Updates in SJS/TEN: collaboration, innovation, and community.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15-20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1-5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28-29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper.

Development of a Skin-Directed Scoring System for Stevens-Johnson Syndrome and Epidermal Necrolysis: A Delphi Consensus Exercise.

Importance: Scoring systems for Stevens-Johnson syndrome and epidermal necrolysis (EN) only estimate patient prognosis and are weighted toward comorbidities and systemic features; morphologic terminology for EN lesions is inconsistent. Objectives: To establish consensus among expert dermatologists on EN terminology, morphologic progression, and most-affected sites, and to build a framework for developing a skin-directed scoring system for EN. Evidence Review: A Delphi consensus using the RAND/UCLA appropriateness criteria was initiated with a core group from the Society of Dermatology Hospitalists to establish agreement on the optimal design for an EN cutaneous scoring instrument, terminology, morphologic traits, and sites of involvement. Findings: In round 1, the 54 participating dermatology hospitalists reached consensus on all 49 statements (30 appropriate, 3 inappropriate, 16 uncertain). In round 2, they agreed on another 15 statements (8 appropriate, 7 uncertain). There was consistent agreement on the need for a skin-specific instrument; on the most-often affected skin sites (head and neck, chest, upper back, ocular mucosa, oral mucosa); and that blanching erythema, dusky erythema, targetoid erythema, vesicles/bullae, desquamation, and erosions comprise the morphologic traits of EN and can be consistently differentiated. Conclusions and Relevance: This consensus exercise confirmed the need for an EN skin-directed scoring system, nomenclature, and differentiation of specific morphologic traits, and identified the sites most affected. It also established a baseline consensus for a standardized EN instrument with consistent terminology.

Free the Bun: Prevalence of Alopecia Among Active Duty Service Women, Fiscal Years 2010-2019.

INTRODUCTION: Active duty service women (ADSW) constitute 16% of the force. The prevalence of alopecia, a dermatologic condition characterized by hair loss, is understudied in regard to hairstyle regulations across the U.S. military services. Alopecia has several causes; one of which is due to tension on the scalp secondary to tight hairstyles. In the U.S., alopecia has a lifetime prevalence of 1.7-2.1%; no previous studies which evaluated this condition in service women were found. MATERIALS AND METHODS: We used the Military Health System Data Repository to perform a retrospective study to assess the prevalence of alopecia in ADSW from fiscal years (FYs) 2010 to 2019. Statistical analyses included descriptive statistics on patient demographics and trend analysis on the prevalence of alopecia over the 10-year study period. RESULTS: A total of 498,219 ADSW were identified over the 10-year study period, of which 2.40% had a diagnosis of alopecia. Overall, the prevalence of alopecia decreases over the 10-year period, with two observed periods of slight increase (FY 2013 to 2014 and FY 2018 to 2019) when comparing prevalence year-to-year. Of those diagnosed, the majority were young, Black, with a senior enlisted rank, and in the U.S. Army. CONCLUSION: The prevalence of alopecia in ADSW is slightly higher than that in civilian populations and is most likely underreported. It is more commonly diagnosed in Black women than would be expected based on ratios of this population in military service. Policy changes to ensure that traction alopecia is a qualifying medical condition for Veterans Affairs disability compensation, mechanisms are in place for more specific coding in the electronic medical record, and treatment options to be covered by TRICARE are recommended. All U.S. military services should consider updating and evaluating regulations to improve the health and quality of life of ADSW.

Recognizing Drug Hypersensitivity in Pigmented Skin.

The imagery of pigmented skin is underrepresented in teaching materials such as textbooks, journals, and online references, and this has resulted in poorer diagnostic and management outcomes of skin pathology, including delayed cutaneous drug hypersensitivity reactions. In this review, we use clinical images to highlight factors that impact clinical presentations and sequelae of drug hypersensitivity reactions in pigmented skin compared with nonpigmented skin. We describe clinical features in some anatomic sites that aid diagnosis or are associated with more severe sequelae. Finally, we discuss strategies that may aid the diagnosis and management of these reactions in pigmented skin.

Imported Monkeypox from International Traveler, Maryland, USA, 2021.

A case of monkeypox was diagnosed in a returning traveler from Nigeria to Maryland, USA. Prompt infection control measures led to no secondary cases in 40 exposed healthcare workers. Given the global health implications, public health systems should be aware of effective strategies to mitigate the potential spread of monkeypox.

Calciphylaxis: Treatment and outlook-CME part II.

