Case Report: Systemic amyloidosis unmasked by progressive hepatomegaly after splenectomy for non-traumatic spleen rupture in a patient with chronic liver disease

Background Non-traumatic splenic rupture (NSR) is a rare manifestation of systemic amyloid light-chain amyloidosis (AL amyloidosis), a plasma cell dyscrasia best known for its cardiorenal involvement. This case is unique because the diagnostic clue from NSR was initially overlooked until the underlying disease unfolded into a multisystem disorder. The diagnostic clues were further obscured by the presence of chronic hepatitis B (HBV) and primary biliary cholangitis (PBC). The pitfalls and challenges, as well as the pathogenic link between AL amyloidosis and coexisting conditions, i.e., chronic HBV infection and PBC, are discussed. Case summary A 46-year-old woman presented initially with non-specific upper gastrointestinal symptoms. Initial workup established the diagnosis of chronic HBV infection and PBC, but the disease progressed despite etiological therapy. NSR occurred 4 months later, and splenectomy pathology was inconclusive. The disease progressed, manifesting as cardiac dysfunction, acute kidney injury, subnephrotic-range proteinuria, and hepatomegaly. Serum and urinary-free light-chain levels and ratios were abnormal. Cardiac MRI suggested myocardial hypertrophy. Biopsy of the liver, bone marrow, and re-examination of the splenic specimen showed extensive amyloid deposition. She was diagnosed with multisystem AL amyloidosis (Mayo 2012 Stage III) and started on daratumumab, leading to significant clinical improvement. Conclusion This case highlights the risk of “premature” attribution of manifestations of rare diseases to common comorbidities. While NSR should always be considered a sentinel event for systemic amyloidosis, the diagnostic clues can be easily overlooked in complex patients with overlapping diagnoses. A high index of suspicion and targeted histological evaluation of splenic tissue are imperative to avoid diagnostic delay and enable earlier treatment initiation for this serious disease.