Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous Lupus Erythematosus.

BACKGROUND: Blood dendritic cell antigen 2 (BDCA2) is a receptor that is exclusively expressed on plasmacytoid dendritic cells, which are implicated in the pathogenesis of lupus erythematosus. Whether treatment with litifilimab, a humanized monoclonal antibody against BDCA2, would be efficacious in reducing disease activity in patients with cutaneous lupus erythematosus has not been extensively studied. METHODS: In this phase 2 trial, we randomly assigned adults with histologically confirmed cutaneous lupus erythematosus with or without systemic manifestations in a 1:1:1:1 ratio to receive subcutaneous litifilimab (at a dose of 50, 150, or 450 mg) or placebo at weeks 0, 2, 4, 8, and 12. We used a dose-response model to assess whether there was a response across the four groups on the basis of the primary end point, which was the percent change from baseline to 16 weeks in the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity score (CLASI-A; scores range from 0 to 70, with higher scores indicating more widespread or severe skin involvement). Safety was also assessed. RESULTS: A total of 132 participants were enrolled; 26 were assigned to the 50-mg litifilimab group, 25 to the 150-mg litifilimab group, 48 to the 450-mg litifilimab group, and 33 to the placebo group. Mean CLASI-A scores for the groups at baseline were 15.2, 18.4, 16.5, and 16.5, respectively. The difference from placebo in the change from baseline in CLASI-A score at week 16 was -24.3 percentage points (95% confidence interval [CI] -43.7 to -4.9) in the 50-mg litifilimab group, -33.4 percentage points (95% CI, -52.7 to -14.1) in the 150-mg group, and -28.0 percentage points (95% CI, -44.6 to -11.4) in the 450-mg group. The least squares mean changes were used in the primary analysis of a best-fitting dose-response model across the three drug-dose levels and placebo, which showed a significant effect. Most of the secondary end points did not support the results of the primary analysis. Litifilimab was associated with three cases each of hypersensitivity and oral herpes infection and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the participant received the last dose of litifilimab. CONCLUSIONS: In a phase 2 trial involving participants with cutaneous lupus erythematosus, treatment with litifilimab was superior to placebo with regard to a measure of skin disease activity over a period of 16 weeks. Larger and longer trials are needed to determine the effect and safety of litifilimab for the treatment of cutaneous lupus erythematosus. (Funded by Biogen; LILAC ClinicalTrials.gov number, NCT02847598.).

Myeloid neoplasm with histiocytosis and spleen tyrosine kinase fusion responds to fostamatinib.

Not available.

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.

Acute Interstitial Inflammation on Skin Biopsies and Positive Tissue Cultures in Cellulitis Patients Are Associated a Worse Prognosis.

BACKGROUND: Cellulitis is a significant public health burden and lacks a gold standard for diagnosis. Up to 1/3 of patients are incorrectly diagnosed. The skin biopsy has been proposed as the gold standard. OBJECTIVE: In this study, we evaluate the histopathologic characteristics and tissue culture positivity of biopsies in patients diagnosed with cellulitis seen by our inpatient dermatology consultation service. METHODS: This retrospective cohort study examined patients who were hospitalized with a skin and soft tissue infection at our institution between 2011 and 2020 and underwent a skin biopsy. RESULTS: Those with a positive tissue culture were more likely to die within 30 days compared with those with negative tissue cultures (26% vs. 6%, P = 0.048). Patients who died within 30 days were more likely to have acute interstitial inflammation as a feature on histopathology (38%, P = 0.03). LIMITATIONS: Single institutional design, unintentional exclusion of patients with organism-specific diagnosis, and selection for a medically complex patient population because of the nonroutine collection of biopsies. CONCLUSION: Positive tissue cultures and histopathology showing acute interstitial space inflammation on skin and soft tissue infection (SSTI) biopsies are associated with increased mortality and thus may serve as indicators of poor prognosis.

Management of Immunotherapy-Related Toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology.

The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions, consisting of medical and hematologic oncologists with expertise across a wide range of disease sites, and experts from the areas of dermatology, gastroenterology, endocrinology, neurooncology, nephrology, cardio-oncology, ophthalmology, pulmonary medicine, and oncology nursing. The content featured in this issue is an excerpt of the recommendations for managing toxicities related to CAR T-cell therapies and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to immune checkpoint inhibitors, visit NCCN.org.

