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Miliary tuberculosis

Clinical History
A 30-year-old Hispanic man with a history of diabetes mellitus had a staphylococcal abscess of the calf several weeks prior to presentation that was treated with antibiotics. He was in his usual state of health until two to three weeks before presentation, when he developed rapidly progressive leg pain, fever, and myalgias. He quickly became unable to walk due to severe leg pain and shortness of breath. On presentation in the emergency department, he was found to be hypotensive, pancytopenic, and in severe acute renal failure, and he had a right upper lobe infiltrate on chest radiograph. A blood culture grew methicillin-resistant Staphylococcus aureus organisms. CT imaging of the chest showed multifocal cavitation of the large area of consolidation in the right upper lobe. The patient’s manifestations of sepsis continued to worsen, and despite aggressive treatment with broad-spectrum antimicrobial agents, he expired a few days after presentation.

Pathological Findings
At autopsy, there was extensive supurrative mediastinal and hilar lymphadenitis, and both lungs were extremely boggy and heavy. Within the right upper and middle lobes, extensive areas of yellow-tan friable necrosis were present. The liver and spleen contained innumerable firm white-yellow punctate lesions in a miliary pattern, and there was a large right paratracheal abscess.

Diagnosis
Miliary tuberculosis with probable superimposed staphylococcal sepsis

Discussion
Miliary tuberculosis generally occurs when Mycobacterium tuberculosis organisms from a focus of infection in the lung travel through the pulmonary venous circulation and are disseminated through the systemic arterial system. The large necrotic focus in the right lung, as well as the miliary lesions in the spleen, liver, and lymph nodes were all shown to contain innumerable acid-fast bacilli. Pre-mortem sputum culture specimens contained rare acid-fast bacilli, and later grew M. tuberculosis. There was no known history of HIV infection at the time of presentation, but tests done shortly before death revealed that the patient was HIV-positive, with a high viral load. Given the patient’s presentation with leg pain and eventual sepsis, and his history of MRSA abscess, disseminated mycobacterial infection was not initially considered to be a likely diagnosis.

Macrophages are the primary cells infected in M. tuberculosis infection. The acid-fast organisms enter macrophages via receptor-mediated endocytosis. Via several mechanisms, the organisms block fusion of the phagosome and lysosome. In primary infection of an unsensitized person, the organisms replicate within pulmonary macrophages and alveolar spaces and are disseminated through the body for several weeks. Mycobacterial antigens drain to the lymph nodes, where T_h1 cells are presented with class II MHC proteins and IL-12 produced by antigen-preseting cells. The T_h1 cells secrete IFN-γ, which stimulates formation of the phagolysosome within the macrophage, as well as production of nitric oxide. After stimulation with IFN-γ, the macrophages secrete TNF, which recruits circulating monocytes to become the epithelioid histiocytes characteristic of the granulomatous response. In many people, this response stops disease progression without causing significant tissue damage. In others, the organisms continue to spread and the ongoing inflammatory response results significant tissue destruction. In this patient, the HIV-induced deficiency in CD4+ T-cell function likely resulted in inadequate stimulation of the macrophage bactericidal response, allowing unchecked replication of the organisms.¹

1. Kumar V, Abbas A, Fausto N. Robbins and Cotran Pathologic Basis of Disease, 7^th ed. 2007. Elsevier.