IPEX Syndrome, A Rare Risk Factor for a Stroke in Children

Case History: Our patient developed first symptoms (atopic dermatitis) at the age of seven month. At 10 month a failure to thrive was diagnosed and he developed watery diarrhea. The bloodwork showed eosinophilia of 28%, high immunoglobulin E (8664 kU/l) and low immunoglobulin M < 0,25 g/l. Endoscopy showed ulcerative inflammation of the duodenum and focal Ulceration of the Colon. The histologic samples showed increased eosinophil granulocytes as well. Eosinophil enterocolitis was diagnosed and a diet with amino-acid-hydrolyzate was started, with add on therapy of Prednisolon (2 mg/kg/d) later on. At the age of 16 month the boy developed steroid-resistent-nephrotic syndrome. Renal biopsy showed membranous Glomerulonephritis and a therapy with Cyclosporin A and Ramipril was started which led to remission. At 18 month (shortly after CSA was started) the boy suffered an ischemic stroke of the right A. cerebri media (therapy with Cyclosporine A, Prednisolon and Ramipril at the time) and showed paresis of the left arm as well as central facialnerve paresis of the right side. Therapy with acetylsalicylic acid (4 mg/kg/d) and unfractionated heparin (2 mg(kg/d) was started. IPEX-Syndrome was suspected and genetic testing showed a hemizygous Missense Mutation in the FOX3 gene (c.1010G>A). Testing of the parents showed no carrier status. At the age of 21 month allogenic bone marrow transplant was performed. Immunosupressive Therapy with cyclosporine A and Prednisolon as well as the therapy with Ramipril were ended 3–5 month later.

Background: The IPEX-Syndrome is a systemic autoimmune disorder due to mutations in the FOX3 gene. The CD4+ and CD25+ T-helper cells are not functioning correctly. The syndrome is characterized by dysregulation of the immune system, poly-endocrinopathy and enteropathy in boys (x-linked)

Discussion: IPEX Syndrome is a rare cause for auto immunologic symptoms. A side from symptoms of the skin (atopic dermatitis), the intestine (eosinophile enterocolitis) and the kidney (Glomerulonephritis) our patient suffered the complication of an ischemic stroke due to an autoimmune vasculitis. Multiple risk factors led to the ischemic event:

• Renal and enteral loss of pro- and antithrombotic factors

• Autoimmune vasculitis due to IPEX syndrome

• Dehydration due to the pulmonary infection

Conclusion: IPEX syndrome should be considered in boys with severe enteropathy and dysregulation of the immune system to prevent sever complications such as cerebral vasculitis resulting in an ischemic stroke. Without therapy these patients have a limited life expectancy due to severe infection.