Safety of dupilumab in a 5-month-old infant with severe atopic dermatitis.

Dupilumab is a fully humanized monoclonal antibody that suppresses Th2-mediated inflammation by inhibiting signaling of interleukin-4 and interleukin-13 through the interleukin-4 alpha receptor subunit, and is approved by the FDA for the treatment of moderate to severe atopic dermatitis (AD) in children 6 years of age and older. While initial data from phase 2 trials in children less than 6 years are promising, dupilumab use in children less than 6 months of age is not well studied. Here we present a case of a 5-month-old boy with severe primary AD, eosinophilia, hypogammaglobulinemia, and poor weight gain, who was successfully treated with dupilumab and experienced no serious adverse effects. To our knowledge, this is the youngest patient to receive dupilumab to date.

New-onset head and neck dermatitis in adolescent patients after dupilumab therapy for atopic dermatitis.

BACKGROUND/OBJECTIVES: Head and neck dermatitis after dupilumab therapy for atopic dermatitis has been frequently reported in adults and only rarely in adolescents. No cases detailing disease course and treatment response have previously been described in adolescents. METHODS/RESULTS: This case series presents five adolescent patients who developed new-onset or worsening head and neck dermatitis after dupilumab therapy for atopic dermatitis. All five patients improved after oral antifungal therapy. CONCLUSIONS: The clinical features, treatment response, and potential disease pathogenesis in pediatric patients are described. Adolescents with new-onset head and neck dermatitis after dupilumab therapy may clinically improve with antifungal therapy, suggesting that Malassezia species may be a contributing factor or antifungal therapy may be an effective antiinflammatory agent.

Shapiro xanthogranuloma: An essential diagnosis for dermatologists and dermatopathologists to recognize to avoid misdiagnosis of a hematopoietic malignancy in infants and neonates.

The Shapiro xanthogranuloma is a histopathologic form of xanthogranuloma that shows closely packed monomorphous cells, which can extend into the subcutaneous fat; it usually lacks routine diagnostic features of xanthogranuloma. Herein we describe two cases of Shapiro xanthogranuloma occurring in a neonate and in an infant, which were initially thought to be hematologic malignancies. One patient's presentation as a "blueberry muffin baby" added to the diagnostic confusion. Pediatric dermatologists, dermatologists, and dermatopathologists need to be aware of the Shapiro xanthogranuloma and its clinicopathologic features to avoid misdiagnosis of a hematopoietic malignancy in neonates and infants.

An atrophic plaque on the breast six years after breast reconstruction surgery.

Necrobiosis lipoidica (NL) is a cutaneous disease entity that typically manifests as atrophic yellow plaques with telangiectasias on the anterior tibial region. Although NL is commonly associated with diabetes mellitus, the role of trauma in disease development is less commonly emphasized. The relationship between NL and the Köbner phenomenon has been established, as a few cases of NL occurring in surgical scars have been reported in the literature. We report the first case of NL occurring in a mastectomy scar on the breast in a non-diabetic female, and explore the relationship between NL, diabetes mellitus, and trauma.

Novel mechanism for Fc{epsilon}RI-mediated signal transducer and activator of transcription 5 (STAT5) tyrosine phosphorylation and the selective influence of STAT5B over mast cell cytokine production.

Previous studies indicate that STAT5 expression is required for mast cell development, survival, and IgE-mediated function. STAT5 tyrosine phosphorylation is swiftly and transiently induced by activation of the high affinity IgE receptor, FcεRI. However, the mechanism for this mode of activation remains unknown. In this study we observed that STAT5 co-localizes with FcεRI in antigen-stimulated mast cells. This localization was supported by cholesterol depletion of membranes, which ablated STAT5 tyrosine phosphorylation. Through the use of various pharmacological inhibitors and murine knock-out models, we found that IgE-mediated STAT5 activation is dependent upon Fyn kinase, independent of Syk, PI3K, Akt, Bruton's tyrosine kinase, and JAK2, and enhanced in the context of Lyn kinase deficiency. STAT5 immunoprecipitation revealed that unphosphorylated protein preassociates with Fyn and that this association diminishes significantly during mast cell activation. SHP-1 tyrosine phosphatase deficiency modestly enhanced STAT5 phosphorylation. This effect was more apparent in the absence of Gab2, a scaffolding protein that docks with multiple negative regulators, including SHP-1, SHP-2, and Lyn. Targeting of STAT5A or B with specific siRNA pools revealed that IgE-mediated mast cell cytokine production is selectively dependent upon the STAT5B isoform. Altogether, these data implicate Fyn as the major positive mediator of STAT5 after FcεRI engagement and demonstrate importantly distinct roles for STAT5A and STAT5B in mast cell function.