate the continued importance of research for more effective vaccines and therapies against smallpox and other orthopoxviruses.¹⁹ A recent review provided a detailed overview of the epidemiology, transmission, dermatologic findings, and management strategies associated with smallpox and other bioweapons.²⁰

In 2023, a case was reported of a patient in a New York City hospital with tinea that was refractory to multiple rounds of topical antifungals, which called attention to the presence of Trichophyton indotineae in the United States.²¹ Since then, additional reports and case series have characterized the clinical presentation of T indotineae as widespread and atypical, refractory to traditional therapies, and most often encountered in travelers returning from Bangladesh or elsewhere in South Asia.²² The diagnosis should be confirmed via DNA testing of fungal culture. Itraconazole 100 to 200 mg/d is the antifungal therapy of choice.²³

Other series have reported cases of tinea genitalis caused by Trichophyton mentagrophytes type VII seen predominately in sex workers and others engaging in high-risk sexual contact, highlighting the spread of dermatophytes through sexual activity.^24-26 Lastly, it is important to culture pustules and consider atypical pathogens in patients with chronic folliculitis not responding to typical therapies such as tetracycline antibiotics. A case series reported the presence of pustules in the beard area of 7 men who have sex with men, with culture data showing Klebsiella aerogenes. Prolonged courses of fluoroquinolones were necessary for clearance.²⁷

Reducing HS Admissions Through Evidence-Based Management

Hidradenitis suppurativa is a frequent cause of emergency department visits and hospital admissions. In an analysis of the Nationwide Readmissions Database, 17.8% (392/2204) of patients admitted to the hospital with HS were readmitted within 30 days, a number comparable to that of heart failure.²⁸

Flaring HS can produce symptoms that mimic sepsis. A retrospective cohort study examining sepsislike features in HS showed that more than 50% (30/58) of those admitted to the hospital with an HS flare were misdiagnosed with sepsis, and more than 80% (53/64) of those patients received intravenous antibiotics.²⁹ A National Inpatient Sample (January 2016-December 2018) study demonstrated minimal rates of true infection in patients admitted with HS flares,³⁰ while patients with HS diagnosed as sepsis do not sustain the mortality expected from true sepsis. Improving recognition of HS and differentiation of the disease from true sepsis could decrease unnecessary antibiotic use, hospital admissions, and cost, underscoring the need for a framework to reliably and reproducibly distinguish sepsis from HS flare.³¹

While severe HS is difficult to manage, there may be a window of opportunity in which appropriate treatment of early disease may prevent progression and decrease inpatient utilization. A prospective cohort study of 335 biologic-naïve patients with mild to moderate HS (Hurley stages I and II) followed over a median of 2 years showed that active smoking, body mass index higher than 25, and the presence of disease in 2 or more anatomic areas were factors predictive of progression to severe disease.³²

Despite high utilization of emergency and inpatient care, there has been no consensus on inpatient management of HS. A Delphi consensus exercise including 26 expert dermatologists reached consensus on 40 statements.³³ Specific recommendations involve multidisciplinary care, including from a dermatologist; consideration of comorbid medical conditions; supportive care measures (wound care, pain control); evidence-based medical management, including initiation or adjustment of biologic therapies; targeted surgical intervention; nutritional support and maintenance of glycemic control; and attention to transitional care at discharge, including home health services, verification of insurance status, and timely outpatient dermatology follow-up.³⁴ A retrospective review of 98 patients treated with intravenous ertapenem for a mean duration of 13 weeks demonstrated improvement in clinical and inflammatory markers.³⁵ Patients with severe or treatment-refractory HS, including those admitted to the hospital, may benefit from initiation of this therapy in select circumstances.

Hospital Dermatology Workforce

Inpatient dermatology consultations are extremely valuable for improving diagnostic accuracy, reducing admissions for pseudocellulitis and inflammatory skin conditions, and keeping cancer patients on needed therapies.^36-38 Despite this clear value added, a cross-sectional analysis of inpatient Medicare claims data from January 2013 to December 2019 found that the number of dermatologists performing more than 10 inpatient consults per year decreased from 356 to 281.³⁹ Additionally, medical centers in which dermatology encounters occurred decreased from 239 to 157 during the same period. Ninety-eight percent of inpatient dermatologists were in metropolitan areas, with large regions lacking access to inpatient dermatology consultation altogether.³⁹

A survey of Society for Pediatric Dermatology members similarly characterized the state of the pediatric dermatology workforce performing hospital consultation.⁴⁰ Seventy-five percent reported a high call burden, defined as more than 11 days or nights per month, more than 1 weekend per month, and/or more than 5 hours per week seeing patients. Ninety-one percent of consultation services are based within academic institutions, reflecting disparities in access.⁴⁰ A prospective cohort study of academic pediatric dermatologists reported that 310 curbside consultations were performed over 24 weeks; of these calls, 17% occurred during weeknights and 23% on weekends. None of these curbside interactions was reimbursed.⁴¹ These findings underscore the burden of uncompensated time a subset of pediatric dermatologists dedicates to inpatient consultations, highlighting the need for improved financial and administrative support and an increased number of physicians performing this role.

A survey study⁴² suggested that unfamiliarity with the inpatient setting, rather than medical knowledge, is the most important barrier to inpatient work among clinical dermatologists. Proposed interventions include resource guides (eg, hospital maps, pager numbers for key individuals, and protocols for urgent specimens). Reference guides and refresher courses may decrease gaps in knowledge or awareness among dermatologists in ambulatory practice.⁴² Another way to bolster the inpatient dermatology workforce may be to provide more guidance to qualified advanced practice providers to triage and address dermatologic emergencies.⁴³

Artificial intelligence (AI) also has been explored as a tool for diagnosing complex dermatologic conditions. One study presented 15 published inpatient dermatology cases to 7 dermatologists. Participants were asked to formulate their top 3 differential diagnoses and were then shown AI-generated differentials and asked to submit a revised differential. Participants showed a diagnostic accuracy of 69% before seeing the AI-generated differential diagnosis and 79% after; however, in cases in which the AI differential was incorrect, diagnostic accuracy of the dermatologists decreased after being shown the AI model.⁴⁴

Final Thoughts

This January 2024 to December 2025 review of research relevant to hospital dermatology highlights important developments and ongoing challenges in SCARs, emerging and re-emerging infectious diseases, HS, and the inpatient dermatology workforce. Dermatologists continue to play a critical role in the care of hospitalized patients with skin disease.

Dermatologists play a central role in the care of hospitalized patients with skin disease. This review summarizes research from January 2024 to December 2025 on severe cutaneous adverse drug reactions, emerging infectious diseases, hidradenitis suppurativa (HS), and inpatient dermatology workforce issues. Key developments include improved recognition and management of drug reactions; updated diagnostic and prognostic tools for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN); and guidance for emerging infections such as measles, dengue, mpox, orthopoxviruses, and resistant dermatophytes. Evidence-based strategies for HS aim to reduce unnecessary admissions and optimize care. Workforce challenges, including limited access, high call burden, and potential for artificial intelligence (AI)–assisted diagnosis, are also highlighted. These findings emphasize the critical contributions of dermatologists to hospital-based care and provide emerging evidence to guide clinical practice.

Dermatologists play a critical role in the care of hospitalized patients. Herein, we review the research developments between January 2024 and December 2025 most relevant to the care of hospitalized patients with skin disease, including severe cutaneous adverse reactions (SCARs), emerging and re-emerging infectious diseases, hidradenitis suppurativa (HS), and access to inpatient dermatology services.

Severe Cutaneous Adverse Drug Reactions

Severe cutaneous adverse drug reactions are among the most frequent reasons for inpatient dermatology consultation. A National Inpatient Sample study identified more than 160,000 cases of drug rash with eosinophilia and systemic symptoms (DRESS syndrome) between January 2016 and December 2020.¹ The overall mortality rate was 2.0%, substantially lower than the rates of up to 10% reported in earlier studies.² Case burden and mortality peaked during the fall months, possibly due to either increased use of antibiotics or increased viral infection or reactivation during these months.¹

A retrospective cohort study of patients with probable or definite DRESS syndrome showed that, among 93 patients with at least 1 viral marker tested, human herpesvirus (HHV) reactivation was found in 42% (39/93), including HHV-6 (28%)(24/85), Epstein-Barr virus (17%)(15/87), and cytomegalovirus (20%)(18/89); furthermore, viral reactivation was associated with higher 1-year mortality (odds ratio, 3.9), dialysis initiation, flares of disease, and longer hospital stay (all P<.05).¹ Multiple reactivations were associated with higher inpatient mortality and 1-year mortality; however, despite apparent prognostic importance, the role of screening for viral reactivation in DRESS syndrome is undefined.³ A 2024 effort using the Delphi technique found consensus for obtaining HHV-6, Epstein-Barr virus, and cytomegalovirus viral load in all patients with suspected DRESS syndrome, but this topic was the subject of greatest uncertainty.⁴

A systematic review of 610 studies including 2122 patients with DRESS syndrome demonstrated that, among 193 causal agents identified, 14 drugs accounted for more than 1% of cases each and therefore were considered high risk. Seventy-eight percent of cases were attributed to these 14 drugs (Table).⁵ A TriNetX Query study analyzed antibiotic exposures across SCARs and reported that sulfonamides (hazard ratio [HR], 7.5), aminoglycosides (HR, 3.7), and tetracyclines (HR, 1.7) were associated with an elevated risk for SCARs. Sulfonamides had the highest absolute incidence of SCARs, followed by cephalosporins and penicillins.⁶

A multicenter randomized clinical trial⁷ compared high-potency topical corticosteroids (clobetasol 30 g/d) to systemic corticosteroids (prednisone 0.5 mg/kg/d) for treatment of moderate DRESS syndrome. On day 30, 53.8% (14/26) of patients in the topical group had achieved remission of visceral involvement, compared to 72.0% (18/25) in the systemic group. Before day 30, 23.1% (6/26) of patients in the topical group worsened, necessitating transition to high-dose systemic steroids. When inpatient monitoring is available, low-dose systemic corticosteroids or high-potency topical steroids may be reasonable management strategies for moderate DRESS syndrome⁷; however, the frequent need for treatment intensification suggests limitations to this strategy.

Since prolonged courses of systemic steroids generally are necessary for management of DRESS syndrome, steroid-sparing options are needed. A retrospective case series examined interleukin 5 inhibition in patients with possible DRESS syndrome (Registry of Severe Cutaneous Adverse Reactions score ≥3). All patients demonstrated rapid eosinophil reduction within 1 to 3 days (mean [SD] time to resolution, 1.4 [0.9] days) after treatment with mepolizumab or benralizumab, with clinical improvement occurring at a mean (SD) of 16 (3.7) days (range, 13-21 days).⁸

A French cohort study of 1221 adult patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) reported in-hospital mortality of 19% and a total mortality of 34% at 1 year.⁹ Risk factors contributing to in-hospital mortality included age, history of/current diagnosis of cancer, dementia, and liver disease, while postdischarge mortality was associated with acute kidney injury and sepsis. Long-term complications included ophthalmologic and mood disorders.⁹

A new set of diagnostic criteria for SJS/TEN, known as the Niigata criteria,¹⁰ includes 3 main items: severe mucosal lesions in cutaneous-mucosal transition zones (eg, eyes, lips, vulva) or generalized erythema with necrotic lesions; fever of 38.5 °C or higher; and necrosis of the epidermis seen on histopathology. Because epidermal detachment involving 10% of the body surface area (BSA) is an important mortality risk predicter, SJS is defined as less than 10% BSA involvement, and TEN has been redefined as 10% or more BSA involvement (not ≥30%). A new prognostic score—clinical risk score for TEN (CRISTEN)—can be tabulated at the point of care without laboratory values. It was developed based on the 10 most important risk factors for death in a retrospective study of 382 patients, which included age 65 years or older; epidermal detachment involving 10% BSA or higher; an antibiotic as causative agent; systemic corticosteroid therapy before the onset of SJS/TEN; involvement of all 3 mucosal surfaces; and medical comorbidities such as renal impairment, diabetes, cardiac disease, active cancer, and bacterial infection.¹¹

New potential therapeutic targets for SJS/TEN include PC111 (monoclonal antibody to Fas ligand), formyl peptide receptor 1 antagonists (which inhibit necroptosis induced by formyl peptide receptor 1–annexin A1 interaction), daratumumab (which depletes cytotoxic CD8-positive and CD38-positive T cells), and Janus kinase (JAK) inhibitors.¹⁰ Spatial proteomics showed marked enrichment of type I and type II interferon signatures as well as activation of signal transducer and activator of transcription 1. In vitro, tofacitinib reduced keratinocyte-directed cytotoxicity, and in vivo JAK inhibitors ameliorated disease severity in 2 TEN mouse models. Patients with TEN that was refractory to corticosteroid therapy received rescue treatment with JAK inhibitors and had re-epithelization within several days with marked reduction in levels of phosphorylated signal transducer and activator of transcription 1.¹² Controlled studies are needed to assess the potential role of JAK inhibitors for SJS/TEN.

Emerging and Re-emerging Infectious Diseases

Dermatologists may encounter emerging or re-emerging infections, performing an essential public health role in the process. In 2025, a total of 2281 confirmed cases of measles had been reported across 45 of the United States.¹³ During the COVID-19 pandemic, measles vaccine coverage in the United States dropped to 93%—down from 95% to 97% prepandemic. Worldwide, 2022 saw an increase of 1.4 million measles cases (18% increase) and 41,200 excess deaths (43% increase) compared to the previous year. Complications of measles include pneumonia, blindness, otitis media, and encephalitis, with 1 in 5 (20%) unvaccinated people with measles in the United States requiring hospitalization.¹⁴ A vaccine coverage rate higher than 95% is needed to prevent community spread of disease. Since efforts to detect and rapidly isolate cases of measles are critical, dermatologists should consider measles in the differential of morbilliform eruptions with viral symptoms and ask about vaccination status.

Since 2023, dengue infection rates have tripled in the Americas, representing the highest levels recorded since tracking began in 1980. In 2024, there were more than 12 million cases, with approximately 8000 deaths reported. Ninety percent of cases occur in Argentina, Brazil, Colombia, and Mexico, but local transmission has been reported in Arizona, California, Florida, Hawaii, and Texas.¹⁵ The characteristic exanthem of dengue is diffuse erythema with islands of sparing.<

Unlike during the 2022 outbreak of mpox clade II, which predominantly impacted men who have sex with men, there now is an ongoing outbreak of mpox clades 1a and 1b in the Democratic Republic of the Congo and surrounding countries that more commonly affects children and heterosexual adults. It is also more transmissible and virulent. Cases of mpox clade I have been reported in several European countries and across the United States, mostly among travelers from areas of active transmission. Vaccination of at-risk individuals is considered effective; however, tecovirimat is not.¹⁶

Outbreaks of 2 emerging zoonotic orthopoxviruses recently have been reported. Buffalopox virus (BPXV) is transmitted via direct contact with the skin of infected cattle and buffalo as well as fomites and has been responsible for human cases in South Asia. Characteristics of BPXV include macules, umbilicated papules, vesicles, pustules, and eschars that evolve over several weeks, with a predilection for the hands and face. It can manifest with prodromal symptoms of fever, malaise, and lymphadenopathy.¹⁷ Borealpox virus (formerly known as Alaskapox) has similar manifestations. Its reservoir includes small mammals such as voles and shrews, but it also has been found in cats and dogs and has been responsible for at least one human fatality. Cidofovir may be an effective therapy for both BPXV and borealpox virus, and prior smallpox vaccination may provide protection.¹⁸ These outbreaks demonstrate the continued importance of research for more effective vaccines and therapies against smallpox and other orthopoxviruses.¹⁹ A recent review provided a detailed overview of the epidemiology, transmission, dermatologic findings, and management strategies associated with smallpox and other bioweapons.²⁰

In 2023, a case was reported of a patient in a New York City hospital with tinea that was refractory to multiple rounds of topical antifungals, which called attention to the presence of Trichophyton indotineae in the United States.²¹ Since then, additional reports and case series have characterized the clinical presentation of T indotineae as widespread and atypical, refractory to traditional therapies, and most often encountered in travelers returning from Bangladesh or elsewhere in South Asia.²² The diagnosis should be confirmed via DNA testing of fungal culture. Itraconazole 100 to 200 mg/d is the antifungal therapy of choice.²³

Other series have reported cases of tinea genitalis caused by Trichophyton mentagrophytes type VII seen predominately in sex workers and others engaging in high-risk sexual contact, highlighting the spread of dermatophytes through sexual activity.^24-26 Lastly, it is important to culture pustules and consider atypical pathogens in patients with chronic folliculitis not responding to typical therapies such as tetracycline antibiotics. A case series reported the presence of pustules in the beard area of 7 men who have sex with men, with culture data showing Klebsiella aerogenes. Prolonged courses of fluoroquinolones were necessary for clearance.²⁷

Reducing HS Admissions Through Evidence-Based Management

Hidradenitis suppurativa is a frequent cause of emergency department visits and hospital admissions. In an analysis of the Nationwide Readmissions Database, 17.8% (392/2204) of patients admitted to the hospital with HS were readmitted within 30 days, a number comparable to that of heart failure.²⁸

Flaring HS can produce symptoms that mimic sepsis. A retrospective cohort study examining sepsislike features in HS showed that more than 50% (30/58) of those admitted to the hospital with an HS flare were misdiagnosed with sepsis, and more than 80% (53/64) of those patients received intravenous antibiotics.²⁹ A National Inpatient Sample (January 2016-December 2018) study demonstrated minimal rates of true infection in patients admitted with HS flares,³⁰ while patients with HS diagnosed as sepsis do not sustain the mortality expected from true sepsis. Improving recognition of HS and differentiation of the disease from true sepsis could decrease unnecessary antibiotic use, hospital admissions, and cost, underscoring the need for a framework to reliably and reproducibly distinguish sepsis from HS flare.³¹

While severe HS is difficult to manage, there may be a window of opportunity in which appropriate treatment of early disease may prevent progression and decrease inpatient utilization. A prospective cohort study of 335 biologic-naïve patients with mild to moderate HS (Hurley stages I and II) followed over a median of 2 years showed that active smoking, body mass index higher than 25, and the presence of disease in 2 or more anatomic areas were factors predictive of progression to severe disease.³²

Despite high utilization of emergency and inpatient care, there has been no consensus on inpatient management of HS. A Delphi consensus exercise including 26 expert dermatologists reached consensus on 40 statements.³³ Specific recommendations involve multidisciplinary care, including from a dermatologist; consideration of comorbid medical conditions; supportive care measures (wound care, pain control); evidence-based medical management, including initiation or adjustment of biologic therapies; targeted surgical intervention; nutritional support and maintenance of glycemic control; and attention to transitional care at discharge, including home health services, verification of insurance status, and timely outpatient dermatology follow-up.³⁴ A retrospective review of 98 patients treated with intravenous ertapenem for a mean duration of 13 weeks demonstrated improvement in clinical and inflammatory markers.³⁵ Patients with severe or treatment-refractory HS, including those admitted to the hospital, may benefit from initiation of this therapy in select circumstances.

Hospital Dermatology Workforce

Inpatient dermatology consultations are extremely valuable for improving diagnostic accuracy, reducing admissions for pseudocellulitis and inflammatory skin conditions, and keeping cancer patients on needed therapies.^36-38 Despite this clear value added, a cross-sectional analysis of inpatient Medicare claims data from January 2013 to December 2019 found that the number of dermatologists performing more than 10 inpatient consults per year decreased from 356 to 281.³⁹ Additionally, medical centers in which dermatology encounters occurred decreased from 239 to 157 during the same period. Ninety-eight percent of inpatient dermatologists were in metropolitan areas, with large regions lacking access to inpatient dermatology consultation altogether.³⁹

A survey of Society for Pediatric Dermatology members similarly characterized the state of the pediatric dermatology workforce performing hospital consultation.⁴⁰ Seventy-five percent reported a high call burden, defined as more than 11 days or nights per month, more than 1 weekend per month, and/or more than 5 hours per week seeing patients. Ninety-one percent of consultation services are based within academic institutions, reflecting disparities in access.⁴⁰ A prospective cohort study of academic pediatric dermatologists reported that 310 curbside consultations were performed over 24 weeks; of these calls, 17% occurred during weeknights and 23% on weekends. None of these curbside interactions was reimbursed.⁴¹ These findings underscore the burden of uncompensated time a subset of pediatric dermatologists dedicates to inpatient consultations, highlighting the need for improved financial and administrative support and an increased number of physicians performing this role.