The epidemiology, impact, and diagnosis of micronutrient nutritional dermatoses. Part 2: B-complex vitamins.

Nutritional dermatoses are traditionally taught in the context of developing countries, famine, population displacement, and limited access to health care. In the United States, nutritional dermatoses may be underdiagnosed, leading to increased morbidity and utilization of hospital resources. These findings underscore the need for providers in developed nations to be able to identify these deficiencies. Dermatologists play a critical role in the diagnosis and management of patients with nutritional deficiencies, as they often present with cutaneous findings. Part 2 of this review series will focus on the epidemiology, impact, manifestations, and diagnosis of B-complex vitamins, which can present with cutaneous findings, including thiamine, riboflavin, niacin, pyridoxine, and biotin.

The evaluation and management of macronutrient deficiency dermatoses.

In industrialized countries, nutritional dermatoses are likely underdiagnosed and result in increased disease morbidity and utilization of hospital resources. These findings underscore the need for physicians to be able to correctly identify these deficiencies. Nutritional dermatoses may be split into micronutrient deficiencies and macronutrient deficiencies. This article is intended to serve as a supplement to a 2-part review of micronutrient deficiency dermatoses and highlights cutaneous findings in patients with protein-energy malnutrition and essential fatty acid deficiency. This article reviews the evaluation, cutaneous manifestations, and management of macronutrient deficiencies.

The epidemiology, impact, and diagnosis of micronutrient nutritional dermatoses part 1: Zinc, selenium, copper, vitamin A, and vitamin C.

Dermatologists play a critical role in diagnosing and managing nutritional deficiencies as they often present with cutaneous findings. Traditionally, nutritional dermatoses are taught in the context of developing countries, famine, population displacement, and poor health care access; however, in the United States, common risk factors include chronic liver disease, alcoholism, psychiatric disease, bariatric surgery, inflammatory bowel disease, and hemodialysis. Additionally, nutritional dermatoses may be underdiagnosed in the United States and result in increased morbidity and utilization of hospital resources. There is a need for providers in developed nations to identify these deficiencies, and this review aims to meet that practice gap and provide relevant context to these diseases for dermatologists. This 2-part review series will focus on the epidemiology, impact, appearance, and diagnostic modalities for micronutrient deficiencies, including zinc, selenium, copper, and vitamins A and C in part 1. The companion review will focus on the B-complex vitamins.

In vitro diagnostics for the medical dermatologist. Part I: Autoimmune tests.

Despite the expansion of available in vitro laboratory tests at a rate far exceeding that of dermatologic pharmaceuticals, the existing literature is dominated by discussion of the latter. With the advent of numerous new tests, it can be difficult for practicing dermatologists to stay up-to-date on the available options, methodologies, and recommendations for when to order one test over another. Understanding the inherent strengths and weaknesses of these options is necessary to inform appropriate ordering and proper interpretation of the results. The first article in this continuing medical education series summarizes information on methodology, test characteristics, and limitations of several in vitro laboratory tests used for the work up of undifferentiated patients suspected of having dermatologic autoimmune diseases and it provides a general guide to ordering these tests.

In vitro diagnostics for the medical dermatologist. Part II: Hypercoagulability tests.

The skin often provides initial clues of hypercoagulability with features such as livedo reticularis, livedo racemosa, retiform purpura, necrosis, and ulcerations. Because these cutaneous manifestations are nonspecific, laboratory testing is often needed to evaluate for underlying causes of hypercoagulability. Importantly, these disorders are reported to be the most common mimicker, resulting in an erroneous diagnosis of pyoderma gangrenosum. Understanding inherent properties of, and indications for, available tests is necessary for appropriate ordering and interpretation of results. Additionally, ordering of these tests in an indiscriminate manner may lead to inaccurate results, complicating the interpretation and approach to management. This second article in this continuing medical education series summarizes information on methodology, test characteristics, and limitations of several in vitro laboratory tests used for the work up of hypercoagulability and vasculopathic disease as it pertains to dermatologic disease.

A virtual faculty exchange program enhances dermatology resident education in the COVID-19 era: a survey study.

