Case
A45-year-old man was admitted to the hospital following 3 weeks of dysphagia; 1 week of nasal regurgitation, nonproductive cough, and breathy voice; and a 25-pound weight loss over the preceding 2 months. He had been diagnosed a year earlier with HIV infection and hepatic tuberculosis. Baseline CD4 count was 7 cells/μL, and following treatment with HAART (highly active antiretroviral therapy) consisting of dolutegravir, emtricitabine, and tenofovir-disoproxil-fumarate, he achieved full virological suppression; however, CD4 counts remained low at 31 cells/μL. He had completed 12 months of directly observed therapy with ethambutol, moxifloxacin, and rifabutin—a liver-sparing regimen—owing to toxic effects from the first-line regimen 1 month prior to admission. Physical examination revealed evidence of perforation of the hard palate (Figure, A). A computed tomographic scan of the chest revealed necrotic lymph nodes, and a palatine biopsy was performed (Figure, B and C).
Figure.
A, Clinical view of the perforation of the hard palate. B, Low-power microscopic view of a biopsy specimen from the hard palate (hematoxylin-eosin). C, Oil immersion image of the same tissue shown panel B stained with Grocott methenamine silver.
What Is Your Diagnosis?
- Tuberculosis of the palate
- Tertiary syphilis
- Histoplasmosis
- Sarcoidosis
- Cryptococcal infection
Discussion
Diagnosis
C. Histoplasmosis
Histoplasmosis, caused by a soil-based fungus,1 is the most common endemic mycosis in the United States, with a reported in-hospital crude mortality rate of 5% for children and 8% for adults.2 Clinical manifestations of histoplasmosis range from asymptomatic infection to rapidly progressive fatal illness.3 Oral histoplasmosis is an important entity to recognize because it is often a manifestation of disseminated disease.4 Moreover, the appearance may mimic other local or systemically manifested oral disease resulting in misdiagnosis.5
Disruption of soil by activities such as spelunking, excavation, outdoor construction, and remodeling of old buildings inhabited by birds or bats1 results in aerosolization of Histoplasmaspores, which are then inhaled by human hosts causing infection. The vast majority of these primary infections are either asymptomatic or result in self-limited influenzalike illness, depending on the intensity of exposure.6 Cellular immunity develops approximately 2 weeks after infection in immunocompetent hosts, producing granulomas3 that either resolve spontaneously or persist as calcifications most commonly seen in mediastinal lymph nodes, liver, and spleen.4 In approximately 8% cases of histoplasmosis, the fungus disseminates.1 Risk of dissemination is greatest in individuals with a compromised immune system, especially those with AIDS and hematological malignant conditions, and in individuals using immunosuppressive medications.7 Dissemination can cause an acute, rapidly fatal sepsis syndrome with low blood pressure and multiorgan failure7 or a more subacute to chronically progressive disease with presence of focal lesions in various organs including the oropharynx.1
Oral manifestations of histoplasmosis range from nodular, papular lesions to plaques, deep ulcers, and perforation.8 In the oral cavity, the most common locations for these lesions are the tongue, palate, buccal mucosa, gingiva, and pharynx.9 Patients can present with a wide variety of symptoms, including hoarseness, loss of weight, pain at the site of the lesion, and malaise.4Approximately 30% to 50% of patients with disseminated histoplasmosis have these oral lesions, and sometimes these could be the initial local presentation of disseminated disease.10
Oral lesions caused by Histoplasma species mimic several other disease entities such as squamous cell carcinoma, tuberculosis, syphilis, and other fungal infections like cryptococcosis, leading to morbid consequences of misdiagnosis.1 Definitive diagnosis is dependent on tissue biopsy and culture of organisms from lesions. Since culture results may take up to a month, pathological evaluation with fungal stains of biopsy material demonstrating oval to round yeast cells measuring 2 to 4 μm can be helpful in rapid identification of Histoplasma.3Detection of Histoplasma antigen in body fluids has very high sensitivity in patients with progressive disseminated histoplasmosis and is the mainstay of diagnosis.1 Treatment is primarily dependent on the severity of infection as well as the underlying immune status of the patient. Lipid-based formulations of amphotericin B are used for severe cases, while itraconazole could be an option in less severe cases with intact immune system.1
The repeatedly low CD4 cell count of the patient in the present case, even after appropriate HAART treatment, was the biggest risk factor for disseminated histoplasmosis. Despite 2 weeks of aggressive antifungal therapy with amphotericin B, he died. The granulomatous response typically present in immunocompetent patients with histoplasmosis was absent in this patient given profound immunosuppression from CD4 T-cell deficiency. Therefore, performing histochemical stains for microorganisms and ideally fungal culture in biopsied material is critically important in these patients, so as not to miss the etiologic agent of infection.
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Article Information
Published Online: May 30, 2019. doi:10.1001/jamaoto.2019.0926
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank the patient’s next of kin for granting permission to publish this information.
References
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