Final Diagnosis -- Disseminated Mycobactrium Avium Complex Infection and CNS Lymphoma

CONTRIBUTOR'S NOTE:

This gay male volunteer tested positive for the human immunodeficiency virus in April 1986. He did well thereafter without report of illness except for acute and chronic aspergillus and bacterial sinusitis following oral surgery in 1993 from which he recovered. He became progressively ill in 1996 but was never hospitalized. One week prior to his death, epistaxis and bleeding from the mouth were reported. Subsequently he died in June 1996 approximately 10-years from seroconversion.

Postmortem examination revealed disseminated Mycobacterium avium complex (MAC) infection involving almost every major organ. All tissues which were cultured postmortem grew the organism. In addition, Klebsiella pneumoniae was also cultured from all specimens leading to the conclusion that he was also septic with this organism. Although Proteus mirabilis was cultured from the kidney and pancreatic fat this most likely represents contamination because no other specimen grew the organism and kidney sections did not show evidence to suggest the presence of the organism. The intestines contained 2-3 liters of blood, both old and fresh, consistent with massive hemorrhage into the gut. There was severe hemorrhagic pancreatitis with extensive fat necrosis. The liver showed severe steatosis and micronodular cirrhosis. The histologic picture of cirrhosis was most consistent with alcohol-induced but immunohistochemical stains were positive for the hepatitis B virus surface antigen.

This man's opportunistic and bacterial infections are secondary to his immunodeficient state caused by infection with the AIDS virus. Hepatic findings can be attributed to the history of ethanol use and hepatitis B exposure

More interestingly however is explaining the cause for the active bleeding prior to death. This may be three-fold. First, the bone marrow contained macrophages with numerous acid-fast bacilli possibly diminishing production of platelets and other precursors. Secondly, the liver may not have been producing the needed clotting factors secondary to its damage. Third, there was splenomegaly possibly with related hypersplenism and thrombocytopenia which has been reported in other cases to produce thrombocytopenia (see below). Because premortem blood counts and other tests were never performed a definitive answer can not be given but this explanation seems most likely.

Mycobacterium avium complex (MAC) represents many related acid fast organisms which grow faster than M. tuberculosis. These organisms are divided into a number of serotypes. One study showed as many as 13 different serovars were observed in 43 HIV-infected patients with serovar 6 being most common (1). These organisms are found in soil and water and in infected animals. MAC isolates recovered from the environment can often differ from those in patients with disease (2). In 1994 drinking water sources were tested in hospitals for MAC isolates (3). The results showed that the drinking water served as a potential source of infection. The question then arose as to whether there would be benefit in drinking bottled water (4). Yajko et al (5) studied water, food and soil samples from the home environments of 290 HIV-infected patients. Each of the sample types had at least one MAC isolate recovered. However, the soil from potted plants had isolates recovered at a much higher percentage suggesting its greater significance. Similar isolates to those recovered in the soil were also recovered from the patients.

Pulmonary infections, lymphadenitis, chronic osteomyelitis, gastrointestinal disease and skin infections are all possible manifestations of MAC infection. Lymphadenitis, skin infections, and pulmonary infection have been reported to occur with or without dissemination (6,7,8). However, those with gastrointestinal manifestations almost always have disseminated disease (9).

Disseminated MAC infections are now the most common cause of systemic bacterial infection in AIDS patients. The nonspecific signs and symptoms of disseminated MAC infection include fever, chills, nausea, vomiting, diarrhea, night sweats, abdominal pain and unexplained weight loss. Hepatomegaly and splenomegaly are not uncommon. In fact in 1994, Levin reported two cases of acute hypersplenism and thrombocytopenia as a new presentation of disseminated MAC infection in AIDS patients (10). The patient presented here, did indeed have splenomegaly (610 grams). However, because of his presentation only after death no blood counts were available. It is likely in this case that he did have thrombocytopenia, thus contributing to his massive hemorrhage as described above.

In conclusion, the cause of death in this patient can be contributed to the disseminated Mycobacterium avium complex and Klebsiella pneumoniae infections, hepatic cirrhosis and the resulting complications leading to massive hemorrhage and subsequently death.

REFERENCES

1. Julander I, Hoffner S, Petrini B, Ostlund L. Multiple serovars Mycobacterium avium complex in patients with AIDS. APMIS 1996;104(4):318-20.
2. Good RC. Opportunistic pathogens in the genus mycobacterium. Ann Rev Microbiol 1985; 39;347-69.
3. von Reyn CF, Maslow JN, Barber TW, Falkinham JO 3rd, Arbeit R. Persistant colonisation of potable water source of Mycobacterium avium infection in AIDS. Lancet 1994; 343:1137-41.
4. Singh N, Yu VL. Potable water and Mycobacterium avium complex in HIV patients: Is prevention possible? Lancet 1994; 343:1110-11.
5. Yajko DM, Chin DP, Gonzalez PC, Nassos PS, Hopewell PC, Reingold AL, Horsburgh CR Jr, Yakrus MA. Ostroff SM, Hadley WK. Mycobacterium avium complex in water, food, and soil samples collected from the environment of HIV-infected individuals. Journal of Acq Imm Def Syn & Hum Retro 1995; 9(2):176-82.
6. Barbaro DJ, Orcutt VL, Coldiron BM. Mycobacterium avium-Mycobacterium intracellulare infection limited to the skin and lymph nodes in patients with AIDS. Rev Infect Dis 1989:11:625-8.
7. Wallace JM, Hannah JB. Mycobacterium avium complex infection in patients with the acquired immunodeficiency syndrome: A clinicopathologic study. Chest 1988; 93: 926-32.
8. Modilevsky T, Sattler FR, Barnes PF. Mycobacterial disease in patients with human immunodeficiency virus infection. Arch Inter Med 1989; 149:2201-5.
9. Gray JR, Rabeneck L. Atypical mycobacterial infection of the gastrointestinal tract in AIDS patient. Am J Gastroenterol 1989; 84:1521-4.
10. Levin M. Acute hypersplenism and thrombocytopenia: a new presentation of disseminated mycobacterial infection in patients with acquired immunodeficiency syndrome. Acta Haematol 1994; 91:28-31.

Contributed by Patricia A. Aronica, MD, and Oliver Ndimbie, MD