Calciphylaxis is a rare and devastating condition with important systemic ramifications. This second-part of our CME aims to educate the practicing dermatologist on the current standard of care once a diagnosis of calciphylaxis is confirmed or highly suspected. The key pathologic findings, as well as the role and limitations of biopsy, are reviewed. We aim to guide readers through the complex hospitalization and posthospitalization management of these medically vulnerable patients. Collaboration with other specialists will be discussed. Experimental and developing treatments are discussed, and the outlook of the condition is reported.

Calciphylaxis: Part I. Diagnosis and pathology.

Calciphylaxis is an uncommon but devastating disorder characterized by vascular calcification and subsequent cutaneous tissue necrosis. This results in exquisitely painful and slow healing wounds that portend exceptionally high morbidity and mortality. The diagnosis of this condition can be complicated because there are no conclusive serologic, radiographic or visual signs that this disease is manifesting. The differential of tissue necrosis is broad, and identifying calciphylaxis requires an adroit understanding of the risk factors and physical signs that should raise suspicion of this condition. Reviews on this subject are uncommon and lack directed commentary from disease experts on the best diagnostic approach for patients suffering from this disease. The goal of this article is to update practicing dermatologists on the current standard of care for calciphylaxis.

The Relationship Between Autoimmune Disease and Disease-Modifying Antirheumatic Drugs on Wound Healing.

Objective: To evaluate the role of disease-modifying antirheumatic drugs (DMARDs) on wound healing outcomes of patients with autoimmune disease at our tertiary wound care center. Approach: Retrospective review of patients presenting to our wound care center between 2014 and 2018 with both chronic wounds and a history of inflammatory disease. Patient demographics, comorbid conditions, and progression to complete wound healing were compared between those taking DMARDs or not at the time of wound onset. The study adheres to the STROBE statement. Results: Fifty-eight patients with a total of 296 wounds were retrospectively reviewed. Patients were taking at least one DMARD at wound onset in 217 (73.3%) of these wounds. The average number of DMARDs at wound onset was 1.5 (standard deviation 1.2). Two hundred ten wounds progressed to heal (70.9%), with a median time to healing of 229.5 days (interquartile range 71.0-490.0). Of the 210 wounds that healed, patients taking at least one DMARD had a significantly shorter time to healing relative to patients who were not on any DMARDs (median 190.5 days vs. 340.0 days, p = 0.0156). Innovation: Characterizing wound healing outcomes at a tertiary hospital with a dedicated wound care center and analyzing the role of DMARDs in wound healing progression. Conclusions: The median time to healing in the studied cohort was 229.5 days, which is much longer than the healing time for noninfected diabetic foot ulcers at our institution. These findings highlight the wound healing challenges posed by underlying autoimmune disease.10.

Graft Versus Host Disease After Intestinal Transplantation: A Single-center Experience.

BACKGROUND: Graft versus host disease (GVHD) is an uncommon but highly morbid complication of intestinal transplantation (ITx). In this study, we reviewed our 17-y experience with GVHD focusing on factors predicting GVHD occurrence and survival. METHODS: Retrospective review of 271 patients who received 1 or more ITx since program inception in 2003 with survival analysis using Cox proportional hazard modeling. RESULTS: Of 271 patients, 28 developed GHVD 34 (18-66) d after ITx presenting with rash or rash with fever in 26, rectosigmoid disease in 1, and hemolysis in 1; other sites, mainly rectosigmoid colon, were involved in 13. Initial skin biopsy demonstrated classic findings in 6, compatible findings in 14, and no abnormalities in 2. Additional sites of GVHD later emerged in 14. Of the 28 patients, 16 died largely from sepsis, the only independent hazard for death (hazard ratio [HR], 37.4181; P = 0.0008). Significant (P < 0.0500) independent hazards for occurrence of GVHD in adults were pre-ITx functional intestinal failure (IF) (HR, 15.2448) and non-IF diagnosis (HR, 20.9952) and early post-ITx sirolimus therapy (HR, 0.0956); independent hazards in children were non-IF diagnosis (HR, 4.3990), retransplantation (HR, 4.6401), donor:recipient age ratio (HR, 7.3190), and graft colon omission (HR, 0.1886). Variant transplant operation was not an independent GVHD hazard. CONCLUSIONS: Initial diagnosis of GVHD after ITx remains largely clinical, supported but not often confirmed by skin biopsy. Although GVHD risk is mainly recipient-driven, changes in donor selection and immunosuppression practice may reduce incidence and improve survival.

Vulvovaginal manifestations in Stevens-Johnson syndrome and toxic epidermal necrolysis: Prevention and treatment.

