Blastomycosis

Abstract

Blastomycosis is a chronic fun gal disease that primarily affects the lower respiratory tract. The acute inflammatory phase of the primary pulmonary infection is characterized by a lymphohematogenous spread to extrapulmonary sites, especially the skin. The presence of disseminated infection with Blastomyces dermatitidis in the larynx is unusual. In areas of the United States where this fungus is endemic, failure to consider laryngeal involvement might lead to inappropriate therapy and thus worsening inflammation and airway compromise.

Introduction

Blastomyces dermatitidis is a dimorphous soil-dwelling fungus that is found in the southeastern and central regions of the United States. Following the inhalation of aerosolized spores into the lungs, the fungus changes into a yeast form, and it can give rise to a spectrum of clinical syndromes ranging from an acute, self-limited, flu-like illness to rapidly progressive, widely disseminated, fatal disease. In northeast Tennessee, 72 patients were diagnosed with blastomycosis from 1980 through 1995; the incidence quadrupled from 1988 through 1995. (1) In our experience with these patients, pulmonary involvement has been the most common feature (84.7% of patients), followed by cutaneous expression (32%). (1)

In this article, we report the case of a patient with laryngeal blastomycosis who came to us with complaints of respiratory distress and stridor that required emergency tracheostomy. Vocal fold involvement is unusual in blastomycosis. Nevertheless, it must be considered in the differential diagnosis of upper airway obstruction by clinicians who practice in geographic areas where blastomycosis is endemic.

Case report

A 55-year-old woman came to the emergency department with respiratory distress and fever. Her problem had begun 4 months earlier, when she developed hoarseness. Her evaluation at that time included an ENT examination, which revealed that her left vocal fold movement was impaired. Findings on computed tomography (CT) of her thorax were unremarkable, but a gallium scan was interpreted as showing bilateral enhancement of the lung parenchyma and the lacrimal glands. This pattern suggested sarcoidosis, and a diagnostic flexible bronchoscopy was performed. No endobronchial lesion was observed. Bronchial washings were negative for tuberculosis, fungal infection, and bacterial infection. Lung biopsy detected nonspecific inflammation. Based on the earlier interpretation of the gallium lung scan, the vocal fold impairment was believed to be consistent with laryngeal sarcoidosis. The patient was started on a daily dose of prednisone.

Two months after the patient started prednisone therapy, her hoarseness worsened and she developed dyspnea and a nonproductive cough. Despite compliance with a maintenance glucocorticosteriod, her dyspnea progressively worsened until she came to the emergency department in respiratory distress with inspiratory stridor.

In addition to her hoarseness and suspected sarcoidosis, the patient's medical history was notable for a diagnosis of systemic lupus erythematosus and chronic thrombocytopenia. She was known to have had a significantly positive purified protein derivative test, and she had completed 12 months of isoniazid prophylaxis 3 years earlier. She had never smoked tobacco and had no thyroid disease or history of malignancy. Approximately 12 months after she had finished her course of isoniazid prophylaxis, she developed a right upper lobe cavitary lesion, which was evident on chest x-ray and CT. Acid-fast bacilli smears and cultures from sputum, bronchial brushings, and washings were all negative. The samples tested for fungal infection and malignancy were also negative. She was treated empirically for active tuberculosis because of cough, a documented 40-lb weight loss, and night sweats. She completed standard therapy with 2 months of four-drug antituberculosis therapy (rifampin, isoniazid, ethambutol, and pyrazinamid e) followed by 4 months of two-drug therapy (rifampin and isoniazid).

Findings on the physical examination were remarkable for wheezing and high-pitched inspiratory breath sounds over the trachea. She had chronic nonpitting edema of both lower extremities. There was no lymphadenopathy, hepatosplenomegaly, or skin lesions. Indirect laryngoscopy detected exophytic lesions on the larynx and impending upper airway obstruction. The supraglottic area was diffusely inflamed (figure 1). An emergency tracheostomy was performed to guarantee a patent airway. Biopsy specimens of the laryngeal lesions contained multiple broad-based budding yeast cells that were consistent with blastomycosis (figure 2). There was an absence of caseating granuloma in the biopsy sample. Non-specific tissue inflammation was again noted.

Laboratory tests showed that the patient's hemoglobin level was 11.3 g/dl, her leukocyte count was 9,800/[mm.sup.3], and her differential count, electrolyte level, and urinalysis findings were within normal limits.

Prednisone was discontinued, and the patient was started on amphotericin B. Four weeks later, a repeat laryngoscopy showed that her laryngeal lesions had completely resolved. The tracheostomy tube was successfully removed, the amphotericin B was discontinued, and itraconazole at 400 mg/day was started.

At the 12-month follow-up, the patient had continued to improve. Her chest x-ray was normal, she was afebrile, and she had gained 10 lbs.

Discussion

Laryngeal blastomycosis is uncommon. Accurate estimates of its prevalence are difficult to obtain because blastomycosis is not reported to the Centers for Disease Control and Prevention. Some insight into the prevalence of laryngeal blastomycosis has been provided by published reports of two large series. Of 102 patients with blastomycosis who had been treated at the Mayo Clinic, laryngeal involvement was seen in five (4.9%). (2) A 10-year collection of data in Mississippi revealed that laryngeal infection had been present in two of 326 blastomycosis patients (0.6%). (3) In their recent review of the English-language medical literature, Hanson et al (4) found that only 18 patients had been reported to have had primary or isolated laryngeal blastomycosis since Dennis (5) described the first case in 1918. Hanson et al added that many of these patients had received an initial incorrect clinical diagnosis of laryngeal carcinoma. (4)

Our patient was mistakenly thought to have had sarcoidosis based on the gallium-scan pattern, which showed an increase in lung and lacrimal uptake, and the fact that previous lung samples had been negative on fungal staining and culture. Because sarcoidosis can manifest as vocal fold paralysis, (6,7) our patient was treated with an oral glucocorticosteroid. The T-lymphocyte suppression brought about by the steroid likely favored the growth of laryngeal B dermatitidis and resulted in the impending upper airway obstruction.

