Oral histoplasmosis associated with hiv infection: a comparative study

J Oral Pathol Med (2004) 33: 445–50ª Blackwell Munksgaard 2004 Æ All rights reserved Oral histoplasmosis associated with HIV infection:a comparative study S. L. Herna´ndez1, S. A. Lo´pez de Blanc1,2, R. H. Sambuelli3,4, H. Roland3, C. Cornelli3, V. Lattanzi1,M. A. Carnelli4 1Clinical Stomatology B, School of Dentistry, National University of Co´rdoba, Co´rdoba; 2Department of Oral Pathology, HeadProfessor of Clinical Stomatology B, Faculty of Dentistry, National University of Co´rdoba, Co´rdoba; 3Rawson Hospital Co´rdoba,Co´rdoba; 4Department of Pathology, Catholic University of Co´rdoba, Co´rdoba, Argentina OBJECTIVE: Histoplasmosis is a granulomatous fungal river valleys of the world between latitudes 45° north disease caused by Histoplasma capsulatum. The objective and 30° south of the equator (1, 4, 6–15). In Argentina, of the present paper was to describe the prevalence the endemic region is around the central, east and of oral histoplasmosis (OH) in two services from an endemic area in Argentina between 1991 and 2002 and to Clinically, histoplasmosis has been classified as: (i) a compare the clinicopathological profile of OH between primary acute pulmonary form, (ii) a chronic pulmonary HIV-positive and HIV-negative patients.
and (iii) a disseminated form (DH) occurring in infants, METHODS: About 733 HIV+ (group A) and 14 260 elderly or in immunocompromised patients (6, 19–23).
patients (group B) were examined. Clinical diagnosis was In 1985, the Centre for Disease Control added DH to confirmed by cytology, biopsy or culture.
the spectrum of infections that characterize the acquired RESULTS: About 21 (3%) and 10 (0.07%) cases of OH immunodeficiency syndrome (AIDS). The main reason were diagnosed in group A and B respectively. Most for the delay in recognizing histoplasmosis as an patients were male. A total of 90% of patients in group A opportunistic infection in those patients was that early were <45 years old whereas 70% of group B were more AIDS cases appeared first in non-endemic areas. With than 45 years old. Palate, gingiva and oropharynx were spread of the disease to endemic areas, it has emerged as the most frequent locations. The importance of including an important opportunistic infection in patients with histoplasmosis in the differential diagnosis of ulcerated AIDS (8, 9, 24, 25). About 30–66% of patients with DH have oral lesions, frequently presenting as the initial sign. Generally lesions of histoplasmosis in the oral cavity, are the local manifestation of pulmonary ordisseminated disease (16, 26) but rarely they may be the Keywords: histoplasmosis; human immunodeficiency virus; oral primary or even the only manifestation of the disease (3, 4, 8, 10, 16, 17, 27–29). The diagnosis is usually basedon clinical signs and symptoms, organ function tests andfungal demonstration or culture from a lesion orsecretion. Serological testing may help together with other suggestive but non-diagnostic clinical criteria (4–6, Histoplasmosis is a granulomatous fungal disease of 11, 17). Recently, molecular typing of H. capsulatum has worldwide distribution caused by Histoplasma capsula- been shown to be useful in distinguishing relapse from tum. The infecting agents are airborne spores from the reinfection, and in defining the likely source of the mycelial form. It is usually found in warm, humid infection (21, 30, 31). Furthermore, molecular typing of environments that contain bird and bat excreta (1–7).
H. capsulatum by the random amplified polymorphic The most endemic areas for H. capsulatum are certain method, is able to discriminate among clinical iso-lates, making it a useful tool for epidemiological investi- Dra Silvia Lo´pez de Blanc, Ca´tedra de Clı´nica Estomatolo´gica I y II B, Facultad de Odontologı´a, Pabello´n Argen-tina, Ciudad Universitaria, Agencia 4, (5016) Co´rdoba, Argentina.
Tel: 0351-4659564, Fax: 0351-4334179-78, E-mail: silopez@odo.unc.
Historically, amphotericin B has been the drug of choice edu.ar, lopezdeblanc@yahoo.com.arAccepted for publication March 11, 2004 for systemic histoplasmosis (1–3, 8, 12, 16, 17, 32–37).
The options have broadened considerably since the CD4 count in HIV+ patients was 60/mm3 and ranged introduction of the azole compounds, ketoconazole and Oral lesions had similar clinical presentation in both The aim of the present paper is to describe the groups, described as painful granulomatous ulceration.
prevalence of OH in two services from an endemic area The lesions began as erythematous, painful red patches in Argentina and to compare the clinicopathological (see Fig. 1) that latter became elevated, granulomatous profile of histoplasmosis oral lesions of HIV-infected and ulcerated as shown in Fig. 2. The ulcerations were (HIV+) and HIV-negative (HIV)) patients.
