|Year : 2013 | Volume
| Issue : 2 | Page : 64-66
Histoplasmosis of the larynx
John M Carter1, Kelsey Williams2, Brian A Moore3
1 Department of Otolaryngology, Tulane University School of Medicine, New Orleans, Louisiana, USA
2 Department of Surgery, University of Southern Alabama, Mobile, Alabama, USA
3 Department of Otolaryngology, Ochsner Clinic Foundation, New Orleans, Louisiana, USA
|Date of Web Publication||7-May-2014|
John M Carter
Tulane University School of Medicine, New Orleans, Louisiana
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Histoplasmosis is an infection caused by the fungus Histoplasma capsulatum. Disseminated histoplasmosis rarely presents in the larynx and may mimic the appearance of a laryngeal neoplasm. Here, we present a case of laryngeal histoplasmosis in an elderly patient undergoing treatment for rheumatoid arthritis with immunosuppressive medications.
Keywords: Histoplasmosis, disseminated, larynx, dysphonia
|How to cite this article:|
Carter JM, Williams K, Moore BA. Histoplasmosis of the larynx. J Laryngol Voice 2013;3:64-6
| Introduction|| |
Histoplasmosis is a granulomatous disease caused by Histoplasma capsulatum that has a variety of presentations, including acute and chronic pulmonary disease or disseminated disease. Laryngeal histoplasmosis, an uncommon presentation of disseminated disease, should be considered in the differential diagnosis for certain patients presenting with hoarseness, particularly those who are immunocompromised. We describe a case of laryngeal histoplasmosis in an elderly woman with rheumatoid arthritis (RA) taking immunosuppressive medications.
| Case Report|| |
A 72-year-old Caucasian female with seropositive RA presented with progressive hoarseness, difficulty in breathing, and mild dysphagia over the previous 6 months. She initially presented to an outside clinic where she was diagnosed with laryngopharyngeal reflux and a paralyzed right vocal cord, and was treated for a throat ulcer of uncertain etiology. When her symptoms and exam did not respond to anti-reflux therapy, a biopsy was performed that was consistent with inflammation with mild atypia and no evidence of carcinoma.
The patient's medical history was significant for 9 years of seropositive RA controlled with infliximab and hydroxychloroquine. She was a lifelong nonsmoker with no significant history of alcohol consumption. She had spent the entirety of her life living in the United States in the Mississippi River Valley region of Southeast Louisiana. She denied recent travel, sick contacts, or incarceration.
Upon initial physical exam, the patient was notably hoarse with mild biphasic stridor. Flexible fiber-optic laryngoscopy revealed multiple exophytic nodular lesions across the laryngeal epiglottis and vocal folds [Figure 1]a. The patient had a fixed right vocal cord and paretic left cord, with a tenuous airway.
The patient was taken to the operating room for direct microlaryngoscopy with biopsy and tracheostomy. Her larynx was noted to be friable, with a diffuse ulceronodular appearance [Figure 1]b. Biopsy revealed fragments of benign squamous mucosa with minor salivary gland tissue exhibiting extensive ulceration, acute and chronic inflammation without dysplasia [Figure 2]. Due to a medical history significant for advanced RA, she was presumptively diagnosed with RA involving the cricoarytenoid joints and rheumatoid nodules of the larynx. A modified barium swallow showed aspiration, and she required gastrostomy tube placement. She was continued on infliximab and hydroxychloroquine with the addition of prednisone, but showed no response to this treatment. After 11 weeks of incubation on Sabouraud dextrose agar followed by lactophenol cotton blue mount, fungal cultures obtained intraoperatively grew H. capsulatum. The patient was switched to a course of itraconazole 150 mg, twice a day. Near complete resolution of the lesions and relative return of normal vocal cord function was seen in 2 months [Figure 1]c and d. She was able to undergo decannulation and removal of her gastrostomy tube.
|Figure 1: (a) Fiber-optic laryngoscopy revealing nodular submucosal lesions of larynx. (b) Direct laryngoscopy displays raised ulcerative lesions of the larynx. (c and d) Resolution of lesions at 2 months|
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|Figure 2: Minor salivary gland tissue with ulceration, acute and chronic inflammation and reactive epithelial atypia (H and E, ×40)|
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| Discussion|| |
Histoplasmosis is a granulomatous disease that is caused by H. capsulatum, a dimorphic intracellular fungus. In the United States, Histoplasma is endemic to the Mississippi and Ohio River valleys and particularly thrives in soil rich with bird and bat droppings. Primary infection occurs from passive exposure where infectious microconidia are inhaled and then transform into their yeast phase within host macrophages. H. capsulatum then travels to mediastinal and hilar lymph nodes, from where it disseminates throughout the reticuloendothelial system of the host. 
