Erosive mediastinal lymphadenitis associated with Mycobacterium avium infection in a pediatric acquired immunodeficiency syndrome patient.

Abstract

Mycobacterium avium and Mycobacterium intracellulare are two closely related species usually presented together as the Mycobacterium avium complex (MAC). Acquisition of MAC appears to be via either ingestion or inhalation of bacteria in the environment.1 After exposure disease is rarely symptomatic in the immunocompetent host. When infection does occur it is more common in children and typically presents as a unilateral cervical lymphadenopathy.2 Disseminated MAC infection is rare in the immunocompetent host, but since the onset of the AIDS epidemic in the early 1980s the number of cases of disseminated infection has risen dramatically.3 With the advent of more effective antiretroviral therapy and improved treatment of AIDS-related opportunistic infections, patients today are able to endure a more immunosuppressed state allowing a greater opportunity for infection.4 MAC infection is now the second most common opportunistic infection of the HIV-positive population after Pneumocystis carinii pneumonia and is recognized as a significant health hazard to the severely immunocompromised patient.5 Case report. A 6-year-old girl was referred to the Medical College of Virginia infectious disease clinic with a history of recurrent fevers after testing positive for HIV. She was diagnosed with AIDS on the basis of weight loss (wasting syndrome) and lymphoid interstitial pneumonitis. Initial blood work revealed a CD4+ count of 10/mm3, and she was given zidovudine, lamivudine, crixivan and trimethoprim-sulfamethoxazole. Two weeks after initial referral she was seen for a newly enlarged lymph node. On examination she had a 4-cm tender, erythematous node in the left supraclavicular fossa. Gram stain and bacterial culture on excisional biopsy material was negative, but acid-fast bacteria stain was positive. Both tissue cultures from that visit and blood cultures from the initial clinic visit grew MAC. Antimycobacterial therapy with azithromycin, ethambutol, ciprofloxacin and rifabutin was begun. Two months later she had a mildly tender 1.5-cm lymph node in the same region; her biopsy site had healed well and she was no longer having recurrent fevers. Azithromycin was changed to clarithromycin, and her other antimycobacterial medications were continued unchanged. Six months later although the previously enlarged lymph node was no longer palpable, a new 3- to 3.5-cm erythematous, tender lymph node was noted in the same area. The lymph node was resected and her current medications were continued. During this time she had undetectable viral loads (<400 copies/ml via Roche Amplicor method), but her CD4 count remained low. Three months later she presented for routine follow-up and complained of a 2-week history of a nonproductive cough. Wheezes and decreased breath sounds were found in the right upper lobe area. Chest radiograph revealed partial right upper lobe collapse and right paratracheal node enlargement. A computerized tomography scan showed enlarged lymph nodes in the mediastinum with at least one abutting the right main stem bronchus. At bronchoscopy two endobronchial masses were found, the first at the junction of the right mainstem and secondary bronchus, and the second at the entrance of the right upper lobe bronchus causing near total obstruction. Washings, taken at the time of bronchoscopy, were positive for acid-fast bacteria and grew MAC. CD4 count was 27/mm3 and viral load was undetectable. A rigid bronchoscopy was performed, and partial debulking of the endobronchial lesions was possible. A central venous catheter was placed during that hospitalization and granulocyte colony-stimulating factor (G-CSF), amikacin and cefoxitin were added to her previous antimycobacterial regimen of clarithromycin, ethambutol, ciprofloxacin and rifabutin. Within a few weeks she had improvement in symptoms and clear breath sounds, and a repeat chest radiograph revealed significant improvement in aeration of the right upper lobe. One month later a second bronchoscopy was performed and revealed complete regression of the previous lesions with no evidence of extrabronchial compression. Her intravenous antibiotics, cefoxitin and amikacin, were stopped after ˜3 months of therapy, whereas her oral antimycobacterial regimen continued unchanged. Eighteen months after her initial presentation she had an absolute CD4 count of 138/mm3, and 2 years after presentation it was 260/mm3. Her viral load has continued to be undetectable and she is currently doing well with no further pulmonary complications. Discussion. MAC-associated lymphadenitis is the most common and a relatively benign presentation in HIV-positive children. Although