Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part II diagnosis and management.

Drug-induced hypersensitivity syndrome, also known as drug reaction with eosinophilia and systemic symptoms, is a severe cutaneous adverse reaction characterized by an exanthem, fever, and hematologic and visceral organ involvement. The differential diagnosis includes other cutaneous adverse reactions, infections, inflammatory and autoimmune diseases, and neoplastic disorders. Three sets of diagnostic criteria have been proposed; however, consensus is lacking. The cornerstone of management is immediate discontinuation of the suspected drug culprit. Systemic corticosteroids remain first-line therapy, but the literature on steroid-sparing agents is expanding. Longitudinal evaluation for sequelae is recommended. Adjunctive tests for risk stratification and drug culprit identification remain under investigation. Part II of this continuing medical education activity begins by exploring the differential diagnosis and diagnosis of drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms and concludes with an evidence-based overview of evaluation and treatment.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part I. Epidemiology, pathogenesis, clinicopathological features, and prognosis.

Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe cutaneous adverse reaction (SCAR) characterized by an exanthem, fever, and hematologic and visceral organ involvement. Anticonvulsants, antibiotics, and allopurinol are the most common triggers. The pathogenesis involves a complex interplay between drugs, viruses, and the immune system primarily mediated by T-cells. DiHS/DRESS typically presents with a morbilliform eruption 2-6 weeks after drug exposure, and is associated with significant morbidity, mortality, and risk of relapse. Long-term sequelae primarily relate to organ dysfunction and autoimmune diseases. Part I of this continuing medical education activity on DiHS/DRESS provides an update on epidemiology, novel insights into pathogenesis, and a description of clinicopathological features and prognosis.

Hospital Dermatology: Review of Research in 2022-2023.

In the inpatient setting, dermatology consultants help reduce mortality, shorten length of stay, and reduce hospital readmissions. Recent research underscores the contributions of dermatology hospitalists, including phenotyping known and new severe cutaneous adverse drug reactions; showing improved progression-free and overall survival among those receiving dermatologic care for cutaneous reactions to immune checkpoint inhibitors; highlighting the role of dermatologists in reducing emergency department and hospital utilization by those with inflammatory skin diseases; and demonstrating ways in which dermatologists can effectively diagnose common and severe cutaneous diseases using asynchronous teledermatology, meeting the growing demand for inpatient dermatology services. This review covers selected highlights from the 2022-2023 inpatient dermatology literature.

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.

Patient Perspectives on Hidradenitis Suppurativa and Infertility: A Survey Study.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory skin condition which predominantly affects women of childbearing age in the USA. There is a lack of research on the association between HS and fertility. OBJECTIVES: The aim of this study was to understand the perspectives of females with HS regarding the impact of their disease on reproductive health, the impact of fertility treatments on HS, and the impact of HS treatments on fertility. METHODS: An anonymous, online survey was disseminated through HS support groups from June to July 2022. Respondents aged 18-50 who were assigned female sex at birth were eligible for participation. Comparative statistics were performed using t tests/χ2 tests to assess associations between respondents' demographics and survey responses. RESULTS: Among the 312 respondents (80.8% White, mean age 35.7 ± 7.4 [range 18-50]), two-thirds of respondents (66.6%, 207/311) had been pregnant before and 79.5% (248/312) had ever tried to conceive. 41.5% (103/248) had unsuccessfully tried to conceive for 12 months or more. Of the 59 respondents who had never attempted to conceive, 39% reported that HS had impacted this decision. Amongst respondents who experienced fertility challenges but did not pursue fertility treatments, top barriers to fertility treatments include concerns about financial support/insurance coverage (47.5%, 29/61) and fertility treatments worsening HS (21.3%, 13/61). Most respondents who used fertility treatments reported either no change (73.7%, 28/38 or 77.8%, 14/18) or improvement (15.8%, 6/38 or 11.1%, 2/18) in their HS symptoms with oral or injectable medications. Respondents were most concerned about the effects of oral antibiotics (44.9%, 140/312), followed by hormonal medications (38.8%, 121/312) and biologics (35.9%, 112/312) on fertility. CONCLUSION: Females with HS reported high rates of infertility compared to the general population. The majority reported no change in HS symptoms with fertility treatments, and clinicians can use this finding to help counsel patients during family planning discussions. Further research in the field of HS and fertility is needed.

