Mycobacterium Avium complex (MAC) refers to multiple related species of nontuberculous mycobacteria (M. avium, M. intracellulare, M. paratuberculosis) that are ubiquitous to the environment. MAC presents with either localized disease or multiorgan involvement. Localized disease is rare and has been reported among patients receiving highly active antiretrovirals.1 Disseminated disease is a late stage complication of advanced human immunodeficiency virus (HIV) and is associated with significant morbidity and mortality.
Oral ulcers of various types are commonly associated with HIV infection.2 Oral ulcer that develops in individuals with disseminated MAC infection is rare and has not been described in children. There have been only 2 reported cases in adults.3,4 Here we report a case of invasive oral MAC infection in an HIV-positive child.
A 10-year-old girl presented to the surgical outpatient department at Chris Hani Baragwanath Hospital on August 2005 with a 5-day history of painful swollen gums associated with swelling of the left upper jaw and cheek. A week before this, she was seen by a dentist who extracted 2 teeth and prescribed 5 day course of amoxicillin and metronidazole. On examination a tender nonfluctuant swelling of the left upper quadrant of the mouth was noted, which extended to the lower border of the left mandible ramus. Oral examination revealed a necrotic superficial ulcer of the hard palate. An HIV ELISA result was reactive. A provisional diagnosis of acute necrotizing peridontitis and possible cancrum oris in an HIV-positive child was made. The palatal lesion was debrided and a biopsy taken. It was later discovered that the biopsy specimen had been misplaced. The patient was discharged following a week's course of intravenous penicillin G, metronidazole, cloxacillin and oral amoxicillin-clavulunate.
The patient then presented on January 2006 to the pediatric outpatient department at Chris Hani Baragwanath Hospital with a 12-day history of diarrhea, vomiting, dysphagia and abdominal cramps. On presentation she appeared cachecic and stunted. Examination showed generalized significant lymphadenopathy, extensive oral candidasis, trismus and hepatomegaly; all in keeping with WHO clinical stage 4 of retroviral disease. A CD4 count of 4/0.48% and a viral load of 140000 RNA copies/mL indicated an immunologic stage 3. Her full blood count demonstrated leucopenia and macrocytic anemia. The serum vitamin B12 concentration was normal; the folate value was not available. Iron studies highlighted anemia of chronic disease. Liver function tests showed hypoalbuminemia with markedly raised transaminases, alkaline phosphatase and γ-glutamyl transferase.
A provisional diagnosis of chronic gastroenteritis with underlying hepatitis, leukopenia and anemia was made. The gastroenteritis improved with oral gentamicin, metronidazole and cholestyramine therapy. Viral serology tests for hepatitis and Ebstein Barr virus were negative. The PP65 antigen for cytomegalovirus was negative as well.
A week after admission, the oral candidasis and trismus improved with appropriate management. A hard palate defect extending from the alveolus of the maxillary bone to the anterior tonsillar pillar with surrounding exudate posteriorly was noted (Fig. 1). Computed tomography of the face showed erosion of the left maxillary alveolar process extending through the inferior and medial maxillary sinus wall into the left maxillary sinus, left nasal cavity with erosion of the left inferior turbinate.
Mycobacterium avium complex was cultured from sputum. Ciprofloxacin (34 mg/kg/d), ethambutol (15 mg/kg/d) and clarithromycin (34 mg/kg/d) therapy was initiated in the view of possible disseminated disease.
The palatal defect was biopsied and showed features of acute and chronic inflammation with no evidence of granulomas. Microbiology, however, revealed Mycobacterium avium complex and Candida krusei. Mycobacterium avium complex was also cultured from blood. Antiretrovirals were commenced after 5 weeks of antimycobacterial treatment. Despite adequate antiretrovirals and antimycobacterials; the leukopenia and anemia persisted.
A bone marrow aspirate and biopsy was done and submitted for histology. The histology demonstrated active hematopoiesis, ill-defined granuloma showing epitheliod histiocytes and decreased megakaryocytes, granulopoeisis and erythropoeisis. Mycobacterium avium complex was then cultured from the bone marrow biopsy. In view of the worsening liver function and the drug interaction of clarithromycin and efavirenz; clarithromycin was replaced by azithromycin.