One of the many consequences of the COVID-19 pandemic was the cancelation of the 2020 American Academy of Dermatology Annual Meeting. This conference historically features lectures from world-renowned experts in all areas of dermatology, thus providing an important educational experience for dermatology residents. We hypothesized that the cancellation of this meeting produced a substantial educational loss for dermatology residents. To mitigate this impact, we developed a virtual faculty exchange program and surveyed dermatology residents' perspectives on its implementation. All participating residents found the virtual faculty exchange useful and would recommend it to other residents/programs. Moreover, all residents wanted to participate in more faculty exchange sessions as well as incorporate them throughout the academic year. Additionally, this educational program eliminated the potential cost of >$15,000 in flights and >24 metric tons of carbon emissions. This virtual faculty exchange program is a viable tool to enhance dermatology resident education in the COVID-19 era.

NCCN Guidelines Insights: Management of Immunotherapy-Related Toxicities, Version 1.2020.

The NCCN Guidelines for Management of Immunotherapy-Related Toxicities provide interdisciplinary guidance on the management of immune-related adverse events (irAEs) resulting from cancer immunotherapy. These NCCN Guidelines Insights describe symptoms that may be caused by an irAE and should trigger further investigation, and summarize the NCCN Management of Immunotherapy-Related Toxicities Panel discussions for the 2020 update to the guidelines regarding immune checkpoint inhibitor-related diarrhea/colitis and cardiovascular irAEs.

Cannabinoids for the treatment of chronic pruritus: A review.

Medical marijuana is becoming widely available to patients in the United States, and with recreational marijuana now legalized in many states, patient interest is on the rise. The endocannabinoid system plays an important role in skin homeostasis in addition to broader effects on neurogenic responses such as pruritus and nociception, inflammation, and immune reactions. Numerous studies of in vitro and animal models have provided insight into the possible mechanisms of cannabinoid modulation on pruritus, with the most evidence behind neuronal modulation of peripheral itch fibers and centrally acting cannabinoid receptors. In addition, human studies, although limited due to differences in the cannabinoids used, disease models, and delivery method, have consistently shown significant reductions in both scratching and symptoms in chronic pruritus. Clinical studies have shown a reduction in pruritus in several dermatologic (atopic dermatitis, psoriasis, asteatotic eczema, prurigo nodularis, and allergic contact dermatitis) and systemic (uremic pruritus and cholestatic pruritus) diseases. These preliminary human studies warrant controlled trials to confirm the benefit of cannabinoids for treatment of pruritus and to standardize treatment regimens and indications. In patients who have refractory chronic pruritus after standard therapies, cannabinoid formulations may be considered as an adjuvant therapy where it is legal.

Predictors of 30-day readmission in Stevens-Johnson syndrome and toxic epidermal necrolysis: A cross-sectional database study.

BACKGROUND: The predictors of readmission in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have not been characterized. OBJECTIVE: To determine the variables predictive of 30-day readmission after SJS/TEN hospitalization. METHODS: We performed a cross-sectional study of the 2010-2014 Nationwide Readmissions Database. Bivariate and multivariable logistic regression was used to evaluate associations of patient demographics, comorbidities, and hospital characteristics with readmission. Aggregate and per-readmission costs were calculated. RESULTS: There were 8837 index admissions with SJS/TEN reported; of these, 910 (10.3%) were readmitted, with diagnoses including systemic infection (22.0%), SJS/TEN (20.6%), and cutaneous infection (9.1%). Associated characteristics included age 45 to 64 years (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.43-2.49), Medicaid insurance (OR, 1.83; 95% CI, 1.48-2.27), and nonmetropolitan hospital admission (OR, 1.67; 95% CI, 1.31-2.13). Associated comorbidities included HIV/AIDS (OR, 2.48; 95% CI, 1.63-3.75), collagen vascular disease (OR, 2.38; 95% CI, 1.88-3.00), and metastatic cancer (OR, 2.16; 95% CI, 1.35-3.46). The median per-readmission cost was $10,019 (interquartile range, $4,788-$16,485). LIMITATIONS: The Nationwide Readmissions Database lacks the ability to track the same patient across calendar years. The diagnostic code lacks specificity for hospitalizations <3 days. CONCLUSIONS: Thirty-day readmissions after SJS/TEN hospitalizations are common. Dedicated efforts to identify at-risk patients may improve peridischarge continuity.

Improved patient access and outcomes with the integration of an eConsult program (teledermatology) within a large academic medical center.

