Background: Bile acids are increasingly recognised as immunomodulatory molecules, including activators of the pyrin inflammasome, but their role in systemic autoinflammation has not been defined. We herein describe a patient with systemic autoinflammatory disease (SAID) associated with a previously unrecognised mechanism.

Case Presentation: A 43-year-old woman presented with long-standing episodic diarrhoea, abdominal pain, and arthralgia, accompanied by persistent acute-phase elevation (CRP 20–50 mg/L). She developed splenomegaly, portal vein thrombosis with portal hypertension (oesophageal varices, ascites), and chronic liver disease. Laboratory findings included low cholesterol levels and elevated liver enzymes of ALT, AST, GGT. Bone marrow biopsy showed hypercellularity with mild megakaryocytic dysplasia and persistent monocytosis. Autoimmune serology revealed low-titre ANA positivity, but repeated liver biopsies excluded autoimmune hepatitis. Despite treatment with colchicine, anakinra, canakinumab, and glucocorticoids, inflammatory activity persisted. She subsequently developed nephrotic-range proteinuria and chronic kidney disease; rectal biopsy confirmed AA amyloidosis. Gastric and duodenal biopsies later demonstrated AA amyloid deposition. She progressed to end-stage renal disease requiring haemodialysis. Clinical exome analysis identified a homozygous early truncating variant in the SLC10A2 gene (p.Cys106Ter), encoding the ileal sodium-dependent bile acid transporter. This variant is predicted to cause severe bile acid malabsorption with disruption of enterohepatic circulation (1). A previous study has described the same SLC10A2 variant only in heterozygous form in a patient with allergic colitis (2). Bile acids and their analogues transformed by colonic microbiome have been shown to activate the pyrin inflammasome and induce IL-18 production (3). Treatment with tocilizumab normalised CRP, while investigations into IL-18–driven inflammation are ongoing.

Learning points for clinical practice: We describe the first case of a homozygous SLC10A2 loss-of-function mutation and propose “Bile Acid–Associated Systemic Inflammatory Syndrome” (BASIS) as a novel autoinflammatory entity, characterised by chronic diarrhoea, impaired bile acid enterohepatic circulation, portal venous thrombosis, chronic liver involvement, systemic inflammatory response, and AA amyloidosis. This case highlights bile acid dysregulation as a previously unrecognised driver of systemic autoinflammation and pyrin inflammasome activation.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.