Soon after the introduction of HAART for the treatment of HIV in the mid-1990s, there emerged a unique set of complications related to restoration of an inflammatory immune response against both infectious and noninfectious antigens. This phenomenon, variously known as the immune reconstitution syndrome, immune restoration disease, or the immune reconstitution inflammatory syndrome, has been defined as "a paradoxical deterioration in clinical status attributable to the recovery of the immune system during HAART."4 The viral and immunologic events underlying immune reconstitution include a rapid (over 2-6 weeks) fall in HIV viral load and a concomitant increase in CD4+ T lymphocytes. This CD4 T-lymphocyte expansion includes an initial redistribution of memory CD4+ cells previously activated by antigen exposure, followed by a proliferation of naive CD4+ cells. It is accompanied by functional improvements in immunity such as increases in delayed hypersensitivity and in vitro lymphocyte proliferative responses to common antigens.4,8
Immune reconstitution syndromes have been associated most frequently with infections common to patients with AIDS such as MAC, M. tuberculosis, Cryptococcus neoformans, cytomegalovirus, and hepatitis B and C. Typical clinical manifestations depend on the underlying infection, but constitutional symptoms such as fever and weight loss are common to all.3,4,8,9
Our patient's clinical course was similar to that described in previous reports of immune reconstitution syndromes related to MAC and M. tuberculosis. Focal lymphadenitis and granulomatous masses are typical.3,4 We were struck by the rapidity with which the hilar mass developed and its rapid resolution with antimycobacterial therapy. The concurrent development of bulky hilar adenopathy with the substantial rise in CD4 lymphocyte count from 6 to 154 cells/μL over 6 weeks, prompt suppression of HIV viral replication on HAART, and histopathology showing granulomatous inflammation are evidence that this atypical presentation of pulmonary M. kansasii was a result of progressive immune reconstitution. The earlier pneumonia, diagnosed presumptively as PCP and treated with TMP-SMX, actually may have been the initial presentation of M. kansasii, manifesting as interstitial infiltrates when our patient's cellular immune system was markedly suppressed. The sulfamethoxazole component of TMP-SMX is active against M. kansasii1 and may have resulted in partial response and suppression of this infection. In 1991, Carpenter and Parks2 described a patient who initially presented with an endobronchial mass caused by M. kansasii and then developed diffuse interstitial infiltrates-a clinical evolution reverse from that of our patient and likely a result of advancing immunodeficiency, as was inevitable before the HAART era.
We considered immune reconstitution in the differential diagnoses of our patient's latter presentation, but did not think that it was related to PCP, as would have been suggested by the initial presumptive diagnosis. She was not hypoxic, and pulmonary infiltrates were not present on chest x-ray. Immune reconstitution PCP is relatively unusual, and intrathoracic lymphadenopathy is not a feature.4,10,11 Lacking a prior diagnosis of mycobacterial infection and the clinical resemblance to primary bronchogenic carcinoma, we did not prescribe an empiric antimycobacterial regimen until granulomatous inflammation was reported on biopsy. This problem underscores the importance, however, of making a definitive diagnosis of an opportunistic infection in antiretroviral-naive patients who will subsequently be considered for HAART.
As immune reconstitution syndromes may be associated with increased short-term morbidity,9 some have suggested that initiation of HAART be delayed in antiretroviral-naive patients with a recent opportunistic infection.12 Our patient, however, had completed a full course of therapy for what was presumed to be PCP, and because immune reconstitution PCP is relatively unusual (comprising only 1 of 182 cases reviewed by Shelburne et al4), we did not feel that further delay in initiating HAART was indicated.
Anti-inflammatory agents, such as nonsteroidal anti-inflammatory drugs or corticosteroids, have been advocated for patients with severe symptoms related to immune reconstitution disorders and seem most appropriate for ophthalmologic (eg, cytomegalovirus) or central nervous system (eg, M. tuberculosis, C. neoformans) infections, where inflammation is poorly tolerated.4,8,12 Our patient had only mild systemic symptoms, which did not appear to warrant anti-inflammatory therapy.
To our knowledge, this is the first reported case of M. kansasii infection developing as an endobronchial mass in an HIV-infected patient during HAART-associated immune reconstitution.
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© 2006 Lippincott Williams & Wilkins, Inc.
12. Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Disease Society of America. MMWR
. 2004;53(no. RR-15):3-4.