D. Blau syndrome
A skin biopsy from the ichthyosiform rash on the right arm showed small noncaseating granulomas, multinucleated giant cells, and neutrophil infiltration in the dermis and subcutis. Acid-fast staining, Gomori methenamine-silver staining, and modified Ziehl-Neelsen staining all showed an absence of microorganisms, and sarcoidosis was confirmed. Whole-exome sequencing revealed a heterozygous missense variation (Arg334Trp) in NOD2 that has previously been detected in Blau syndrome.1 Accordingly, the diagnosis of Blau syndrome was confirmed.
Blau syndrome is an autosomal dominant inflammatory disease characterized by a triad of granulomatous dermatitis, uveitis, and systemic polyarthritis. Variations in NOD2/CARD15 on chromosome 16q12 have been identified in patients with Blau syndrome. NOD2/CARD15 is primarily expressed in monocytes, a cell type capable of differentiation into multinucleated giant cells and epithelioid cells.2 It has been hypothesized that NOD2/CARD15 variation is associated with increased NF-kB activation, macrophage death, and granulomatous inflammation.2