IPEX SYNDROME
Key features
X-linked recessive disorder due to mutations in FOXP3
Cutaneous findings include a widespread eczematous dermatitis during infancy and a variety of autoimmune skin conditions
Also features enteropathy and endocrinopathies with autoimmune etiologies
IPEX – immune dysregulation, polyendocrinopathy, enteropathy, X-linked – syndrome is an X-linked recessive disorder caused by FOXP3 mutations that result in abnormal development of regulatory T cells. Affected individuals typically present during infancy with severe diarrhea secondary to autoimmune enteropathy and develop a variety of autoimmune endocrinopathies such as early-onset type 1 diabetes mellitus, thyroiditis, and cytopenias. Most IPEX patients have a widespread eczematous dermatitis and elevated IgE levels during early infancy, and this is often complicated by staphylococcal superinfections and sepsis. Cutaneous manifestations of IPEX can also include psoriasiform dermatitis, cheilitis, nail dystrophy, and autoimmune skin conditions such as alopecia areata, chronic urticaria, and bullous pemphigoid.
IPEX-like clinical presentations can occur in patients with IL-2 receptor α-chain (CD25) deficiency, LPS-responsive beige-like anchor protein (LRBA) deficiency, gain-of-function STAT1 or STAT3 mutations, and loss-of-function STAT5B mutations (see Tables 60.4, 60.13, 60.15). In addition, an autosomal recessive disorder due to mutations in ADAM17, which encodes the TNF converting enzyme, features a widespread psoriasiform dermatitis with pustular flares, brittle hair, staphylococcal skin infections, and chronic diarrhea.
Table 60.4 Variants of chronic mucocutaneous candidiasis (CMC) in children and adolescents.