Retrospectively, one can appreciate that our patient had a typical presentation of laryngeal blastomycosis. The most common symptom of laryngeal involvement is persistent hoarseness over a period of several months. Often, patients will also have sore throat and dysphagia. (8,9) Systemic symptoms such as fever, night sweats, malaise, and fatigue have also been described. (2)

Blastomycosis is believed to be a primary pulmonary infection that is caused by the inhalation of spores that change into the yeast form in the warm environment of the lung. An intense inflammatory reaction follows, during which time the organism can reach extrapulmonary sites by lymphohematogenous spread. (10) The initial pulmonary infection might go unnoticed by the patient; subclinical pulmonary infections are frequently self-limited and resolve without specific intervention. (11) When a patient does seek medical attention, the chest x-ray might show a variety of pulmonary parenchymal lesions, including local consolidation (28% of patients), mass-like lesions (23%), diffuse alveolar infiltrates (13%), and cavitary lung lesions (10%). (1)

Involvement of the larynx can occur as a result of the spread of quiescent pulmonary disease via a hematogenous route or as a result of fungus-laden sputum traversing the larynx and causing infection by direct inoculation. (12) Our patient had a right upper lobe cavitary lung lesion that, in the absence of a positive smear or culture, was treated as a tuberculosis reactivation. It is possible that her cavitary lesion, weight loss, and night sweats were expressions of pulmonary blastomycosis.

In such patients, examination of the larynx usually reveals erythematous and granular exophytic changes in the mucosa, which can involve any site between the epiglottis and subglottis. (4) Minute grayish papules or larger yellow nodules, which represent small abscesses, might be seen superficially. (8,9) Vocal fold movement might be impaired by the surrounding inflammatory processes, a condition that mimics vocal fold paralysis. (4)

Findings on standard laboratory tests are nonspecific. The intradermal skin test for blastomycosis has proved to be useless because of its low degree of specificity and sensitivity. (13) Serologic tests are available, but poor specificity also limits their utility, particularly in areas of the country where other deep mycoses are endemic. (14)

A definitive diagnosis can be made by the identification of the yeast form of B dermatitidis grown in colonies on Sabouraud's dextrose agar at 37[degrees] C after a 1- to 4-week delay. (15) Unfortunately, it is difficult to culture the organism from diseased tissue. A presumptive diagnosis rests on the identification of the yeast form in the submitted tissue. (4) The spherical, thick-walled, broad-based yeast cells (diameter: 10 to 20 [micro]m) can be identified in frozen sections or by any of the fungal-wall stains (potassium hydroxide, Gomori, and PAS) and on Papanicolaou stain. (9) Making the diagnosis without identification of the yeast form is hazardous because the histologic findings can be misleading. Essentially, there is a nonspecific inflammatory infiltrate associated with surface epithelial changes that can be confused with squamous cell carcinoma. (4)

Oral itraconazole at 200 to 400 mg/day for 6 months is the drug of choice for treatment of pulmonary, cutaneous, or extrapulmonary blastomycosis that is not life-threatening. (16) As an alternative, oral fluconazole at 400 to 800 mg/day for at least 6 months is effective in more than 85% of patients. (17) In patients who do have life-threatening infections, the drug of choice is amphotericin B at 0.5 mg/kg/day to a total of 1.5 g. (18)

By 1998, 72 cases of blastomycosis had been identified in northeast Tennessee. (1) The prevalence of the disease in this area is high. At the time of this writing, an additional 36 local cases have been identified, including a few cases of acute respiratory failure similar to acute respiratory distress syndrome. (19) We have determined that the incidence of laryngeal blastomycosis in northeast Tennessee is 1.1% (1/90), a figure that is consistent with those reported in other large series. (2,3)

In geographic areas where blastomycosis is endemic, physicians should be aware that in addition to the more common pulmonary and cutaneous manifestations, laryngeal involvement is also possible, and it should be considered in patients who have persistent hoarseness. Other diagnoses in patients with laryngeal involvement (e.g., cancer, tuberculosis, and sarcoidosis) might be more likely, but a failure to consider blastomycosis could lead to a critical or fatal outcome as a result of acute airway obstruction.

Acknowledgments

The authors thank Dr. David Soike, director of pathology at the Johnson City (Tenn.) Medical Center, and Dr. Louis Modica of the Department of Surgery at the East Tennessee State University in Johnson City for their assistance in preparing this manuscript.

References

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(17.) Pappas PG, Bradsher RW, Kauffman CA, et al. Treatment of blastomycosis with higher doses of fluconazole. The National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis 1997;25:200-5.

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(19.) Mukkamala R, Mehta JB, Myers JW, Cole CP. Pulmonary blastomycosis with acute respiratory failure as predominant clinical feature. South Med J 1997;90:847-50.

From the Department of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, Johnson City.

Reprint requests: Jay B. Mehta, MD, Department of Internal Medicine, P.O. Box 70622, James H. Quillen College of Medicine, Johnson City, TN 37614-1709. Phone: (423) 439-6368; fax: (423) 439-6387; e-mail: mehtaj@etsu.edu

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