Abstract
Introduction: The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is a rare X-linked recessive disorder resulting in a complex immune dysregulation with autoimmunity. The main clinical features of IPEX are intractable diarrhoea occurring within the first few months of life along with insulin-dependent diabetes mellitus, and eczematic dermatitis. Recently, mutations in the FOXP3 gene on the X-chromosome were identified causing the immune dysfunction which is typical for IPEX. The evolution of IPEX was reported to be lethal. Here, we report a survey of 11 boys, all treated in our centre. Methods: Clinical data were obtained from the charts. FOXP3 genetics and immunological evaluations were performed using established standard methods. Results: The main clinical symptom in all patients was the occurrence of severe diarrhoea with protein-loosing enteropathy, requiring TPN, at a mean age of 4.1 months (range 1week-11months). According to the clinical presentation the boys can be divided into three subgroups: group1: 5 boys presented with associated diabetes mellitus preceding the occurrence of digestive and cutaneous symptoms in 3 cases. Group 2: In 3 children without diabetes extremely high IgE levels (range 3.000–11.000 IU/ml) associated to severe eczematic dermatitis were observed. Group 3: The remaining three patients did not present with associated endocrinopathy, one had severe arthritis and IgE levels were less elevated (200–300 IU/ml). Genetic analysis revealed different FOXP-3 mutations in 7/11 patients, whereas the remaining 4 patients are not yet tested. Interestingly, all patients with diabetes had FOXP3 mutations. 4/5 patients with diabetes died, whereas 5/6 children without diabetes as well as 1/5 patient with diabetes are doing well under high-dose maintenance Tacrolimus-medication after inducing remission with steroid-pulses and Tacrolimus. In one patient of the diabetes group successful bone-marrow transplantation was performed, however, almost 2years after BMT he died from an unclear hemophagocytosis syndrome. Mean follow-up for the children in remission was 4.3 years (range: 1.2 to 9.1 y). Conclusion: In our series, IPEX can be divided into several subtypes according to the occurrence of diabetes or the presence of extremely high IgE levels. The overall outcome in IPEX is largely dependent on the subtype: boys without diabetes and high IgE levels seem to have a better longterm prognosis especially when they are treated with tacrolimus compared to patients with diabetes.