Abstract
Laryngeal histoplasmosis is very rare among patients with HIV and very few cases have so far been documented. We report a case of laryngeal histoplasmosis in a patient with no prior AIDS defining diagnosis, which mimicked epithelial neoplasia, and was treated successfully with oral fluconazole.
INTRODUCTION
The dimorphic fungus, Histoplasma capsulatum, is the organism responsible for histoplasmosis infection, which primarily affects the lungs. It grows in soil and material contaminated with bird droppings. The infection is often acquired through the inhalation of fungal spores.
Histoplasmosis is endemic in the Mississippi, Ohio river valleys in the USA 1 and various areas of south-east Asia. 2 Reported cases are likely to be an underestimate due to difficulty in diagnosis, as similar clinical features occur in tuberculosis infection. 3 Histoplasmosis may be a localized infection or can become disseminated affecting multiple organs, including the reticulo-endothelial system, via haematogenous spread. 1
Disseminated histoplasmosis is a common and potentially fatal opportunistic mycotic infection among patients with HIV in areas of high prevalence of H. capsulatum infection, especially in individuals with a CD4 lymphocyte count of less than 150 cells/μL. 1,4,5 It either may be an acute episode characterized by fever, myalgia and typical X-ray changes, or may occur as a reactivation of latent infection, as probably occurred in this case. The condition is rarely diagnosed in patients outside endemic areas, unless they have a travel history to areas of high prevalence.
To our knowledge, we are reporting only the fourth reported case of laryngeal histoplasmosis in an AIDS patient, who presented with hoarseness of voice.
CASE REPORT
A 51-year-old Malaysian man who has sex with men was diagnosed HIV-positive in 2002, but was lost to follow-up. He re-presented in 2008 to his general practitioner with a five-month history of hoarseness of voice, a symptom that had worsened over the previous two months. He also had loss of appetite and weight loss but denied any fever, night sweats or cough. He was referred to an otolaryngologist for investigation of possible malignancy.
The patient was raised in Malaysia and had a history of working in both Australia and Singapore before moving to England. His past medical history was unremarkable apart from HIV infection.
On examination, he had cervical lymphadenopathy but systemic examination was unremarkable. Flexible nasal endoscopy showed thickening and slightly reduced mobility of the left vocal cord consistent with neoplasm. He had profound immunosuppression with a CD4 count of 80 cells/μL and a HIV viral load of 780,000 copies/mL.
Other blood investigations, including full blood count (except low lymphocyte count consistent with the degree of HIV infection), serum renal and liver profiles were all within normal limits. The computed tomography of the head, neck and thorax revealed an irregular mass on the base of the tongue, pharyngeal wall, vocal cords (Figure 1) and multiple nodules throughout the lung fields. A laryngeal biopsy showed a dense histiocytic infiltrate, which demonstrated H. capsulatum using a Grocott stain (Figure 2). At this stage, Histoplasma serology (immunodiffusion) was equivocal. The serum sample was found to be anticomplimentary and therefore was not suitable for a compliment fixation test. Fungal blood cultures were negative. He subsequently developed multiple papular skin lesions on the face and neck.
Laryngeal biopsy specimen showing H. capsulatum using a Grocott stain
Computed tomography scan showing asymmetrical thickening of the left vocal fold (black arrow)
The patient was started on oral fluconazole, 200 mg twice daily, as there was a query of possible itraconazole allergy. When we could not find any evidence of itraconazole allergy, fluconazole was switched to itraconazole 200 mg twice daily based on the evidence of lower relapse rate with itraconazole. Following the switch of therapy, he developed a widespread urticarial rash; therefore, fluconazole was restarted, which he continued for one year. He was commenced on antiretroviral therapy (ART) with once daily tenofovir 300 mg/emtricitabine 200 mg and efavirenz 600 mg two weeks postinitiation of histoplasmosis therapy.
His symptoms of hoarseness of voice and skin lesions had completely resolved after completion of four weeks of treatment with fluconazole. After eight weeks of initiation of ART, his CD4 lymphocyte count had increased to 224 cells/μL.
DISCUSSION
Disseminated histoplasmosis in patients infected with Histoplasma is a known consequence of immunosuppression. 1,4,5 Although there are well documented cases of laryngeal histoplasmosis in immunocompetent patients, 6 it is rarely the presenting feature in immunosuppressed patients, where symptoms of widespread disease are the usual presenting feature.
Itraconazole is the drug of choice for histoplasmosis infection; however, fluconazole may be used as an alternative for mild to moderate histoplasmosis. 7 Wheat et al. 8 demonstrated that although clinical responses to itraconazole and fluconazole are equivalent, the clearance of fungaemia is more likely to be successful with the use of itraconazole. In severely ill patients, including those with meningitis, the use of amphotericin as an induction agent is recommended.
Histoplasmosis should be considered as one of the differential diagnoses in HIV-positive patients presenting with the relatively common symptom of hoarseness of voice. Prompt diagnosis and early and effective treatment is necessary to ensure that the infection does not disseminate, leading to potentially life-threatening disseminated histoplasmosis among patients with severe immunosuppression.