The child's appetite and weight gradually improved with virologic suppression (<25 RNA copies/mL) and elevation of CD4 count of 16 × 106/L (1.08%). Atypical mycobacteria continued to be cultured on blood after 10 weeks of treatment. The patient continues to be followed up at the pediatric HIV unit.
Disseminated MAC infection is a common complication of HIV/AIDS, affecting as many as 30%–40% of patients.5 Disseminated disease rarely occurs during the first year of life in pediatric HIV infection. Its frequency increases with age and declining CD4 count (<200 cells/μL).6
Oral presentation of disseminated MAC infection is rare and has only been described in adults.3,4 In this case the patient was severely immunosuppressed and presented with a necrotic ulcer of the hard palate that gradually invaded underlying bone and soft tissue. Despite antibiotics and debridement MAC was detected microbiologically from an area of the oral lesion. Findings of systemic illness and evidence of disseminated atypical mycobacteria was also present in previously described cases.3,4
In patients with AIDS, disseminated disease is the result of recent acquisition of atypical mycobacteria and not from reactivation. The gastrointestinal tract is the portal of entry in 90% of cases and is the most common site of colonization and dissemination.7 Any area of the gastrointestinal tract may be involved. In our case, the oral cavity could have been the site for local disease before dissemination. Because the biopsy did not show characteristic histologic features and did not have an adequate representation of an ulcer; the possibility of nonspecific colonization cannot be excluded. However, supporting evidence of bone marrow involvement and microbiologic culture of atypical mycobacteria can be used to conclude that the oral lesion was not due to secondary infection. The variable histologic features also noted in previous reports3,4 could have been related to the degree of immunosuppression.
The interplay of malnutrition, poor oral hygiene and advanced HIV predisposes to periodontal disease. Malnutrition and HIV infection have both direct and indirect effects on oral mucosal immunity, affecting the cellular and humoral immunity as well as the specific and innate immunity.8–12 Oral ulceration reflects damage to the mucosal barrier and waning local immunity. These are important features as the gingival inflammatory response in children is characterized by the presence of T lymphocytes,13 which explains why periodontal tissue is more susceptible to periodontal disease.
1. Horsburgh CR, Gettings J, Alexander LN, et al. Disseminated Mycobacterium avium
complex disease among patients infected with human immunodeficiency virus, 1985–2000. HIV/AIDS CID
2. Greenspan D, Greenspan JS. Oral manifestations of HIV infection. Aids Clin Care
3. Robinson P, Farthing P, Scott GM, et al. Oral Mycobacterium avium
complex infection in a patient with HIV-related disease. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
4. Volpe F, Schwimmer A, Barr C, et al. Oral manifestation of disseminated Mycobacterium avium
intracellulare in a patient with AIDS. Oral Surgery
5. Hoover DR, Saah AJ, Ballar H, et al. Clinical manifestation of AIDS in the era of pneumocystis prophylaxis. N Eng J Med
6. CDC, the National Institute of Health and the Infectious Diseases Society of America. Treating opportunistic infections among HIV exposed and infected Children. MMWR Morb Mortal Wkly Rep
7. Horsburgh CR. The pathophysiology of disseminated mycobacterium avium complex disease in AIDS. J Infect Dis
. 1999;179(suppl 3):S461–S465.
8. Chandra RK. Inducer and suppressor T cell subsets in protein-energy malnutrition:analysis of monoclonal antibodies. Nutr Res
9. Beisel WR. Nutrition in pediatric HIV infection: setting the research agenda. J Nutr
10. Chandra RK. Numerical and functional deficiency in T helper cells in protein energy malnutrition. Clin Exp Immunol
11. Chandra RK. Nutrition and immunity: lessons from the past and new insights into the future. Am J Clin Nutr
12. Challacombe SJ, Naglik JR. The effects of HIV infection on oral mucosal immunity. Adv Dent Res
13. Seymour GJ, Crouch MS, Powell RN, et al. The identification of lymphoid cell subpopulation in sections of human lymphoid tissue and gingivitis in children using monoclonal antibodies. J Periodontal Res