Dermatologic and immunologic findings in the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.
BACKGROUND
The immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare genodermatosis associated with dermatitis, enteropathy, type 1 diabetes, thyroiditis, hemolytic anemia, and thrombocytopenia. IPEX results from mutations of FOXP3, a gene located on the X chromosome that encodes a DNA-binding protein required for development of regulatory T cells. If untreated, affected males die early in life from malabsorption and other complications. To our knowledge, this syndrome has never been described in the dermatology literature.


METHODS
We studied an 11-year-old boy with IPEX. Mutation analysis revealed a G-->A transition (1150G>A) in exon 11, resulting in a putative substitution of Ala-->Thr at residue 384, within the DNA-binding site. Histopathologic examination of an active skin lesion revealed psoriasiform dermatitis. The lesions improved with clobetasol ointment. The patient also displayed alopecia universalis, which had been present since age 18 months, accompanied by longitudinal ridging of the nails. Lymphocyte challenge tests revealed a profound inability to synthesize interferon gamma (INF-gamma) and dysregulated production of other cytokines.


CONCLUSIONS
IPEX is an often fatal genodermatosis associated with multiple autoimmune disorders. Cutaneous findings may include dermatitis, bullae, urticaria, alopecia universalis, and trachyonychia. Recognition of this life-threatening disorder is crucial for optimal treatment and genetic counseling.
Nieves
David S
DS
Department of Dermatology, University of Rochester, Rochester, NY, USA. dsnieves@hotmail.com
Phipps
Richard P
RP
Pollock
Stephen J
SJ
Ochs
Hans D
HD
Zhu
Qili
Q
Scott
Glynis A
GA
Ryan
Charlotte K
CK
Kobayashi
Ichiro
I
Rossi
Thomas M
TM
Goldsmith
Lowell A
LA
D001483:Base Sequence; D001707:Biopsy, Needle; D002648:Child; D004268:DNA-Binding Proteins / Q000032:analysis*; D018450:Disease Progression; D005500:Follow-Up Studies; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D016884:Polyendocrinopathies, Autoimmune / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D016133:Polymerase Chain Reaction; D018570:Risk Assessment; D012720:Severity of Illness Index
D004268:DNA-Binding Proteins