A survey study⁴² suggested that unfamiliarity with the inpatient setting, rather than medical knowledge, is the most important barrier to inpatient work among clinical dermatologists. Proposed interventions include resource guides (eg, hospital maps, pager numbers for key individuals, and protocols for urgent specimens). Reference guides and refresher courses may decrease gaps in knowledge or awareness among dermatologists in ambulatory practice.⁴² Another way to bolster the inpatient dermatology workforce may be to provide more guidance to qualified advanced practice providers to triage and address dermatologic emergencies.⁴³

Artificial intelligence (AI) also has been explored as a tool for diagnosing complex dermatologic conditions. One study presented 15 published inpatient dermatology cases to 7 dermatologists. Participants were asked to formulate their top 3 differential diagnoses and were then shown AI-generated differentials and asked to submit a revised differential. Participants showed a diagnostic accuracy of 69% before seeing the AI-generated differential diagnosis and 79% after; however, in cases in which the AI differential was incorrect, diagnostic accuracy of the dermatologists decreased after being shown the AI model.⁴⁴

Final Thoughts

This January 2024 to December 2025 review of research relevant to hospital dermatology highlights important developments and ongoing challenges in SCARs, emerging and re-emerging infectious diseases, HS, and the inpatient dermatology workforce. Dermatologists continue to play a critical role in the care of hospitalized patients with skin disease.

Dermatologists play a central role in the care of hospitalized patients with skin disease. This review summarizes research from January 2024 to December 2025 on severe cutaneous adverse drug reactions, emerging infectious diseases, hidradenitis suppurativa (HS), and inpatient dermatology workforce issues. Key developments include improved recognition and management of drug reactions; updated diagnostic and prognostic tools for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN); and guidance for emerging infections such as measles, dengue, mpox, orthopoxviruses, and resistant dermatophytes. Evidence-based strategies for HS aim to reduce unnecessary admissions and optimize care. Workforce challenges, including limited access, high call burden, and potential for artificial intelligence (AI)–assisted diagnosis, are also highlighted. These findings emphasize the critical contributions of dermatologists to hospital-based care and provide emerging evidence to guide clinical practice.

Dermatologists play a critical role in the care of hospitalized patients. Herein, we review the research developments between January 2024 and December 2025 most relevant to the care of hospitalized patients with skin disease, including severe cutaneous adverse reactions (SCARs), emerging and re-emerging infectious diseases, hidradenitis suppurativa (HS), and access to inpatient dermatology services.

Severe Cutaneous Adverse Drug Reactions

Severe cutaneous adverse drug reactions are among the most frequent reasons for inpatient dermatology consultation. A National Inpatient Sample study identified more than 160,000 cases of drug rash with eosinophilia and systemic symptoms (DRESS syndrome) between January 2016 and December 2020.¹ The overall mortality rate was 2.0%, substantially lower than the rates of up to 10% reported in earlier studies.² Case burden and mortality peaked during the fall months, possibly due to either increased use of antibiotics or increased viral infection or reactivation during these months.¹

A retrospective cohort study of patients with probable or definite DRESS syndrome showed that, among 93 patients with at least 1 viral marker tested, human herpesvirus (HHV) reactivation was found in 42% (39/93), including HHV-6 (28%)(24/85), Epstein-Barr virus (17%)(15/87), and cytomegalovirus (20%)(18/89); furthermore, viral reactivation was associated with higher 1-year mortality (odds ratio, 3.9), dialysis initiation, flares of disease, and longer hospital stay (all P<.05).¹ Multiple reactivations were associated with higher inpatient mortality and 1-year mortality; however, despite apparent prognostic importance, the role of screening for viral reactivation in DRESS syndrome is undefined.³ A 2024 effort using the Delphi technique found consensus for obtaining HHV-6, Epstein-Barr virus, and cytomegalovirus viral load in all patients with suspected DRESS syndrome, but this topic was the subject of greatest uncertainty.⁴

A systematic review of 610 studies including 2122 patients with DRESS syndrome demonstrated that, among 193 causal agents identified, 14 drugs accounted for more than 1% of cases each and therefore were considered high risk. Seventy-eight percent of cases were attributed to these 14 drugs (Table).⁵ A TriNetX Query study analyzed antibiotic exposures across SCARs and reported that sulfonamides (hazard ratio [HR], 7.5), aminoglycosides (HR, 3.7), and tetracyclines (HR, 1.7) were associated with an elevated risk for SCARs. Sulfonamides had the highest absolute incidence of SCARs, followed by cephalosporins and penicillins.⁶

A multicenter randomized clinical trial⁷ compared high-potency topical corticosteroids (clobetasol 30 g/d) to systemic corticosteroids (prednisone 0.5 mg/kg/d) for treatment of moderate DRESS syndrome. On day 30, 53.8% (14/26) of patients in the topical group had achieved remission of visceral involvement, compared to 72.0% (18/25) in the systemic group. Before day 30, 23.1% (6/26) of patients in the topical group worsened, necessitating transition to high-dose systemic steroids. When inpatient monitoring is available, low-dose systemic corticosteroids or high-potency topical steroids may be reasonable management strategies for moderate DRESS syndrome⁷; however, the frequent need for treatment intensification suggests limitations to this strategy.

Since prolonged courses of systemic steroids generally are necessary for management of DRESS syndrome, steroid-sparing options are needed. A retrospective case series examined interleukin 5 inhibition in patients with possible DRESS syndrome (Registry of Severe Cutaneous Adverse Reactions score ≥3). All patients demonstrated rapid eosinophil reduction within 1 to 3 days (mean [SD] time to resolution, 1.4 [0.9] days) after treatment with mepolizumab or benralizumab, with clinical improvement occurring at a mean (SD) of 16 (3.7) days (range, 13-21 days).⁸

A French cohort study of 1221 adult patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) reported in-hospital mortality of 19% and a total mortality of 34% at 1 year.⁹ Risk factors contributing to in-hospital mortality included age, history of/current diagnosis of cancer, dementia, and liver disease, while postdischarge mortality was associated with acute kidney injury and sepsis. Long-term complications included ophthalmologic and mood disorders.⁹

A new set of diagnostic criteria for SJS/TEN, known as the Niigata criteria,¹⁰ includes 3 main items: severe mucosal lesions in cutaneous-mucosal transition zones (eg, eyes, lips, vulva) or generalized erythema with necrotic lesions; fever of 38.5 °C or higher; and necrosis of the epidermis seen on histopathology. Because epidermal detachment involving 10% of the body surface area (BSA) is an important mortality risk predicter, SJS is defined as less than 10% BSA involvement, and TEN has been redefined as 10% or more BSA involvement (not ≥30%). A new prognostic score—clinical risk score for TEN (CRISTEN)—can be tabulated at the point of care without laboratory values. It was developed based on the 10 most important risk factors for death in a retrospective study of 382 patients, which included age 65 years or older; epidermal detachment involving 10% BSA or higher; an antibiotic as causative agent; systemic corticosteroid therapy before the onset of SJS/TEN; involvement of all 3 mucosal surfaces; and medical comorbidities such as renal impairment, diabetes, cardiac disease, active cancer, and bacterial infection.¹¹

New potential therapeutic targets for SJS/TEN include PC111 (monoclonal antibody to Fas ligand), formyl peptide receptor 1 antagonists (which inhibit necroptosis induced by formyl peptide receptor 1–annexin A1 interaction), daratumumab (which depletes cytotoxic CD8-positive and CD38-positive T cells), and Janus kinase (JAK) inhibitors.¹⁰ Spatial proteomics showed marked enrichment of type I and type II interferon signatures as well as activation of signal transducer and activator of transcription 1. In vitro, tofacitinib reduced keratinocyte-directed cytotoxicity, and in vivo JAK inhibitors ameliorated disease severity in 2 TEN mouse models. Patients with TEN that was refractory to corticosteroid therapy received rescue treatment with JAK inhibitors and had re-epithelization within several days with marked reduction in levels of phosphorylated signal transducer and activator of transcription 1.¹² Controlled studies are needed to assess the potential role of JAK inhibitors for SJS/TEN.

Emerging and Re-emerging Infectious Diseases

Dermatologists may encounter emerging or re-emerging infections, performing an essential public health role in the process. In 2025, a total of 2281 confirmed cases of measles had been reported across 45 of the United States.¹³ During the COVID-19 pandemic, measles vaccine coverage in the United States dropped to 93%—down from 95% to 97% prepandemic. Worldwide, 2022 saw an increase of 1.4 million measles cases (18% increase) and 41,200 excess deaths (43% increase) compared to the previous year. Complications of measles include pneumonia, blindness, otitis media, and encephalitis, with 1 in 5 (20%) unvaccinated people with measles in the United States requiring hospitalization.¹⁴ A vaccine coverage rate higher than 95% is needed to prevent community spread of disease. Since efforts to detect and rapidly isolate cases of measles are critical, dermatologists should consider measles in the differential of morbilliform eruptions with viral symptoms and ask about vaccination status.

Since 2023, dengue infection rates have tripled in the Americas, representing the highest levels recorded since tracking began in 1980. In 2024, there were more than 12 million cases, with approximately 8000 deaths reported. Ninety percent of cases occur in Argentina, Brazil, Colombia, and Mexico, but local transmission has been reported in Arizona, California, Florida, Hawaii, and Texas.¹⁵ The characteristic exanthem of dengue is diffuse erythema with islands of sparing.<

Unlike during the 2022 outbreak of mpox clade II, which predominantly impacted men who have sex with men, there now is an ongoing outbreak of mpox clades 1a and 1b in the Democratic Republic of the Congo and surrounding countries that more commonly affects children and heterosexual adults. It is also more transmissible and virulent. Cases of mpox clade I have been reported in several European countries and across the United States, mostly among travelers from areas of active transmission. Vaccination of at-risk individuals is considered effective; however, tecovirimat is not.¹⁶

Outbreaks of 2 emerging zoonotic orthopoxviruses recently have been reported. Buffalopox virus (BPXV) is transmitted via direct contact with the skin of infected cattle and buffalo as well as fomites and has been responsible for human cases in South Asia. Characteristics of BPXV include macules, umbilicated papules, vesicles, pustules, and eschars that evolve over several weeks, with a predilection for the hands and face. It can manifest with prodromal symptoms of fever, malaise, and lymphadenopathy.¹⁷ Borealpox virus (formerly known as Alaskapox) has similar manifestations. Its reservoir includes small mammals such as voles and shrews, but it also has been found in cats and dogs and has been responsible for at least one human fatality. Cidofovir may be an effective therapy for both BPXV and borealpox virus, and prior smallpox vaccination may provide protection.¹⁸ These outbreaks demonstrate the continued importance of research for more effective vaccines and therapies against smallpox and other orthopoxviruses.¹⁹ A recent review provided a detailed overview of the epidemiology, transmission, dermatologic findings, and management strategies associated with smallpox and other bioweapons.²⁰

In 2023, a case was reported of a patient in a New York City hospital with tinea that was refractory to multiple rounds of topical antifungals, which called attention to the presence of Trichophyton indotineae in the United States.²¹ Since then, additional reports and case series have characterized the clinical presentation of T indotineae as widespread and atypical, refractory to traditional therapies, and most often encountered in travelers returning from Bangladesh or elsewhere in South Asia.²² The diagnosis should be confirmed via DNA testing of fungal culture. Itraconazole 100 to 200 mg/d is the antifungal therapy of choice.²³

Other series have reported cases of tinea genitalis caused by Trichophyton mentagrophytes type VII seen predominately in sex workers and others engaging in high-risk sexual contact, highlighting the spread of dermatophytes through sexual activity.^24-26 Lastly, it is important to culture pustules and consider atypical pathogens in patients with chronic folliculitis not responding to typical therapies such as tetracycline antibiotics. A case series reported the presence of pustules in the beard area of 7 men who have sex with men, with culture data showing Klebsiella aerogenes. Prolonged courses of fluoroquinolones were necessary for clearance.²⁷

Reducing HS Admissions Through Evidence-Based Management

Hidradenitis suppurativa is a frequent cause of emergency department visits and hospital admissions. In an analysis of the Nationwide Readmissions Database, 17.8% (392/2204) of patients admitted to the hospital with HS were readmitted within 30 days, a number comparable to that of heart failure.²⁸

Flaring HS can produce symptoms that mimic sepsis. A retrospective cohort study examining sepsislike features in HS showed that more than 50% (30/58) of those admitted to the hospital with an HS flare were misdiagnosed with sepsis, and more than 80% (53/64) of those patients received intravenous antibiotics.²⁹ A National Inpatient Sample (January 2016-December 2018) study demonstrated minimal rates of true infection in patients admitted with HS flares,³⁰ while patients with HS diagnosed as sepsis do not sustain the mortality expected from true sepsis. Improving recognition of HS and differentiation of the disease from true sepsis could decrease unnecessary antibiotic use, hospital admissions, and cost, underscoring the need for a framework to reliably and reproducibly distinguish sepsis from HS flare.³¹

While severe HS is difficult to manage, there may be a window of opportunity in which appropriate treatment of early disease may prevent progression and decrease inpatient utilization. A prospective cohort study of 335 biologic-naïve patients with mild to moderate HS (Hurley stages I and II) followed over a median of 2 years showed that active smoking, body mass index higher than 25, and the presence of disease in 2 or more anatomic areas were factors predictive of progression to severe disease.³²

Despite high utilization of emergency and inpatient care, there has been no consensus on inpatient management of HS. A Delphi consensus exercise including 26 expert dermatologists reached consensus on 40 statements.³³ Specific recommendations involve multidisciplinary care, including from a dermatologist; consideration of comorbid medical conditions; supportive care measures (wound care, pain control); evidence-based medical management, including initiation or adjustment of biologic therapies; targeted surgical intervention; nutritional support and maintenance of glycemic control; and attention to transitional care at discharge, including home health services, verification of insurance status, and timely outpatient dermatology follow-up.³⁴ A retrospective review of 98 patients treated with intravenous ertapenem for a mean duration of 13 weeks demonstrated improvement in clinical and inflammatory markers.³⁵ Patients with severe or treatment-refractory HS, including those admitted to the hospital, may benefit from initiation of this therapy in select circumstances.

Hospital Dermatology Workforce

Inpatient dermatology consultations are extremely valuable for improving diagnostic accuracy, reducing admissions for pseudocellulitis and inflammatory skin conditions, and keeping cancer patients on needed therapies.^36-38 Despite this clear value added, a cross-sectional analysis of inpatient Medicare claims data from January 2013 to December 2019 found that the number of dermatologists performing more than 10 inpatient consults per year decreased from 356 to 281.³⁹ Additionally, medical centers in which dermatology encounters occurred decreased from 239 to 157 during the same period. Ninety-eight percent of inpatient dermatologists were in metropolitan areas, with large regions lacking access to inpatient dermatology consultation altogether.³⁹

A survey of Society for Pediatric Dermatology members similarly characterized the state of the pediatric dermatology workforce performing hospital consultation.⁴⁰ Seventy-five percent reported a high call burden, defined as more than 11 days or nights per month, more than 1 weekend per month, and/or more than 5 hours per week seeing patients. Ninety-one percent of consultation services are based within academic institutions, reflecting disparities in access.⁴⁰ A prospective cohort study of academic pediatric dermatologists reported that 310 curbside consultations were performed over 24 weeks; of these calls, 17% occurred during weeknights and 23% on weekends. None of these curbside interactions was reimbursed.⁴¹ These findings underscore the burden of uncompensated time a subset of pediatric dermatologists dedicates to inpatient consultations, highlighting the need for improved financial and administrative support and an increased number of physicians performing this role.

A survey study⁴² suggested that unfamiliarity with the inpatient setting, rather than medical knowledge, is the most important barrier to inpatient work among clinical dermatologists. Proposed interventions include resource guides (eg, hospital maps, pager numbers for key individuals, and protocols for urgent specimens). Reference guides and refresher courses may decrease gaps in knowledge or awareness among dermatologists in ambulatory practice.⁴² Another way to bolster the inpatient dermatology workforce may be to provide more guidance to qualified advanced practice providers to triage and address dermatologic emergencies.⁴³

Artificial intelligence (AI) also has been explored as a tool for diagnosing complex dermatologic conditions. One study presented 15 published inpatient dermatology cases to 7 dermatologists. Participants were asked to formulate their top 3 differential diagnoses and were then shown AI-generated differentials and asked to submit a revised differential. Participants showed a diagnostic accuracy of 69% before seeing the AI-generated differential diagnosis and 79% after; however, in cases in which the AI differential was incorrect, diagnostic accuracy of the dermatologists decreased after being shown the AI model.⁴⁴

Final Thoughts

This January 2024 to December 2025 review of research relevant to hospital dermatology highlights important developments and ongoing challenges in SCARs, emerging and re-emerging infectious diseases, HS, and the inpatient dermatology workforce. Dermatologists continue to play a critical role in the care of hospitalized patients with skin disease.

To the Editor:

Segmental vitiligo (SV) accounts for a minority of vitiligo cases and most frequently occurs in children.¹ It characteristically manifests unilaterally and affects a single body area with a sharp midline demarcation. In contrast to nonsegmental vitiligo (NSV), SV typically stabilizes early in the disease progression.¹ The pathophysiology of this vitiligo subtype is not well established, but possible autoinflammatory mechanisms associated with somatic mosaicism, neuronal mechanisms, and/or microvascular skin-homing have been proposed.² We present the case of a pediatric patient with segmental vitiligo of the right hemiface treated with a combination of a topical calcineurin inhibitor and narrow-band UVB (NB-UVB) phototherapy.

An otherwise healthy 7-year-old boy presented to the dermatology department for evaluation of depigmented macules and patches affecting the right hemiface (temporal, periorbital, malar, perioral, preauricular, and mandibular regions) and neck associated with homolateral leukotrichia of the scalp and facial hair as well as the eyelashes of 5 years’ duration. The findings were consistent with SV (Figure 1). The patient previously had been diagnosed based on the clinical findings and treated with continuous application of topical calcineurin inhibitors plus oral cyclosporine (3 mg/kg/d) for 1 year, but the response was poor. The condition had a severe impact on the patient’s quality of life and social relationships. Therapeutic options were discussed with the patient’s caregivers, and ultimately NB-UVB phototherapy was started twice weekly with 10% increases in the dose at each treatment. Topical tacrolimus ointment (1 mg/g) also was started, and the cyclosporine was stopped. Evaluation of treatment progress occurred every 3 months, with progressive repigmentation of the patches following a perifollicular pattern. After 6 months of phototherapy, there was notable repigmentation of the affected areas, particularly in the malar, perioral, and perinasal regions (Figure 2) and the therapeutic response improved after 1 year of treatment (Figure 3). No adverse events were noted during the treatment period.

Segmental vitiligo lacks consistently effective treatment options. This subtype of vitiligo is classically resistant to conventional therapeutic options. Surgery may be a more effective and long-lasting treatment option but is not suitable for every patient.^1,3 Janus kinase (JAK) inhibitors are the newest treatment options being explored for topical and systemic treatment of vitiligo, with promising results in active and stable NSV lesions^4,5; however, SV rarely is represented in case reports and clinical trials. The topical JAK inhibitor ruxolitinib has been approved for use in NSV,⁵ and a phase 2 trial with oral ritlecitinib only included patients with NSV.⁴ Furthermore, JAK inhibitors have been studied and approved for children aged 12 years or older as well as for adults,^4,5 but younger age groups (4-10 years)—in whom SV most frequently manifests, as in our patient—have been excluded from these studies.¹ We present a novel case of SV of the right hemiface in a child that was successfully treated with NB-UVB phototherapy in association with topical calcineurin inhibitors.

The role of phototherapy for the treatment of vitiligo has been well documented, and it frequently is combined with other therapeutic modalities, such as topical anti-inflammatory drugs or, most recently, laser and micrografting techniques.^6,7 The most frequently used modality is NB-UVB. In the active phase, it performs an immunomodulatory role, while in the stable phase, it stimulates migration and activity of perilesional and hair follicle melanocytes.⁸ Initiating therapy early is advisable, particularly during the first 6 months of progression, as there is a higher probability of response^1,3,8; nevertheless, a good response was achieved despite the 5-year evolution of vitiligo in our patient. This is a safe option for a skin condition that may begin early in life and require long-term treatment.⁸ A main concern would be an increased risk for skin cancer associated with repeated NB-UVB exposure, which has not been verified in a recent analysis.⁹

Segmental vitiligo can considerably impact the patient’s quality of life, affecting social interactions and self-perception, particularly in younger patients with facial involvement; thus, effective and safe therapeutic strategies adapted to the individual and their vitiligo lesions should be discussed. Classical treatment options remain valid and provide good results for some patients; therefore, they should not be disregarded even with the rise of innovative therapies.

