P672 A tertiary multicenter cohort of patients with chronic intestinal pseudo-obstruction and Crohn’s disease: a rare association with a high prevalence of monogenic disorders.
De Castelbajac, F.(1);Charbit-Henrion, F.(2);Goulet, O.(3);Cerf-Bensussan, N.(4);Treton, X.(1);Stefanescu, C.(1);Cazals-Hatem, D.(5);Billiauws, L.(1);Bouhnik, Y.(1);Joly, F.(1);Uzzan, M.(1);
(1)Hôpital Beaujon AP-HP-, Gastro-entérologie, Paris, France;(2)Hôpital Necker APHP, Génétique, Paris, France;(3)Hôpital Necker APHP, Gastro-entérologie, Paris, France;(4)INSERM Paris, Immunologie, Paris, France;(5)Hôpital Beaujon AP-HP-, Anatomopathologie, Paris, France
Background
Chronic intestinal pseudo-obstruction (CIPO) is a rare condition that is not commonly associated with Crohn’s disease (CD).
We performed a cohort study aiming at identifying clinical, immunological and genetic features as well as response to conventional CD treatments of patients co-affected with CIPO and CD.
Methods
We conducted an observational retrospective cohort study in two tertiary CIPO and IBD centers.
Patients with parenteral nutrition-dependent CIPO and features of CD including large intestinal or perianal ulcers, strictures, abscesses and fistula with pathology findings compatible with CD, were included.
We used flow-cytometry and targeted-next generation sequencing to identify immune defects and monogenic causes in 129 predefined genes responsible for monogenic enteropathies
Results
Eight unrelated patients were studied. 5 had a myogenic phenotype and 3 had a neurogenic form with histological exam for all patients. CD involved small bowel in all cases whereas one patient had ileocolonic involvement. Two patients had perianal complex fistula. Seven patients had a stricturing form and 1 had an inflammatory-only behavior. No patient had a penetrating form. All patients were diagnosed with CIPO prior to CD. Median age at CIPO diagnosis was 11.5 years old (IQR 0,31.5) while it was 22.5 (IQR 19,29) at CD diagnosis. At CD diagnosis, mean fecal calprotectin level was 551 ug/g (range 390 - 1200) and citrulline averaged 23.6 umol/l (range 15-35 umol/l).
Histopathological analyses of intestinal specimens revealed ulcerations for half of the patients, increase in intraepithelial lymphocytes in 3, granuloma and cryptitis in 1 patient.
Abnormalities in peripheral lymphocytes’ subsets were found in 2 patients. 5 patients were ultimately diagnosed with monogenic forms of enteropathy: 2 in ACTG2, with an autosomal dominant inheritance, 1 with a STAT1gain of function, (GOF) and two with recessive inheritance: TYMP. All patients received steroids with clinical response in 2. 6 patients received antiTNF, with only one sustained remission. Two patients received vedolizumab and 2 were treated with ustekinumab. Except for antiTNF in 1 patient, common CD treatments did not lead to any improvement. Of note, antiJAK therapy in a patient with STAT1GOF failed to induce remission.
Conclusion
Herein is described the first cohort of extensively genetically and immunologically explored patients co-affected with CIPO and CD. Immune defects were common and monogenic forms were found with a high prevalence. Rates of response to biologic treatment were very low. Identification of monogenic cause through immunological and genetic explorations is warranted in patient with CIPO-CD association as it could lead to targeted therapy and genetic counseling.