Demographics, Cutaneous Manifestations, and Comorbidities Associated with Progressive Cutaneous Sarcoidosis: A Retrospective Cohort Study.

Background: Sarcoidosis is a multisystem granulomatous disease with a wide variety of presentations and clinical courses. Cutaneous manifestations and comorbidities associated with sarcoid prognosis remain understudied. Methods: An EPIC query was run for patients age 18+ at the Johns Hopkins Hospital with a diagnosis of sarcoidosis of the skin according to the ICD-10-CM code D86.3. Data were obtained from a population-based sample of 240 patients from 2015 to 2020. Results: A total of 240 patients were included in the cohort study. The mean (SD) age was 43.76 (11.72) years, and 30% of participants were male; 76.25% of patients identified as black, 19.58% as white, and 4.17% as other. The average age of onset in remissive patients was significantly higher than progressive (47 ± 12 vs. 40 ± 10, p = 0.0005); 49% of black patients experienced progressive sarcoid compared to 32.6% of white patients (p = 0.028). Progressive disease was associated with the presence of lupus pernio (aOR = 3.29, 95% CI, 1.60-6.77) and at least one autoimmune comorbidity (aOR 6.831, 95% CI 1.819-11.843). Conclusions: When controlling for patient demographics, lupus pernio and the presence of at least one autoimmune condition were associated with progressive cutaneous sarcoidosis.

Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study.

Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observational pharmacovigilance study using VigiBase, the World Health Organization's global database of individual case safety reports from over 130 member countries (ClinicalTrials.gov, number NCT04898751). We compared adverse event reporting in patients who received immune checkpoint inhibitors (91,323 adverse events) with those of the full reporting database (18,919,358 adverse events). There were 10,933 cases of cirAEs within 51 distinct dermatologic types, with 27 specific eruptions with disproportionate signal represented (information component [IC]025 > 0). Of these 27 eruptions, there were eight cirAEs with n > 100 reports, including vitiligo (IC025 = 4.87), bullous pemphigoid (IC025 = 4.08), lichenoid dermatitis (IC025 = 3.69), erythema multiforme (IC025 = 1.03), toxic epidermal necrolysis (IC025 = 0.95), Stevens‒Johnson syndrome (IC025 = 0.41), drug eruption (IC025 = 0.11), and eczematous dermatitis (IC025 = 0.11). There were differences in time to onset after immune checkpoint inhibitor initiation, with a median of approximately 1 month (erythema multiforme, Stevens‒Johnson syndrome, and toxic epidermal necrolysis), 2 months (drug eruption and eczematous dermatitis), 4 months (lichenoid dermatitis), and 5‒6 months (bullous pemphigoid and vitiligo). CirAEs are diverse, dependent on cancer type, and have distinct and different onset times that are linked to the cirAE subtype.

Comorbidities Associated with Granuloma Annulare: A Cross-Sectional, Case-Control Study.

Background: Granuloma annulare (GA) is a cutaneous granulomatous disorder of unknown etiology. There are conflicting data on the association between GA and multiple systemic conditions. As a result, we aimed to clarify the reported associations between GA and systemic conditions. Methods: A retrospective, cross-sectional, case-control study was performed in which the medical records of biopsy-confirmed GA patients ≥18 years of age, who presented to the Johns Hopkins Hospital System between 1 January 2009 and 1 June 2019, were reviewed. GA patients were compared to controls matched for age, race, and sex. Results: After adjusting for confounders, GA patients (n = 82) had higher odds of concurrent type II diabetes (odds ratio (OR) = 5.27; 95% confidence interval (CI), 1.73-16.07; p < 0.01), non-migraine headache (OR = 8.70; 95% CI, 1.61-46.88; p = 0.01), and a positive smoking history (OR = 1.93; 95% CI, 1.10-3.38; p = 0.02) compared to controls (n = 164). Among GA patients, women were more likely to have ophthalmic conditions (p = 0.04), and men were more likely to have cardiovascular disease (p < 0.01) and type II diabetes (p = 0.05). No differences in systemic condition associations were observed among GA subtypes. Conclusions: Our results support the reported association between GA and type II diabetes. Furthermore, our findings indicate that GA may be associated with cigarette smoking and non-migraine headache disorders.

Correlation of clinical and pathologic evaluation of scarring alopecia.

BACKGROUND: Differentiating scarring and nonscarring alopecia poses a diagnostic dilemma for clinicians, with histopathology used to distinguish. The extent to which dermatologists are able to clinically classify alopecia has not been evaluated. METHODS: A retrospective study of pathology reports on 458 patients was used to calculate a kappa coefficient to correlate clinical presence of scarring or nonscarring alopecia to histopathologic presence of scarring or nonscarring. A multivariate analysis was performed to assess for associations with scarring. RESULTS: The kappa correlation coefficient was 0.59 (P < 0.0001), indicating moderate agreement and varied by race and sex. There were 15 times higher odds of making the clinical diagnosis of scarring alopecia (OR 14.64 95% CI [8.64-24.18]; P < 0.001), and this increased with age. CONCLUSIONS: These results suggest that clinical exam is moderately reliable in distinguishing between scarring and nonscarring alopecia. Our results highlight the need for education and diagnostic schemata for evaluation of alopecia based on gender and in skin of color.

Levamisole adulterated cocaine associated ANCA vasculitis: review of literature and update on pathogenesis.

