Inflammatory Enteropathy of Infancy- Is It Always Veoibd?

Abstract Very early-onset inflammatory bowel disease (VEOIBD) is defined as IBD with onset before 6 years-old, while infantile IBD refers to diagnosis before 2 years-old. In the VEOIBD population, genetic factors appear to play a more prominent role, particularly in patients diagnosed before one year of age. These patients often experience higher morbidity, including frequent hospitalizations, dependence on total parenteral nutrition (TPN), and are often refractory to conventional IBD therapies. We present a unique cohort of eleven patients who presented with severe inflammatory enterocolitis during infancy that eventually came off treatment and continue to stay in remission off treatment. Patients presented at a mean age of 3.1 months (range: 2-26 months) with watery diarrhea (11/11), hematochezia (3/11), malnutrition (2/11), dehydration (5/11), and fever (1/11). None responded to amino acid-based formula, and a comprehensive evaluation ruled out infectious, malabsorptive, and congenital diarrheal illness, including tufting enteropathy and microvillous inclusion disease. Endoscopic evaluation revealed active colitis, with histological findings including villous blunting, crypt dropout, apoptosis, absent goblet cells, and penetrating ulcers. Eight patients (72%) underwent targeted sequencing panels that revealed variants of unknown significance in six patients and RBM8A (TAR syndrome, Chr1q21.1 del) and 22q.1.2 deletion in two patients. Initial hospitalization duration was a mean of 56 days (range: 22-100 days). Nine patients (82%) were started on corticosteroids, with a median treatment of 68.5 days (range: 1-649 days). Maintenance therapies included sirolimus (36%), cyclosporine (9%), and 5-aminosalicylic acid (9%). Ten patients (91%) required TPN for a mean of 50 days, and three (27%) received intravenous immunoglobulin. All patients showed improvement or normalization in fecal calprotectin with follow-up endoscopy, and imaging also normalized (see figure 1). Ten patients (91%) have been weaned off treatment; one patient remains on sirolimus with trough levels ranging between 2 and 5ng/ml. All patients have been weaned off TPN while remaining asymptomatic. This cohort demonstrates a novel, severe but short-lasting phenotype of transient infantile-onset inflammatory enteropathy that mimics VEOIBD but differs in its course and outcomes. These cases expand our understanding of early-onset intestinal inflammation and highlight the need to recognize this phenotype to aid in limiting exposure to long-term immunosuppression and prognostication. Table 1:Demographics of the patients included in the studyFigure 1:(A) Contrast enhanced CT of the abdomen and pelvis demonstrating diffuse small bowel wall thickening (solid arrows). (B) Follow-up CT 5 months later demonstrates normal small bowel wall thickness (open arrows), suggesting resolution of previous enteropathy