covered by yellowish pseudomembranes difficult toremove and tender to palpation. Most of the patientsin both groups, had more than two lesions. The most frequent locations were hard and soft palate, gingiva In this retrospective study, the clinical records made by and oropharynx, followed by tongue. Gingival lesions us in HIV+ patients of Rawson Hospital: group A, and were associated with bone loss. Presence of histoplas- in those attended in Clinical Stomatology B (a referral mosis was diagnosed by cytology, culture, biopsy or clinic for oral soft-tissue lesions): group B, between December 1991 and December 2002 were revised inorder to analyse and compare the prevalence of OH in both groups. Group A included 733 patients and group Yeast forms were quite easily visualized in cytological B 14 260. Written consent was obtained from each smears or biopsies. The smears revealed in addition to patient before the study; oral examinations and the squamous cells of the oral mucosa, several erythrocytes, diagnosis at both centres were made by the same trained neutrophils and macrophages-containing intracellular professionals and supervised by the head professor. All spherical to ovoid bodies each surrounded by a small the patients with OH were tested for HIV infection and light halo (Fig. 3). Biopsy specimens showed a normal the HIV-positive excluded of group B. When an maturing, thinly stretched and ulcerated stratified squ- ulcerated granulomatous lesion suggesting OH was amous epithelium. The lamina propia showed focal found, the diagnosis was based on the demonstration accumulations of mononuclear macrophages stuffed of the microorganism in biopsies, cytological smears or with 2–5 micron fungal yeasts and some isolated culture (4–7, 11, 16). Biopsies were stained with haem- organisms that stained highly positive with PAS and atoxylin and eosin and with periodic acid-Schiff (PAS) 1 GSM. Yeast forms were seen intracellularly within the stain reaction; in some cases the Grocott silver methen- histiocytes, and as described in the literature, they had a amine (GSM) procedure was used. Cytological smears thin wall instead of a true capsule (39). The ulcerated were stained with May Gru¨ndwald Giemsa (MGG) and surface was coated with fibrin and the area beneath the with Papanicolaou stain (EA36-Hematoxylin). Addi- ulcer showed a moderate acute inflammatory infiltrate.
tional confirmation was obtained by isolation and Several small microorganisms, with frequent transepi- identification of the organism from tissue or secretion thelial migration were found in group A, whereas in cultures. The tissue was added to the following media: group B they were scarce but more voluminous. On the Sabouraud dextrose agar + chloramphenicol, ampicil- contrary, conspicuous granulomas with giant cells were lin and gentamicin. The tubes were incubated at 28°C observed in HIV) patients (Fig. 4), whereas in group A to observe the mycelial and at 35°C to observe the they were exceptional. Vasculitis phenomena were levaduriform or infecting form. Positive colonies were occasionally observed. Cultures were positive in seven then transferred to blood agar plates and incubated at 35°C, eventually resulting in conversion to the yeast The OH was marker disease in 10 HIV+ patients form. The diagnosis was confirmed by the dimorphism (48%). The treatment was dependant on the immuno- logical condition of the patient, and on the availabilityof drugs in our public hospital. In 14 cases of the groupA the treatment begun with amphotericin B, and when the infection was controlled, an azole antifungal was In group A (HIV+ patients), 21 (3%) had OH, while used; in six cases it was controlled only with itracon- in group B (HIV)) only 10 (0.07%) did. The analysed azole. This was the drug of choice in group B. The data on age, gender, general condition, other involve- evolution was good in all patients but three of group A ment and diagnosis of these patients are shown in relapsed some months later, only two died after therapy Table 1. The age ranged from 23 to 77 years. Nineteen but histoplasmosis was not the cause of death.
patients (90%) in group A, were <45 years oldwhereas seven (70%) in group B were more than 45 years old, indicating a positive correlation betweenage and HIV infection in patients with OH (P ¼ 0.001, Most investigators believe that human infection occurs Fisher’s exact test). Most of the patients were male, via inhalation of aleuriospores in dust (5, 6, 15). Ritter 81% in group A and 90% in group B. Weight loss (40) and Gordon et al. (41), however, suggest that at followed by persistent cough and dysphagia, were the least in some instances the spores gain entry to the most frequent symptoms in both groups; in addition, gastrointestinal tract from contaminated drinking water.
67% of the HIV+ patients had fever. The average of On the contrary, some investigators claim that primary Oral histoplasmosis in HIV+ patientsHerna´ndez et al.
Clinical features of an HIV+ patient. Red patch involved Cytological smear from an HIV+ patient, showing several the marginal and attached gingiva of the anterior area; ulcerated macrophages containing intracellular spherical to ovoid bodies, each lesions of the premolar area are also present.
surrounded by a small light halo (papanicolaou stain, originalmagnification ·100).
Clinical features of an HIV patient showing an elevated granulomatous lesion in hard palate and right maxillary gingiva.
Biopsy specimen showing a granulomatous suppurated lesion from an HIV patient and the Histoplasma capsulatum within a OH is possible and may occur from direct inoculation of giant cell (haematoxylin and eosin stain, original magnification ·60).
the fungus into the mucosa (4, 5, 24). The possibility ofhuman-to-human transmission between sexual partnersis still an intriguing question (42). In the cases analysed among females was found in HIV+ patients, a in this paper OH lesions were found 43 times more tendency also observed by Casariego et al. (45). Most frequently in HIV+ vs. HIV) patients; in addition all patients had a favourable response to the therapy; only the HIV) patients lived on a farm or worked in contact two died after therapy but histoplasmosis was not the with bird and bat excreta, whereas it was very difficult to establish the source of contamination in HIV+ This report shows the importance of including OH in patients. Clinical presentation and location of the oral the differential diagnosis of ulcerated lesions in immu- lesions as well as the average of CD4 count (60/mm3) nocompromised patients. Early recognition and prompt were similar to those reported by other authors (11, management of these infections are of paramount 32). Although histoplasmosis is a disease that tradi- importance in maintaining the health and prolonging tionally affects old people (12, 16), since the appearance of AIDS its prevalence has increased in younger peopleas in the present study (32, 43, 44). From these resultsit can be inferred that if histoplasmosis is diagnosed in a young patient, then a search for current HIV 1. Miller RL, Gould AR, Skolnick JL, Epstein WM.
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