Levamisole is an antihelminth drug and a common cocaine contaminant, present in an estimated 71% of cocaine samples in the US. Levamisole-contaminated cocaine has been linked to an ANCA-associated vasculitis with cutaneous, renal, and pulmonary manifestations. We report the case of a 46 year old woman with known cocaine exposure who presents with recurrent, large purpuric and maculopapular rash of the extremities and face and review existing cases of levamisole/cocaine-associated ANCA vasculitis, We summarize the clinical presentation, treatment, and outcomes of levamisole induced vasculitis. There is emerging research on pathogenesis relating to neutrophil extracellular traps (NETs). We review studies implicating role of NETs in the pathogenesis of levamisole induced vasculitis. Further research to explore the use of NETs as therapeutic targets in drug induced vasculitis is needed.

Aprepitant for the Treatment of Chronic Refractory Pruritus.

Chronic pruritus is a difficult condition to treat and is associated with several comorbidities, including insomnia, depression, and decreased quality of life. Treatment for chronic itch includes corticosteroids, antihistamines, and systemic therapies such as naltrexone, gabapentin, UV light therapy, and immunomodulatory treatments, including azathioprine, methotrexate, and cellcept. However, some patients still remain refractory to conventional therapy. Aprepitant is a neurokinin-1 receptor antagonist approved for the prevention of chemotherapy-induced and postoperative nausea and vomiting (CINV, PONV). Recently, aprepitant has demonstrated effectiveness in several case series and open label trials in relieving pruritus for patients refractory to other treatments. Patients with pruritus associated with Sézary syndrome, mycosis fungoides, lung adenocarcinoma, breast carcinoma, sarcomas, metastatic solid tumors, chronic kidney disease, hyperuricemia, iron deficiency, brachioradial pruritus, and Hodgkin's lymphoma have experienced considerable symptom relief with short-term use of aprepitant (up to two weeks). Due to differences in reporting and evaluation of drug effects, the mechanism of aprepitant's role is difficult to understand based on the current literature. Herein, we evaluate aprepitant's antipruritic effects and discuss its mechanism of action and adverse effects. We propose that aprepitant is an alternative for patients suffering from pruritus who do not obtain enough symptom relief from conventional therapy.

Two cases of alopecia areata treated with ruxolitinib: a discussion of ideal dosing and laboratory monitoring.

BACKGROUND: Alopecia areata is a relatively common condition affecting patients seen in community dermatology clinics. A 2014 study implicated the JAK1/JAK2 inhibitor, ruxolitinib in short-term treatment of alopecia, however little information exists about the long-term use in otherwise healthy individuals in the community setting. METHODS: A patient with chronic alopecia areata and a patient with acute onset alopecia universalis were treated with oral ruxolitinib for over a year. RESULTS: Both patients experienced sustained, near-complete regrowth without hematologic or other complications after one year of treatment. Oral ruxolitinib effectively and safely treated alopecia in two women. CONCLUSIONS: Ruxolitinib should be considered for cases of unresponsive alopecia in the community.

Treatment of mycosis fungoides with total skin electron beam: response and relapse by ethnicity and sex.

OBJECTIVE: To determine whether clinical response to total skin electron beam (TSEB) and relapse after TSEB differs by ethnicity and sex. METHODS: Retrospective chart review of 77 patients with mycosis fungoides (MF), treated with TSEB in 2002 to 2008 at Yale University School of Medicine, Departments of Dermatology and Therapeutic Radiology. RESULTS: Women had better odds of response to TSEB than men (OR=6.4; 95% CI, 1.45-28.5; P=0.01). No significant difference was observed in response to TSEB between white and black patients (OR=0.69; 95% CI, 0.16-2.91; P=0.62). When stratified by race and sex, in comparison with black females, all other groups had lower odds of complete response (CR) to TSEB: black males (OR=0.39; 95% CI, 0.002-0.70; P=0.03), white females (OR=0.24; 95% CI, 0.02-2.53; P=0.24), and white males (OR=0.06; 95% CI, 0.006-0.60; P=0.02). Clinical CR was significantly predicted by the duration of symptoms (OR=0.98; 95% CI, 0.97-0.99; P=0.01); and nearly significant by clinical stage; stage III to stage I (OR=0.17; 95% CI, 0.02-1.02; P=0.07). Adjuvant treatment, previous treatment, and time from diagnosis to treatment have no significant effect on CR to TSEB. There was no statistically significant association between relapse after treatment and race, sex, clinical stage, or symptom duration. CONCLUSIONS: The odds of achieving a CR to TSEB decrease when diagnosis of MF is delayed and when patients present with advanced-stage disease. Women with MF were more likely to have a CR to treatment, and this response was even more significant in black women.

Long-term retention of gadolinium in tissues from nephrogenic systemic fibrosis patient after multiple gadolinium-enhanced MRI scans: case report and implications.

Nephrogenic systemic fibrosis (NSF) is a painful and debilitating fibrosing disorder of the skin and systemic tissues. It is associated with exposure to Gd, used in MRIs and MRAs, in patients with renal insufficiency. We here present an illustrative example of a young patient who underwent multiple Gd-enhanced scans, both before and after developing severe NSF. We examined biopsy tissues for quantification of detectable insoluble Gd deposits using automated scanning electron microscopy/energy dispersive X-ray spectroscopy. High concentrations of Gd associated with calcium and phosphorus in skin persisted even 3 years after the last exposure to Gd. Such long-term retention of Gd raises further concerns about the utility and safety of Gd-based contrast agents. Residual Gd chelates, after initial and rapid renal clearance, can dissociate into insoluble, toxic Gd(3+) that precipitates with tissue anions. Bone serves as a site for Gd storage. Subsequent clearance and mobilization from such stores may explain the variable latency of onset of NSF. We hypothesize that long-term persistence and slow release of Gd(3+) from bone stores can be a cause for concern of Gd-associated toxicity with long latency.