Puzzler Answer and Case Report

Biopsy results revealed:

Figure 3. Acid-fast bacillus present in granulomatous inflammation of airway (Ziehl-Nielsen, X100).

Figure 4. Granulomatous inflammation with scattered histiocytes and acute inflammatory cells in airway biopsy (hematoxylin-eosin, X20).

Figure 5. Inflamed bronchial mucosa (hematoxylin-eosin, X20).n

Acute and chronic inflammation with necrotizing granulomas with acid-fast bacilli was present, consistent with mycobacterial infection. Flow cytometry findings were negative for lymphoma.

The patient continued HAART therapy and was treated for presumptive Mycobacterium avium-intracellulare (MAI) infection, given the low CD4+ count, with azithromycin, rifabutin, isoniazid, and ethambutol. Trimethoprim and sulfamethoxazole were continued for PCP prophylaxis. The patient’s fever abated and cough improved, and she was weaned off oxygen. Four weeks later, the BAL and tissue cultures confirmed MAI, and the isoniazid was stopped.

Outpatient follow-up 6 months later showed the patient to be doing well with resolution of her endobronchial disease and continuing antibiotics as planned.

Pathologic Diagnosis: Mycobacterium avium-intracellulare complex endobronchial disease
Clinical Diagnosis: Immune reconstitution syndrome after initiation of HAART

Key points

1. Mycobacerial disease is a well known cause of disease in patients with AIDS1 and nontuberculous mycobacteria frequently colonize respiratory secretions of patients with HIV. However, endobronchial lesions and isolated pulmonary infections are uncommon.²
2. The introduction of HAART has dramatically improved the outcomes of patients with HIV/AIDS,^3,4 but successful suppression of viral replication and subsequent increase in CD4⁺ lymphocytes with partial recovery of cellular immune response can have untoward effects, such as a dramatic inflammatory reaction directed against pathogens causing latent or subclinical infection.
3. This immune reconstitution syndrome may be mild and resolve without treatment or severe enough to cause death.^5-7
4. MAC-induced reconstitution syndrome incidence was 3.5% among AIDS patients starting HAART with CD4+ less than 100 cells/μL.⁸
5. The few cases of endobronchial MAC reported in the literature describe immune reconstitution within 2 months of HAART initiation.⁹ There are at least two cases describing endobronchial MAC in patients with AIDS receiving AZT monotherapy.^10,11
6. We decided to continue HAART and treat the MAC infection with a combination regimen including three active drugs (rifabutin, ethambutol, and azithromycin) with a good outcome at 6 months.

References

1. Centers for Disease Control and Prevention. 1993 Revised Classification System for HIV Infection and Expanded Surveillance Definition for AIDS Among Adolescents and Adults. MMWR Morb Mortal Wkly Rep 1992; 41:1-19
2. Salama C, Policar M, Venkataraman M. Isolated pulmonary Mycobacterium avium complex infection in patients with human immunodeficiency virus infection: case reports and literature review. CID 2003; 37:e35-40
3. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection: HIV Outpatient Study Investigators. N Engl J Med 1998; 338:853-860
4. Folch E, Hernández I, Vetter T, et al. AIDS-related mortality: improved survival with HAART but causes of death unchanged (abstract 756W). In: Programs and Abstracts of the 9th Conference on Retroviruses and Opportunistic Infections (Seattle). Alexandria, VA: Foundation for Retrovirology and Human Health, 2002;327
5. Shelburne SA, Hamill RJ, Rodriguez-Barradas MC, et al. Immune reconstitution inflammatory syndrome: emergence of a unique syndrome during highly active antiretroviral therapy. Medicine 2002; 81:213-227
6. Huttner H, Kollmar R, Hug A, et al. Fatal tuberculous meningitis caused by immune reconstitution disease. J Neurol 2004; 251:1522-1523
7. Vendrelly A, Bienvenu B, Gasnault J, et al. Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy. Acta Neuropathol 2005; 109:449-455
8. Phillips P, Bonner S, Gataric N, et al. Nontuberculous mycobacterial immune reconstitution syndrome in HIV-infected patients: spectrum of disease and long-term follow up. Clin Infect Dis 2005; 41:1483-1497
9. Bartley PB, Allworth AM, Eisen DP. Mycobacterium avium complex causing endobronchial disease in AIDS patients after partial immune restoration. Int J Tuberc Lung Dis 1999; 3:1132-1136
10. Mehle ME, Adamo JP, Mehta AC, et al. Mycobacterium avium-intracellulare infection in a patient with AIDS. Chest 1989; 96:199-201
11. Packer SJ, Cesario T, Williams JH Jr. Mycobacterium avium complex infection presenting as endobronchial lesions in immunosuppresed patients. Ann Intern Med 1988; 109:389-393

Puzzler and case report submitted by:
Eric Folch, MD and Michael S Machuzak, MD
Respiratory Institute
Cleveland Clinic
Cleveland, OH