To the Editor:

Segmental vitiligo (SV) accounts for a minority of vitiligo cases and most frequently occurs in children.¹ It characteristically manifests unilaterally and affects a single body area with a sharp midline demarcation. In contrast to nonsegmental vitiligo (NSV), SV typically stabilizes early in the disease progression.¹ The pathophysiology of this vitiligo subtype is not well established, but possible autoinflammatory mechanisms associated with somatic mosaicism, neuronal mechanisms, and/or microvascular skin-homing have been proposed.² We present the case of a pediatric patient with segmental vitiligo of the right hemiface treated with a combination of a topical calcineurin inhibitor and narrow-band UVB (NB-UVB) phototherapy.

An otherwise healthy 7-year-old boy presented to the dermatology department for evaluation of depigmented macules and patches affecting the right hemiface (temporal, periorbital, malar, perioral, preauricular, and mandibular regions) and neck associated with homolateral leukotrichia of the scalp and facial hair as well as the eyelashes of 5 years’ duration. The findings were consistent with SV (Figure 1). The patient previously had been diagnosed based on the clinical findings and treated with continuous application of topical calcineurin inhibitors plus oral cyclosporine (3 mg/kg/d) for 1 year, but the response was poor. The condition had a severe impact on the patient’s quality of life and social relationships. Therapeutic options were discussed with the patient’s caregivers, and ultimately NB-UVB phototherapy was started twice weekly with 10% increases in the dose at each treatment. Topical tacrolimus ointment (1 mg/g) also was started, and the cyclosporine was stopped. Evaluation of treatment progress occurred every 3 months, with progressive repigmentation of the patches following a perifollicular pattern. After 6 months of phototherapy, there was notable repigmentation of the affected areas, particularly in the malar, perioral, and perinasal regions (Figure 2) and the therapeutic response improved after 1 year of treatment (Figure 3). No adverse events were noted during the treatment period.

Segmental vitiligo lacks consistently effective treatment options. This subtype of vitiligo is classically resistant to conventional therapeutic options. Surgery may be a more effective and long-lasting treatment option but is not suitable for every patient.^1,3 Janus kinase (JAK) inhibitors are the newest treatment options being explored for topical and systemic treatment of vitiligo, with promising results in active and stable NSV lesions^4,5; however, SV rarely is represented in case reports and clinical trials. The topical JAK inhibitor ruxolitinib has been approved for use in NSV,⁵ and a phase 2 trial with oral ritlecitinib only included patients with NSV.⁴ Furthermore, JAK inhibitors have been studied and approved for children aged 12 years or older as well as for adults,^4,5 but younger age groups (4-10 years)—in whom SV most frequently manifests, as in our patient—have been excluded from these studies.¹ We present a novel case of SV of the right hemiface in a child that was successfully treated with NB-UVB phototherapy in association with topical calcineurin inhibitors.

The role of phototherapy for the treatment of vitiligo has been well documented, and it frequently is combined with other therapeutic modalities, such as topical anti-inflammatory drugs or, most recently, laser and micrografting techniques.^6,7 The most frequently used modality is NB-UVB. In the active phase, it performs an immunomodulatory role, while in the stable phase, it stimulates migration and activity of perilesional and hair follicle melanocytes.⁸ Initiating therapy early is advisable, particularly during the first 6 months of progression, as there is a higher probability of response^1,3,8; nevertheless, a good response was achieved despite the 5-year evolution of vitiligo in our patient. This is a safe option for a skin condition that may begin early in life and require long-term treatment.⁸ A main concern would be an increased risk for skin cancer associated with repeated NB-UVB exposure, which has not been verified in a recent analysis.⁹

Segmental vitiligo can considerably impact the patient’s quality of life, affecting social interactions and self-perception, particularly in younger patients with facial involvement; thus, effective and safe therapeutic strategies adapted to the individual and their vitiligo lesions should be discussed. Classical treatment options remain valid and provide good results for some patients; therefore, they should not be disregarded even with the rise of innovative therapies.

To the Editor:

Segmental vitiligo (SV) accounts for a minority of vitiligo cases and most frequently occurs in children.¹ It characteristically manifests unilaterally and affects a single body area with a sharp midline demarcation. In contrast to nonsegmental vitiligo (NSV), SV typically stabilizes early in the disease progression.¹ The pathophysiology of this vitiligo subtype is not well established, but possible autoinflammatory mechanisms associated with somatic mosaicism, neuronal mechanisms, and/or microvascular skin-homing have been proposed.² We present the case of a pediatric patient with segmental vitiligo of the right hemiface treated with a combination of a topical calcineurin inhibitor and narrow-band UVB (NB-UVB) phototherapy.

An otherwise healthy 7-year-old boy presented to the dermatology department for evaluation of depigmented macules and patches affecting the right hemiface (temporal, periorbital, malar, perioral, preauricular, and mandibular regions) and neck associated with homolateral leukotrichia of the scalp and facial hair as well as the eyelashes of 5 years’ duration. The findings were consistent with SV (Figure 1). The patient previously had been diagnosed based on the clinical findings and treated with continuous application of topical calcineurin inhibitors plus oral cyclosporine (3 mg/kg/d) for 1 year, but the response was poor. The condition had a severe impact on the patient’s quality of life and social relationships. Therapeutic options were discussed with the patient’s caregivers, and ultimately NB-UVB phototherapy was started twice weekly with 10% increases in the dose at each treatment. Topical tacrolimus ointment (1 mg/g) also was started, and the cyclosporine was stopped. Evaluation of treatment progress occurred every 3 months, with progressive repigmentation of the patches following a perifollicular pattern. After 6 months of phototherapy, there was notable repigmentation of the affected areas, particularly in the malar, perioral, and perinasal regions (Figure 2) and the therapeutic response improved after 1 year of treatment (Figure 3). No adverse events were noted during the treatment period.

Segmental vitiligo lacks consistently effective treatment options. This subtype of vitiligo is classically resistant to conventional therapeutic options. Surgery may be a more effective and long-lasting treatment option but is not suitable for every patient.^1,3 Janus kinase (JAK) inhibitors are the newest treatment options being explored for topical and systemic treatment of vitiligo, with promising results in active and stable NSV lesions^4,5; however, SV rarely is represented in case reports and clinical trials. The topical JAK inhibitor ruxolitinib has been approved for use in NSV,⁵ and a phase 2 trial with oral ritlecitinib only included patients with NSV.⁴ Furthermore, JAK inhibitors have been studied and approved for children aged 12 years or older as well as for adults,^4,5 but younger age groups (4-10 years)—in whom SV most frequently manifests, as in our patient—have been excluded from these studies.¹ We present a novel case of SV of the right hemiface in a child that was successfully treated with NB-UVB phototherapy in association with topical calcineurin inhibitors.

The role of phototherapy for the treatment of vitiligo has been well documented, and it frequently is combined with other therapeutic modalities, such as topical anti-inflammatory drugs or, most recently, laser and micrografting techniques.^6,7 The most frequently used modality is NB-UVB. In the active phase, it performs an immunomodulatory role, while in the stable phase, it stimulates migration and activity of perilesional and hair follicle melanocytes.⁸ Initiating therapy early is advisable, particularly during the first 6 months of progression, as there is a higher probability of response^1,3,8; nevertheless, a good response was achieved despite the 5-year evolution of vitiligo in our patient. This is a safe option for a skin condition that may begin early in life and require long-term treatment.⁸ A main concern would be an increased risk for skin cancer associated with repeated NB-UVB exposure, which has not been verified in a recent analysis.⁹

Segmental vitiligo can considerably impact the patient’s quality of life, affecting social interactions and self-perception, particularly in younger patients with facial involvement; thus, effective and safe therapeutic strategies adapted to the individual and their vitiligo lesions should be discussed. Classical treatment options remain valid and provide good results for some patients; therefore, they should not be disregarded even with the rise of innovative therapies.

THE DIAGNOSIS: Black Dermographism

Black dermographism is characterized by asymptomatic black discoloration on the skin caused by contact with various metals, most commonly gold but also silver, nickel, zinc, lead, and aluminum.¹ These metallic particles have a black appearance as they do not reflect light.² Our patient was wearing gold hoop earrings at presentation, which were near the black patches. Certain topical products (eg, makeup, sunscreens [especially those containing zinc oxide or titanium oxide], toothpaste) can abrade metal, causing it to deposit on the skin and absorb light.³ The black discoloration is not permanent and can be prevented by avoiding contact between inciting products and metals.² No further diagnostic testing is necessary, and the patches will self-resolve if contact with the product is avoided.

Our patient noted that she wore a physical sunscreen daily, but the black patches were present only when she wore the gold hoop earrings. Given this history and physical examination findings in the office, it was suspected she had black dermographism due to her gold earrings and topical sunscreen. The patient was advised to avoid wearing the gold earrings.

Black dermographism is a misnomer because it is not a true urticarial reaction but rather a false dermographism; therefore, patients will not experience pruritus or erythema.¹ True dermographism is an inducible urticarial eruption from pressure or trauma to the skin. The clinical appearance is notable for erythematous wheals in the shape of the external force applied.⁴ Two other types of false dermographism include white dermographism, which occurs secondary to allergic contact dermatitis, and yellow dermographism, which is caused by bile deposits on the skin.⁴

Additional diagnoses were able to be ruled out for the following reasons: cutaneous mastocytosis can manifest with red-brown maculopapular lesions often accompanied by the Darier sign, which includes swelling, pruritus, and erythema but was not present in our patient.⁴ Allergic contact dermatitis manifests as a delayed eczematous reaction around 48 to 72 hours after exposure to an allergen. Our patient’s lesions formed while wearing gold earrings but did not manifest with a hypersensitivity reaction. Of note, symptomatic dermographism has been reported to mimic latex allergy.⁵ Ecchymosis may appear as erythematous, violaceous, or yellow-green patches depending on the stage but develops due to leakage from broken blood vessels secondary to trauma, which was not reported in our patient. Type I hypersensitivity reactions can occur minutes to hours after exposure to an allergen but typically manifest with a wheal-and-flare presentation.

Black dermographism from gold earrings can mimic concerning skin disorders or poor hygiene, causing unnecessary anxiety. Understanding that it is a harmless reaction between gold and certain topical products can reassure patients and prevent unnecessary testing or treatments.

THE DIAGNOSIS: Black Dermographism

Black dermographism is characterized by asymptomatic black discoloration on the skin caused by contact with various metals, most commonly gold but also silver, nickel, zinc, lead, and aluminum.¹ These metallic particles have a black appearance as they do not reflect light.² Our patient was wearing gold hoop earrings at presentation, which were near the black patches. Certain topical products (eg, makeup, sunscreens [especially those containing zinc oxide or titanium oxide], toothpaste) can abrade metal, causing it to deposit on the skin and absorb light.³ The black discoloration is not permanent and can be prevented by avoiding contact between inciting products and metals.² No further diagnostic testing is necessary, and the patches will self-resolve if contact with the product is avoided.

Our patient noted that she wore a physical sunscreen daily, but the black patches were present only when she wore the gold hoop earrings. Given this history and physical examination findings in the office, it was suspected she had black dermographism due to her gold earrings and topical sunscreen. The patient was advised to avoid wearing the gold earrings.

Black dermographism is a misnomer because it is not a true urticarial reaction but rather a false dermographism; therefore, patients will not experience pruritus or erythema.¹ True dermographism is an inducible urticarial eruption from pressure or trauma to the skin. The clinical appearance is notable for erythematous wheals in the shape of the external force applied.⁴ Two other types of false dermographism include white dermographism, which occurs secondary to allergic contact dermatitis, and yellow dermographism, which is caused by bile deposits on the skin.⁴

Additional diagnoses were able to be ruled out for the following reasons: cutaneous mastocytosis can manifest with red-brown maculopapular lesions often accompanied by the Darier sign, which includes swelling, pruritus, and erythema but was not present in our patient.⁴ Allergic contact dermatitis manifests as a delayed eczematous reaction around 48 to 72 hours after exposure to an allergen. Our patient’s lesions formed while wearing gold earrings but did not manifest with a hypersensitivity reaction. Of note, symptomatic dermographism has been reported to mimic latex allergy.⁵ Ecchymosis may appear as erythematous, violaceous, or yellow-green patches depending on the stage but develops due to leakage from broken blood vessels secondary to trauma, which was not reported in our patient. Type I hypersensitivity reactions can occur minutes to hours after exposure to an allergen but typically manifest with a wheal-and-flare presentation.

Black dermographism from gold earrings can mimic concerning skin disorders or poor hygiene, causing unnecessary anxiety. Understanding that it is a harmless reaction between gold and certain topical products can reassure patients and prevent unnecessary testing or treatments.

THE DIAGNOSIS: Black Dermographism

Black dermographism is characterized by asymptomatic black discoloration on the skin caused by contact with various metals, most commonly gold but also silver, nickel, zinc, lead, and aluminum.¹ These metallic particles have a black appearance as they do not reflect light.² Our patient was wearing gold hoop earrings at presentation, which were near the black patches. Certain topical products (eg, makeup, sunscreens [especially those containing zinc oxide or titanium oxide], toothpaste) can abrade metal, causing it to deposit on the skin and absorb light.³ The black discoloration is not permanent and can be prevented by avoiding contact between inciting products and metals.² No further diagnostic testing is necessary, and the patches will self-resolve if contact with the product is avoided.

Our patient noted that she wore a physical sunscreen daily, but the black patches were present only when she wore the gold hoop earrings. Given this history and physical examination findings in the office, it was suspected she had black dermographism due to her gold earrings and topical sunscreen. The patient was advised to avoid wearing the gold earrings.

Black dermographism is a misnomer because it is not a true urticarial reaction but rather a false dermographism; therefore, patients will not experience pruritus or erythema.¹ True dermographism is an inducible urticarial eruption from pressure or trauma to the skin. The clinical appearance is notable for erythematous wheals in the shape of the external force applied.⁴ Two other types of false dermographism include white dermographism, which occurs secondary to allergic contact dermatitis, and yellow dermographism, which is caused by bile deposits on the skin.⁴

Additional diagnoses were able to be ruled out for the following reasons: cutaneous mastocytosis can manifest with red-brown maculopapular lesions often accompanied by the Darier sign, which includes swelling, pruritus, and erythema but was not present in our patient.⁴ Allergic contact dermatitis manifests as a delayed eczematous reaction around 48 to 72 hours after exposure to an allergen. Our patient’s lesions formed while wearing gold earrings but did not manifest with a hypersensitivity reaction. Of note, symptomatic dermographism has been reported to mimic latex allergy.⁵ Ecchymosis may appear as erythematous, violaceous, or yellow-green patches depending on the stage but develops due to leakage from broken blood vessels secondary to trauma, which was not reported in our patient. Type I hypersensitivity reactions can occur minutes to hours after exposure to an allergen but typically manifest with a wheal-and-flare presentation.

Black dermographism from gold earrings can mimic concerning skin disorders or poor hygiene, causing unnecessary anxiety. Understanding that it is a harmless reaction between gold and certain topical products can reassure patients and prevent unnecessary testing or treatments.

THE DIAGNOSIS: Disseminate and Recurrent Infundibulofolliculitis

Histopathology demonstrated a lymphocyte-predominant infundibular infiltrate with mild spongiosis and lymphocytic exocytosis; a mild, superficial perivascular infiltrate also was present. The surrounding skin was largely normal with no notable papillomatosis, acanthosis, or hyperkeratosis (Figure 1). The clinical presentation and histopathologic findings led to the diagnosis of disseminate and recurrent infundibulofolliculitis (DRIF). The patient was started on a 2-week course of once-daily ammonium lactate lotion 12% and urea cream 40% and twice-daily triamcinolone ointment 0.1%. The patient was instructed to take a 1-week break before this regimen was repeated. Isotretinoin 0.5 mg/kg/d for 2 to 4 months was considered and will be an option if there is no improvement at follow-up.

Disseminate and recurrent infundibulofolliculitis is a rare noninfectious folliculitis that initially was described by Hitch and Lund¹ in 1968. Males of African descent are most commonly affected by DRIF, but the condition is not limited to this population.^2,3 It manifests as asymptomatic, flesh-colored, monomorphic, follicular papules distributed on the trunk and proximal extremities. Pustules can be present, and hair may be seen protruding from them. As the name suggests, DRIF is associated with histopathologic changes that are prominent at the infundibulum of hair follicles.^3,4 Disseminate and recurrent infundibulofolliculitis can persist for months to years because it often is resistant to treatment. Treatments include topical monotherapies such as corticosteroids, calcineurin inhibitors, or retinoids; combination topical treatments; antibiotics; and isotretinoin.² Recurrent remission and exacerbation occurs in many patients.³

The classic manifestations of DRIF, including follicular, monomorphic, flesh-colored papules distributed on the neck, trunk, and proximal upper extremities, were seen in our patient (Figure 2). These findings along with the skin biopsy identifying a lymphocytic infundibular infiltrate led to the diagnosis of DRIF. The papules associated with DRIF can be recurrent or chronic. The lesions in this patient were chronic and persistent.

Despite limited evidence, it has been suggested that DRIF may be a manifestation of atopic dermatitis in patients with darker skin tones. In our case, the patient had a history of childhood eczema. Other hypotheses have proposed that DRIF could be a nonspecific reaction to a currently unknown antigen. A causative infectious agent has not been identified, although the search continues. There is speculation that DRIF could be an overt expression of normal follicular prominence, but the presence of occasional pustules and lymphocyte- predominant infundibular infiltrate negates that.³

Confluent and reticulated papillomatosis was included in the differential for our patient and manifests as asymptomatic hyperpigmented papules and plaques frequently occurring on the upper trunk, neck, and axilla; however, these lesions have a peripheral netlike configuration, as the name suggests. Additionally, this condition is thought to have an infectious component (Dietzia papillomatosis) and responds to antibiotic treatment.⁵ Follicular eczema also was high in the differential diagnosis but usually is seasonal and pruritic, and histopathology typically shows the features of spongiotic dermatitis. It also would respond well to topical steroids.⁶ Another condition high on the differential was juxtaclavicular beaded lines, which also manifests as flesh-colored follicular papules distributed on the upper trunk; however, histopathology usually shows features of hyperplastic pilosebaceous units along with spongiosis and exocytosis.⁷ Pityrosporum folliculitis initially was considered, but the patient only endorsed occasional pruritus. Additionally, no fungal elements were observed.

Currently, there are no definitive treatments for DRIF. The topical treatments available include midpotency corticosteroids, tretinoin, calcineurin inhibitors, 12% lactic acid, and 20% to 40% urea. The systemic therapies are high-dose oral vitamin A (100,000 IU/d), isotretinoin, and psoralen plus UVA.^8-10

THE DIAGNOSIS: Disseminate and Recurrent Infundibulofolliculitis

Histopathology demonstrated a lymphocyte-predominant infundibular infiltrate with mild spongiosis and lymphocytic exocytosis; a mild, superficial perivascular infiltrate also was present. The surrounding skin was largely normal with no notable papillomatosis, acanthosis, or hyperkeratosis (Figure 1). The clinical presentation and histopathologic findings led to the diagnosis of disseminate and recurrent infundibulofolliculitis (DRIF). The patient was started on a 2-week course of once-daily ammonium lactate lotion 12% and urea cream 40% and twice-daily triamcinolone ointment 0.1%. The patient was instructed to take a 1-week break before this regimen was repeated. Isotretinoin 0.5 mg/kg/d for 2 to 4 months was considered and will be an option if there is no improvement at follow-up.

Disseminate and recurrent infundibulofolliculitis is a rare noninfectious folliculitis that initially was described by Hitch and Lund¹ in 1968. Males of African descent are most commonly affected by DRIF, but the condition is not limited to this population.^2,3 It manifests as asymptomatic, flesh-colored, monomorphic, follicular papules distributed on the trunk and proximal extremities. Pustules can be present, and hair may be seen protruding from them. As the name suggests, DRIF is associated with histopathologic changes that are prominent at the infundibulum of hair follicles.^3,4 Disseminate and recurrent infundibulofolliculitis can persist for months to years because it often is resistant to treatment. Treatments include topical monotherapies such as corticosteroids, calcineurin inhibitors, or retinoids; combination topical treatments; antibiotics; and isotretinoin.² Recurrent remission and exacerbation occurs in many patients.³

The classic manifestations of DRIF, including follicular, monomorphic, flesh-colored papules distributed on the neck, trunk, and proximal upper extremities, were seen in our patient (Figure 2). These findings along with the skin biopsy identifying a lymphocytic infundibular infiltrate led to the diagnosis of DRIF. The papules associated with DRIF can be recurrent or chronic. The lesions in this patient were chronic and persistent.

