When Immunosuppression Fails: Cardiac Myxoma Mimicking Systemic Lupus Erythematosus Flare With a Diagnostic Delay

A 36-year-old woman with well-controlled systemic lupus erythematosus (SLE) and prior pulmonary tuberculosis (TB) developed fever, weight loss, anemia (hemoglobin 7.6 g/dL), thrombocytopenia (78,000/mm³), and elevated inflammatory markers (ESR 89 mm/hr, CRP 67 mg/L), with symptom onset five months earlier (Month 0). Complement levels were normal, anti-dsDNA was negative, ANA remained unchanged, and she had no new rash, serositis, or renal involvement. Notably, she had no cardiac symptoms or abnormal findings on examination at that time. During the first month (Month 1), she was presumptively diagnosed with a clinically active but serologically quiescent SLE flare, based on fever, cytopenias, and elevated inflammatory markers in the context of her established SLE, despite normal complement levels and negative anti-dsDNA. Over the next three months (Months 1-3), infections with common bacterial, viral, and fungal pathogens were systematically excluded and typical causes of cytopenias were evaluated. During this period, she received escalating immunosuppression with corticosteroids, mycophenolate, and cyclophosphamide. Initial mild symptom relief was observed but waned within 2-3 weeks, and after three months, both symptoms and objective markers showed minimal improvement: ESR and CRP remained elevated, while hemoglobin and platelet counts remained essentially unchanged. At month four (Month 4), persistent fever despite immunosuppression raised concern for TB reactivation; empirical four-drug antitubercular therapy was briefly initiated but complicated by hepatotoxicity requiring cessation. TB cultures returned negative. At month five (Month 5), syncope prompted echocardiography, revealing a large (3.9×3.2 cm) pedunculated left atrial myxoma attached to the interatrial septum, prolapsing through the mitral valve during diastole. Cardiac MRI confirmed the diagnosis. Interleukin-6 was markedly elevated (107 pg/mL, normal <7). Following surgical excision, complete symptom resolution occurred with normalization of cytopenias by three months, a progressive decline in inflammatory markers, and IL-6 reduction to 12 pg/mL by six months. Immunosuppression was de-escalated to hydroxychloroquine alone with no recurrence at 14-month follow-up. This case illustrates diagnostic delay resulting from cognitive biases, including anchoring on her established SLE diagnosis and confirmation bias from partial steroid response, while highlighting underappreciated clinical red flags. Echocardiography was probably not performed during the course of the disease, given the absence of cardiac symptoms or abnormal findings on examination, and because the systemic symptoms were attributed to inflammatory causes. Critical underappreciated features included seronegative inflammation with normal complements and inadequate response to immunosuppression-atypical for genuine lupus flares. Inadequate treatment response within 4-6 weeks should trigger diagnostic reassessment before escalation. Syncope or orthostatic symptoms in systemic illness mandate urgent echocardiography. Cardiac myxomas produce IL-6 in the majority of patients (frequency >75%), and systemic constitutional signs are observed in a substantial proportion, though not uniformly. This can produce IL-6-mediated inflammation indistinguishable from autoimmune flares.