less common, identification of pulmonary MAC infection is important, in that 72% of patients having pulmonary involvement without dissemination will develop disseminated MAC within a mean time of 8 months.6 Disseminated MAC infection is clinically severe and increasingly is being recognized as a major health hazard to HIV-infected children; it is estimated that 11 to 40% of these children will develop this complication at some time.2, 7 Disseminated MAC typically presents at the end stage of the AIDS illness. A low CD4 count is believed to be the most important risk factor for the development of this complication. Patients with disseminated MAC have a CD4 average of <60/mm3, whereas patients with CD4 counts >100/mm3 are not believed to be at significant risk.3, 8 This infection, previously thought to represent only the natural history of advanced HIV infection, has been shown recently to increase the morbidity and mortality associated with AIDS, independently of other pathogenic processes.9, 10 Not only does a severely compromised immune system, as represented by a low CD4 cell count, predispose patients to MAC infection, but also the response to a disseminated infection may be poor, thereby impairing diagnosis.11 Recently there are increasing reports of patients with disseminated MAC who present shortly after the start of antiretroviral therapy with fever, lymphadenopathy and leukocytosis. It is believed that immune reconstitution allows the body to mount an immune response against the MAC infection, resulting in the unexpected clinical manifestations. Consequently assessment and treatment of patients with low CD4 counts for MAC infection are important before the initiation of antiretroviral immune reconstitution therapy.12 Treatment for MAC infection is extremely successful in the immunocompetent patient, and after surgical intervention antimycobacterial therapy is often not necessary.6 Before the development of the macrolide antibiotics, azithromycin and clarithromycin, success of antimycobacterial therapy for the treatment of MAC infection in the immunocompromised host was difficult.2, 6 These antibiotics are helpful in the treatment of both disseminated MAC and MAC pulmonary infection. The United States Public Health Service recommends the lifelong treatment of disseminated MAC in HIV-positive patients with a regimen of at least two drugs including a macrolide.13 Ethambutol is the most common second drug used, although rifabutin, rifampin, ciprofloxacin and amikacin are commonly used alternatives.13 Many physicians choose to treat with a combination of these medications. Clofazamine, which has been used in the past as an alternative to ethambutol, has been shown in at least one study to be associated with an increased rate of mortality and therefore it is no longer recommended.14 The United States Public Health Service recommends prophylactic macrolide therapy for all HIV-infected patients with CD4 counts below 50/mm3, whereas prophylaxis for HIV-infected children typically begins with CD4 counts below 100/mm3.15 Prophylactic therapy significantly reduces the risk of the development of MAC infection but is also associated with the development of macrolide-resistant strains of MAC.16 Seventy-nine percent of patients failing macrolide prophylaxis can be found to have macrolide-resistant MAC.17 The treatment of disseminated MAC in HIV-infected persons is difficult not only because of inherent resistance to antimicrobials but also because the polypharmacy of HIV is associated with significant drug-drug interactions that are enhanced only by the addition of antibiotics for disseminated MAC. A detailed account of all the possible drug reactions is beyond the scope of this paper; however, MAC medicines have been shown to interact both among themselves and with standard antiretroviral medications.1, 18 The use of G-CSF as an adjunct to antimicrobial therapy for disseminated MAC has been reported in several retrospective cohort studies suggesting that the addition of G-CSF to macrolide therapy is associated with an improved survival in this group of patients.19 Furthermore it has been shown in vitro that G-CSF stimulated neutrophils will kill MAC.20 Additional data are needed to determine the usefulness of this agent. The advent of increasingly effective therapies for HIV-infection has changed the spectrum of opportunistic infections in this population. In our patient the use of highly active antiretroviral therapy was associated with the development of clinically symptomatic disseminated MAC infection that was more severe than it was before highly active antiretroviral therapy. We believe that ongoing viral suppression with immune reconstitution and aggressive antimicrobial therapy including G-CSF was responsible for her good therapeutic response.