A case of laryngeal paracoccidioidomycosis masquerading as chronic obstructive lung disease.

Abstract: Paracoccidioidomycosis (South American blastomycosis) is a systemic infection caused by a dimorphic fungus (Paracoccidioides brasiliensis). It is common in the rural areas of Latin America. The majority of the reported cases come from Brazil, Colombia and Venezuela. Paracoccidioidomycosis is the most important systemic mycosis of the tropical Americas and can affect any organ, causing symptomatic or asymptomatic lesions. Paracoccidioidomycosis can mimic other diseases, which must be considered in making the differential diagnosis. Patients get infected by inhaling mycelia found in the natural environment or rarely from traumatic inoculation via mucous membranes. The most common lesions frequently occur in the buccal pharynx mucosa. Others lesions occur in the larynx, adrenal glands, liver, bones, gastrointestinal tract, lungs and nervous system.

Key Words: laryngeal paracoccidioidomycosis, Paracoccidioides brasiliensis, chronic obstructive lung disease

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Paracoccidioidomycosis (South American blastomycosis) is a systemic infection caused by a dimorphic fungus (Paracoccidioides brasiliensis). (1) It is common in the rural areas of Latin America. (1,2) The majority of the reported cases come from Brazil, Colombia and Venezuela. (1) Paracoccidioidomycosis is the most important systemic mycosis of the tropical Americas and can affect any organ, causing symptomatic or asymptomatic lesions. Paracoccidioidomycosis can mimic other diseases, which must be considered in making the differential diagnosis. (3) Patients get infected by inhaling mycelia found in the natural environment or rarely from traumatic inoculation via mucous membranes. (1) The most common lesions frequently occur in the buccal pharynx mucosa.

Others lesions occur in the larynx, adrenal glands, liver, bones, gastrointestinal tract, lungs and nervous system. (1-4)

Case Report

A 54-year-old male farmworker, who was well until 8 months prior to presentation, presented with acute dyspnea and exercise intolerance that had been episodic over the preceding months. On examination, the patient was diaphoretic in respiratory distress with little air movement. The patient's family described several similar episodes occurring over the last few months not requiring hospitalization. Each time, the patient was diagnosed and treated for chronic obstructive lung disease with little result.

Weight loss of approximately 50 to 60 pounds, cough and fatigue also occurred. He had a history of smoking for more than forty years. Physical examination revealed an emaciated patient. Lymph nodes were not palpable. Chest x-ray showed signs of chronic bronchitis. Because the patient also noticed voice changes (hoarseness), a laryngeal examination was performed, which revealed multiple tumor-like lesions involving the true and false vocal cords (Fig.). A tracheostomy was performed as a consequence of the obstruction. The first diagnostic impression was carcinoma but histopathological examination and culture of a specimen obtained by biopsy reported Paracoccidioides brasiliensis. Laboratory studies including hemogram, ESR, urea, creatinine, glucose, liver tests, and electrolytes were normal and human immunodeficiency virus was negative. Treatment with amphotericin B (0.5 mg/kg/d) was initiated and the patient was subsequently discharged several weeks later in good condition. Amphotericin B was maintained until the tumor-like lesions disappeared (total accumulated dose of 2.5 g).

Discussion

Paracoccidioidomycosis of the head and neck is usually associated with high morbidity because patients may present with poor nutritional status due to dysphagia and/or impairment of mastication. (5) Clinical manifestations include hoarseness, odynophagia, sore throat and dyspnea, while the lesions include inflammatory lesions of the lips, tongue, oral and pharyngeal mucosa, epiglottis, aryepiglottic folds, vestibular and vocal folds. (6) The chronic form of the disease may develop in patients many years after they have left the endemic region, in contrast to the acute form which develops soon after exposure to the fungus. (7) Paniago et al (2) found lesions in the oropharynx in 66.4% of 422 cases of paracoccidioidomycosis seen at the University Hospital of Universidade Federal de Mato Grosso do Sul; 31.4% presented with dysphonia and 50.7% presented with cough. do Valle et al, (8) in a systematic examination of the upper respiratory and digestive tracts that was performed in a group of 80 paracoccidioidomycosis patients, found oropharyngeal lesions in 50 patients (41 alone, 7 in association with the larynx, and 2 with the nasal mucosa); larynx, in 30 patients (23 alone and 7 in association); and nasal mucosa, in 3 patients (1 alone and 2 in association). Enlargement of the lymph nodes draining these lesions may be present, and in the chronic form, it generally represents secondary involvement. Morphologically, three types of lymph node enlargement may be defined: nonsuppurative inflammatory type, tumoral type, and suppurative type. (6)

Laryngeal paracoccidioidomycosis may be a difficult diagnosis for the unsuspecting clinician to make. In the case presented here, the patient's symptoms (dyspnea, cough), smoking history, and chest x-ray images indicated as first diagnosis a lung disease. However, more subtle symptoms like weight loss, and hoarseness were not taken in to account at the beginning. We thought that the patient also had a chronic obstructive lung disease, which probably masked his laryngeal infection.

