Introduction:

Light chain (AL) amyloidosis is a rare plasma cell dyscrasia characterized by extracellular deposition of light chains in various organs, showing distinctive Congo Red (CR) staining on involved organ biopsy. Most patients with plasma cell dyscrasias will have evidence of a monoclonal protein in the serum or urine but it can be absent in approximately 3% of patients. For such patients, serum free light chain (FLC) assay is a critical component of diagnostic evaluation. Amyloidosis can have broad clinical findings with non-specific manifestations including cutaneous, musculoskeletal, and cardiac, that overlap with certain rheumatological disorders like scleroderma. This makes amyloidosis a challenging diagnosis, which is often diagnosed after significant delay or misdiagnosed as another entity. We present a case of amyloidosis initially misdiagnosed as scleroderma.

Case presentation:

A 54-year-old woman with a past medical history of ulcerative colitis and rectal adenocarcinoma treated with surgical resection presented with severe skin thickening, pruritus, macroglossia, Raynaud’s phenomenon, and inflammatory arthritis. An extensive serologic workup for rheumatologic conditions was negative for a definitive diagnosis. As part of the workup, serum protein electrophoresis (SPEP) was obtained which showed hypogammaglobulinemia, however, no immunofixation (IFE) or FLC assay was ordered. Despite the negative serologic workup, due to high clinical suspicion, she was treated for a presumed diagnosis of scleroderma with sequential trials of prednisone, methotrexate, and mycophenolate mofetil, without improvement in her symptoms. About 2 years later with macroglossia still present, repeat SPEP, IFE, and FLC were obtained and revealed no M spike but did show lambda light chains elevated to 36.58 mg/dL, kappa light chains 0.5 mg/dL, with a FLC ratio of 73 (normal 0.26 to 1.65). Subsequently, a bone marrow (BM) biopsy was performed, which showed mildly hypocellular BM for her age (30% cellularity) and an abnormal plasma cell population constituting approximately 30% of the marrow, identified by immunohistochemistry against CD138, and they were found to be lambda light chain restricted by in-situ hybridization. CR stain was negative on the BM biopsy. Due to suspicion of underlying amyloidosis given history of macroglossia, an echocardiogram was ordered, which revealed moderate concentric hypertrophy of the left ventricle, consistent with infiltrative cardiomyopathy, which was then confirmed on cardiac MRI. An endomyocardial biopsy was subsequently performed, which stained positive for CR, and liquid chromatography/mass spectrometry confirmed AL amyloidosis. The patient was treated with amyloidosis directed therapies followed by an autologous peripheral blood stem cell transplant. Her prior symptoms resolved after treatment and macroglossia improved by over 50%.

Discussion:

Amyloidosis may initially present with non-specific manifestations like skin thickening and infiltrative cardiomyopathy that can have clinical overlap with various rheumatologic disorders such as scleroderma. Our patient was initially misdiagnosed with scleroderma. Increased awareness and checking FLC may have led to earlier diagnosis and improvement in morbidity. This case highlights the need to consider an alternative diagnosis when symptoms fail to respond to appropriate therapy and the need for provider awareness regarding complete workup for paraproteinemia including FLC with SPEP and IFE when looking for amyloidosis as 50% of amyloidosis cases have light chain only involvement.