P142 Inflammatory bowel diseases associated with primary immunodeficiency: a multicenter study
Malamut, G.(1);Simon, M.(2);Nachury, M.(3);Uzzan, M.(4);Serrero, M.(5);Fumery, M.(6);Trang-Poisson, C.(7);Zallot, C.(8);Abitbol, V.(1);Charbit-Henrion, F.(9);Gornet, J.M.(2);Picard, C.(10);Cerf-Bensussan, N.(11);Chaussade, S.(1);Sokol, H.(12);
(1)AP-HP. Centre- Université de Paris- Hôpital Cochin- Paris- France., Gastroenterology, Paris, France;(2)AP-HP. Nord-Université de Paris- Hôpital Saint Louis- Paris- France., Gastroenterology, Paris, France;(3)Hôpital Huriez CHRU de Lille, Gastroenterology, Lille, France;(4)AP-HP. Nord-Université de Paris- Hôpital Beaujon- Clichy- France., Gastroenterology, Clichy, France;(5)APHM Hôpital Nord, Gastroenterology, Marseille, France;(6)CHU Amiens-Picardie, Gastroenterology, Amiens, France;(7)CHU de Nantes, Gastroenterology, Nantes, France;(8)CHRU de Nancy, Gastroenterology, Gastroenterology, France;(9)AP-HP. Centre-Université de Paris- Hôpital Necker-Enfants Malades, Molecular Genetics, Paris, France;(10)AP-HP. Centre-Université de Paris- Hôpital Necker-Enfants Malades, Study Center of Primary Immunodeficiency, Paris, France;(11)Université de Paris- INSERM UMR 1163 and Imagine Institute, Laboratory of intestinal immunology, Paris, France;(12)AP-HP. Sorbonne Université- Hôpital Saint Antoine, Gastroenterology, Paris, France; GETAID (Groupe d'Étude Thérapeutique des Affections Inflammatoires du tube Digestif)
Background
Inflammatory bowel diseases (IBD) associated with primary immunodeficiency (PID) remain poorly known. We aimed to isolate characteristics of IBD associated with PID.
Methods
Using a GETAID register, we reviewed medical files of recorded patients with PID and IBD (Crohn’s disease, ulcerative colitis (UC) or microscopic colitis) followed in 9 adult university hospitals.
Results
Results of genetic investigations were available for 46 patients (62%).74 patients (30 F, 44M) were included with a mean age of 26 years (median: 24 years) at diagnosis of IBD. Forty-four (59%) patients had Crohn’s disease with anoperineal lesions in 12, 26(35%) patients had microscopic (mainly lymphocytic) colitis and 4 patients had UC. PID was predominantly antibody deficiency in 40(54%) patients [34 common variable immunodeficiency, 4 X-linked agammaglobulinemia, 2 selective IgA deficiencies], disease of immune dysregulation in 18(24%) patients [CTLA4, LRBA, NFKB1, TNFAi3, XIAP deficiencies, STAT3 and STAT1 hyperactivation], phagocytosis deficiency in 15(20%) patients (12 chronic granulomatous diseases (CGD), 3 congenital neutropenia] and C1s deficiency (n=1). In order of frequency, Crohn’s disease was associated with antibody deficiencies (52%), phagocytosis deficiencies (29%) and immune dysregulation (18%), microscopic colitis with antibody deficiencies (65%), immune dysregulation (27%) and more rarely with phagocytosis deficiencies (8%) and UC with antibody deficiencies (75%) and immune dysregulation (25%). 46% of patients received immunoglobulin supplementation, 70% steroids, equally corticosteroids and budesonide, 49% biotherapy mainly anti-TNF-alpha antibody (38%) and ustekinumab (16%), 23% immunosuppressive drugs, mainly azathioprine and sirolimus and 18% aminosalicylates. Three patients (2 CGD, 1 XIAP) had been treated with allogeneic stem cell transplantation (SCT) and one patient (TNFRS13B deficiency) with autologous SCT. Eleven (15%) patients had intestinal surgery, mainly ileocecal resection. During follow-up [mean: 16 years], 51% of patients had transient or sustained clinical remission mainly with an anti-TNF-alpha antibody, ustekinumab, steroids (budesonide) and specific therapy (targeted therapy such as abatacept and ASCT), 41% of patients had severe infections, 22% developed neoplasia mainly gastrointestinal dysplasia and/or cancers (n=8), B cell lymphoma (n=3) and 4 patients died.
Conclusion
At adulthood in our series, IBD associated with PID are mainly Crohn’s disease and lymphocytic colitis. The first most frequent associated PID is antibody deficiency. Biotherapies (anti-TNF-alpha antibody, ustekinumab), steroids and specific therapies are commonly used to induce clinical remission.