Despite limited evidence, it has been suggested that DRIF may be a manifestation of atopic dermatitis in patients with darker skin tones. In our case, the patient had a history of childhood eczema. Other hypotheses have proposed that DRIF could be a nonspecific reaction to a currently unknown antigen. A causative infectious agent has not been identified, although the search continues. There is speculation that DRIF could be an overt expression of normal follicular prominence, but the presence of occasional pustules and lymphocyte- predominant infundibular infiltrate negates that.³

Confluent and reticulated papillomatosis was included in the differential for our patient and manifests as asymptomatic hyperpigmented papules and plaques frequently occurring on the upper trunk, neck, and axilla; however, these lesions have a peripheral netlike configuration, as the name suggests. Additionally, this condition is thought to have an infectious component (Dietzia papillomatosis) and responds to antibiotic treatment.⁵ Follicular eczema also was high in the differential diagnosis but usually is seasonal and pruritic, and histopathology typically shows the features of spongiotic dermatitis. It also would respond well to topical steroids.⁶ Another condition high on the differential was juxtaclavicular beaded lines, which also manifests as flesh-colored follicular papules distributed on the upper trunk; however, histopathology usually shows features of hyperplastic pilosebaceous units along with spongiosis and exocytosis.⁷ Pityrosporum folliculitis initially was considered, but the patient only endorsed occasional pruritus. Additionally, no fungal elements were observed.

Currently, there are no definitive treatments for DRIF. The topical treatments available include midpotency corticosteroids, tretinoin, calcineurin inhibitors, 12% lactic acid, and 20% to 40% urea. The systemic therapies are high-dose oral vitamin A (100,000 IU/d), isotretinoin, and psoralen plus UVA.^8-10

THE DIAGNOSIS: Disseminate and Recurrent Infundibulofolliculitis

Histopathology demonstrated a lymphocyte-predominant infundibular infiltrate with mild spongiosis and lymphocytic exocytosis; a mild, superficial perivascular infiltrate also was present. The surrounding skin was largely normal with no notable papillomatosis, acanthosis, or hyperkeratosis (Figure 1). The clinical presentation and histopathologic findings led to the diagnosis of disseminate and recurrent infundibulofolliculitis (DRIF). The patient was started on a 2-week course of once-daily ammonium lactate lotion 12% and urea cream 40% and twice-daily triamcinolone ointment 0.1%. The patient was instructed to take a 1-week break before this regimen was repeated. Isotretinoin 0.5 mg/kg/d for 2 to 4 months was considered and will be an option if there is no improvement at follow-up.

Disseminate and recurrent infundibulofolliculitis is a rare noninfectious folliculitis that initially was described by Hitch and Lund¹ in 1968. Males of African descent are most commonly affected by DRIF, but the condition is not limited to this population.^2,3 It manifests as asymptomatic, flesh-colored, monomorphic, follicular papules distributed on the trunk and proximal extremities. Pustules can be present, and hair may be seen protruding from them. As the name suggests, DRIF is associated with histopathologic changes that are prominent at the infundibulum of hair follicles.^3,4 Disseminate and recurrent infundibulofolliculitis can persist for months to years because it often is resistant to treatment. Treatments include topical monotherapies such as corticosteroids, calcineurin inhibitors, or retinoids; combination topical treatments; antibiotics; and isotretinoin.² Recurrent remission and exacerbation occurs in many patients.³

The classic manifestations of DRIF, including follicular, monomorphic, flesh-colored papules distributed on the neck, trunk, and proximal upper extremities, were seen in our patient (Figure 2). These findings along with the skin biopsy identifying a lymphocytic infundibular infiltrate led to the diagnosis of DRIF. The papules associated with DRIF can be recurrent or chronic. The lesions in this patient were chronic and persistent.

Despite limited evidence, it has been suggested that DRIF may be a manifestation of atopic dermatitis in patients with darker skin tones. In our case, the patient had a history of childhood eczema. Other hypotheses have proposed that DRIF could be a nonspecific reaction to a currently unknown antigen. A causative infectious agent has not been identified, although the search continues. There is speculation that DRIF could be an overt expression of normal follicular prominence, but the presence of occasional pustules and lymphocyte- predominant infundibular infiltrate negates that.³

Confluent and reticulated papillomatosis was included in the differential for our patient and manifests as asymptomatic hyperpigmented papules and plaques frequently occurring on the upper trunk, neck, and axilla; however, these lesions have a peripheral netlike configuration, as the name suggests. Additionally, this condition is thought to have an infectious component (Dietzia papillomatosis) and responds to antibiotic treatment.⁵ Follicular eczema also was high in the differential diagnosis but usually is seasonal and pruritic, and histopathology typically shows the features of spongiotic dermatitis. It also would respond well to topical steroids.⁶ Another condition high on the differential was juxtaclavicular beaded lines, which also manifests as flesh-colored follicular papules distributed on the upper trunk; however, histopathology usually shows features of hyperplastic pilosebaceous units along with spongiosis and exocytosis.⁷ Pityrosporum folliculitis initially was considered, but the patient only endorsed occasional pruritus. Additionally, no fungal elements were observed.

Currently, there are no definitive treatments for DRIF. The topical treatments available include midpotency corticosteroids, tretinoin, calcineurin inhibitors, 12% lactic acid, and 20% to 40% urea. The systemic therapies are high-dose oral vitamin A (100,000 IU/d), isotretinoin, and psoralen plus UVA.^8-10

Accurate procedural coding is essential to appropriate reimbursement and regulatory compliance in dermatology. This article reviews commonly misunderstood areas of procedural coding, including new biopsy codes; coding for shave removals, destruction, excision and repair, and adjacent tissue transfer (flap closure); the National Correct Coding Initiative; Medicare payment edits; Mohs micrographic surgery (MMS) codes; and correct use of key modifiers. Practical guidance is provided to help avoid frequent errors.

NEW BIOPSY CODES

The most common questions about procedural coding relate to the new Current Procedural Terminology (CPT) biopsy codes, which are reported based on method of removal. Primary codes include the following:

• 11102: tangential biopsy of skin (eg, shave, scoop, saucerize, curette) for a single lesion
• 11104: punch biopsy of skin, including simple closure, when performed, for a single lesion
• 11106: incisional biopsy of skin (eg, wedge), including simple closure, when performed, for a single lesion

Add-on codes are used for each separate or additional lesion:

• 11103: tangential biopsy
• 11105: punch biopsy
• 11107: incisional biopsy

When multiple biopsy types are performed on the same date of service, only one primary code is reported along with add-on codes for any additional biopsies. The primary code reported should have the highest relative value unit (generally incisional > punch > tangential) plus the add-on codes for additional biopsies performed. Sampling of the stratum corneum only (eg, skin scraping or tape stripping) does not constitute a skin biopsy and is not reportable as a procedure.

SHAVE REMOVAL CODES

Shave removal codes are appropriate when the intent is removal of the entire lesion and there is only dermis remaining at the base of the wound. Tangential biopsy codes are appropriate when the intent is to sample a portion of a lesion for diagnosis. If saucerization of a lesion is appropriate and only fat remains at the base of the wound, the procedure is correctly coded as an excision. If any dermis remains at the base of the wound, the procedure is properly coded as shave removal. Shave codes do not distinguish between benign and malignant lesions and do not include the margin of normal skin, only the diameter of the lesion itself.

DESTRUCTION CODES

Destruction codes include both premalignant and benign lesions and may be reported as add-on codes or standalone codes, depending on lesion type and number. The 17000 series is used for destruction of premalignant lesions such as actinic keratosis, large cell acanthoma, actinic cheilitis, and porokeratosis:

• 17000: destruction of the first premalignant lesion
• 17003: destruction of each additional premalignant lesion (up to 13 lesions); reported in addition to 17000
• 17004: destruction of 15 or more premalignant lesions; reported as a standalone code (not in addition to 17000)

The following codes are used for destruction of benign lesions:

• 17110: destruction of benign lesions (up to 14 lesions)
• 17111: destruction of 15 or more benign lesions; reported as a standalone code (not in addition to 17110)

EXCISION AND REPAIR CODES

Individual excisions are reported separately, while repairs are reported as the sum of the lengths within grouped anatomic zones. The groupings differ for intermediate and complex closures, so be sure to refer to your coding manual. Intermediate or complex closures should be reported separately for skin excisions, whereas simple closures are already included in the excision code and are not reported separately. Excision diameter includes the margins necessary to ensure complete removal of the tumor for both benign and malignant tumors. For neoplasms of uncertain behavior, defer billing until pathology results are available to ensure accurate reporting as either a benign or malignant tumor excision. Lesion size is measured prior to excision and includes the lesion plus the narrowest intended clinical margin; this measurement reflects the width of the excised specimen rather than the length of the repair.

Malignant tumor excisions continue to be worth more because of the greater risk and preservice and postservice work involved. Only about 50% of payment relates to the procedure itself; the other 50% relates to risk and preoperative and postoperative counseling as well as bundled follow-up visits in the global period. That accounts for the difference in compensation for benign vs malignant tumors as well as the 50% multiple surgical reduction for multiple lesions, as the equipment and cognitive portion bundled into the procedure are not separate for each procedure.

Historically, Medicare has bundled complex closures with benign excisions under 0.5 cm. Medicare also applies medically unlikely edits that may limit payment when more than 5 excisions, closures, or destruction procedures (excluding add-on codes) are reported on the same date of service. Medicare may pay for the additional procedures if a copy of the record and a letter of medical necessity are included.

CODING FOR ADJACENT TISSUE TRANSFER (FLAP CLOSURE)

When reporting adjacent tissue transfers, the total size of the defect includes primary and secondary defects when calculating the area of the flap. The areas of the primary and secondary defects are added together when the flap represents a single repair. The sums are reported separately if they are distinct repairs. Adjacent tissue transfer already includes payment for the excision of malignant or benign lesions. Do not code separately for the excision.

CORRECT CODING INITIATIVE

On January 1, 1996, the Medicare program implemented the National Correct Coding Initiative (https://www.cms.gov/national-correct-coding-initiative-ncci), employing nearly 83,000 code edits, in an attempt to eliminate unbundling or other inappropriate reporting of CPT codes. When procedures are performed on separate and distinct lesions, a modifier is required to bypass the edit that would otherwise deny payment for the second procedure. Medicare publishes lists of paired codes (column 1 paired with column 2). The code in column 2 is the one that requires modifier 59 or 79.

MEDICARE PAYMENT EDITS

Mutually Exclusive Edits

Mutually exclusive edits seek to identify services that cannot reasonably be performed in the same session. The “comprehensive” code will be paid and the “component” code disallowed.

Medically Unlikely Edits

The Centers for Medicare & Medicaid Services stop paying when multiples of a procedure exceed the medically unlikely edits, but payment may be made if accompanied by a copy of the medical record and letter of medical necessity. A common example would be a transplant recipient requiring destruction of many malignant lesions in a single session, exceeding the medically unlikely edits for the procedure.

MOHS MICROGRAPHIC SURGERY CODES

Mohs micrographic surgery codes require that a single physician act as both surgeon and pathologist. Do not report 88305 separately, as the pathology interpretation is already included in the MMS reimbursement. Repairs, grafts, and adjacent tissue transfer are separately reportable with the CPT codes for MMS.

The CPT codes for MMS include skin biopsy and excision services (11102-11107, 11600-11646, and 17260-17286); however, if a suspected skin cancer is biopsied for pathologic diagnosis prior to MMS, the biopsy (11102-11107) and frozen section pathology (88331) may be reported separately utilizing modifier 59 or 58 to distinguish the diagnostic biopsy from the definitive MMS. The biopsy should not duplicate a prior biopsy unless that biopsy result cannot be located; it must be performed before MMS and must determine the subsequent procedure. Although CPT indicates that modifier 59 should be used, it also is acceptable to utilize modifier 58 to indicate that the diagnostic skin biopsy and MMS were staged or planned procedures. This may be appropriate in the following scenarios:

• The lesion for which MMS is planned has not been biopsied within the previous 60 days,
• The surgeon cannot obtain a pathology report, with reasonable effort, from the referring physician, or
• The biopsy is performed on a lesion that is not associated with the MMS.

KEY MODIFIERS AND HOW THEY ARE USED

Modifiers are essential tools in dermatology coding that are used to indicate when procedures or evaluation and management (E/M) services are distinct, staged, bilateral, or related to specific global periods. Correct application ensures accurate reimbursement, prevents claim denials, and reflects the true work performed. The following list summarizes commonly used modifiers and guidance for their proper use.

Modifier 59: Distinct Procedural Service

Modifier 59 is used to clearly designate when distinct, independent, and separate multiple procedures are provided. The procedure must not be a component of another procedure. Examples include:

• Different procedures or surgeries
• Surgery on different sites or organ systems
• Separate incision/excision
• Separate lesions

When code 17000 is paired with the new biopsy codes, modifier 59 is paired with code 17000.

Modifier 79: Distinct Procedural Service During a Postoperative Period

Modifier 79 is used to clearly designate when distinct, independent, and separate multiple procedures are provided. The procedure must not be a component of another procedure. Examples include:

• Different procedures or surgeries
• Surgery on different sites or organ systems
• Separate incision/excision
• Separate lesions

Modifier 58: Staged or Planned Procedure

Modifier 58 is most commonly used when a staged excision is planned in advance or when a positive tumor margin requires further excision during a global period.

Modifier 25: Significant, Separately Identifiable E/M Service

Modifier 25 is defined as a significant and separately identifiable E/M service performed by the same physician on the same day as a procedure or other service. It is used to describe a separate, distinctly identifiable E/M service rendered during the same visit as another procedure. The modifier must be appended to the E/M code. The decision to perform a 0- or 10-day global procedure on the same date of service is already bundled into the payment for the procedure and does not qualify as a separate billable service.

Modifier 24: Unrelated E/M Service During a Postoperative Period

Modifier 24 is defined as an unrelated E/M service performed by the same physician during a postoperative period. It is used when a separate, unrelated E/M service is provided during the global period of a surgical procedure.

Modifiers 24 and 25: Documentation and Distinction

The CPT definition of modifier 25 states that an E/M service may be prompted by the system or condition for which a separate procedure or service is needed. Neither modifier requires a separate diagnosis; however, both require clearly distinguishable cognitive services beyond those typically associated with the procedure itself. This includes evaluation beyond the examination of the lesion, discussion of risks, benefits, and alternatives, and the decision to perform a 0- or 10-day global procedure.

Modifier 50: Bilateral Procedure

Modifier 50 is defined as a bilateral procedure and is used when the same procedure is performed on both sides of the body, such as application of Unna boots. When reporting this modifier, specify the quantity applied. Because Unna boots may be required on the arms as well as the legs, the billing system cannot determine how many were applied unless the quantity is clearly indicated.

Modifier 57: Decision for Surgery

Modifier 57 is reported when an E/M service involves the decision to perform a 90-day global procedure on the same date of service. For 10-day global procedures, the decision to perform surgery on the same day does not justify a separate E/M service. The global period timing begins at midnight, with the 10-day global starting on the day of the procedure and the 90-day global starting the day before the procedure; for example, if an excision is performed today and an adjacent tissue transfer is performed tomorrow, the excision is considered within the global period.

FINAL THOUGHTS

Physicians remain responsible for accurately selecting diagnosis and procedure codes that reflect medically necessary services, and CPT codes continue to define the procedures that are reported. The Relative Value Scale Update Committee determines the value of each procedure based on physician survey data, including time and follow-up visit utilization, as well as practice expense, which represents a substantial portion of each code’s value. Our specialty relies on dedicated volunteers who devote significant time and effort to ensuring accurate representation of the work we perform for our patients. When the opportunity arises, please thank them for their service.

Accurate procedural coding is essential to appropriate reimbursement and regulatory compliance in dermatology. This article reviews commonly misunderstood areas of procedural coding, including new biopsy codes; coding for shave removals, destruction, excision and repair, and adjacent tissue transfer (flap closure); the National Correct Coding Initiative; Medicare payment edits; Mohs micrographic surgery (MMS) codes; and correct use of key modifiers. Practical guidance is provided to help avoid frequent errors.

NEW BIOPSY CODES

The most common questions about procedural coding relate to the new Current Procedural Terminology (CPT) biopsy codes, which are reported based on method of removal. Primary codes include the following:

• 11102: tangential biopsy of skin (eg, shave, scoop, saucerize, curette) for a single lesion
• 11104: punch biopsy of skin, including simple closure, when performed, for a single lesion
• 11106: incisional biopsy of skin (eg, wedge), including simple closure, when performed, for a single lesion

Add-on codes are used for each separate or additional lesion:

• 11103: tangential biopsy
• 11105: punch biopsy
• 11107: incisional biopsy

When multiple biopsy types are performed on the same date of service, only one primary code is reported along with add-on codes for any additional biopsies. The primary code reported should have the highest relative value unit (generally incisional > punch > tangential) plus the add-on codes for additional biopsies performed. Sampling of the stratum corneum only (eg, skin scraping or tape stripping) does not constitute a skin biopsy and is not reportable as a procedure.

SHAVE REMOVAL CODES

Shave removal codes are appropriate when the intent is removal of the entire lesion and there is only dermis remaining at the base of the wound. Tangential biopsy codes are appropriate when the intent is to sample a portion of a lesion for diagnosis. If saucerization of a lesion is appropriate and only fat remains at the base of the wound, the procedure is correctly coded as an excision. If any dermis remains at the base of the wound, the procedure is properly coded as shave removal. Shave codes do not distinguish between benign and malignant lesions and do not include the margin of normal skin, only the diameter of the lesion itself.

DESTRUCTION CODES

Destruction codes include both premalignant and benign lesions and may be reported as add-on codes or standalone codes, depending on lesion type and number. The 17000 series is used for destruction of premalignant lesions such as actinic keratosis, large cell acanthoma, actinic cheilitis, and porokeratosis:

• 17000: destruction of the first premalignant lesion
• 17003: destruction of each additional premalignant lesion (up to 13 lesions); reported in addition to 17000
• 17004: destruction of 15 or more premalignant lesions; reported as a standalone code (not in addition to 17000)

The following codes are used for destruction of benign lesions:

• 17110: destruction of benign lesions (up to 14 lesions)
• 17111: destruction of 15 or more benign lesions; reported as a standalone code (not in addition to 17110)

EXCISION AND REPAIR CODES

Individual excisions are reported separately, while repairs are reported as the sum of the lengths within grouped anatomic zones. The groupings differ for intermediate and complex closures, so be sure to refer to your coding manual. Intermediate or complex closures should be reported separately for skin excisions, whereas simple closures are already included in the excision code and are not reported separately. Excision diameter includes the margins necessary to ensure complete removal of the tumor for both benign and malignant tumors. For neoplasms of uncertain behavior, defer billing until pathology results are available to ensure accurate reporting as either a benign or malignant tumor excision. Lesion size is measured prior to excision and includes the lesion plus the narrowest intended clinical margin; this measurement reflects the width of the excised specimen rather than the length of the repair.

Malignant tumor excisions continue to be worth more because of the greater risk and preservice and postservice work involved. Only about 50% of payment relates to the procedure itself; the other 50% relates to risk and preoperative and postoperative counseling as well as bundled follow-up visits in the global period. That accounts for the difference in compensation for benign vs malignant tumors as well as the 50% multiple surgical reduction for multiple lesions, as the equipment and cognitive portion bundled into the procedure are not separate for each procedure.

Historically, Medicare has bundled complex closures with benign excisions under 0.5 cm. Medicare also applies medically unlikely edits that may limit payment when more than 5 excisions, closures, or destruction procedures (excluding add-on codes) are reported on the same date of service. Medicare may pay for the additional procedures if a copy of the record and a letter of medical necessity are included.

CODING FOR ADJACENT TISSUE TRANSFER (FLAP CLOSURE)

When reporting adjacent tissue transfers, the total size of the defect includes primary and secondary defects when calculating the area of the flap. The areas of the primary and secondary defects are added together when the flap represents a single repair. The sums are reported separately if they are distinct repairs. Adjacent tissue transfer already includes payment for the excision of malignant or benign lesions. Do not code separately for the excision.

