Clinical and Laboratory Observation
Successful Use of the New Immune-suppressor Sirolimus in IPEX (Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked Syndrome)

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IPEX (immune-dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome is an autoimmune disorder with an often lethal outcome in spite of immunosuppressive therapy. We report the successful use of sirolimus in 3 patients with IPEX. The efficacy of sirolimus is probably due to its different mode of action compared to calcineurin-dependent agents.

Section snippets

Clinical Report

Patient 1 is the only male child of unrelated white parents, born at term with an uneventful medical history. At the age of 7 years, he had development of dermatitis, affecting hands and feet, and bloody-watery diarrhea without any evidence of infection. Initially, food allergy was suspected on the basis of markedly elevated serum immunoglobulin E (IgE) levels (17370 kU/L). Dramatic worsening of diarrhea, unresponsive to steroid treatment and an elemental diet with an amino acid–based formula

Discussion

Therapeutic options to control the life-threatening symptoms, caused by mutations of FOXP3, are limited. The most common immunosuppressive treatment, a combination of steroids and the calcineurin suppressive agents, CsA or tacrolimus, is only partially effective, and the dose is limited in large part by renal toxicity. Because of these shortfalls, we explored the clinical utility of sirolimus in 3 patients with IPEX caused by mutations of FOXP3. Unlike CsA or tacrolimus, sirolimus does not

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    The most common immunosuppressive treatment, a combination of steroids and the calcineurin suppressive agents CsA or tacrolimus, is partially effective, and the dose is limited in large part by renal toxicity. There is a report that sirolimus controlled the gastrointestinal and dermatologic symptoms of IPEX in three patients without significant side effects (Bindl et al., 2005). Presently, hematopoietic stem cell transplantation (HSCT) is the best hope to cure IPEX even though its success is uncertain.

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