A 56-year-old man with advanced AIDS comes to the emergency department due to several weeks of progressive fever, night sweats, weight loss, diarrhea, and generalized weakness. Physical examination shows mucosal pallor, generalized lymphadenopathy, and hepatosplenomegaly. Laboratory studies reveal anemia and elevated alkaline phosphatase and lactate dehydrogenase levels. CD4 count is 16/mm3. Bone marrow biopsy shows aggregates of epithelioid histiocytes with foamy cytoplasm and numerous acid-fast intracellular organisms. Nucleic acid amplification test of the sample for Mycobacterium tuberculosis is negative. Which of the following pathogens is the most likely cause of this patient's illness?
This patient's subacute systemic symptoms (eg, fever, night sweats, weight loss, weakness), lymphadenopathy, hepatosplenomegaly, elevated alkaline phosphatase, and intracellular acid-fast bacteria raise strong suspicion for disseminated Mycobacterium avium complex (MAC). MAC is an infection caused by the nontuberculous mycobacteria M avium and Mycobacterium intracellulare. Although these infections can occur in both immunocompetent and immunosuppressed hosts, most cases arise in patients with untreated AIDS who have CD4 counts <50/mm3.
MAC organisms are acquired by ingestion or inhalation. They are phagocytosed by macrophages but initially evade destruction due to microbial virulence factors that prevent phagolysosome formation. In healthy individuals, the infection is controlled with the cell-mediated immune response. However, in patients with advanced AIDS, the body is unable to generate sufficient CD4-mediated cytokines (eg, interferon-gamma) to activate macrophages, which allows the pathogen to spread through the bloodstream and reticuloendothelial system.
Most patients with disseminated infection have nonspecific symptoms (eg, fever, weight loss, diarrhea). Widespread involvement of the reticuloendothelial system often causes anemia, hepatosplenomegaly, and/or elevated alkaline phosphatase and lactate dehydrogenase. The diagnosis is usually made with blood cultures, but results may take weeks because mycobacteria grow slowly. Histologic findings in the bone marrow include foamy macrophages with intracellular, acid-fast bacilli. Granulomata may be seen.
(Choice A) Cryptococcus neoformans, an encapsulated yeast, is a common cause of meningoencephalitis in patients with advanced AIDS. Although it is a facultative intracellular pathogen, it does not stain with acid-fast preparations. The pathogen is usually visualized with India ink, mucicarmine, or methenamine stains.
(Choice B) Cryptosporidium parvum is a common cause of high-volume diarrhea and biliary disease in patients with advanced AIDS. This organism's oocytes can be visualized with modified acid-fast stain, and the pathogen is intracellular. However, it infects epithelial cells and does not spread through the reticuloendothelial system to the bone marrow or lymph nodes.
(Choice C) Legionella pneumophila is a gram-negative, intracellular bacteria that often causes gastrointestinal symptoms prior to pneumonia. However, it does not stain with acid-fast and does not generally cause lymphadenopathy or bone marrow infection.
(Choice E) Mycobacterium marinum is a nontuberculous mycobacterium that can cause skin and soft tissue infection following exposure to water (eg, fish tanks). It does not generally cause several weeks of diarrhea, lymphadenopathy, and hepatosplenomegaly.
(Choice F) Nocardia asteroides, a partially acid-fast organism, typically causes pneumonia and/or brain abscess. Gastrointestinal symptoms, lymphadenopathy, and bone marrow involvement would be atypical.
Educational objective:
Mycobacterium avium complex (MAC) infections are common in patients with advanced AIDS. The bacterium often spreads through the bloodstream and reticuloendothelial system and causes nonspecific symptoms (eg, fever, fatigue, weight loss, diarrhea), lymphadenopathy, and hepatosplenomegaly. Diagnosis is often made on blood culture or bone marrow aspirate (intracellular acid-fast bacteria that are not Mycobacterium tuberculosis).