The main predisposing factors for histoplasmosis, particularly the disseminated form, include increasing age and decreasing cell-mediated immunity due to immunosuppressive agents.  Endemic fungal infections have been increasing in frequency in recent years, which may be related to increasing use of aggressive chemotherapeutic agents, organ transplantation, and use of immunosuppressive drugs for autoimmune or rheumatologic diseases. In addition, because cell-mediated immunity tends to wane with aging, the increasing longevity in today's population indicates that more people are at risk. 
The disease can manifest in several ways after primary inhalation of the spores, determined by inoculum size and immunity status of the host. Various presentations can be classified as acute pulmonary, chronic pulmonary and disseminated disease.  For the majority of immunocompetent patients, the disease is asymptomatic or presents with mild influenza-like symptoms which resolve without treatment in <4 weeks.  In those exposed to a high inoculum or in immunocompromised patients, acute severe pulmonary infection may occur, which can progress to acute respiratory distress syndrome and death. Chronic pulmonary histoplasmosis is most often seen in older patients, particularly those with underlying pulmonary disease.  In acutely disseminated cases, predominantly seen in the severely immunocompromised, patients present with fever and respiratory distress, as well as meningitis, endocarditis, and adrenalitis.  In the chronic disseminated form of the disease, seen in immunocompetent adults, pulmonary symptoms are often less prominent and lesions of the skin and mucous membranes are more common, particularly oropharyngeal ulcerations. 
Laryngeal involvement occurs in the chronic disseminated form of histoplasmosis. Distinguishing laryngeal histoplasmosis from laryngeal carcinoma can be challenging, as in this case. Clinical suspicion and timely diagnosis of this disease is important in order to ensure that the patients receive appropriate treatment. Typical initial manifestations include hoarseness, dysphagia, and odynophagia, as well as fatigue and weight loss.  Painful raised mucosal ulcerations may involve the oral cavity, tongue, pharynx, and larynx. Nodules appear as submucosal masses. 
When histoplasmosis is suspected, laboratory technicians should be warned of this possibility, as special stains and cultures must be used for identification of the organism. Diagnosis can be achieved using clinical examination, cultures, histopathologic examination, antigen detection, or antibody assays, including complement fixation (CF) and immunodiffusion (ID).
Growth of H. capsulatum from tissue or body fluids is the definitive diagnostic test. Samples can be obtained from various sites in patients with disseminated infection, including blood, skin, or mucosal lesions.  Organisms can be successfully isolated on Sabouraud's agar, although this process can take up to 6 weeks. 
Histopathologic examination can be performed on biopsies of oral and laryngeal masses. Special stains such as Gomori silver methenamine or periodic acid-Schiff stain should be used and will reveal multiple small, oval, budding yeast, typically found within macrophages.  Furthermore, typical of histoplasmosis is granuloma formation with caseous necrosis. Biopsy will reveal granulomatous tissue infiltrated with giant cells, lymphocytes, and numerous macrophages. 
Circulating H. capsulatum antigen can be detected in the urine or serum of patients with disseminated disease. Antigen levels can also be followed to detect response to treatment or recurrence of disease. However, for patients with less severe and chronic forms of pulmonary histoplasmosis, antigen detection only occurs in 10-20% of cases. 
Assays for antibodies to H. capsulatum include the CF test and the ID assay. A CF titer of 1:32 or a four-fold rise in titer is indicative of active infection. The ID assay is more specific than the CF assay and tests for M and H precipitin bands.  However, serologic assays are rarely helpful in immunosuppressed patients who are unable to mount a significant antibody response.
Laryngeal histoplasmosis, as a form of disseminated infection, should initially be treated with amphotericin B for 1-2 weeks followed by itraconazole for severe cases, or only oral itraconazole for mild cases.  Mucosal lesions typically respond within 6-8 weeks. 
| Conclusions|| |
Histoplasmosis of the head and neck may be more commonly encountered due to rising numbers of immunocompromised patients and increasing frequency of endemic fungal infections. Laryngeal histoplasmosis should be suspected in patients with chronic hoarseness or a laryngeal mass, particularly if immunosuppressed or living in endemic regions. If suspected, specific diagnostic modalities can be utilized in order to ensure that appropriate treatment is offered.
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[Figure 1], [Figure 2]