Diverticulosis and nine connective tissue disorders: epidemiological support for an association

Purpose: An underlying connective tissue disorder (CTD) may predispose to formation of intestinal diverticula. We assess the association of diverticulosis with nine selected CTDs, to inform the pathophysiology of diverticula. Methods: A population-based period-prevalence study. Individuals (3.5 million New Zealand residents born 1901-1986) with a health system record 1999-2016 were grouped into those with a hospital diagnosis of diverticulosis or diverticulitis (ICD-10-AM K57), and those without. Also recorded were any hospital diagnoses of nine selected CTDs. The association of exposure to diverticulosis and each CTD was assessed using logistic regressions adjusted for age, gender, ethnicity and region. Results: In all, 85,958 (2.4%) people had a hospital diagnosis of diverticulosis. Hospitalisation with diverticulosis was highly significantly associated with rectal prolapse (adjusted odds ratio [OR] = 3.9), polycystic kidney disease (OR = 3.8), heritable syndromes (Marfan or Ehlers-Danlos) (OR = 2.4), female genital prolapse (OR = 2.3), non-aortic aneurysm (OR = 2.3), aortic aneurysm (OR = 2.2), inguinal hernia (OR = 1.9) and dislocations of shoulder and other joints (OR = 1.7), but not subarachnoid haemorrhage (OR = 1.0). Conclusion: People with diverticulosis are more likely to have colonic extracellular matrix (ECM)/connective tissue alterations in anatomical areas other than the bowel, suggesting linked ECM/connective tissue pathology. Although biases may exist, the results indicate large-scale integrated studies are needed to investigate underlying genetic pathophysiology of colonic diverticula, together with fundamental biological studies to investigate cellular phenotypes and ECM changes.