BACKGROUND: Insurance, racial, and socioeconomic health disparities continue to pose significant challenges for access to dermatologic care. Studies applying teledermatology to increase access to underinsured individuals and ethnic minorities are limited. OBJECTIVE: To determine how the implementation of a teledermatology program affects access to health care and patient outcomes. METHODS: A cross-sectional evaluation was performed of all ambulatory dermatology referrals and electronic dermatology consultations (eConsults) at Ohio State University within a 25-month period. RESULTS: Compared with ambulatory referrals, eConsults served more nonwhite patients (612 of 1698 [36.0%] vs 4040 of 16,073 [25.1%]; P < .001) and more Medicaid enrollees (459 of 1698 patients [27.0%] vs 3266 of 16,073 [20.3%]; P < .001). In addition, ambulatory referral patients were significantly less likely to attend their scheduled appointment compared with eConsult patients, as either "no-shows" (246 of 2526 [9.7%] vs 3 of 62 [4.8%]) or cancellations (742 of 2526 [29.4%] vs 8 of 62 [12.9%]; P = .003). There were fewer median days to extirpation for eConsult patients compared with ambulatory referral patients (interquartile range; 80.7 ± 79.8 vs 116.9 ± 86.6 days; P = .004). CONCLUSION: Integrating dermatologic care through a telemedicine system can result in improved access for underserved patients through improved efficiency outcomes.

Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.

Dermatology-specific and all-cause 30-day and calendar-year readmissions and costs for dermatologic diseases from 2010 to 2014.

BACKGROUND: Readmissions for skin disease, particularly for the same diagnosis and over time, have not been well studied. OBJECTIVE: To characterize hospital readmissions for skin disease. METHODS: A cross-sectional observational study examined the Nationwide Readmissions Database from 2010 to 2014, a national sample of hospital discharges in the United States. RESULTS: Of the patients in 3,602,599 dermatologic hospitalizations from 2010 to 2014, 9.8% were readmitted for any cause, 3.3% were admitted for the same diagnosis within 30 days, and 7.8% were readmitted for the same diagnosis within the calendar year (CY). The cost of all CY same-cause readmissions was $508 million per year. Mycosis fungoides had the highest 30-day all-cause readmission rate (32%), vascular hamartomas and dermatomyositis had the highest 30-day same-cause readmission rates (21% and 18%, respectively), and dermatomyositis and systemic lupus erythematosus had the highest CY same-cause readmission rates (31% and 24%, respectively). Readmission rates stayed stable from 2010 to 2014. Readmission for the same diagnosis was strongly associated with Medicaid and morbid obesity. LIMITATIONS: This study is a broad description of hospitalizations for skin disease. Conclusions for individual diseases are not intended. CONCLUSION: The rates and costs of readmissions for skin diseases remained high from 2010 to 2014. This study identifies diseases associated with high risk of hospital readmission, but disease-specific studies are needed. The diseases and risk factors presented should guide additional studies focused on strategies to reduce readmissions in specific skin diseases.

Distinguishing Stevens-Johnson syndrome/toxic epidermal necrolysis from clinical mimickers during inpatient dermatologic consultation-A retrospective chart review.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions that may present with similar findings to other severe dermatologic diseases. OBJECTIVE: The primary objective of this exploratory study was to explore factors associated with SJS/TEN and develop a model that provides the predicted probability of SJS/TEN for patients for whom the diagnosis of SJS/TEN is considered. METHODS: Retrospective review of consultations for patients with suspected SJS, TEN, or overlap at 4 academic dermatology consultation services. RESULTS: Overall, 208 patients were included; 59 (28.4%) had a final diagnosis of SJS/TEN, and 149 (71.6%) were given a different diagnosis. The most common mimickers were drug hypersensitivity syndrome (n = 21, 10.1%), morbilliform drug eruption (n = 18, 8.7%), erythema multiforme (n = 15, 7.2%), and acute generalized exanthematous pustulosis (n = 13, 6.2%). Nikolsky sign, atypical targets, fever, and lymphopenia were included in a model for predicting the probability of SJS/TEN. LIMITATIONS: All cases were obtained from academic centers, which may limit the generalization of findings to community-based settings. This was an exploratory study with a small number of cases, and external validation of the model performance is needed. CONCLUSION: Early dermatologic evaluation of patients with suspected SJS/TEN is key to separating patients with this condition from those who ultimately receive diagnoses of other serious skin diseases.