CORRECT CODING INITIATIVE

On January 1, 1996, the Medicare program implemented the National Correct Coding Initiative (https://www.cms.gov/national-correct-coding-initiative-ncci), employing nearly 83,000 code edits, in an attempt to eliminate unbundling or other inappropriate reporting of CPT codes. When procedures are performed on separate and distinct lesions, a modifier is required to bypass the edit that would otherwise deny payment for the second procedure. Medicare publishes lists of paired codes (column 1 paired with column 2). The code in column 2 is the one that requires modifier 59 or 79.

MEDICARE PAYMENT EDITS

Mutually Exclusive Edits

Mutually exclusive edits seek to identify services that cannot reasonably be performed in the same session. The “comprehensive” code will be paid and the “component” code disallowed.

Medically Unlikely Edits

The Centers for Medicare & Medicaid Services stop paying when multiples of a procedure exceed the medically unlikely edits, but payment may be made if accompanied by a copy of the medical record and letter of medical necessity. A common example would be a transplant recipient requiring destruction of many malignant lesions in a single session, exceeding the medically unlikely edits for the procedure.

MOHS MICROGRAPHIC SURGERY CODES

Mohs micrographic surgery codes require that a single physician act as both surgeon and pathologist. Do not report 88305 separately, as the pathology interpretation is already included in the MMS reimbursement. Repairs, grafts, and adjacent tissue transfer are separately reportable with the CPT codes for MMS.

The CPT codes for MMS include skin biopsy and excision services (11102-11107, 11600-11646, and 17260-17286); however, if a suspected skin cancer is biopsied for pathologic diagnosis prior to MMS, the biopsy (11102-11107) and frozen section pathology (88331) may be reported separately utilizing modifier 59 or 58 to distinguish the diagnostic biopsy from the definitive MMS. The biopsy should not duplicate a prior biopsy unless that biopsy result cannot be located; it must be performed before MMS and must determine the subsequent procedure. Although CPT indicates that modifier 59 should be used, it also is acceptable to utilize modifier 58 to indicate that the diagnostic skin biopsy and MMS were staged or planned procedures. This may be appropriate in the following scenarios:

• The lesion for which MMS is planned has not been biopsied within the previous 60 days,
• The surgeon cannot obtain a pathology report, with reasonable effort, from the referring physician, or
• The biopsy is performed on a lesion that is not associated with the MMS.

KEY MODIFIERS AND HOW THEY ARE USED

Modifiers are essential tools in dermatology coding that are used to indicate when procedures or evaluation and management (E/M) services are distinct, staged, bilateral, or related to specific global periods. Correct application ensures accurate reimbursement, prevents claim denials, and reflects the true work performed. The following list summarizes commonly used modifiers and guidance for their proper use.

Modifier 59: Distinct Procedural Service

Modifier 59 is used to clearly designate when distinct, independent, and separate multiple procedures are provided. The procedure must not be a component of another procedure. Examples include:

• Different procedures or surgeries
• Surgery on different sites or organ systems
• Separate incision/excision
• Separate lesions

When code 17000 is paired with the new biopsy codes, modifier 59 is paired with code 17000.

Modifier 79: Distinct Procedural Service During a Postoperative Period

Modifier 79 is used to clearly designate when distinct, independent, and separate multiple procedures are provided. The procedure must not be a component of another procedure. Examples include:

• Different procedures or surgeries
• Surgery on different sites or organ systems
• Separate incision/excision
• Separate lesions

Modifier 58: Staged or Planned Procedure

Modifier 58 is most commonly used when a staged excision is planned in advance or when a positive tumor margin requires further excision during a global period.

Modifier 25: Significant, Separately Identifiable E/M Service

Modifier 25 is defined as a significant and separately identifiable E/M service performed by the same physician on the same day as a procedure or other service. It is used to describe a separate, distinctly identifiable E/M service rendered during the same visit as another procedure. The modifier must be appended to the E/M code. The decision to perform a 0- or 10-day global procedure on the same date of service is already bundled into the payment for the procedure and does not qualify as a separate billable service.

Modifier 24: Unrelated E/M Service During a Postoperative Period

Modifier 24 is defined as an unrelated E/M service performed by the same physician during a postoperative period. It is used when a separate, unrelated E/M service is provided during the global period of a surgical procedure.

Modifiers 24 and 25: Documentation and Distinction

The CPT definition of modifier 25 states that an E/M service may be prompted by the system or condition for which a separate procedure or service is needed. Neither modifier requires a separate diagnosis; however, both require clearly distinguishable cognitive services beyond those typically associated with the procedure itself. This includes evaluation beyond the examination of the lesion, discussion of risks, benefits, and alternatives, and the decision to perform a 0- or 10-day global procedure.

Modifier 50: Bilateral Procedure

Modifier 50 is defined as a bilateral procedure and is used when the same procedure is performed on both sides of the body, such as application of Unna boots. When reporting this modifier, specify the quantity applied. Because Unna boots may be required on the arms as well as the legs, the billing system cannot determine how many were applied unless the quantity is clearly indicated.

Modifier 57: Decision for Surgery

Modifier 57 is reported when an E/M service involves the decision to perform a 90-day global procedure on the same date of service. For 10-day global procedures, the decision to perform surgery on the same day does not justify a separate E/M service. The global period timing begins at midnight, with the 10-day global starting on the day of the procedure and the 90-day global starting the day before the procedure; for example, if an excision is performed today and an adjacent tissue transfer is performed tomorrow, the excision is considered within the global period.

FINAL THOUGHTS

Physicians remain responsible for accurately selecting diagnosis and procedure codes that reflect medically necessary services, and CPT codes continue to define the procedures that are reported. The Relative Value Scale Update Committee determines the value of each procedure based on physician survey data, including time and follow-up visit utilization, as well as practice expense, which represents a substantial portion of each code’s value. Our specialty relies on dedicated volunteers who devote significant time and effort to ensuring accurate representation of the work we perform for our patients. When the opportunity arises, please thank them for their service.

Accurate procedural coding is essential to appropriate reimbursement and regulatory compliance in dermatology. This article reviews commonly misunderstood areas of procedural coding, including new biopsy codes; coding for shave removals, destruction, excision and repair, and adjacent tissue transfer (flap closure); the National Correct Coding Initiative; Medicare payment edits; Mohs micrographic surgery (MMS) codes; and correct use of key modifiers. Practical guidance is provided to help avoid frequent errors.

NEW BIOPSY CODES

The most common questions about procedural coding relate to the new Current Procedural Terminology (CPT) biopsy codes, which are reported based on method of removal. Primary codes include the following:

• 11102: tangential biopsy of skin (eg, shave, scoop, saucerize, curette) for a single lesion
• 11104: punch biopsy of skin, including simple closure, when performed, for a single lesion
• 11106: incisional biopsy of skin (eg, wedge), including simple closure, when performed, for a single lesion

Add-on codes are used for each separate or additional lesion:

• 11103: tangential biopsy
• 11105: punch biopsy
• 11107: incisional biopsy

When multiple biopsy types are performed on the same date of service, only one primary code is reported along with add-on codes for any additional biopsies. The primary code reported should have the highest relative value unit (generally incisional > punch > tangential) plus the add-on codes for additional biopsies performed. Sampling of the stratum corneum only (eg, skin scraping or tape stripping) does not constitute a skin biopsy and is not reportable as a procedure.

SHAVE REMOVAL CODES

Shave removal codes are appropriate when the intent is removal of the entire lesion and there is only dermis remaining at the base of the wound. Tangential biopsy codes are appropriate when the intent is to sample a portion of a lesion for diagnosis. If saucerization of a lesion is appropriate and only fat remains at the base of the wound, the procedure is correctly coded as an excision. If any dermis remains at the base of the wound, the procedure is properly coded as shave removal. Shave codes do not distinguish between benign and malignant lesions and do not include the margin of normal skin, only the diameter of the lesion itself.

DESTRUCTION CODES

Destruction codes include both premalignant and benign lesions and may be reported as add-on codes or standalone codes, depending on lesion type and number. The 17000 series is used for destruction of premalignant lesions such as actinic keratosis, large cell acanthoma, actinic cheilitis, and porokeratosis:

• 17000: destruction of the first premalignant lesion
• 17003: destruction of each additional premalignant lesion (up to 13 lesions); reported in addition to 17000
• 17004: destruction of 15 or more premalignant lesions; reported as a standalone code (not in addition to 17000)

The following codes are used for destruction of benign lesions:

• 17110: destruction of benign lesions (up to 14 lesions)
• 17111: destruction of 15 or more benign lesions; reported as a standalone code (not in addition to 17110)

EXCISION AND REPAIR CODES

Individual excisions are reported separately, while repairs are reported as the sum of the lengths within grouped anatomic zones. The groupings differ for intermediate and complex closures, so be sure to refer to your coding manual. Intermediate or complex closures should be reported separately for skin excisions, whereas simple closures are already included in the excision code and are not reported separately. Excision diameter includes the margins necessary to ensure complete removal of the tumor for both benign and malignant tumors. For neoplasms of uncertain behavior, defer billing until pathology results are available to ensure accurate reporting as either a benign or malignant tumor excision. Lesion size is measured prior to excision and includes the lesion plus the narrowest intended clinical margin; this measurement reflects the width of the excised specimen rather than the length of the repair.

Malignant tumor excisions continue to be worth more because of the greater risk and preservice and postservice work involved. Only about 50% of payment relates to the procedure itself; the other 50% relates to risk and preoperative and postoperative counseling as well as bundled follow-up visits in the global period. That accounts for the difference in compensation for benign vs malignant tumors as well as the 50% multiple surgical reduction for multiple lesions, as the equipment and cognitive portion bundled into the procedure are not separate for each procedure.

Historically, Medicare has bundled complex closures with benign excisions under 0.5 cm. Medicare also applies medically unlikely edits that may limit payment when more than 5 excisions, closures, or destruction procedures (excluding add-on codes) are reported on the same date of service. Medicare may pay for the additional procedures if a copy of the record and a letter of medical necessity are included.

CODING FOR ADJACENT TISSUE TRANSFER (FLAP CLOSURE)

When reporting adjacent tissue transfers, the total size of the defect includes primary and secondary defects when calculating the area of the flap. The areas of the primary and secondary defects are added together when the flap represents a single repair. The sums are reported separately if they are distinct repairs. Adjacent tissue transfer already includes payment for the excision of malignant or benign lesions. Do not code separately for the excision.

CORRECT CODING INITIATIVE

On January 1, 1996, the Medicare program implemented the National Correct Coding Initiative (https://www.cms.gov/national-correct-coding-initiative-ncci), employing nearly 83,000 code edits, in an attempt to eliminate unbundling or other inappropriate reporting of CPT codes. When procedures are performed on separate and distinct lesions, a modifier is required to bypass the edit that would otherwise deny payment for the second procedure. Medicare publishes lists of paired codes (column 1 paired with column 2). The code in column 2 is the one that requires modifier 59 or 79.

MEDICARE PAYMENT EDITS

Mutually Exclusive Edits

Mutually exclusive edits seek to identify services that cannot reasonably be performed in the same session. The “comprehensive” code will be paid and the “component” code disallowed.

Medically Unlikely Edits

The Centers for Medicare & Medicaid Services stop paying when multiples of a procedure exceed the medically unlikely edits, but payment may be made if accompanied by a copy of the medical record and letter of medical necessity. A common example would be a transplant recipient requiring destruction of many malignant lesions in a single session, exceeding the medically unlikely edits for the procedure.

MOHS MICROGRAPHIC SURGERY CODES

Mohs micrographic surgery codes require that a single physician act as both surgeon and pathologist. Do not report 88305 separately, as the pathology interpretation is already included in the MMS reimbursement. Repairs, grafts, and adjacent tissue transfer are separately reportable with the CPT codes for MMS.

The CPT codes for MMS include skin biopsy and excision services (11102-11107, 11600-11646, and 17260-17286); however, if a suspected skin cancer is biopsied for pathologic diagnosis prior to MMS, the biopsy (11102-11107) and frozen section pathology (88331) may be reported separately utilizing modifier 59 or 58 to distinguish the diagnostic biopsy from the definitive MMS. The biopsy should not duplicate a prior biopsy unless that biopsy result cannot be located; it must be performed before MMS and must determine the subsequent procedure. Although CPT indicates that modifier 59 should be used, it also is acceptable to utilize modifier 58 to indicate that the diagnostic skin biopsy and MMS were staged or planned procedures. This may be appropriate in the following scenarios:

• The lesion for which MMS is planned has not been biopsied within the previous 60 days,
• The surgeon cannot obtain a pathology report, with reasonable effort, from the referring physician, or
• The biopsy is performed on a lesion that is not associated with the MMS.

KEY MODIFIERS AND HOW THEY ARE USED

Modifiers are essential tools in dermatology coding that are used to indicate when procedures or evaluation and management (E/M) services are distinct, staged, bilateral, or related to specific global periods. Correct application ensures accurate reimbursement, prevents claim denials, and reflects the true work performed. The following list summarizes commonly used modifiers and guidance for their proper use.

Modifier 59: Distinct Procedural Service

Modifier 59 is used to clearly designate when distinct, independent, and separate multiple procedures are provided. The procedure must not be a component of another procedure. Examples include:

• Different procedures or surgeries
• Surgery on different sites or organ systems
• Separate incision/excision
• Separate lesions

When code 17000 is paired with the new biopsy codes, modifier 59 is paired with code 17000.

Modifier 79: Distinct Procedural Service During a Postoperative Period

Modifier 79 is used to clearly designate when distinct, independent, and separate multiple procedures are provided. The procedure must not be a component of another procedure. Examples include:

• Different procedures or surgeries
• Surgery on different sites or organ systems
• Separate incision/excision
• Separate lesions

Modifier 58: Staged or Planned Procedure

Modifier 58 is most commonly used when a staged excision is planned in advance or when a positive tumor margin requires further excision during a global period.

Modifier 25: Significant, Separately Identifiable E/M Service

Modifier 25 is defined as a significant and separately identifiable E/M service performed by the same physician on the same day as a procedure or other service. It is used to describe a separate, distinctly identifiable E/M service rendered during the same visit as another procedure. The modifier must be appended to the E/M code. The decision to perform a 0- or 10-day global procedure on the same date of service is already bundled into the payment for the procedure and does not qualify as a separate billable service.

Modifier 24: Unrelated E/M Service During a Postoperative Period

Modifier 24 is defined as an unrelated E/M service performed by the same physician during a postoperative period. It is used when a separate, unrelated E/M service is provided during the global period of a surgical procedure.

Modifiers 24 and 25: Documentation and Distinction

The CPT definition of modifier 25 states that an E/M service may be prompted by the system or condition for which a separate procedure or service is needed. Neither modifier requires a separate diagnosis; however, both require clearly distinguishable cognitive services beyond those typically associated with the procedure itself. This includes evaluation beyond the examination of the lesion, discussion of risks, benefits, and alternatives, and the decision to perform a 0- or 10-day global procedure.

Modifier 50: Bilateral Procedure

Modifier 50 is defined as a bilateral procedure and is used when the same procedure is performed on both sides of the body, such as application of Unna boots. When reporting this modifier, specify the quantity applied. Because Unna boots may be required on the arms as well as the legs, the billing system cannot determine how many were applied unless the quantity is clearly indicated.

Modifier 57: Decision for Surgery

Modifier 57 is reported when an E/M service involves the decision to perform a 90-day global procedure on the same date of service. For 10-day global procedures, the decision to perform surgery on the same day does not justify a separate E/M service. The global period timing begins at midnight, with the 10-day global starting on the day of the procedure and the 90-day global starting the day before the procedure; for example, if an excision is performed today and an adjacent tissue transfer is performed tomorrow, the excision is considered within the global period.

FINAL THOUGHTS

Physicians remain responsible for accurately selecting diagnosis and procedure codes that reflect medically necessary services, and CPT codes continue to define the procedures that are reported. The Relative Value Scale Update Committee determines the value of each procedure based on physician survey data, including time and follow-up visit utilization, as well as practice expense, which represents a substantial portion of each code’s value. Our specialty relies on dedicated volunteers who devote significant time and effort to ensuring accurate representation of the work we perform for our patients. When the opportunity arises, please thank them for their service.

THE DIAGNOSIS: Pigmented Bowen Disease

Histopathology revealed atypical keratinocytes throughout the entire thickness of a pigmented epidermis extending from the basal layer (Figure). Diffuse epidermal hyperpigmentation and melanophages in the papillary dermis were present. There was no dermal invasion or atypical melanocytic proliferation. On dermoscopy, this lesion had small brown globules, smudging, and an asymmetric nonspecific homogeneous pattern. Based on these features as well as the clinical findings, a diagnosis of pigmented Bowen disease (PBD), a rare subtype of squamous cell carcinoma in situ, was made. Complete removal of the lesion was achieved via the biopsy, and the patient was counselled regarding the malignant but noninvasive nature of the lesion. Appropriate follow-up was recommended to monitor for recurrence.

Our case presentation of PBD on the right upper arm in a female patient with a light skin tone is not classic, as PBD lesions usually manifest as well-demarcated scaly plaques on sun-protected sites in men with darker skin tones who are in the sixth to seventh decades of life.¹

Dermoscopy of PBD in patients with lighter skin tones can present diagnostic challenges because characteristic clustered glomerular vessels may be faint or absent, particularly in small lesions such as this one. In such cases, PBD may instead demonstrate structureless brown pigmentation and irregular globules, patterns that overlap with pigmented actinic keratosis (PAK) and melanoma.³

Our case underscores the importance of maintaining a broad differential when evaluating small pigmented macules and reinforces biopsy as the diagnostic gold standard for PBD when dermoscopic findings are nonspecific.

THE DIAGNOSIS: Pigmented Bowen Disease

Histopathology revealed atypical keratinocytes throughout the entire thickness of a pigmented epidermis extending from the basal layer (Figure). Diffuse epidermal hyperpigmentation and melanophages in the papillary dermis were present. There was no dermal invasion or atypical melanocytic proliferation. On dermoscopy, this lesion had small brown globules, smudging, and an asymmetric nonspecific homogeneous pattern. Based on these features as well as the clinical findings, a diagnosis of pigmented Bowen disease (PBD), a rare subtype of squamous cell carcinoma in situ, was made. Complete removal of the lesion was achieved via the biopsy, and the patient was counselled regarding the malignant but noninvasive nature of the lesion. Appropriate follow-up was recommended to monitor for recurrence.

Our case presentation of PBD on the right upper arm in a female patient with a light skin tone is not classic, as PBD lesions usually manifest as well-demarcated scaly plaques on sun-protected sites in men with darker skin tones who are in the sixth to seventh decades of life.¹

Dermoscopy of PBD in patients with lighter skin tones can present diagnostic challenges because characteristic clustered glomerular vessels may be faint or absent, particularly in small lesions such as this one. In such cases, PBD may instead demonstrate structureless brown pigmentation and irregular globules, patterns that overlap with pigmented actinic keratosis (PAK) and melanoma.³

Our case underscores the importance of maintaining a broad differential when evaluating small pigmented macules and reinforces biopsy as the diagnostic gold standard for PBD when dermoscopic findings are nonspecific.

THE DIAGNOSIS: Pigmented Bowen Disease

Histopathology revealed atypical keratinocytes throughout the entire thickness of a pigmented epidermis extending from the basal layer (Figure). Diffuse epidermal hyperpigmentation and melanophages in the papillary dermis were present. There was no dermal invasion or atypical melanocytic proliferation. On dermoscopy, this lesion had small brown globules, smudging, and an asymmetric nonspecific homogeneous pattern. Based on these features as well as the clinical findings, a diagnosis of pigmented Bowen disease (PBD), a rare subtype of squamous cell carcinoma in situ, was made. Complete removal of the lesion was achieved via the biopsy, and the patient was counselled regarding the malignant but noninvasive nature of the lesion. Appropriate follow-up was recommended to monitor for recurrence.

