Lingual ulcer as the only sign of recurrent mycobacterial infection in
an HIV/AIDS-infected patient
Ulcera lingual como signo único de infección recurrente por micobacteria en un paciente con VIH/SIDA

Velia Ramírez Amador ⁽¹⁾, Gabriela Anaya Saavedra ⁽²⁾, Imelda González Ramírez ⁽³⁾, Juan Luis Mosqueda Gómez ⁽⁴⁾,
Lilly Esquivel Pedraza ⁽⁵⁾, Edgardo Reyes Gutiérrez ⁽⁶⁾, Juan Sierra Madero ⁽⁷⁾

(1) Coordinadora Curso Especialización en Patología y Medicina Bucal. Head of the Oral Pathology and Oral Medicine Specialization Course.
Universidad Autónoma Metropolitana-Xochimilco
(2) Alumna Doctorado en Ciencias Biológicas. PhD fellow. Universidad Autónoma Metropolitana- Xochimilco-Iztapalapa
(3) Profesor Asociado. Associate Lecturer. Universidad Autónoma Metropolitana- Xochimilco
(4) Residente Departamento de Infectología. Resident. Infectious Diseases Department.
Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"
(5) Médico adscrito al Departamento de Dermatología. Staff Dentist. Department of Dermatology.
Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"
(6) Médico adscrito al Departamento de Patología. Medical Staff. Pathology Department.
Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"
(7) Jefe de la Clínica de VIH/SIDA. Departamento de Infectología. Head of the HIV Clinic. Infectious Diseases Department.
Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"

Address:
Velia Ramírez-Amador.
Camino Sta. Teresa 277-9.
Col. Parques del Pedregal
Mexico D.F., 14010
Teléfono: (5255) 5606-1781,
Fax: (5255) 5483-7218
E-mail: veliaram@hotmail.com

Received: 13-06-2004. Accepted: 5-11-2004

INTRODUCTION

Mycobacterium avium complex (MAC) and Mycobacterium tuberculosis (MTB) are the two most common mycobacteriae causing infections in patients with HIV/AIDS. Although MAC infection was one of the most important AIDS-associated opportunistic infections (OI), presently, tuberculosis is one of the main infectious complication in HIV-infected individuals (1). The prevalence of MTB/HIV coinfection in adults has been estimated at 0.36% worldwide, which equals approximately 11.4 million people, the majority of them living in developing countries (2).

During the first years of the AIDS epidemic in Mexico, the frequency of MAC infection was reported at 4 to 9% (3); in a recent study of 746 AIDS patients (4), while a frequency of 8.4% was reported for MAC, 18.2% was observed for MTB infection, representing one of the most common OI in AIDS patients after candidosis and P. jiroveci (previously named P. carinii) pneumonia in Mexico (3,4).

Descriptions of the oral manifestations of mycobacterial infection in AIDS patients (5-11) are few in the literature, so characterizing the clinical features of these oral lesions is important. Thus, the purpose of the present report is to depict the clinical and histological findings in an HIV/AIDS-infected patient, who was treated successfully for lymph node tuberculosis and 4 years later presented with a lingual ulcer as a unique sign that suggested recurrence of mycobacterial infection, probably M. tuberculosis.

CASE REPORT

A 39-year-old man seen in the HIV clinic of the INCMNSZ in Mexico City since 1991 for HIV infection. In 1999 he presented with weight loss, fever, diaphoresis, and generalized lymph node enlargement. A 5 U tuberculin skin test was of 35 mm. His viral load (VL) was of 12 254 copies/ml and a CD4⁺ lymphocyte count of 356 cells/mm³. A biopsy of the cervical lymph node showed granulomatous lymphadenitis with caseous necrosis and Langhans multinucleated giant cells, suggestive of lymph node tuberculosis, however, the culture was negative. Antituberculous treatment was administered during four months with rifampin (600 mg/d), isoniazide (300 mg/d), pyrazinamide (1 200 mg/d) and ethambutol (1 200 mg/d); continued by rifampin (600 mg/d) and isoniazide (600 mg/d) for 8 months, with improvement of the lymphadenopathy and disappearance of the systemic symptoms. 

During follow-up, oral candidosis and hairy leukoplakia were identified. In December of 2001, the plasma VL was of 52 800 copies/ml and the CD4+ count of 141 cells/mm³. Antiretroviral treatment was not initiated because patient refused.

