Endobronchial Mycobacterium kansasii During Highly Active Antiretroviral Therapy-Associated Immune Reconstitution

LaRocco, Anthony Jr MD, FACP*; Lucado, Courtney S. MD†; McGinley, Mark J. MD, FCCP‡

Infectious Diseases in Clinical Practice: January 2006 - Volume 14 - Issue 1 - pp 62-64
doi: 10.1097/01.idc.0000189087.59864.af
Case Reports

Abstract: Inflammatory reactions to latent Mycobacterium avium complex and Mycobacterium tuberculosis have been reported in patients with AIDS who experience immune reconstitution soon after starting highly active antiretroviral therapy, but clinical manifestations caused by Mycobacterium kansasii in this setting are rare. This report describes a patient with AIDS who developed an endobronchial mass caused by M. kansasii during highly active antiretroviral therapy-associated immune reconstitution.

Departments of *Infectious Disease, †Internal Medicine and ‡Pulmonary Division, Eastern Virginia Medical School, Norfolk, VA.

Address correspondence and reprint requests to Anthony LaRocco, Jr, MD, FACP, Assistant Professor, Division of Infectious Diseases, Department of Internal Medicine, Eastern Virginia Medical School, 825 Fairfax Avenue, Norfolk, Virginia 23507-1912. E-mail: larocca@evms.edu.

Article Outline

Mycobacterium kansasii infection in patients coinfected with HIV may present as focal or diffuse, alveolar or interstitial pulmonary infiltrates, or limited extrapulmonary disease or as a widely disseminated process with mycobacteremia.1,2 Inflammatory reactions to latent Mycobacterium avium complex (MAC) and Mycobacterium tuberculosis have been reported in patients experiencing immune reconstitution soon after starting highly active antiretroviral therapy (HAART),3,4 but clinical manifestations caused by M. kansasii in this setting are rare.5 Endobronchial lesions caused by M. kansasii are also unusual, but have been reported in patients with and without HIV coinfection.6,7 This report describes a patient with AIDS who developed an endobronchial mass caused by M. kansasii during HAART-associated immune reconstitution.

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A 27-year-old African-American woman with AIDS was hospitalized on January 23, 2002, with dyspnea and diffuse interstitial pulmonary infiltrates. Her CD4 lymphocyte count was 6 cells/μL, and quantitative HIV RNA level by polymerase chain reaction (viral load) was 271,183 copies/μL. High-dose trimethoprim-sulfamethoxazole (TMP-SMX) and a tapering course of prednisone were started for presumed Pneumocystis carinii pneumonia (PCP), and weekly azithromycin was started for MAC prophylaxis. She did well, and no abnormalities were seen on the chest x-ray at a follow-up visit on February 19. Prednisone was discontinued and, because of a rash attributed to TMP-SMX, dapsone was started for secondary PCP prophylaxis. HAART was begun on February 27 with efavirenz, stavudine, and nelfinavir. Two to three weeks later, she developed right anterior pleuritic chest pain, subjective low-grade fevers, night sweats, and mild dyspnea. There was no history of abdominal pain or recent weight loss. Vital signs at a clinic visit on March 19 were normal, including an oral temperature of 97.9°F. Chest auscultation revealed mild focal inspiratory and expiratory wheezes over the right upper lung field. Peripheral lymphadenopathy was absent. Oxygen saturation was 97% on room air by pulse oximetry and did not change with moderate exertion. Liver function tests and serum lactic dehydrogenase were within normal limits. A chest x-ray on March 26 showed a right hilar mass and clear lung fields (Fig. 1). After some delay caused by scheduling problems, a computed tomographic scan of the chest was performed on April 17 and showed a 6-cm, spiculated, hilar mass encasing the right upper and middle lobe bronchi. Her CD4 lymphocyte count on April 16, 6 weeks after starting HAART, had risen to 154 cells/μL, and her HIV viral load was undetectable (<400 copies/μL). Fiber-optic bronchoscopy showed a fungating, polypoid, tumorlike mass in the posterior subsegment of the right upper lobe and a similar endobronchial abnormality partially obstructing the opening to the superior segment of the right lower lobe (Fig. 2). Cytology on brush and wash samples and a biopsy of the lesions were negative for malignancy. Histopathology revealed granulomatous inflammation but was negative for acid-fast and fungal organisms. Bronchial washings showed acid-fast bacilli by fluorescent microscopy but were negative for M. tuberculosis DNA by polymerase chain reaction. Isoniazid, rifabutin, ethambutol, pyrazinamide, and clarithromycin were started on May 4. A culture of the bronchial wash specimen later grew M. kansasii, and pyrazinamide and clarithromycin were discontinued. In mid-May, the patient experienced 2 to 3 days of fever that was not associated with other symptoms and which spontaneously resolved. Chest pain and wheezing resolved within 3 weeks, and a second chest computed tomographic scan showed almost complete resolution of the hilar mass 9 weeks after the start of antimycobacterial therapy. The CD4 lymphocyte count rose to 224 cells/μL by August 2002 and to 647 cells/μL by July 2003; the HIV viral load has remained undetectable. Antimycobacterial therapy was discontinued on November 2003. The patient continues to do well on HAART.

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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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