Our case presentation of PBD on the right upper arm in a female patient with a light skin tone is not classic, as PBD lesions usually manifest as well-demarcated scaly plaques on sun-protected sites in men with darker skin tones who are in the sixth to seventh decades of life.¹

Dermoscopy of PBD in patients with lighter skin tones can present diagnostic challenges because characteristic clustered glomerular vessels may be faint or absent, particularly in small lesions such as this one. In such cases, PBD may instead demonstrate structureless brown pigmentation and irregular globules, patterns that overlap with pigmented actinic keratosis (PAK) and melanoma.³

Our case underscores the importance of maintaining a broad differential when evaluating small pigmented macules and reinforces biopsy as the diagnostic gold standard for PBD when dermoscopic findings are nonspecific.

To the Editor:

Psoriasis is a chronic immune-mediated inflammatory skin disease that affects approximately 2% to 3% of the global population and an estimated 7.5 million adults in the United States.¹ The condition is characterized by recurrent episodes of erythematous scaly plaques driven by dysregulated immune responses, particularly involving the interleukin (IL) 23/T-helper (Th) 17 axis.² Although cutaneous symptoms are the most visible manifestation, psoriasis is a systemic disorder with broad multisystem involvement. Comorbidities include psoriatic arthritis, metabolic syndrome, cardiovascular disease, inflammatory bowel disease, depression, and anxiety.¹ These conditions contribute to a heightened risk for premature mortality, increased health care utilization, and an estimated direct cost burden exceeding $11 billion annually in the United States alone.³ Patients with moderate to severe disease frequently require systemic therapy, and long-term disease control is essential to prevent cumulative inflammatory damage and reduce associated morbidity.⁴

Globally, psoriasis prevalence and disease severity vary by geography, ethnicity, and environmental factors, with higher rates in Northern Europe and North America and lower reported prevalence in East Asia and ­sub-Saharan Africa.⁵ In lower-resource settings, access to advanced therapies is limited, and patients often are treated with less effective or more toxic systemic agents, such as methotrexate or cyclosporine.⁵ These disparities not only affect quality of life but also may influence comorbidity and malignancy patterns, underscoring the importance of studying biologic safety in diverse real-world populations.

Over the past decade, the therapeutic landscape for psoriasis has been transformed by biologic agents targeting specific immune pathways.⁶ Interleukin 17 inhibitors (eg, secukinumab, ixekizumab, brodalumab, bimekizumab) act by neutralizing IL-17A, IL-17F, or the IL-17 receptor, thereby reducing keratinocyte activation, neutrophil recruitment, and downstream cytokine production.⁶ Interleukin 23 inhibitors (eg, guselkumab, risankizumab, tildrakizumab) block the p19 subunit of IL-23, halting the expansion and maintenance of pathogenic Th17 cells.⁶ Ustekinumab, an IL-12/23 inhibitor, targets the shared p40 subunit of IL-12 and IL-23, attenuating both Th1 and Th17 signaling.⁶ These agents achieve rapid, durable skin clearance in a large proportion of patients, improve psoriatic arthritis symptoms, and generally are well tolerated, even with long-term use.⁶

Although efficacy is well established, the immunomodulatory nature of IL inhibitors raises theoretical concerns about malignancy risk. Immune surveillance plays a critical role in detecting and eliminating emerging tumor cells.⁷ Data from other systemic immunosuppressants, such as cyclosporine, show increased risks for certain cancers⁸; however, the IL-17 and IL-23 pathways have dual roles in cancer biology.⁷ In some tumor contexts, these cytokines promote carcinogenesis through angiogenesis, epithelial proliferation, and suppression of antitumor immunity; therefore, inhibiting these pathways could theoretically reduce cancer risk.⁷ The uncertainty around this risk-benefit balance has made malignancy a central consideration for dermatologists, particularly when initiating therapy in patients with a history of cancer or other risk factors.

The perception of malignancy risk can influence patient willingness to start biologics as well as physician prescribing patterns.⁹ Some clinicians opt for alternative therapies in individuals with a personal or family history of cancer despite limited direct evidence of harm from IL inhibitors. Conversely, a reassuring malignancy safety profile may support broader adoption of these therapies, especially in patients requiring lifelong disease control.⁹ Shared decision-making in this context requires robust, real-world evidence that accounts for both common and rare malignancy outcomes.

Randomized controlled trials of IL inhibitors have not demonstrated a consistent malignancy signal, but these studies often are underpowered for rare outcomes and limited by short follow-up durations, typically less than 1 year. They also frequently exclude high-risk populations, limiting generalizability.¹⁰ Observational studies using real-world data can address these gaps by including more diverse patient populations, longer observation windows, and larger sample sizes capable of detecting differences in uncommon outcomes.

The TriNetX Analytics Network (http://www.trinetx.com) offers a unique platform for large-scale, real-world pharmacoepidemiologic research. This federated database aggregates deidentified electronic health record data from more than 100 million patients across the United States and internationally, including at academic medical centers, integrated delivery networks, and community hospitals.⁴ Data contributors refresh their datasets regularly, ensuring near-contemporary representation of prescribing trends and clinical outcomes. Standardized terminology mapping, consistent International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding, and centralized data-quality checks enhance the reliability of analyses. Governance protocols and compliance with the Health Insurance Portability and Accountability Act deidentification standards further ensure ethical use of the data. The breadth and depth of the TriNetX network make it possible to evaluate not only common malignancies but also rare cancer types that smaller studies cannot assess with sufficient statistical power.

We performed a retrospective matched-cohort study, querying data from January 1, 2014, through December 31, 2024, using TriNetX to examine whether IL inhibitor exposure is associated with differences in incident malignancy risk among adults with psoriasis. Patients aged 18 years or older with a psoriasis diagnosis (ICD-10-CM code L40.x) and documented exposure to an IL-17, IL-23, or IL-12/23 inhibitor were eligible. Patients with a prior malignancy diagnosis were excluded to reduce prevalence bias. To ensure that malignancies were incident, we included only those diagnosed at least 1 day after initiation of an IL inhibitor.

The comparison cohort consisted of psoriasis patients without IL inhibitor exposure during their observation period. We used 1:1 propensity score matching based on age, sex, race, and ethnicity, applying a caliper of 0.1 to balance baseline characteristics and minimize demographic confounding. The index date for unexposed patients was randomly assigned within their observation period to align follow-up timing with exposed patients. Outcomes were identified by ICD-10-CM codes grouped by skin, hematologic, and solid-organ malignancies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, with statistical significance set at P<.05. Odds ratios were selected over hazard ratios due to variability in precise follow-up time capture and the primary analytic goal of comparing proportional odds within matched follow-up windows.

Propensity score matching was employed because it is a well-established technique in pharmacoepidemiology to mimic some of the balance achieved in randomized trials. By equating treatment and control groups on measured confounders, matching helps isolate the treatment effect, particularly important in nonrandomized datasets in which prescribing decisions may be influenced by baseline characteristics. Grouping cancers into clinically relevant categories allowed us to assess patterns of association, as some cancer types (eg, melanoma, lymphomas) may have pathophysiologic links to inflammatory pathways targeted by IL inhibitors.

The final cohort included 133,352 patients, with 66,676 in each group. The mean (SD) age was 49.3 (16.0) years, and demographic variables were well balanced after matching. The mean follow-up was approximately 3.8 years. Interleukin 17 inhibitors were the most frequently prescribed, followed by IL-23 inhibitors and ustekinumab. Baseline comorbidities such as cardiovascular disease, diabetes, and obesity were comparable between groups, reducing the likelihood of confounding from these factors.

Interleukin inhibitor exposure was associated with significantly reduced odds of several malignancies (eTable). Among skin cancers, melanoma risk was reduced by 36% (OR, 0.641; 95% CI, 0.534-0.77; P<.0001), basal cell carcinoma by 43% (OR, 0.565; 95% CI, 0.48-0.665; P<.0001), and squamous cell carcinoma by 18% (OR, 0.821; 95% CI, 0.676-0.996; P=.0452). Hematologic malignancies showed similar reductions, with non-Hodgkin lymphoma odds reduced by 35% (OR, 0.646; 95% CI, 0.512-0.815; P=.0002) and Hodgkin lymphoma by 50% (OR, 0.5; 95% CI, 0.292-0.855; P=.0098).

Protective associations also were observed for several solid tumors: lung (OR, 0.528; 95% CI, 0.452-0.617; P<.0001), liver (OR, 0.528; 95% CI, 0.399-0.698; P<.0001), pancreatic (OR, 0.65; 95% CI, 0.49-0.861; P=.0025), breast (OR, 0.663; 95% CI, 0.582-0.754; P<.0001), prostate (OR, 0.543; 95% CI, 0.468-0.629; P<.0001), colorectal (OR, 0.592; 95% CI, 0.414-0.846; P=.0036), colon (OR, 0.466; 95% CI, 0.375-0.579; P<.0001), and oropharyngeal (OR, 0.55; 95% CI, 0.327-0.925; P=.0222) cancers. Cervical cancer (OR, 0.604; 95% CI, 0.381-0.958; P=.0304) and anal cancer (OR, 0.4; 95% CI, 0.224-0.714; P=.0013) also showed significant reductions. Vaginal, vulvar, and penile cancers demonstrated no significant differences, likely due to their low incidence and limited statistical power.

The biological plausibility of these findings is supported by preclinical studies implicating IL-17 and IL-23 in tumor-promoting inflammation.¹¹ These cytokines can recruit myeloid-derived suppressor cells, promote angiogenesis, and facilitate tumor-immune evasion. Inhibition may shift the immune microenvironment toward enhanced tumor surveillance, reduce protumorigenic cytokine signaling, and normalize regulatory T-cell function.¹¹ These mechanisms could explain observed reductions in melanoma, lymphomas, and certain solid tumors.

Our results are consistent with several large registry studies showing no increased cancer incidence in IL inhibitor users and extend prior findings by demonstrating significant reductions in multiple cancer types.¹² The melanoma reduction contrasts with the findings in earlier biologic safety studies, possibly due to our larger sample size, broader geographic representation, and inclusion of multiple IL inhibitor classes.¹³ Similar reductions have not been consistently observed with tumor necrosis factor α inhibitors, which have different immunologic targets and a more complex malignancy safety history.¹⁴

Limitations of our study include the retrospective design, potential misclassification of cancer diagnoses, and lack of data on unmeasured confounders such as sun exposure, smoking, alcohol use, and family cancer history. Surveillance bias is possible, though it would likely bias toward higher, not lower, cancer detection in biologic users. Our mean follow-up period of 3.8 years may not be sufficient for cancers with long latency periods.

If replicated, our findings could have meaningful public health implications. Reassurance regarding malignancy safety may increase patient acceptance and physician confidence in prescribing IL inhibitors, particularly for patients requiring long-term therapy. From a payer perspective, the potential for reduced cancer incidence could translate into substantial cost savings over time, offsetting the high up-front cost of biologics. Additionally, these results may be relevant to other IL inhibitor indications, including psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease, in which similar pathophysiologic mechanisms may be at play.

In conclusion, this large matched-cohort study found that IL inhibitor therapy in psoriasis was associated with significantly reduced odds of multiple malignancies, including melanoma, lymphomas, and several solid tumors. These findings contribute to the growing body of real-world evidence supporting the long-term safety of IL inhibitors and underscore the need for continued pharmacovigilance and mechanistic research.

To the Editor:

Psoriasis is a chronic immune-mediated inflammatory skin disease that affects approximately 2% to 3% of the global population and an estimated 7.5 million adults in the United States.¹ The condition is characterized by recurrent episodes of erythematous scaly plaques driven by dysregulated immune responses, particularly involving the interleukin (IL) 23/T-helper (Th) 17 axis.² Although cutaneous symptoms are the most visible manifestation, psoriasis is a systemic disorder with broad multisystem involvement. Comorbidities include psoriatic arthritis, metabolic syndrome, cardiovascular disease, inflammatory bowel disease, depression, and anxiety.¹ These conditions contribute to a heightened risk for premature mortality, increased health care utilization, and an estimated direct cost burden exceeding $11 billion annually in the United States alone.³ Patients with moderate to severe disease frequently require systemic therapy, and long-term disease control is essential to prevent cumulative inflammatory damage and reduce associated morbidity.⁴

Globally, psoriasis prevalence and disease severity vary by geography, ethnicity, and environmental factors, with higher rates in Northern Europe and North America and lower reported prevalence in East Asia and ­sub-Saharan Africa.⁵ In lower-resource settings, access to advanced therapies is limited, and patients often are treated with less effective or more toxic systemic agents, such as methotrexate or cyclosporine.⁵ These disparities not only affect quality of life but also may influence comorbidity and malignancy patterns, underscoring the importance of studying biologic safety in diverse real-world populations.

Over the past decade, the therapeutic landscape for psoriasis has been transformed by biologic agents targeting specific immune pathways.⁶ Interleukin 17 inhibitors (eg, secukinumab, ixekizumab, brodalumab, bimekizumab) act by neutralizing IL-17A, IL-17F, or the IL-17 receptor, thereby reducing keratinocyte activation, neutrophil recruitment, and downstream cytokine production.⁶ Interleukin 23 inhibitors (eg, guselkumab, risankizumab, tildrakizumab) block the p19 subunit of IL-23, halting the expansion and maintenance of pathogenic Th17 cells.⁶ Ustekinumab, an IL-12/23 inhibitor, targets the shared p40 subunit of IL-12 and IL-23, attenuating both Th1 and Th17 signaling.⁶ These agents achieve rapid, durable skin clearance in a large proportion of patients, improve psoriatic arthritis symptoms, and generally are well tolerated, even with long-term use.⁶

Although efficacy is well established, the immunomodulatory nature of IL inhibitors raises theoretical concerns about malignancy risk. Immune surveillance plays a critical role in detecting and eliminating emerging tumor cells.⁷ Data from other systemic immunosuppressants, such as cyclosporine, show increased risks for certain cancers⁸; however, the IL-17 and IL-23 pathways have dual roles in cancer biology.⁷ In some tumor contexts, these cytokines promote carcinogenesis through angiogenesis, epithelial proliferation, and suppression of antitumor immunity; therefore, inhibiting these pathways could theoretically reduce cancer risk.⁷ The uncertainty around this risk-benefit balance has made malignancy a central consideration for dermatologists, particularly when initiating therapy in patients with a history of cancer or other risk factors.

The perception of malignancy risk can influence patient willingness to start biologics as well as physician prescribing patterns.⁹ Some clinicians opt for alternative therapies in individuals with a personal or family history of cancer despite limited direct evidence of harm from IL inhibitors. Conversely, a reassuring malignancy safety profile may support broader adoption of these therapies, especially in patients requiring lifelong disease control.⁹ Shared decision-making in this context requires robust, real-world evidence that accounts for both common and rare malignancy outcomes.

Randomized controlled trials of IL inhibitors have not demonstrated a consistent malignancy signal, but these studies often are underpowered for rare outcomes and limited by short follow-up durations, typically less than 1 year. They also frequently exclude high-risk populations, limiting generalizability.¹⁰ Observational studies using real-world data can address these gaps by including more diverse patient populations, longer observation windows, and larger sample sizes capable of detecting differences in uncommon outcomes.

The TriNetX Analytics Network (http://www.trinetx.com) offers a unique platform for large-scale, real-world pharmacoepidemiologic research. This federated database aggregates deidentified electronic health record data from more than 100 million patients across the United States and internationally, including at academic medical centers, integrated delivery networks, and community hospitals.⁴ Data contributors refresh their datasets regularly, ensuring near-contemporary representation of prescribing trends and clinical outcomes. Standardized terminology mapping, consistent International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding, and centralized data-quality checks enhance the reliability of analyses. Governance protocols and compliance with the Health Insurance Portability and Accountability Act deidentification standards further ensure ethical use of the data. The breadth and depth of the TriNetX network make it possible to evaluate not only common malignancies but also rare cancer types that smaller studies cannot assess with sufficient statistical power.

We performed a retrospective matched-cohort study, querying data from January 1, 2014, through December 31, 2024, using TriNetX to examine whether IL inhibitor exposure is associated with differences in incident malignancy risk among adults with psoriasis. Patients aged 18 years or older with a psoriasis diagnosis (ICD-10-CM code L40.x) and documented exposure to an IL-17, IL-23, or IL-12/23 inhibitor were eligible. Patients with a prior malignancy diagnosis were excluded to reduce prevalence bias. To ensure that malignancies were incident, we included only those diagnosed at least 1 day after initiation of an IL inhibitor.

The comparison cohort consisted of psoriasis patients without IL inhibitor exposure during their observation period. We used 1:1 propensity score matching based on age, sex, race, and ethnicity, applying a caliper of 0.1 to balance baseline characteristics and minimize demographic confounding. The index date for unexposed patients was randomly assigned within their observation period to align follow-up timing with exposed patients. Outcomes were identified by ICD-10-CM codes grouped by skin, hematologic, and solid-organ malignancies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, with statistical significance set at P<.05. Odds ratios were selected over hazard ratios due to variability in precise follow-up time capture and the primary analytic goal of comparing proportional odds within matched follow-up windows.

Propensity score matching was employed because it is a well-established technique in pharmacoepidemiology to mimic some of the balance achieved in randomized trials. By equating treatment and control groups on measured confounders, matching helps isolate the treatment effect, particularly important in nonrandomized datasets in which prescribing decisions may be influenced by baseline characteristics. Grouping cancers into clinically relevant categories allowed us to assess patterns of association, as some cancer types (eg, melanoma, lymphomas) may have pathophysiologic links to inflammatory pathways targeted by IL inhibitors.

The final cohort included 133,352 patients, with 66,676 in each group. The mean (SD) age was 49.3 (16.0) years, and demographic variables were well balanced after matching. The mean follow-up was approximately 3.8 years. Interleukin 17 inhibitors were the most frequently prescribed, followed by IL-23 inhibitors and ustekinumab. Baseline comorbidities such as cardiovascular disease, diabetes, and obesity were comparable between groups, reducing the likelihood of confounding from these factors.

Interleukin inhibitor exposure was associated with significantly reduced odds of several malignancies (eTable). Among skin cancers, melanoma risk was reduced by 36% (OR, 0.641; 95% CI, 0.534-0.77; P<.0001), basal cell carcinoma by 43% (OR, 0.565; 95% CI, 0.48-0.665; P<.0001), and squamous cell carcinoma by 18% (OR, 0.821; 95% CI, 0.676-0.996; P=.0452). Hematologic malignancies showed similar reductions, with non-Hodgkin lymphoma odds reduced by 35% (OR, 0.646; 95% CI, 0.512-0.815; P=.0002) and Hodgkin lymphoma by 50% (OR, 0.5; 95% CI, 0.292-0.855; P=.0098).

Protective associations also were observed for several solid tumors: lung (OR, 0.528; 95% CI, 0.452-0.617; P<.0001), liver (OR, 0.528; 95% CI, 0.399-0.698; P<.0001), pancreatic (OR, 0.65; 95% CI, 0.49-0.861; P=.0025), breast (OR, 0.663; 95% CI, 0.582-0.754; P<.0001), prostate (OR, 0.543; 95% CI, 0.468-0.629; P<.0001), colorectal (OR, 0.592; 95% CI, 0.414-0.846; P=.0036), colon (OR, 0.466; 95% CI, 0.375-0.579; P<.0001), and oropharyngeal (OR, 0.55; 95% CI, 0.327-0.925; P=.0222) cancers. Cervical cancer (OR, 0.604; 95% CI, 0.381-0.958; P=.0304) and anal cancer (OR, 0.4; 95% CI, 0.224-0.714; P=.0013) also showed significant reductions. Vaginal, vulvar, and penile cancers demonstrated no significant differences, likely due to their low incidence and limited statistical power.

The biological plausibility of these findings is supported by preclinical studies implicating IL-17 and IL-23 in tumor-promoting inflammation.¹¹ These cytokines can recruit myeloid-derived suppressor cells, promote angiogenesis, and facilitate tumor-immune evasion. Inhibition may shift the immune microenvironment toward enhanced tumor surveillance, reduce protumorigenic cytokine signaling, and normalize regulatory T-cell function.¹¹ These mechanisms could explain observed reductions in melanoma, lymphomas, and certain solid tumors.

Our results are consistent with several large registry studies showing no increased cancer incidence in IL inhibitor users and extend prior findings by demonstrating significant reductions in multiple cancer types.¹² The melanoma reduction contrasts with the findings in earlier biologic safety studies, possibly due to our larger sample size, broader geographic representation, and inclusion of multiple IL inhibitor classes.¹³ Similar reductions have not been consistently observed with tumor necrosis factor α inhibitors, which have different immunologic targets and a more complex malignancy safety history.¹⁴

Limitations of our study include the retrospective design, potential misclassification of cancer diagnoses, and lack of data on unmeasured confounders such as sun exposure, smoking, alcohol use, and family cancer history. Surveillance bias is possible, though it would likely bias toward higher, not lower, cancer detection in biologic users. Our mean follow-up period of 3.8 years may not be sufficient for cancers with long latency periods.