On May, 2003, the patient was seen because of a painful superficial lingual ulcer, of 4 months duration, that measured 0.7 cm in diameter, well circumscribed, with crateriform aspect and slightly elevated and indurated borders (Fig 1). Laboratory studies showed a decrease in the CD4⁺ lymphocyte count to 113 cells/mm³. The histopathological examination showed chronic granulomatous inflammation with giant multinucleated cells (Fig 2). Ziehl-Neelsen, Grocott and periodic acid-Schiff stains and the culture were negative. An attempt to extract DNA from paraffin embedded tissue to identify mycobacteria by polymerase chain reaction was unsuccessful because of the scarcity of the remaining tissue.

Although, the identification and isolation of the causative mycobacteria was not possible, based on the histopathologic findings, it was considered that the clinical characteristics were suggestive of a recurrence of tuberculosis with a lingual manifestation. He was treated with antituberculous drugs: rifampin (600 mg/d), isoniazide (300 mg/d), pyrazinamide (1 200 mg/d), ethambutol (1 200 mg/d) and streptomycin (1 000 mg/d). In June of 2003, the patient began highly active antiretroviral therapy (HAART) that included zidovudine (600 mg/d), lamivudine (300 mg/d) and efavirenz (600 mg/d). The lingual lesion improved with partial healing at first week of the antituberculous treatment and total remission was observed at 45 days of management. After 7 months of the onset of the lingual lesion, the clinical response was satisfactory, remaining free of of the oral lesion (Fig 3).

DISCUSSION

In studies carried out at the AIDS Clinic of the INCMNSZ, we have found a prevalence of 11. 5% for oral ulcers in 1 000 individuals with HIV/AIDS (12), however, the present report describes the only patient in our cohort of patients with HIV/AIDS in whom an ulcerative lesion, associated with mycobacteria, probably MTB, was identified.

In subjects not co-infected with HIV, mycobacteria related oral lesions, particularly MTB, occur with a frequency that varies from 0.05 to 5% (13), oral manifestations of Mycobacterium bovis have been reported less commonly (14). In AIDS patients, the description of oral manifestations associated with MTB, MAC and Mycobacterium kansasii have been isolated case reports (5-11).

The most frequent clinical presentation of oral TB and other mycobacterial infections, as in the present case, is an ulcer, solitary or multiple, painless or painful, described as a superficial, indurated, with irregular borders, undermined edges or well circumscribed lesion (5,6,8,10,11,13-15). In non co-infected individuals, the lingual mucosa and palate are frequently involved; other affected areas are the gingival, buccal and labial mucosa and floor of the mouth (13-15). In HIV-infected individuals, oral tuberculosis and mycobacterial infection have been described in lingual and labial mucosa, gingiva, palate and alveolar ridge (5-11) (Table 1).

In the described case, the diagnosis of MTB infection in lingual mucosa was suggested based on the history of previous tuberculosis, the granulomatous inflammation with presence of multinucleated giant cells in the affected lingual tissue, the absence of other pathogens and the satisfactory response to the established treatment. The CD4⁺ cell count above 100 cell/mm³ of the patient was more consistent with the possibility of MTB rather than MAC, given the well known presentation of the latter at CD4+ cell counts lower than 50 cell/mm³ (16). Considering that the acid-fast bacilli stain and the culture were negative, it was not possible to confirm a definitive diagnosis of MTB or to rule out other mycobacteria as the etiologic factor. It is likely that the low bacillary load found in these lesions partly explains the absence of bacilli in the tissue and culture (17)

Differential diagnosis of oral ulcers in patients with HIV/AIDS is broad comprising entities such as malignancy, fungal, viral or bacterial infections and autoimmune processes as aphthous ulcers (18). As exemplified by this case, mycobacterial infection, particularly MTB, should be included in the differential diagnosis of these lesions.

In our 15 years of experience at the AIDS Clinic of the INCMNSZ, this is the first patient with HIV/AIDS in whom a mycobacterial related oral lesion was identified. Although, the limitations in the diagnosis, a characteristic of the present case is that the lingual ulcer was the only sign of mycobacterial infection suggestive of tuberculosis in an HIV/AIDS patient, that probably represented a recurrence of a previous episode of TB. The diagnosis of the oral ulcer led to the patient's appropriate management and the total resolution of the lingual lesion.

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