Hui, Ken

INTRODUCTION: We examined autoimmunity markers (AIM) and autonomic dysfunction in patients with chronic neurogastroenterological symptoms and their relationship to joint hypermobility/hypermobility spectrum disorder (JH/HSD). METHODS: AIM positivity was defined as a diagnosis of known autoimmune/autoinflammatory disorder with at least 1 positive seromarker of autoimmunity or at least 2 positive seromarkers by themselves. Three cohorts were studied: (i) retrospective (n = 300), (ii) prospective validation cohort (n = 133), and (iii) treatment cohort (n = 40), administered open-label intravenous immunoglobulin (IVIG). RESULTS: AIM positivity was found in 40% and 29% of the retrospective and prospective cohorts, the majority of whom (71% and 69%, respectively) had autoinflammatory disorder. Significantly more patients with AIM had elevations of C-reactive protein (31% vs 15%, P < 0.001) along with an increased proportion of cardiovascular autonomic dysfunction (48% vs 29%; P < 0.001), small fiber neuropathy (20% vs 9%; P = 0.002), and HLADQ8 positivity (24% vs 13%, P = 0.01). Patients with JH/HSD were more likely to have AIM (43% vs 15%, P = 0.001) along with more severe autonomic and gastrointestinal (GI) symptom scores. IVIG treatment was associated with robust improvement in pain, GI, and autonomic symptoms, but adverse events were experienced by 62% of patients. DISCUSSION: Autoimmune markers and autonomic dysfunction are common in patients with unexplained GI symptoms, especially in those with JH/HSD. Many patients seem to respond to IVIG treatment, but this needs to be confirmed by controlled trials. These results highlight the need for vigilance for autoimmune and autonomic factors and JH/HSD in patients with neurogastroenterological disorders. Clinicaltrials.gov, NCT04859829.

Objective Braak’s hypothesis states that Parkinson’s disease (PD) originates in the gastrointestinal (GI) tract, and similar associations have been established for Alzheimer’s disease (AD) and cerebrovascular diseases (CVD). We aimed to determine the incidence of GI syndromes and interventions preceding PD compared with negative controls (NCs), AD and CVD. Design We performed a combined case-control and cohort study using TriNetX, a US based nationwide medical record network. Firstly, we compared subjects with new onset idiopathic PD with matched NCs and patients with contemporary diagnoses of AD and CVD, to investigate preceding GI syndromes, appendectomy and vagotomy. Secondly, we compared cohorts with these exposures to matched NCs for the development of PD, AD and CVD within 5 years. Results We identified 24 624 PD patients in the case-control analysis and matched 18 cohorts with each exposure to their NCs. Gastroparesis, dysphagia, irritable bowel syndrome (IBS) without diarrhoea and constipation showed specific associations with PD (vs NCs, AD and CVD) in both the case-control (odds ratios (ORs) vs NCs 4.64, 3.58, 3.53 and 3.32, respectively, all p<0.0001) and cohort analyses (relative risks (RRs) vs NCs 2.43, 2.27, 1.17 and 2.38, respectively, all p<0.05). While functional dyspepsia, IBS with diarrhoea, diarrhoea and faecal incontinence were not PD specific, IBS with constipation and intestinal pseudo-obstruction showed PD specificity in the case-control (OR 4.11) and cohort analysis (RR 1.84), respectively. Appendectomy decreased the risk of PD in the cohort analysis (RR 0.48). Neither inflammatory bowel disease nor vagotomy were associated with PD. Conclusion Dysphagia, gastroparesis, IBS without diarrhoea and constipation might specifically predict Parkinson’s disease.