The prevalence of acute vulvovaginal involvement in toxic epidermal necrolysis can be as high as 70%; up to 28% of female patients will also develop chronic vulvovaginal sequelae. There is little consensus regarding prevention and treatment of the gynecologic sequelae of both Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). We review acute and chronic sequelae, including erosions, scar formation, chronic skin changes, urethral complications, adenosis, malignant transformation, vulvodynia, and dyspareunia. We provide comprehensive recommendations for acute and long-term vulvovaginal care in adult and pediatric SJS/TEN patients. Treatment should include an ultrapotent topical steroid, followed by a nonirritating barrier cream applied to vulvar and perineal lesions. A steroid should be used intravaginally along with vaginal dilation in all adults (but should be avoided in prepubertal adolescents) with vaginal involvement. Menstrual suppression should be considered in all reproductive age patients until vulvovaginal lesions have healed. Last, referrals for pelvic floor physical therapy and to surgical subspecialties should be offered on a case-by-case basis. This guide summarizes the current available literature combined with expert opinion of both dermatologists and gynecologists who treat a high volume of SJS/TEN patients.

Vulvovaginal and ocular involvement and treatment in female patients with Stevens-Johnson syndrome and toxic epidermal necrolysis: A review.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious adverse cutaneous drug reactions, characterized by epidermal detachment and mucous membrane involvement. SJS/TEN is more common in female patients, with unique findings in the ocular and vulvar regions. Early recognition and intervention, as well as long-term follow-up, are crucial to prevent devastating scarring and sequelae. This review examines the vulvar and ocular manifestations of SJS/TEN and describes the current treatment recommendations for female patients, requiring close consultation and collaboration among dermatology, ophthalmology, and gynecology.

Drivers and sequelae of burnout in U.S. dermatology trainees.

BACKGROUND: Burnout is a health care epidemic. Although burnout has been shown to affect dermatologists in multispecialty studies, there are no such studies in dermatology trainees. OBJECTIVE: We conducted a survey-based study of burnout in U.S. dermatology trainees to identify its drivers and sequelae. METHODS: All residents enrolled in a U.S. dermatology training program were eligible. The 45-question survey included the Maslach Burnout Inventory, a validated quality of life index, and 31 questions based on known drivers of burnout and new research questions. No identifying data were collected. RESULTS: A total of 180 residents responded, for a response rate of 14.4%. Notably, an analysis of the cohort showed that our sample was not statistically different from the national complement of trainees based both on proportion of female respondents and mean age (p = .9449 and .2376, respectively). Of the respondents, 59% were female. The average age was 30.6 years. Sixty-nine percent of trainees (124 of 180) met the criteria for burnout. On univariate analysis, age, sex, training year, and relationship status were not associated with burnout. Good work-life balance (p = .032), autonomy in the workplace (p = .0027), intradisciplinary respect (p = .022), and increased work hours (p = .0110) were protective. On multivariate analysis, autonomy in the workplace (odds ratio: 3.580; confidence interval, 1.32-9.71; p = .012) and good work-life balance (odds ratio: 0.262; confidence interval, 0.095-0.722; p = .0097) remained significant. CONCLUSION: Improving control over working environment, as evidenced by the impact of work-life balance and autonomy, may lessen burnout in trainees. Further studies analyzing regional and program-specific variations will help improve trainee experience.

CD69+ resident memory T cells are associated with graft-versus-host disease in intestinal transplantation.

Graft-versus-host disease (GvHD) is a common, morbid complication after intestinal transplantation (ITx) with poorly understood pathophysiology. Resident memory T cells (TRM ) are a recently described CD69+ memory T cell subset localizing to peripheral tissue. We observed that T effector memory cells (TEM ) in the blood increase during GvHD and hypothesized that they derive from donor graft CD69+TRM migrating into host blood and tissue. To probe this hypothesis, graft and blood lymphocytes from 10 ITx patients with overt GvHD and 34 without were longitudinally analyzed using flow cytometry. As hypothesized, CD4+ and CD8+CD69+TRM were significantly increased in blood and grafts of GvHD patients, alongside higher cytokine and activation marker expression. The majority of CD69+TRM were donor derived as determined by multiplex immunostaining. Notably, CD8/PD-1 was significantly elevated in blood prior to transplantation in patients who later had GvHD, and percentages of HLA-DR, CD57, PD-1, and naïve T cells differed significantly between GvHD patients who died vs. those who survived. Overall, we demonstrate that (1) there were significant increases in TEM at the time of GvHD, possibly of donor derivation; (2) donor TRM in the graft are a possible source; and (3) potential biomarkers for the development and prognosis of GvHD exist.