Differential diagnoses included other granulomatous infectious diseases such as laryngeal tuberculosis, mucocutaneous leishmaniasis, and chronic histoplasmosis. Finally, paracoccidioidomycosis should also be differentiated from cancers of the oropharynx and larynx, most commonly the result of squamous cell carcinoma and lymphoma. (5,9) Examination of the larynx can reveal lesions similar to laryngeal cancer; therefore, diagnosis of carcinoma must be ruled out by histopathological examination or culture of a specimen. Absence of clinical suspicion or delay in the diagnosis may dramatically worsen the prognosis. Sant'Anna et al (10) reviewed the hospital records of 7 patients with laryngeal paracoccidioidomycosis diagnosed by histopathological examination. All patients were men and were middle-aged (range, 43-65 yr), and most (86% [6/7]) were farmworkers. All 7 patients regularly used tobacco, but only (43% [3/7]) were alcohol users. Clinical manifestations were dysphonia (86% [6/7]), dyspnea (71% [5/7]), dysphagia (43% [3/7]), and cough (29% [2/7]). Laryngeal examination revealed ulcerative lesions with a mulberry-like appearance in 3 patients and vegetative lesions in 4 patients. Many had multiple laryngeal lesions with involvement of the true and false vocal cords, the epiglottis, and the arytenoid and interarytenoid areas. The first diagnostic impression was carcinoma in all patients.

In conclusion, paracoccidioidomycosis is the most important systemic mycosis of the tropical Americas and can affect any organ, causing symptomatic or asymptomatic lesions. The prevalence and incidence of this mycosis is different in each country, but the majority of the cases have been assigned to Brazil with a prevalence of 5.6 to 17.5%. (11) However, the incidence in endemic areas of the tropical Americas has been calculated between 1 to 3 new cases/100,000 inhabitants per year. (12) Paracoccidioidomycosis can mimic other diseases, which must be considered in making the differential diagnosis. As shown in our case, the diagnosis of laryngeal paracoccidioidomycosis requires a high clinical suspicion to achieve a timely diagnosis and decrease morbidity and mortality.

References

1. Saravia J, Toro G. Paracoccidioidomicosis del SNC. Enfermedades Infecciosasy Parasitarias. Colombia 1985, pp. 238-243.

2. Paniago AM, Aguiar JI, Aguiar ES, et al. Paracoccidioidomycosis: a clinical and epidemiological study of 422 cases observed in Mato Grosso do Sul. Rev Soc Bras Med Trop 2003;36:455-459.

3. Rios-Goncalves AJ, Terra GMF, Rozenbaum R, et al. Paracoccidioidomicose: uma seleta de formas incomuns, raras e interessantes. Arq bras Med 1995;69:607-625.

4. Tristano AG. Chollet ME, Willson M, et al. Central nervous system paracoccidioidomycosis: case report and review. Invest Clin 2004;45: 277-288.

5. de Castro CC, Bernard G, Ygaki Y, et al. MRI of head and neck paracoccidioidomycosis. Br J Radiol 1999;72:717-722.

6. Mendes RP. The gamut of clinical manifestations. Paracoccidioidomyosis. Franco M, Lacaz CS, Del Negro G (eds). Boca Raton, CRC Press, 1994, pp. 233-258.

7. Franco M, Montenegro MR, Mendes RP, et al. Paracoccidioidomycosis: a recently proposed classification of its clinical forms. Rev Soc Bras Med Trop 1987;20:129-132.

8. do Valle AC, Aprigliano Filho F, Moreira JS, et al. Clinical and endoscopic findings in the mucosae of the upper respiratory and digestive tracts in post-treatment follow-up of paracoccidioidomycosis patients. Rev Inst Med Trop Sao Paulo 1995;37:407-413.

9. Reder PA, Neel HB III. Blastomycosis in otolaryngology: review of a large series. Laryngoscope 1993;103:53-58.

10. Sant'Anna GD, Mauri M, Arrarte JL, et al. Laryngeal manifestations of paracoccidioidomycosis (South American blastomycosis). Arch Otolaryngol Head Neck Surg 1999;125:1375-1378.

11. Fava S di C, Netto CF. Epidemiologic surveys of histoplasmin and paracoccidioidin sensitivity in Brazil. Rev Inst Med Trop Sao Paulo 1998;40:155-164.

12. Shikanai-Yasuda MA, Telles Filho Fde Q, Mendes RP. et al. Guidelines in paracoccidioidomycosis. Rev Soc Bras Med Trop 2006;39:297-310.

In prosperity our friends know us; in adversity we know our friends.
--John Churton Collins

Antonio G. Tristano, MD, MSc, and Lizmer Diaz, MD

From the Department of Internal Medicine, Hospital Dr. Domingo Luciani, Caracas, Venezuela.

Reprint requests to Dr. Antonio G. Tristano, Nova Southeastern University, HPD, College of Pharmacy. 3200 S University Drive, Fort Lauderdale, FL 33328. Email: [e-mail]

Accepted January 3, 2007.

RELATED ARTICLE: Key Points

* Paracoccidioidomycosis of the head and neck is usually associated with high morbidity because patients may present with poor nutritional status due to dysphagia and/or impairment of mastication.

* Other clinical manifestations include hoarseness, odynophagia, sore throat and dyspnea.

* Paracoccidioidomycosis can mimic other diseases, which must be considered in making the differential diagnosis.

* Differential diagnoses include other granulomatous infectious diseases, and cancers of the oropharynx and larynx.

* The absence of clinical suspicion or delay in the diagnosis may dramatically worsen the prognosis.

* Early diagnosis and adequate therapy may prevent extensive tissue destruction. Long-term follow-up is mandatory.