A 13-year old male, a native of Kerala, India, a student was referred in January 2006 for high grade intermittent fever with rigors and chills of one month duration. He did not complain of cough, hemoptysis, neck swellings or other associated symptoms. He had not traveled outside his district. The young man reported a history of bronchial asthma for last 10 years requiring very occasional treatment with bronchodilators. He did not use alcohol or tobacco. No significant family history except that his father having diabetes. His parents noticed significant weight loss and loss of appetite. On physical examination he was moderately built, anicteric and poorly nourished with pallor with pulse: 108/mt. and temp. 101  F. There was no lymphadenopathy, bleeding manifestations, rash or eschar. Abdominal examination revealed a firm non-nodular liver 5 cm below the right costal margin and an enlarged spleen of 10 cm below the left costal margin (Fig. 1). No ascites was noted. Optic fundi examination was normal.
His CBC on admission (01/29/06) was showed a leukocyte count of 1000/mm3, platelet count 17,000/mm3 and Hb 7.7 g/dL. Repeated on 02/05/06, the CBC revealed leukocyte count of 500, platelet count 25,000 and Hb 6.2. Urine analysis was normal. Liver function tests showed normal ALT (33 IU/L) and total bilirubin (0.2 mg/dL) with low albumin (2.5 g/dL), total protein (5.8 g/dL) and mildly elevated alkaline phosphatase (240 IU/L). A tuberculin skin test was negative. HIV ELISA, hepatitis B surface antigen, monospot and ANA were all negative. A chest X-ray was unremarkable. An abdominal ultrasound confirmed hepatosplenomegaly and also found enlarged paraaortic lymph nodes and ascites which were felt to be suggestive of lymphoma. A bone marrow aspiration was interpreted as showing maturation arrest and a bone marrow trephine biopsy was done.
The patient's overall clinical status worsened. He continued to be febrile, and developed epistaxis, and purpurae as well as enlargement of several cervical lymph nodes. He was supported with packed RBC and platelet rich plasma. Urine and blood cultures for common bacteria were negative and echocardiogram was unremarkable. High temperature spikes of 101-105  F, weight loss and mucosal bleeds persisted. At that point, his bone marrow trephine biopsy pathology was reported to show the presence of epithelioid cell granulomata with Langhans giant cells and focal necrosis consistent with tuberculosis (Fig. 2). AFB stain was negative.
Antituberculous treatment (ATT) with a combination of isoniazid, rifampin, ethambutol pyrazinamide was initiated. The patient developed an urticarial rash with wheezing. Suspecting hypersensitivity, his ATT was changed to ofloxacin, ethambutol and streptomycin for one month and then switched back to the original therapy which he then tolerated without incident. The young man became afebrile after 3 weeks and his blood counts slowly improved. He was continued on the 4 drug ATT for 2 months after restarting and then switched to the combination of isoniazid and rifampin for 10 additional months. Follow up laboratory results are given in Table 1.
On follow up after 6 months, he was afebrile and had normal growth milestones. His abdominal ultrasound examination documented decreasing size of his liver and spleen. The final diagnosis of extrapulmonary tuberculosis with hepatosplenomegaly and bone marrow infiltration with pancytopenia was made. In 2015, nine years after presentation of his illness, he remained healthy, asymptomatic and weighing 64 kg.