Assessment of Cutaneous Vasculitis and Quality of Life.

This survey study assesses the health-related quality of life outcomes in adult patients with cutaneous manifestations of vasculitis.

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.

Penicillin allergy evaluation in hospitalized patients with hematologic malignancy.

A penicillin allergy testing service (PATS) assessed penicillin allergy in patients with hematologic malignancies; 17 patients who met criteria had negative skin testing. Patients who underwent penicillin challenge passed and were delabeled. Of delabeled patients, 87% received and tolerated ß-lactams during follow-up. Providers found the PATS valuable.

Delayed diagnosis of DRESS syndrome in a patient with skin of color.

We describe a particularly severe case of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome with hemodynamic instability, erythroderma, profound eosinophilia, and severe organ dysfunction. We attribute the severity in part to a delay in diagnosis due to patient's skin of color, as the erythroderma was not noticed until a dermatologist was consulted. This case highlights how even severe skin disease can present less conspicuously in patients with darker skin types. We outline several strategies that can help clinicians to recognize DRESS and other skin disease phenotypes in patients of color, thereby avoiding delays in diagnosis as seen in this case.

Cutaneous Small Vessel Vasculitis: A Practical Guide to Diagnosis and Management.

Cutaneous vasculitis may be a cutaneous manifestation of systemic vasculitis, a skin-limited variant of systemic vasculitis, or a type of single-organ vasculitis limited to the skin. Careful evaluation is necessary to distinguish these possibilities, differentiate skin-limited from systemic disease, and identify important underlying conditions, if present. Appropriate management depends on disease type and severity. In the case of cutaneous small vessel vasculitis (CSVV), treatment is primarily based on case reports and expert opinion, using a range of immunomodulatory or immunosuppressive therapies. This manuscript presents a systematic and stepwise approach to the evaluation of patients presenting with cutaneous vasculitis, as well as the management of those diagnosed with CSVV, using best available evidence. Studies relevant to the classification, evaluation, and management of skin vasculitis are ongoing.

Identification of a neutrophil-specific PIK3R1 mutation facilitates targeted treatment in a patient with Sweet syndrome.

BackgroundAcute febrile neutrophilic dermatosis (Sweet syndrome) is a potentially fatal multiorgan inflammatory disease characterized by fever, leukocytosis, and a rash with a neutrophilic infiltrate. The disease pathophysiology remains elusive, and current dogma suggests that Sweet syndrome is a process of reactivity to an unknown antigen. Corticosteroids and steroid-sparing agents remain frontline therapies, but refractory cases pose a clinical challenge.MethodsA 51-year-old woman with multiorgan Sweet syndrome developed serious corticosteroid-related side effects and was refractory to steroid-sparing agents. Blood counts, liver enzymes, and skin histopathology supported the diagnosis. Whole-genome sequencing, transcriptomic profiling, and cellular assays of the patient's skin and neutrophils were performed.ResultsWe identified elevated IL-1 signaling in lesional Sweet syndrome skin caused by a PIK3R1 gain-of-function mutation specifically found in neutrophils. This mutation increased neutrophil migration toward IL-1ß and neutrophil respiratory burst. Targeted treatment of the patient with an IL-1 receptor 1 antagonist resulted in a dramatic therapeutic response and enabled a tapering off of corticosteroids.ConclusionDysregulated PI3K/AKT signaling is the first signaling pathway linked to Sweet syndrome and suggests that this syndrome may be caused by acquired mutations that modulate neutrophil function. Moreover, integration of molecular data across multiple levels identified a distinct subtype within a heterogeneous disease that resulted in a rational and successful clinical intervention. Future patients will benefit from efforts to identify potential mutations. The ability to directly interrogate the diseased skin allows this method to be generalizable to other inflammatory diseases and demonstrates a potential personalized medicine approach for patients with clinically challenging disease.Funding SourcesBerstein Foundation, NIH, Veterans Affairs (VA) Administration, Moseley Foundation, and H.T. Leung Foundation.

Treatment of cutaneous vasculitis.

Cutaneous vasculitis encompasses a spectrum of disease states, with varied morphology, severity, and potential for systemic involvement. Even vasculitis which is skin-limited can have a significant quality-of-life impact, necessitating treatment. This manuscript summarizes the available evidence for management of various types of skin-limited vasculitis and provides a proposed therapeutic ladder based on published studies and expert opinion.