Mycobacterium avium Complex-Associated Hemophagocytic Lymphohistiocytosis in a Sickle Cell Patient: An Unusual Fatal Association

Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome, characterized clinically by fever, splenomegaly, cytopenia, and high ferritin. Infectious causes have been associated with secondary HLH, with viruses being the most common. We report a case of Mycobacterium avium complex-associated HLH in a sickle cell anemia patient. To the best of our knowledge, this association has never been reported in sickle cell anemia. 1. Introduction HLH is a rare inflammatory disease caused by macrophage and cytotoxic T-cell activation leading to uncontrolled hemophagocytosis and cytokine production. It can be divided into primary (genetic) causes, idiopathic, and secondary causes associated with infections, hematological malignancies, and autoimmune diseases [1]. Mycobacterium avium complex (MAC) is a nontuberculous mycobacterium known to cause pulmonary and disseminated disease in patients with immunodeficiency. We report the first case of HLH in the setting of MAC infection in a sickle cell anemia patient, initially presenting with fever of unknown origin. 2. Case Presentation A 22-year-old female with sickle cell anemia presented with 1-month history of fever, night sweats, and weight loss. On presentation, vital signs were stable except for fever of 102？F. Cardiopulmonary examination was normal, and there was no lymphadenopathy. The rest of physical examination was unremarkable. Laboratory studies showed leukocytosis of 17.000/uL and hemoglobin of 10.4？g/dL. Erythrocyte sedimentation rate and C-reactive protein were elevated at 44？mm/hr and 8.47？mg/dL, respectively. Patient had negative bacterial and fungal cultures, viral serologies, and tuberculin skin testing. Chest X-ray showed bilateral nodular opacities, and computed tomography (CT) revealed ground glass opacity in the left lower lobe with surrounding nodules (Figure 1). Bronchoalveolar lavage with biopsies showed granulomas with no organisms. Wedge biopsy was pursued and histopathology showed necrotizing granulomas (Figure 2(a)) with acid-fast bacilli (Figure 2(b)). Polymerase chain reaction and tissue cultures were positive for MAC, and patient was started on azithromycin, ethambutol, and rifampin. Figure 1: Compute tomography (CT) of chest showing wedge-shaped ground glass opacity in the left lower lobe, with surrounding centrilobular nodules (arrow). Additional 1-2？mm centrilobular nodules noted in the right lower lobe. Figure 2: (a) Necrotizing granuloma evident on wedge-resected lung tissue. (b) Ziehl-Neelsen stain revealing acid-fast bacilli in resected lung tissue, consistent