Clinical Heterogeneity of Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome: A French Multicenter Retrospective Study.

OBJECTIVE: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an autoimmune disease caused by mutations in the forkhead box protein 3 gene (FOXP3), which encodes a key regulator of immune tolerance. The aim of this study was to describe the clinical heterogeneity of the disease in a national French cohort. METHODS: Multicenter retrospective study of patients diagnosed with IPEX syndrome caused by mutations in FOXP3. RESULTS: Thirty children from 26 families were included. Age at disease onset (median [first to third quartile]) was 1.5 mo [0-84] and at death 3.5 years [0-10.5] (n = 15) indicating a high heterogeneity. Initial presentation was diarrhoea (68%), type 1 diabetes (T1D; 25%), skin lesions (7%) and nephropathy (3%). During the course of the disease the following main symptoms were observed: diarrhoea (100%), skin lesions (85%), T1DM (50%), severe food allergies (39%), haematological disorders (28%), nephropathies (25%), hepatitis (14%) as well as the presence of a variety of autoantibodies. Immunosuppressive mono- or combination therapy led to improvement in eight children. Three boys displayed a stable disease course without any immunosuppressive medication. Overall 10-year survival rate was 43% (42% in transplanted patients and 52% in patients on immunosuppressive therapy). Five out of 22 identified FOXP3 mutations have not been described yet: c.-23 + 1G > A, c.-23 + 5G > A, c.264delC, c.1015C > T and c.1091A > G. The first two produced atypical, attenuated phenotypes. Missense and frameshift mutations affecting the forkhead domain were associated with poor survival (Gehan-Wilcoxon p = 0.002). CONCLUSION: The broad phenotypic heterogeneity of IPEX raises questions about modifying factors and justifies early FOXP3 sequencing in suspected cases.

[Is alfa-interferon still current in the management of Kasabach-Merritt syndrome?]. / L'interferon alfa a-t-il encore des indications dans la prise en charge du syndrome de Kasabach-Merrit ?

Kasabach-Merritt syndrome (KMS), characterized by thrombocytopenia, may complicate vascular tumors such as kaposiform hemangioendothelioma and tufted angioma. We report on two infants, respectively 2 months and 15 days old at the onset of symptoms, the first of whom presented with a left cervico-occipito-scapular hemangioma with parotid extension, and the second with a vascular tumor located on the left shoulder with fast extension on the left inferior hemithorax and the left arm. Thrombocytopenia (< 20 G/L) was associated in both cases. Treatment comprised first high-dose corticosteroids (2mg/kg) in association with vincristine (1mg/m(2)/week). Interferon was introduced as third-line treatment at 3 MIU/m(2)/day. In the first patient, interferon was effective both on thrombocytopenia and tumor in 2 months. In the second patient, the first interferon treatment was not effective despite 6 months of therapy. However, a second treatment 8 years later was successful. After 10 and 3 years follow-up, respectively, there were no side effects and most particularly no neurologic complications. These two observations open the discussion of the role of interferon (3 MIU/m(2)/day) as well as new therapies in the control of angiogenesis in case of failure of first-line treatment of complicated KMS vascular tumors.

[Helicobacter pylori infection, a classic but often unrecognized cause of iron deficiency anemia in teenagers]. / Anémie ferriprive de l'adolescent liée à une infection àHelicobacter pylori, à propos d'un cas.

We report a case of a 15-year-old teenager who presented with iron deficiency anemia due to Helicobacter pylori infection. Iron deficiency is frequent in infants and during puberty. H. pylori gastritis is a frequent but underdiagnosed cause of refractory anemia. In the case reported herein, the recurrent character of the patient's anemia raised this diagnosis, which was confirmed by endoscopy. Treatment of the H. pylori infection, associated with iron supplementation, successfully corrected the anemia.