If replicated, our findings could have meaningful public health implications. Reassurance regarding malignancy safety may increase patient acceptance and physician confidence in prescribing IL inhibitors, particularly for patients requiring long-term therapy. From a payer perspective, the potential for reduced cancer incidence could translate into substantial cost savings over time, offsetting the high up-front cost of biologics. Additionally, these results may be relevant to other IL inhibitor indications, including psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease, in which similar pathophysiologic mechanisms may be at play.

In conclusion, this large matched-cohort study found that IL inhibitor therapy in psoriasis was associated with significantly reduced odds of multiple malignancies, including melanoma, lymphomas, and several solid tumors. These findings contribute to the growing body of real-world evidence supporting the long-term safety of IL inhibitors and underscore the need for continued pharmacovigilance and mechanistic research.

To the Editor:

Psoriasis is a chronic immune-mediated inflammatory skin disease that affects approximately 2% to 3% of the global population and an estimated 7.5 million adults in the United States.¹ The condition is characterized by recurrent episodes of erythematous scaly plaques driven by dysregulated immune responses, particularly involving the interleukin (IL) 23/T-helper (Th) 17 axis.² Although cutaneous symptoms are the most visible manifestation, psoriasis is a systemic disorder with broad multisystem involvement. Comorbidities include psoriatic arthritis, metabolic syndrome, cardiovascular disease, inflammatory bowel disease, depression, and anxiety.¹ These conditions contribute to a heightened risk for premature mortality, increased health care utilization, and an estimated direct cost burden exceeding $11 billion annually in the United States alone.³ Patients with moderate to severe disease frequently require systemic therapy, and long-term disease control is essential to prevent cumulative inflammatory damage and reduce associated morbidity.⁴

Globally, psoriasis prevalence and disease severity vary by geography, ethnicity, and environmental factors, with higher rates in Northern Europe and North America and lower reported prevalence in East Asia and ­sub-Saharan Africa.⁵ In lower-resource settings, access to advanced therapies is limited, and patients often are treated with less effective or more toxic systemic agents, such as methotrexate or cyclosporine.⁵ These disparities not only affect quality of life but also may influence comorbidity and malignancy patterns, underscoring the importance of studying biologic safety in diverse real-world populations.

Over the past decade, the therapeutic landscape for psoriasis has been transformed by biologic agents targeting specific immune pathways.⁶ Interleukin 17 inhibitors (eg, secukinumab, ixekizumab, brodalumab, bimekizumab) act by neutralizing IL-17A, IL-17F, or the IL-17 receptor, thereby reducing keratinocyte activation, neutrophil recruitment, and downstream cytokine production.⁶ Interleukin 23 inhibitors (eg, guselkumab, risankizumab, tildrakizumab) block the p19 subunit of IL-23, halting the expansion and maintenance of pathogenic Th17 cells.⁶ Ustekinumab, an IL-12/23 inhibitor, targets the shared p40 subunit of IL-12 and IL-23, attenuating both Th1 and Th17 signaling.⁶ These agents achieve rapid, durable skin clearance in a large proportion of patients, improve psoriatic arthritis symptoms, and generally are well tolerated, even with long-term use.⁶

Although efficacy is well established, the immunomodulatory nature of IL inhibitors raises theoretical concerns about malignancy risk. Immune surveillance plays a critical role in detecting and eliminating emerging tumor cells.⁷ Data from other systemic immunosuppressants, such as cyclosporine, show increased risks for certain cancers⁸; however, the IL-17 and IL-23 pathways have dual roles in cancer biology.⁷ In some tumor contexts, these cytokines promote carcinogenesis through angiogenesis, epithelial proliferation, and suppression of antitumor immunity; therefore, inhibiting these pathways could theoretically reduce cancer risk.⁷ The uncertainty around this risk-benefit balance has made malignancy a central consideration for dermatologists, particularly when initiating therapy in patients with a history of cancer or other risk factors.

The perception of malignancy risk can influence patient willingness to start biologics as well as physician prescribing patterns.⁹ Some clinicians opt for alternative therapies in individuals with a personal or family history of cancer despite limited direct evidence of harm from IL inhibitors. Conversely, a reassuring malignancy safety profile may support broader adoption of these therapies, especially in patients requiring lifelong disease control.⁹ Shared decision-making in this context requires robust, real-world evidence that accounts for both common and rare malignancy outcomes.

Randomized controlled trials of IL inhibitors have not demonstrated a consistent malignancy signal, but these studies often are underpowered for rare outcomes and limited by short follow-up durations, typically less than 1 year. They also frequently exclude high-risk populations, limiting generalizability.¹⁰ Observational studies using real-world data can address these gaps by including more diverse patient populations, longer observation windows, and larger sample sizes capable of detecting differences in uncommon outcomes.

The TriNetX Analytics Network (http://www.trinetx.com) offers a unique platform for large-scale, real-world pharmacoepidemiologic research. This federated database aggregates deidentified electronic health record data from more than 100 million patients across the United States and internationally, including at academic medical centers, integrated delivery networks, and community hospitals.⁴ Data contributors refresh their datasets regularly, ensuring near-contemporary representation of prescribing trends and clinical outcomes. Standardized terminology mapping, consistent International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding, and centralized data-quality checks enhance the reliability of analyses. Governance protocols and compliance with the Health Insurance Portability and Accountability Act deidentification standards further ensure ethical use of the data. The breadth and depth of the TriNetX network make it possible to evaluate not only common malignancies but also rare cancer types that smaller studies cannot assess with sufficient statistical power.

We performed a retrospective matched-cohort study, querying data from January 1, 2014, through December 31, 2024, using TriNetX to examine whether IL inhibitor exposure is associated with differences in incident malignancy risk among adults with psoriasis. Patients aged 18 years or older with a psoriasis diagnosis (ICD-10-CM code L40.x) and documented exposure to an IL-17, IL-23, or IL-12/23 inhibitor were eligible. Patients with a prior malignancy diagnosis were excluded to reduce prevalence bias. To ensure that malignancies were incident, we included only those diagnosed at least 1 day after initiation of an IL inhibitor.

The comparison cohort consisted of psoriasis patients without IL inhibitor exposure during their observation period. We used 1:1 propensity score matching based on age, sex, race, and ethnicity, applying a caliper of 0.1 to balance baseline characteristics and minimize demographic confounding. The index date for unexposed patients was randomly assigned within their observation period to align follow-up timing with exposed patients. Outcomes were identified by ICD-10-CM codes grouped by skin, hematologic, and solid-organ malignancies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, with statistical significance set at P<.05. Odds ratios were selected over hazard ratios due to variability in precise follow-up time capture and the primary analytic goal of comparing proportional odds within matched follow-up windows.

Propensity score matching was employed because it is a well-established technique in pharmacoepidemiology to mimic some of the balance achieved in randomized trials. By equating treatment and control groups on measured confounders, matching helps isolate the treatment effect, particularly important in nonrandomized datasets in which prescribing decisions may be influenced by baseline characteristics. Grouping cancers into clinically relevant categories allowed us to assess patterns of association, as some cancer types (eg, melanoma, lymphomas) may have pathophysiologic links to inflammatory pathways targeted by IL inhibitors.

The final cohort included 133,352 patients, with 66,676 in each group. The mean (SD) age was 49.3 (16.0) years, and demographic variables were well balanced after matching. The mean follow-up was approximately 3.8 years. Interleukin 17 inhibitors were the most frequently prescribed, followed by IL-23 inhibitors and ustekinumab. Baseline comorbidities such as cardiovascular disease, diabetes, and obesity were comparable between groups, reducing the likelihood of confounding from these factors.

Interleukin inhibitor exposure was associated with significantly reduced odds of several malignancies (eTable). Among skin cancers, melanoma risk was reduced by 36% (OR, 0.641; 95% CI, 0.534-0.77; P<.0001), basal cell carcinoma by 43% (OR, 0.565; 95% CI, 0.48-0.665; P<.0001), and squamous cell carcinoma by 18% (OR, 0.821; 95% CI, 0.676-0.996; P=.0452). Hematologic malignancies showed similar reductions, with non-Hodgkin lymphoma odds reduced by 35% (OR, 0.646; 95% CI, 0.512-0.815; P=.0002) and Hodgkin lymphoma by 50% (OR, 0.5; 95% CI, 0.292-0.855; P=.0098).

Protective associations also were observed for several solid tumors: lung (OR, 0.528; 95% CI, 0.452-0.617; P<.0001), liver (OR, 0.528; 95% CI, 0.399-0.698; P<.0001), pancreatic (OR, 0.65; 95% CI, 0.49-0.861; P=.0025), breast (OR, 0.663; 95% CI, 0.582-0.754; P<.0001), prostate (OR, 0.543; 95% CI, 0.468-0.629; P<.0001), colorectal (OR, 0.592; 95% CI, 0.414-0.846; P=.0036), colon (OR, 0.466; 95% CI, 0.375-0.579; P<.0001), and oropharyngeal (OR, 0.55; 95% CI, 0.327-0.925; P=.0222) cancers. Cervical cancer (OR, 0.604; 95% CI, 0.381-0.958; P=.0304) and anal cancer (OR, 0.4; 95% CI, 0.224-0.714; P=.0013) also showed significant reductions. Vaginal, vulvar, and penile cancers demonstrated no significant differences, likely due to their low incidence and limited statistical power.

The biological plausibility of these findings is supported by preclinical studies implicating IL-17 and IL-23 in tumor-promoting inflammation.¹¹ These cytokines can recruit myeloid-derived suppressor cells, promote angiogenesis, and facilitate tumor-immune evasion. Inhibition may shift the immune microenvironment toward enhanced tumor surveillance, reduce protumorigenic cytokine signaling, and normalize regulatory T-cell function.¹¹ These mechanisms could explain observed reductions in melanoma, lymphomas, and certain solid tumors.

Our results are consistent with several large registry studies showing no increased cancer incidence in IL inhibitor users and extend prior findings by demonstrating significant reductions in multiple cancer types.¹² The melanoma reduction contrasts with the findings in earlier biologic safety studies, possibly due to our larger sample size, broader geographic representation, and inclusion of multiple IL inhibitor classes.¹³ Similar reductions have not been consistently observed with tumor necrosis factor α inhibitors, which have different immunologic targets and a more complex malignancy safety history.¹⁴

Limitations of our study include the retrospective design, potential misclassification of cancer diagnoses, and lack of data on unmeasured confounders such as sun exposure, smoking, alcohol use, and family cancer history. Surveillance bias is possible, though it would likely bias toward higher, not lower, cancer detection in biologic users. Our mean follow-up period of 3.8 years may not be sufficient for cancers with long latency periods.

If replicated, our findings could have meaningful public health implications. Reassurance regarding malignancy safety may increase patient acceptance and physician confidence in prescribing IL inhibitors, particularly for patients requiring long-term therapy. From a payer perspective, the potential for reduced cancer incidence could translate into substantial cost savings over time, offsetting the high up-front cost of biologics. Additionally, these results may be relevant to other IL inhibitor indications, including psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease, in which similar pathophysiologic mechanisms may be at play.

In conclusion, this large matched-cohort study found that IL inhibitor therapy in psoriasis was associated with significantly reduced odds of multiple malignancies, including melanoma, lymphomas, and several solid tumors. These findings contribute to the growing body of real-world evidence supporting the long-term safety of IL inhibitors and underscore the need for continued pharmacovigilance and mechanistic research.

Practice Gap

Intralesional cryosurgery is a highly effective treatment for dermatologic conditions, notably keloids and hypertrophic scars.¹ Conventional methods typically use specialized double-lumen intralesional probes or Luer lock adapters connected to hypodermic or lumbar puncture needles, allowing cryogen to flow internally to cool the probe or needle and treat the lesion via conduction.² However, specialized intralesional probes are expensive and often are difficult to obtain. Furthermore, Luer lock adapters with needles directly attached to the handle unit can be ergonomically challenging, as the procedure requires simultaneous maintenance of a perpendicular handheld position, precise needle passage through the exact center of the lesion, and protection of the surrounding perilesional healthy skin from cold injury. Consequently, these limitations restrict widespread adoption, necessitating simpler, more accessible, and cost-effective alternatives. Herein, we present a novel, practical, and economical cryogen delivery method that adapts a disposable infusion set to a standard cryospray nozzle.

The Technique

This technique involves detaching the infusion set tubing and securely connecting it to the cryospray nozzle (Figure 1). Brief activation of the cryospray to constrict the nozzle or a small incision in the tubing may be required to ensure a tight fit, which can be secured with medical tape to maintain consistent cryogen flow. Local anesthesia is administered directly into and around the lesion, particularly translesionally for keloids, to avoid unnecessary trauma to the surrounding healthy skin, which could trigger further keloid formation. A needle is inserted through the lesion with the tip extending beyond its distal boundary, ensuring the tip remains outside the lesion during cryogen application to prevent cryoinsufflation. If necessary, gentle bending of the needle helps ensure optimal cryogen distribution within the lesion (Figures 2A and 2B). However, this may slightly reduce flow and extend freezing duration; therefore, bending the needle should be performed cautiously and is specifically recommended for effectively treating lesions on curved anatomic sites (eg, the auricle of the ear) to optimize freezing and protect surrounding tissues.

During initial cryogen release, covering the needle tip with gauze prevents aerosolization of biological debris, while placing a wooden tongue depressor between the needle tip and the patient’s skin prevents inadvertent cold injury. After cryogen flow is initiated, the lesion begins to freeze at both the needle entry and exit points, forming what is referred to as ice balls. Over time, typically within several seconds to a few minutes depending on lesion size and tissue characteristics, these ice balls merge centrally, forming a single ice ball encompassing the entire lesion (Figure 2C). Cryogen flow should be maintained during a single application until the unified ice ball appearance is achieved, confirming effective cooling.

Practice Implications

Studies have consistently shown that intralesional cryosurgery is associated with a reduction in the size and symptoms of hypertrophic scars and keloids.^1,2 Multimodal treatment approaches, including intralesional methods, are especially valued for their targeted efficacy and minimal adverse effects. Our simplified method offers practical economic advantages, making it highly suitable for broad adoption across diverse clinical settings, particularly those that are resource limited. Clinicians can safely and effectively utilize this technique without specialized or costly equipment, considerably enhancing clinical efficiency and accessibility. The straightforwardness of this method also facilitates the training of medical personnel, enabling rapid integration into clinical practice and the flexibility to treat various lesion types and sizes effectively.

Practice Gap

Intralesional cryosurgery is a highly effective treatment for dermatologic conditions, notably keloids and hypertrophic scars.¹ Conventional methods typically use specialized double-lumen intralesional probes or Luer lock adapters connected to hypodermic or lumbar puncture needles, allowing cryogen to flow internally to cool the probe or needle and treat the lesion via conduction.² However, specialized intralesional probes are expensive and often are difficult to obtain. Furthermore, Luer lock adapters with needles directly attached to the handle unit can be ergonomically challenging, as the procedure requires simultaneous maintenance of a perpendicular handheld position, precise needle passage through the exact center of the lesion, and protection of the surrounding perilesional healthy skin from cold injury. Consequently, these limitations restrict widespread adoption, necessitating simpler, more accessible, and cost-effective alternatives. Herein, we present a novel, practical, and economical cryogen delivery method that adapts a disposable infusion set to a standard cryospray nozzle.

The Technique

This technique involves detaching the infusion set tubing and securely connecting it to the cryospray nozzle (Figure 1). Brief activation of the cryospray to constrict the nozzle or a small incision in the tubing may be required to ensure a tight fit, which can be secured with medical tape to maintain consistent cryogen flow. Local anesthesia is administered directly into and around the lesion, particularly translesionally for keloids, to avoid unnecessary trauma to the surrounding healthy skin, which could trigger further keloid formation. A needle is inserted through the lesion with the tip extending beyond its distal boundary, ensuring the tip remains outside the lesion during cryogen application to prevent cryoinsufflation. If necessary, gentle bending of the needle helps ensure optimal cryogen distribution within the lesion (Figures 2A and 2B). However, this may slightly reduce flow and extend freezing duration; therefore, bending the needle should be performed cautiously and is specifically recommended for effectively treating lesions on curved anatomic sites (eg, the auricle of the ear) to optimize freezing and protect surrounding tissues.

During initial cryogen release, covering the needle tip with gauze prevents aerosolization of biological debris, while placing a wooden tongue depressor between the needle tip and the patient’s skin prevents inadvertent cold injury. After cryogen flow is initiated, the lesion begins to freeze at both the needle entry and exit points, forming what is referred to as ice balls. Over time, typically within several seconds to a few minutes depending on lesion size and tissue characteristics, these ice balls merge centrally, forming a single ice ball encompassing the entire lesion (Figure 2C). Cryogen flow should be maintained during a single application until the unified ice ball appearance is achieved, confirming effective cooling.

Practice Implications

Studies have consistently shown that intralesional cryosurgery is associated with a reduction in the size and symptoms of hypertrophic scars and keloids.^1,2 Multimodal treatment approaches, including intralesional methods, are especially valued for their targeted efficacy and minimal adverse effects. Our simplified method offers practical economic advantages, making it highly suitable for broad adoption across diverse clinical settings, particularly those that are resource limited. Clinicians can safely and effectively utilize this technique without specialized or costly equipment, considerably enhancing clinical efficiency and accessibility. The straightforwardness of this method also facilitates the training of medical personnel, enabling rapid integration into clinical practice and the flexibility to treat various lesion types and sizes effectively.

Practice Gap

Intralesional cryosurgery is a highly effective treatment for dermatologic conditions, notably keloids and hypertrophic scars.¹ Conventional methods typically use specialized double-lumen intralesional probes or Luer lock adapters connected to hypodermic or lumbar puncture needles, allowing cryogen to flow internally to cool the probe or needle and treat the lesion via conduction.² However, specialized intralesional probes are expensive and often are difficult to obtain. Furthermore, Luer lock adapters with needles directly attached to the handle unit can be ergonomically challenging, as the procedure requires simultaneous maintenance of a perpendicular handheld position, precise needle passage through the exact center of the lesion, and protection of the surrounding perilesional healthy skin from cold injury. Consequently, these limitations restrict widespread adoption, necessitating simpler, more accessible, and cost-effective alternatives. Herein, we present a novel, practical, and economical cryogen delivery method that adapts a disposable infusion set to a standard cryospray nozzle.

The Technique

This technique involves detaching the infusion set tubing and securely connecting it to the cryospray nozzle (Figure 1). Brief activation of the cryospray to constrict the nozzle or a small incision in the tubing may be required to ensure a tight fit, which can be secured with medical tape to maintain consistent cryogen flow. Local anesthesia is administered directly into and around the lesion, particularly translesionally for keloids, to avoid unnecessary trauma to the surrounding healthy skin, which could trigger further keloid formation. A needle is inserted through the lesion with the tip extending beyond its distal boundary, ensuring the tip remains outside the lesion during cryogen application to prevent cryoinsufflation. If necessary, gentle bending of the needle helps ensure optimal cryogen distribution within the lesion (Figures 2A and 2B). However, this may slightly reduce flow and extend freezing duration; therefore, bending the needle should be performed cautiously and is specifically recommended for effectively treating lesions on curved anatomic sites (eg, the auricle of the ear) to optimize freezing and protect surrounding tissues.

During initial cryogen release, covering the needle tip with gauze prevents aerosolization of biological debris, while placing a wooden tongue depressor between the needle tip and the patient’s skin prevents inadvertent cold injury. After cryogen flow is initiated, the lesion begins to freeze at both the needle entry and exit points, forming what is referred to as ice balls. Over time, typically within several seconds to a few minutes depending on lesion size and tissue characteristics, these ice balls merge centrally, forming a single ice ball encompassing the entire lesion (Figure 2C). Cryogen flow should be maintained during a single application until the unified ice ball appearance is achieved, confirming effective cooling.

Practice Implications

Studies have consistently shown that intralesional cryosurgery is associated with a reduction in the size and symptoms of hypertrophic scars and keloids.^1,2 Multimodal treatment approaches, including intralesional methods, are especially valued for their targeted efficacy and minimal adverse effects. Our simplified method offers practical economic advantages, making it highly suitable for broad adoption across diverse clinical settings, particularly those that are resource limited. Clinicians can safely and effectively utilize this technique without specialized or costly equipment, considerably enhancing clinical efficiency and accessibility. The straightforwardness of this method also facilitates the training of medical personnel, enabling rapid integration into clinical practice and the flexibility to treat various lesion types and sizes effectively.

