Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C.

Background:  Blockade of tumour necrosis factor (anti-TNF) is effective in patients with Crohn's Disease but has been associated with infection risk and neurological complications such as demyelination. Niemann-Pick disease Type C1 (NPC1) is a lysosomal storage disorder presenting in childhood with neurological deterioration, liver damage and respiratory infections. Some NPC1 patients develop severe Crohn's disease. Our objective was to investigate the safety and effectiveness of anti-TNF in NPC1 patients with Crohn's disease. Methods: Retrospective data on phenotype and therapy response were collected in 2019-2020 for the time period 2014 to 2020 from patients in the UK, France, Germany and Canada with genetically confirmed NPC1 defects and intestinal inflammation. We investigated TNF secretion in peripheral blood mononuclear cells treated with NPC1 inhibitor in response to bacterial stimuli . Results: NPC1 inhibitor treated peripheral blood mononuclear cells (PBMCs) show significantly increased TNF production after lipopolysaccharide or bacterial challenge providing a rationale for anti-TNF therapy. We identified 4 NPC1 patients with Crohn's disease (CD)-like intestinal inflammation treated using anti-TNF therapy (mean age of onset 8.1 years, mean treatment length 27.75 months, overall treatment period 9.25 patient years). Anti-TNF therapy was associated with reduced gastrointestinal symptoms with no apparent adverse neurological events. Therapy improved intestinal inflammation in 4 patients. Conclusions: Anti-TNF therapy appears safe in patients with NPC1 and is an effective treatment strategy for the management of intestinal inflammation in these patients.

Niemann-Pick disease type C presenting as very early onset inflammatory bowel disease.

Niemann-Pick disease type C (NPC) has been reported in association with inflammatory bowel disease. In cases where colitis has been reported in association with NPC, the neurological manifestations of NPC often precede the development of colitis. We report a rare case of a child who presented at age 2 with perianal Crohn's disease. Initial imaging studies to characterise the disease revealed an incidental finding of splenomegaly. Extensive workup for splenomegaly revealed NPC1 mutations consistent with NPC disease. He did not have any typical neurological symptoms at the time of his diagnosis. He is currently doing well on biweekly adalimumab injections for his Crohn's disease and biweekly intrathecal injections of 2-hydroxypropyl-ß-cyclodextrin (VTS-270) for the NPC.

Pediatric Celiac Disease and Eosinophilic Esophagitis: Outcome of Dietary Therapy.

OBJECTIVE: The coexistence of celiac disease (CeD) and eosinophilic esophagitis (EoE) in pediatric patients has been increasingly recognized. In the current study, we have aimed to assess the outcomes of therapeutic dietary interventions in a cohort of pediatric patients with CeD and EoE. METHODS: Pediatric patient records obtained from the University of Chicago Celiac Center Database from August 2008 to July 2013 were reviewed. Information was collected on patients with concomitant CeD and EoE regarding age, sex, dates of diagnoses, presenting symptoms, length of symptoms before diagnosis, familial and personal atopic history, dietary therapy, and esophageal histologic response to dietary therapy. RESULTS: A total of 350 records of patients with CeD were reviewed. Twenty-two (6.3%) had a confirmed diagnosis of CeD and EoE, 17 had repeat biopsies. Four of 17 (23.5%) had resolution of esophageal eosinophilia on an exclusive gluten-free diet, 10 of 17 (59%) required additional eliminations to show histologic resolution, 1 of 17 (6%) had not reached histological remission, and 2 of 17 (12%) were lost to follow-up. Success rates of single food reintroductions were: soy 5 of 5 (100%), eggs 3 of 5 (60%), dairy 3 of 7 (43%), nuts 2 of 4 (50%), and fish 2 of 4 (50%). CONCLUSIONS: To our knowledge, this is the largest pediatric study to assess the histologic outcome of EoE-associated esophageal eosinophilia in response to dietary management of pediatric patients with concomitant CeD and EoE. We demonstrate that soy is well tolerated in this cohort, and suggest that reintroducing this food first, or trialing a soy-inclusive elimination diet is a viable strategy.

Food Sensitivities: Fact Versus Fiction.

Food allergies are on the rise, for reasons that are not fully understood. However, there is a tendency to overestimate their frequency, mostly based on parents' reports or on the assumption that a positive skin or blood IgE test implies the existence of clinically relevant allergy. It is imperative to base food allergy diagnosis on well-defined criteria, avoiding "alternative" tests that are available to the general public. Non-celiac gluten sensitivity is a misnomer and should be abandoned in favor of non-celiac wheat intolerance, an entity suffering from lack of biomarkers and still not convincingly described in children.