1/4. 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. OBSERVATIONS: 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.- - - - - - - - - - ranking = 1keywords = diabetes (Clic here for more details about this article) |
2/4. Prospective immunological profiling in a case of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX).IPEX syndrome is a genetic autoimmune disease characterized by immune-mediated polyendocrinopathy, enteropathy, and X-linked inheritance. We describe a case of IPEX in which lymphocyte phenotypes were assessed at birth, before initiation of Cyclosporin A therapy, and at frequent intervals to 18 months of age. We performed flow cytometry for lymphocyte subtypes and for activation markers (HLA-DR, CD25, and CD69 or CD71). The ratios of both T to B cells and CD4 to CD8 cells were elevated at birth, but CD4 cells were not activated. HLA-DR and CD25 activated T-cells increased in association with two episodes of clinical deterioration: colitis and the onset of type I diabetes mellitus. These results indicate that measures of activation, particularly HLA-DR and CD25 frequency, correlate well with the development of early active disease and may presage clinical episodes. Continuous maintenance of immunosuppression, once started, appears critical for prevention of permanent tissue damage.- - - - - - - - - - ranking = 1keywords = diabetes (Clic here for more details about this article) |
3/4. Efficacy of COX-2 inhibitors in a case of congenital nephrogenic diabetes insipidus.A 17-month-old boy presented with failure to thrive, polyuria, and vomiting. He had been diagnosed clinically with nephrogenic diabetes insipidus and treated by amiloride and hydrochlorothiazide combination without a satisfactory outcome at another center since 1 year of age. The diagnosis was confirmed by genetic analysis (AVPR2mutation), and the treatment was modified to include rofecoxib (a selective cyclooxygenase-2 inhibitor) in addition to hydrochlorothiazide and amiloride. This combination along with a low-salt diet resulted in a dramatic decrease in urinary free-water loss, while no side effect was noted. Because of prohibition of rofecoxib, it had to be substituted first by indomethacin and then by ibuprofen. However, both drugs were ineffective in controlling water diuresis. Thus, we had to replace these drugs by celecoxib (another selective cyclooxygenase-2 inhibitor). We conclude that the combination hydrochlorothiazide/amiloride/cyclooxygenase-2 inhibitor could be successfully used to treat congenital nephrogenic diabetes insipidus.- - - - - - - - - - ranking = 689.46542394644keywords = diabetes insipidus, insipidus, diabetes (Clic here for more details about this article) |
4/4. Mechanistic associations of a mild phenotype of immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome.BACKGROUND & AIMS: The syndrome of immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is a rare disorder resulting in the expression of multiple autoimmune and allergic features. Early onset enteropathy and type 1 diabetes (T1D) are the most common clinical features. The IPEX syndrome is caused by mutations of the FOXP3 gene, which is essential for the development of regulatory T cells (Treg). We describe 2 unrelated patients with IPEX syndrome with a mild clinical phenotype and with novel FOXP3 mutations and the phenotypic and functional characterization of their Treg cells. methods: The FOXP3 gene was analyzed by sequencing amplimers from genomic dna. Treg cells were characterized by evaluating the number of CD4 CD25 T cells and their functional ability to suppress the proliferation of autologous CD4 CD25- effector T cells stimulated with anti-CD3 and anti-CD28 antibodies. RESULTS: A 7-year-old boy and a 24-year-old man presented with autoimmune enteropathy characterized by early onset persistent diarrhea not associated with T1D or other endocrinopathies. These 2 patients carry novel FOXP3 mutations that do not abrogate the function of the forkhead domain. They have normal numbers of CD4 CD25 T lymphocytes, however, these show severely defective suppressive function in vitro. CONCLUSIONS: Our 2 patients show that IPEX patients may present with early onset enteropathy and long-term survival without T1D or other endocrinopathies. This milder phenotype may be associated with FOXP3 mutations that do not abrogate the function of the forkhead domain.- - - - - - - - - - ranking = 1keywords = diabetes (Clic here for more details about this article) |