THE DIAGNOSIS: Adult-Onset Asthma With Periocular Xanthogranuloma

In the context of pre-existing sinonasal disease and features consistent with adult-onset asthma, the constellation of clinical findings including linear periorbital yellow-orange plaques, imaging demonstrating extension of xanthogranulomatous lesions into the orbital fat, histopathologic features, and serologic abnormalities including elevated IgG4 levels supported a diagnosis of adult-onset asthma with periocular xanthogranuloma (AAPOX).

Adult-onset xanthogranuloma is a non–Langerhans cell histiocytosis (historically classified as type II) within the group of adult orbital xanthogranulomatous diseases resulting from infiltration and proliferation of histiocytes in the orbital and ocular adnexal structures and eyelids. Adult orbital xanthogranulomatous diseases are classified as 4 distinct conditions: adult-onset xanthogranuloma, AAPOX, Erdheim-Chester disease, and necrobiotic xanthogranuloma (NXG). Erdheim-Chester disease is the most severe among this group and often is fatal due to infiltration of the xanthogranulomas into multiple organ systems and tissues, including the long bones, heart, lungs, and retroperitoneum. Neurologic symptoms such as incoordination can occur. Adult-onset xanthogranuloma manifests as an isolated cutaneous lesion without systemic involvement. This entity often is self-limited and does not require aggressive treatment. Adult-onset asthma with periocular xanthogranuloma affects more males than females.¹ Clinically, it manifests as bilateral yellow-orange, thickened, indurated eyelid plaques that can extend to the extraocular muscles or lacrimal glands. As the name suggests, this entity is associated with adult-onset asthma or rhinosinusitis as well as lymphadenopathy and extension into the orbital fat.¹

When patients present with periorbital lesions and optic symptoms such as visual disturbances, tearing, and/ or a foreign body sensation in the eyes, a work-up should be performed to rule out infiltration of orbital adnexal structures and other organ systems, as AAPOX can be associated with IgG4-related disease. Histologically, adult xanthogranulomatous diseases are characterized by sheets of foamy histiocytes accompanied by variable numbers of lymphoid aggregates, plasma cells, and Touton giant cells. These infiltrating xanthoma cells appear as a garland or wreathlike nuclei surrounded by foamy cytoplasm. Oil-red O staining of frozen sections confirms the lipid content of the xanthoma cells.² Immunohistochemically, the foamy histiocytes are strongly positive for CD68, CD163, and factor XIIIa but usually are negative for S100, CD1a and Birbeck granules.³ More distinctively, AAPOX is associated with prominent lymphoid aggregates containing reactive germinal centers.¹

Given that AAPOX is a systemic multiorgan disease, local therapies such as surgical debulking or intralesional corticosteroids generally are insufficient to address the underlying pathology and therefore necessitate systemic, often multimodal, treatment within a multidisciplinary framework.^1,4 Systemic corticosteroids remain first-line therapy, with steroid-sparing agents (eg, methotrexate, azathioprine, cyclophosphamide) used in refractory cases or to reduce steroid dependence.^4,5 Rituximab has demonstrated efficacy in AAPOX, further highlighting the association between AAPOX and IgG4-related disease.⁵ Inebilizumab, a B-cell–depleting monoclonal antibody targeting CD19 and approved for the treatment of IgG4- related disease, represents a theoretically promising therapeutic option; however, additional studies are needed to establish its efficacy and safety in AAPOX.⁵

Necrobiotic xanthogranuloma is another xanthogranulomatous disorder that manifests as yellow-orange papules or nodules that gradually form infiltrative plaques. Scarring and ulceration can occur in 40% to 50% of patients.⁶ The most common site of involvement is the periorbital area, affecting 80% of cases, often resulting in ophthalmologic complications.⁶ Necrobiotic xanthogranuloma lesions also can involve the trunk, arms, and legs. Extracutaneous sites include the lungs, myocardium, larynx, pharynx, skeletal muscles, kidneys, ovaries, and intestines. The prognosis of NXG is poor due to associated hematologic malignancies such as multiple myeloma and lymphoma. About 80% of patients have a serum monoclonal gammopathy.⁶ Histologically, NXG shows features overlapping with other xanthogranulomatous disorders, such as foamy histiocytes, multinucleated giant cells, Touton giant cells, and nodular lymphocytic aggregates^6,7; however, broad zones of necrobiosis are a distinct histologic finding in NXG that helps differentiate it from other xanthogranulomatous disorders (Figure 1).⁶

Xanthelasma manifests as yellow plaques on the medial upper and lower eyelids and lateral canthi resulting from accumulation of cholesterol-rich material in the skin, soft tissue, and sometimes the tendons. Fifty percent of patients have a primary or secondary lipid disorder such as familial dyslipidemia, thyroid disease, diabetes mellitus, or primary biliary cholangitis.⁸ Histologically, xanthelasmas demonstrate lipid-laden foamy histiocytes in the superficial dermis (Figure 2).⁸ Despite some clinical overlap in our case, the depth of orbital involvement and supportive systemic and histopathologic findings (including Touton giant cells) supported the diagnosis of AAPOX rather than xanthelasma.

Juvenile xanthogranuloma manifests as solitary to multiple firm, yellow-orange papules or nodules on the face, neck, and upper torso. The lesions develop in early childhood, with 75% of lesions appearing in the first year of life, but rarely it may develop in adulthood.⁹ The most common extracutaneous manifestation involves ocular structures, most frequently the iris, followed by the lungs. Cutaneous lesions usually are asymptomatic and involute over the span of a few years. Ocular lesions can result in blindness, and juvenile xanthogranuloma also has been associated with neurofibromatosis type 1 and juvenile chronic myelogenous leukemia.⁹ The histopathology of juvenile xanthogranuloma often will show a dense histiocytic infiltrate in the dermis with blunting of the overlying rete ridges admixed with lymphocytes, plasma cells, and eosinophils. In the more mature phase, foam cells, foreign body giant cells, and Touton giant cells predominate. Touton giant cells have a garlandlike appearance (Figure 3).⁹

Reticulohistiocytoma (or solitary epithelioid histiocytoma) and multicentric reticulohistiocytosis are rare histiocytic proliferations. Multicentric reticulohistiocytosis refers to a systemic disease with arthropathy and multiple cutaneous histiocytic lesions located on acral sites and the face. Solitary reticulohistiocytoma manifests as papules or nodules found in many body locations, such as the trunk, arms, and legs. The lesions are uncommon on the face, which almost always is involved in multicentric reticulohistiocytosis. Solitary reticulohistiocytomas tend not to recur once excised and do not demonstrate systemic involvement. Histologically, the lesions demonstrate large eosinophilic epithelioid histiocytes with abundant glassy cytoplasm (Figure 4). Some of the epithelioid histiocytes are multinucleated, and immunophenotyping will show positivity for lysozyme, CD68, and CD163.¹⁰

THE DIAGNOSIS: Adult-Onset Asthma With Periocular Xanthogranuloma

In the context of pre-existing sinonasal disease and features consistent with adult-onset asthma, the constellation of clinical findings including linear periorbital yellow-orange plaques, imaging demonstrating extension of xanthogranulomatous lesions into the orbital fat, histopathologic features, and serologic abnormalities including elevated IgG4 levels supported a diagnosis of adult-onset asthma with periocular xanthogranuloma (AAPOX).

Adult-onset xanthogranuloma is a non–Langerhans cell histiocytosis (historically classified as type II) within the group of adult orbital xanthogranulomatous diseases resulting from infiltration and proliferation of histiocytes in the orbital and ocular adnexal structures and eyelids. Adult orbital xanthogranulomatous diseases are classified as 4 distinct conditions: adult-onset xanthogranuloma, AAPOX, Erdheim-Chester disease, and necrobiotic xanthogranuloma (NXG). Erdheim-Chester disease is the most severe among this group and often is fatal due to infiltration of the xanthogranulomas into multiple organ systems and tissues, including the long bones, heart, lungs, and retroperitoneum. Neurologic symptoms such as incoordination can occur. Adult-onset xanthogranuloma manifests as an isolated cutaneous lesion without systemic involvement. This entity often is self-limited and does not require aggressive treatment. Adult-onset asthma with periocular xanthogranuloma affects more males than females.¹ Clinically, it manifests as bilateral yellow-orange, thickened, indurated eyelid plaques that can extend to the extraocular muscles or lacrimal glands. As the name suggests, this entity is associated with adult-onset asthma or rhinosinusitis as well as lymphadenopathy and extension into the orbital fat.¹

When patients present with periorbital lesions and optic symptoms such as visual disturbances, tearing, and/ or a foreign body sensation in the eyes, a work-up should be performed to rule out infiltration of orbital adnexal structures and other organ systems, as AAPOX can be associated with IgG4-related disease. Histologically, adult xanthogranulomatous diseases are characterized by sheets of foamy histiocytes accompanied by variable numbers of lymphoid aggregates, plasma cells, and Touton giant cells. These infiltrating xanthoma cells appear as a garland or wreathlike nuclei surrounded by foamy cytoplasm. Oil-red O staining of frozen sections confirms the lipid content of the xanthoma cells.² Immunohistochemically, the foamy histiocytes are strongly positive for CD68, CD163, and factor XIIIa but usually are negative for S100, CD1a and Birbeck granules.³ More distinctively, AAPOX is associated with prominent lymphoid aggregates containing reactive germinal centers.¹

Given that AAPOX is a systemic multiorgan disease, local therapies such as surgical debulking or intralesional corticosteroids generally are insufficient to address the underlying pathology and therefore necessitate systemic, often multimodal, treatment within a multidisciplinary framework.^1,4 Systemic corticosteroids remain first-line therapy, with steroid-sparing agents (eg, methotrexate, azathioprine, cyclophosphamide) used in refractory cases or to reduce steroid dependence.^4,5 Rituximab has demonstrated efficacy in AAPOX, further highlighting the association between AAPOX and IgG4-related disease.⁵ Inebilizumab, a B-cell–depleting monoclonal antibody targeting CD19 and approved for the treatment of IgG4- related disease, represents a theoretically promising therapeutic option; however, additional studies are needed to establish its efficacy and safety in AAPOX.⁵

Necrobiotic xanthogranuloma is another xanthogranulomatous disorder that manifests as yellow-orange papules or nodules that gradually form infiltrative plaques. Scarring and ulceration can occur in 40% to 50% of patients.⁶ The most common site of involvement is the periorbital area, affecting 80% of cases, often resulting in ophthalmologic complications.⁶ Necrobiotic xanthogranuloma lesions also can involve the trunk, arms, and legs. Extracutaneous sites include the lungs, myocardium, larynx, pharynx, skeletal muscles, kidneys, ovaries, and intestines. The prognosis of NXG is poor due to associated hematologic malignancies such as multiple myeloma and lymphoma. About 80% of patients have a serum monoclonal gammopathy.⁶ Histologically, NXG shows features overlapping with other xanthogranulomatous disorders, such as foamy histiocytes, multinucleated giant cells, Touton giant cells, and nodular lymphocytic aggregates^6,7; however, broad zones of necrobiosis are a distinct histologic finding in NXG that helps differentiate it from other xanthogranulomatous disorders (Figure 1).⁶

Xanthelasma manifests as yellow plaques on the medial upper and lower eyelids and lateral canthi resulting from accumulation of cholesterol-rich material in the skin, soft tissue, and sometimes the tendons. Fifty percent of patients have a primary or secondary lipid disorder such as familial dyslipidemia, thyroid disease, diabetes mellitus, or primary biliary cholangitis.⁸ Histologically, xanthelasmas demonstrate lipid-laden foamy histiocytes in the superficial dermis (Figure 2).⁸ Despite some clinical overlap in our case, the depth of orbital involvement and supportive systemic and histopathologic findings (including Touton giant cells) supported the diagnosis of AAPOX rather than xanthelasma.

Juvenile xanthogranuloma manifests as solitary to multiple firm, yellow-orange papules or nodules on the face, neck, and upper torso. The lesions develop in early childhood, with 75% of lesions appearing in the first year of life, but rarely it may develop in adulthood.⁹ The most common extracutaneous manifestation involves ocular structures, most frequently the iris, followed by the lungs. Cutaneous lesions usually are asymptomatic and involute over the span of a few years. Ocular lesions can result in blindness, and juvenile xanthogranuloma also has been associated with neurofibromatosis type 1 and juvenile chronic myelogenous leukemia.⁹ The histopathology of juvenile xanthogranuloma often will show a dense histiocytic infiltrate in the dermis with blunting of the overlying rete ridges admixed with lymphocytes, plasma cells, and eosinophils. In the more mature phase, foam cells, foreign body giant cells, and Touton giant cells predominate. Touton giant cells have a garlandlike appearance (Figure 3).⁹

Reticulohistiocytoma (or solitary epithelioid histiocytoma) and multicentric reticulohistiocytosis are rare histiocytic proliferations. Multicentric reticulohistiocytosis refers to a systemic disease with arthropathy and multiple cutaneous histiocytic lesions located on acral sites and the face. Solitary reticulohistiocytoma manifests as papules or nodules found in many body locations, such as the trunk, arms, and legs. The lesions are uncommon on the face, which almost always is involved in multicentric reticulohistiocytosis. Solitary reticulohistiocytomas tend not to recur once excised and do not demonstrate systemic involvement. Histologically, the lesions demonstrate large eosinophilic epithelioid histiocytes with abundant glassy cytoplasm (Figure 4). Some of the epithelioid histiocytes are multinucleated, and immunophenotyping will show positivity for lysozyme, CD68, and CD163.¹⁰

THE DIAGNOSIS: Adult-Onset Asthma With Periocular Xanthogranuloma

In the context of pre-existing sinonasal disease and features consistent with adult-onset asthma, the constellation of clinical findings including linear periorbital yellow-orange plaques, imaging demonstrating extension of xanthogranulomatous lesions into the orbital fat, histopathologic features, and serologic abnormalities including elevated IgG4 levels supported a diagnosis of adult-onset asthma with periocular xanthogranuloma (AAPOX).

Adult-onset xanthogranuloma is a non–Langerhans cell histiocytosis (historically classified as type II) within the group of adult orbital xanthogranulomatous diseases resulting from infiltration and proliferation of histiocytes in the orbital and ocular adnexal structures and eyelids. Adult orbital xanthogranulomatous diseases are classified as 4 distinct conditions: adult-onset xanthogranuloma, AAPOX, Erdheim-Chester disease, and necrobiotic xanthogranuloma (NXG). Erdheim-Chester disease is the most severe among this group and often is fatal due to infiltration of the xanthogranulomas into multiple organ systems and tissues, including the long bones, heart, lungs, and retroperitoneum. Neurologic symptoms such as incoordination can occur. Adult-onset xanthogranuloma manifests as an isolated cutaneous lesion without systemic involvement. This entity often is self-limited and does not require aggressive treatment. Adult-onset asthma with periocular xanthogranuloma affects more males than females.¹ Clinically, it manifests as bilateral yellow-orange, thickened, indurated eyelid plaques that can extend to the extraocular muscles or lacrimal glands. As the name suggests, this entity is associated with adult-onset asthma or rhinosinusitis as well as lymphadenopathy and extension into the orbital fat.¹

When patients present with periorbital lesions and optic symptoms such as visual disturbances, tearing, and/ or a foreign body sensation in the eyes, a work-up should be performed to rule out infiltration of orbital adnexal structures and other organ systems, as AAPOX can be associated with IgG4-related disease. Histologically, adult xanthogranulomatous diseases are characterized by sheets of foamy histiocytes accompanied by variable numbers of lymphoid aggregates, plasma cells, and Touton giant cells. These infiltrating xanthoma cells appear as a garland or wreathlike nuclei surrounded by foamy cytoplasm. Oil-red O staining of frozen sections confirms the lipid content of the xanthoma cells.² Immunohistochemically, the foamy histiocytes are strongly positive for CD68, CD163, and factor XIIIa but usually are negative for S100, CD1a and Birbeck granules.³ More distinctively, AAPOX is associated with prominent lymphoid aggregates containing reactive germinal centers.¹

Given that AAPOX is a systemic multiorgan disease, local therapies such as surgical debulking or intralesional corticosteroids generally are insufficient to address the underlying pathology and therefore necessitate systemic, often multimodal, treatment within a multidisciplinary framework.^1,4 Systemic corticosteroids remain first-line therapy, with steroid-sparing agents (eg, methotrexate, azathioprine, cyclophosphamide) used in refractory cases or to reduce steroid dependence.^4,5 Rituximab has demonstrated efficacy in AAPOX, further highlighting the association between AAPOX and IgG4-related disease.⁵ Inebilizumab, a B-cell–depleting monoclonal antibody targeting CD19 and approved for the treatment of IgG4- related disease, represents a theoretically promising therapeutic option; however, additional studies are needed to establish its efficacy and safety in AAPOX.⁵

Necrobiotic xanthogranuloma is another xanthogranulomatous disorder that manifests as yellow-orange papules or nodules that gradually form infiltrative plaques. Scarring and ulceration can occur in 40% to 50% of patients.⁶ The most common site of involvement is the periorbital area, affecting 80% of cases, often resulting in ophthalmologic complications.⁶ Necrobiotic xanthogranuloma lesions also can involve the trunk, arms, and legs. Extracutaneous sites include the lungs, myocardium, larynx, pharynx, skeletal muscles, kidneys, ovaries, and intestines. The prognosis of NXG is poor due to associated hematologic malignancies such as multiple myeloma and lymphoma. About 80% of patients have a serum monoclonal gammopathy.⁶ Histologically, NXG shows features overlapping with other xanthogranulomatous disorders, such as foamy histiocytes, multinucleated giant cells, Touton giant cells, and nodular lymphocytic aggregates^6,7; however, broad zones of necrobiosis are a distinct histologic finding in NXG that helps differentiate it from other xanthogranulomatous disorders (Figure 1).⁶

Xanthelasma manifests as yellow plaques on the medial upper and lower eyelids and lateral canthi resulting from accumulation of cholesterol-rich material in the skin, soft tissue, and sometimes the tendons. Fifty percent of patients have a primary or secondary lipid disorder such as familial dyslipidemia, thyroid disease, diabetes mellitus, or primary biliary cholangitis.⁸ Histologically, xanthelasmas demonstrate lipid-laden foamy histiocytes in the superficial dermis (Figure 2).⁸ Despite some clinical overlap in our case, the depth of orbital involvement and supportive systemic and histopathologic findings (including Touton giant cells) supported the diagnosis of AAPOX rather than xanthelasma.

Juvenile xanthogranuloma manifests as solitary to multiple firm, yellow-orange papules or nodules on the face, neck, and upper torso. The lesions develop in early childhood, with 75% of lesions appearing in the first year of life, but rarely it may develop in adulthood.⁹ The most common extracutaneous manifestation involves ocular structures, most frequently the iris, followed by the lungs. Cutaneous lesions usually are asymptomatic and involute over the span of a few years. Ocular lesions can result in blindness, and juvenile xanthogranuloma also has been associated with neurofibromatosis type 1 and juvenile chronic myelogenous leukemia.⁹ The histopathology of juvenile xanthogranuloma often will show a dense histiocytic infiltrate in the dermis with blunting of the overlying rete ridges admixed with lymphocytes, plasma cells, and eosinophils. In the more mature phase, foam cells, foreign body giant cells, and Touton giant cells predominate. Touton giant cells have a garlandlike appearance (Figure 3).⁹

Reticulohistiocytoma (or solitary epithelioid histiocytoma) and multicentric reticulohistiocytosis are rare histiocytic proliferations. Multicentric reticulohistiocytosis refers to a systemic disease with arthropathy and multiple cutaneous histiocytic lesions located on acral sites and the face. Solitary reticulohistiocytoma manifests as papules or nodules found in many body locations, such as the trunk, arms, and legs. The lesions are uncommon on the face, which almost always is involved in multicentric reticulohistiocytosis. Solitary reticulohistiocytomas tend not to recur once excised and do not demonstrate systemic involvement. Histologically, the lesions demonstrate large eosinophilic epithelioid histiocytes with abundant glassy cytoplasm (Figure 4). Some of the epithelioid histiocytes are multinucleated, and immunophenotyping will show positivity for lysozyme, CD68, and CD163.¹⁰