IBD may be a manifestation of a genetically driven immune disorder (GID). We present a case of previously healthy 19-year-old female with new onset IBD acutely complicated by colon perforation and hemorrhagic shock, renal failure, and acute liver injury secondary to multi-organ thrombi, likely due to catastrophic antiphospholipid syndrome.
The patient presented with constipation, abdominal pain, and rectal bleeding for 6 months; symptomatic treatments were given pending diagnostic evaluation. Over the next 1-2 months, her symptoms worsened; she developed low-grade fevers and was admitted for expedited evaluation and management. Initial workup consistent with IBD without certainty regarding type. She appeared to respond to treatment with IV steroid and infliximab but then experienced acute deterioration notable for hemorrhagic shock secondary to severe GI bleed and colon perforation; evidence of thrombi in liver and kidney leading to acute liver and renal failure briefly requiring dialysis; viral, bacterial, and fungal infections, including bacteremia.
Diagnostic Workup:
-CT: pancolitis, filling defect in hepatic veins, small renal infarcts.
-Colonoscopy: diffuse severe/moderate inflammation on descending colon with atypical purple discoloration.
-Pathology: glandular architectural distortion of colonic mucosa, lymphoplasmacytosis, cryptitis, and crypt abscesses; no granulomas.
-Incidental NET of appendix.
-Serology: +Cardiolipin IgM antibody (-IgG); +anti-PR3.
-Immunoglobulin, lymphocyte subset WNL (after discharge, off medication); noted to have protective titers for 3/14 pneumococcal serotypes.
-Evidence of complement activation acutely, normalized after discharge.
-Genetic IBD panel: two missense variants in LRBA, missense variant in TNFAIP3, all VUS.
Underwent abdominal surgeries, including subtotal colectomy with ileostomy, and recovered well. Currently with no GI symptoms off steroids, biologicals, and anticoagulation therapies. However, still with persistent inflammation on recent MRE and cytokine panel (elevated IL-6, IL-8, IL-10, and IL-13).
Unusual presentation of IBD with extraintestinal manifestation—notably multi-organ thrombi with autoantibody and complement activation—initial immunological and genetic workup concerning for genetically driven immune dysregulation. This case highlights the importance of interdisciplinary multimodal diagnostic efforts to guide care for patients with acute hyperinflammatory diatheses, even after resolution of the acute state. Ongoing studies include trio-WGS, functional studies to validate LRBA and TNFAIP3 variants, and additional immune studies, including IFN and inflammasome activations screens.
