Cutaneous Langerhans Cell Histiocytosis Responsive to Topical Nitrogen Mustard.

Langerhans cell histiocytosis (LCH) limited to the skin is rare in adult patients. Given the challenges of prospective clinical trials for this rare disease, there is paucity in data to guide the management of cutaneous LCH. Topical nitrogen mustard is a possible treatment for cutaneous LCH with positive responses in five known adult cases in the literature. In this report, we present two adult patients with recalcitrant cutaneous LCH and no evidence of systemic involvement who had rapid and complete response on topical nitrogen mustard therapy. We provide support for topical nitrogen mustard as a treatment option for primary cutaneous LCH which may spare patients from requiring systemic immunosuppressive treatments. J Drugs Dermatol. 2020;19(8):803-805. doi:10.36849/JDD.2020.4943.

Acquired acrodermatitis enteropathica after gastric bypass surgery responsive to IV supplementation.

Nutritional deficiency is rare in developed countries, but can be acquired from decreased nutrient intake, reduced absorption, and increased gastrointestinal excretion. We report a patient with acquired acrodermatitis enteropathica (AE) who exhibited low plasma zinc levels and concurrent nutritional deficiencies (pyridoxine, selenium and fatty acids). Our patient had undergone Roux-en-Y gastric bypass 13 years prior to presentation. The rash, consistent with AE clinically and histologically, nearly resolved one week after starting IV zinc supplementation, total parenteral nutrition, and micronutrient supplements. This case highlights the importance of long-term post-operative follow-up for gastric bypass patients who are at high risk for micronutrient and macronutrient deficiencies and illustrates the potential for rapid improvement with IV supplementation.

Severe Tacrolimus-Induced Granulomatous Rosacea Recalcitrant to Oral Tetracyclines.

Topical tacrolimus has been observed to induce granulomatous rosacea (GR) in prior case reports and series. In most cases, patients recover fully after withdrawing tacrolimus and initiating doxycycline or minocycline. Herein, we describe a case of severe GR, which required further therapy. Clinicians should be aware of this rare complication because of the frequent use of topical tacrolimus.

Association between BRAFV600E and NRASQ61R mutations and clinicopathologic characteristics, risk factors and clinical outcome of primary invasive cutaneous melanoma.

PURPOSE: Previous studies suggest that solar UV exposure in early life is predictive of cutaneous melanoma risk in adulthood, whereas the relation of BRAF mutation with sun exposure and disease prognosis has been less certain. We investigated the associations between BRAF(V600E) and NRAS(Q61R) mutations and known risk factors, clinicopathologic characteristics and clinical outcomes of melanoma in a case series of primary invasive cutaneous melanoma from the Nurses' Health Study (NHS). METHODS: Somatic BRAF(V600E) and NRAS(Q61R) mutations of 127 primary invasive melanomas from the NHS cohort were determined by pyrosequencing using formalin-fixed, paraffin-embedded block tissues. Logistic regression analyses were performed to detect the associations of mutations with melanoma risk factors, and Kaplan-Meier method was used to examine associations between mutations and survival. RESULTS: The odds ratios for harboring BRAF(V600E) mutations were 5.54 (95% CI 1.19-25.8, p(trend) = 0.02) for women residing in states with UV index ≥ 7 versus those residing in states with UV index ≤5 at 30 years of age. Patients with BRAF(V600E) mutations tended to have shorter melanoma-specific survival when compared to patients with wild type at both loci (median survival time 110 vs. 159 months) (p = 0.03). No association was found between NRASQ61R mutation and melanoma risk factors or melanoma-specific survival. CONCLUSIONS: BRAF(V600E) mutations in primary cutaneous melanomas were associated with residence in locations with medium and high UV indices in mid-life. BRAF(V600E) mutation may be associated with an unfavorable prognosis among melanoma patients.

CXCR4 pathway associated with family history of melanoma.

PURPOSE: Genetic predisposition plays a major role in the etiology of melanoma, but known genetic markers only account for a limited fraction of family-history-associated melanoma cases. Expression microarrays have offered the opportunity to identify further genomic profiles correlated with family history of melanoma. We aimed to distinguish mRNA expression signatures between melanoma cases with and without a family history of melanoma. METHODS: Based on the Nurses' Health Study, family history was defined as having one or more first-degree family members diagnosed with melanoma. Melanoma diagnosis was confirmed by reviewing pathology reports, and tumor blocks were collected by mail from across the USA. Genomic interrogation was accomplished through evaluating expression profiling of formalin-fixed paraffin-embedded tissues from 78 primary cutaneous invasive melanoma cases, on either a 6K or whole-genome (24K) Illumina gene chip. Gene set enrichment analysis was performed for each batch to determine the differentially enriched pathways and key contributing genes. RESULTS: The CXC chemokine receptor 4 (CXCR4) pathway was consistently up-regulated within cases of familial melanoma in both platforms. Leading edge analysis showed four genes from the CXCR4 pathway, including MAPK1, PLCG1, CRK, and PTK2, were among the core members that contributed to the enrichment of this pathway. There was no association between the enrichment of CXCR4 pathway and NRAS, BRAF mutation, or Breslow thickness of the primary melanoma cases. CONCLUSIONS: We found that the CXCR4 pathway might constitute a novel susceptibility pathway associated with family history of melanoma in first-degree relatives.