Castleman disease (CD) is a disorder characterized by lymphoid proliferation. It is not usually the first differential for pyrexia of unknown origin (PUO) because of the extremely rare incidence worldwide. We report the case of a 24-year-old man with PUO for six months. He had been previously investigated for infective, rheumatological, and immunological causes. Extrapulmonary tuberculosis was considered as the most likely diagnosis because of his clinical presentation and locality. Based on this, he was given a trial of anti-tuberculous therapy. However, he did not show any signs of improvement despite being compliant with the medications. His condition was further complicated by the development of ascites. Upon treatment failure, the patient presented to our tertiary care hospital and was investigated for a possible revision of diagnosis. Based on clinical assessment and histopathology of the lymph nodes, he was diagnosed with idiopathic multicentric CD overlapping with systemic lupus erythematosus. He was started on azathioprine and prednisone and showed a positive response, indicated by a decreasing erythrocyte sedimentation rate and C-reactive protein. The patient continues to be healthy and in remission to date.
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