Gorgas Case 2022-03 |
The following patient was seen in the inpatient ward of Cayetano Heredia Hospital in Lima by the 2022 Gorgas Course participants. History: A 60-year-old male patient presented with a 3-year history of cough, occasional hemoptysis, and worsening dysphonia. Five months before admission, he became aphonic and reported odynophagia and progressive dysphagia for liquids then solids. 4 months before admission, a laryngoscopy at a private hospital found granular changes in his vocal cords, but he did not receive any treatment. One and a half months before admission, repeat laryngoscopy at our hospital [Video A], found central granulomatous lesions in the vocal cords with incomplete closure of cords and preserved motility. He did not recall having fever throughout the course of the disease; but reported weight loss of 15 kg. Epidemiology: He was born in La Oroya, in the central highlands in Peru. Thirty years ago, he spent six years working as a farmer in Oxapampa, in the central jungle, harvesting coffee and other fruits. He has lived in Lima for thirty years, where he worked in public transport for 18 years, and currently works as a clerk in a hotel. No known TB contacts, no risky sexual or social behaviors. Physical Examination: T: 36.9°C, BP 140/90 mmHg, HR 82 bpm, RR 18 rpm, SatO2 96% on room air. Laboratory Results: Hb 13.4, Leu 14 (bands 0%, seg 91.2%, eos 0%, baso 0.1%, mono 2.6%, lymph 5.3%), Plt 391 000; PT 13.8, INR 1.01; BUN 28, Cr 0.59, Na 137, K 4.32, Cl 92; ALT 15, AST 19, LDH 149. PPD was 15 mm. Imaging: Chest X ray [Image B] showed a cavitary lesion in the left upper lung field. Thoracic CT scan [Image C] showed centrilobular nodules in a tree pattern, diffusely distributed but predominantly in superior lobes, and tubular bronchiectasis in the right basal posterior segment and left apical segment; the biggest one 50x59mm. Neck CT showed pathological thickening of both aryepiglottic folds (predominantly right) with irregular contrast enhancement, and a 7mm lymph node in left group III suspicious for lymphadenopathy.
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Diagnosis: Paracoccidioides braziliensis, chronic multifocal form. Discussion: On biopsy of the larynx, a dense chronic inflammatory reaction with granuloma formation with yeast forms of varying sizes was observed [Image D]. Subsequent sputum samples tested positive for yeast cells in KOH preps [Image E]. Sputum AFB was negative x3, GeneXpert TB in sputum was negative. HIV testing was negative. COVID-19 testing was negative as well. The chronic form of paracoccidioidomycosis most often involves pulmonary disease with oral mucosal involvement as a frequent complication [Gorgas Case 2004-05]. The differential diagnosis for the lung disease includes TB, histoplasmosis, lymphoma, cancer and cryptococcosis. Tuberculosis was the leading diagnosis in this case, but extensive investigations revealed negative results. The findings on the biopsy and cultures ruled-out other conditions. The typical radiographic pattern of paracoccidioidomycosis is with bilateral mixed infiltrates (alveolar and interstitial), mainly located in the middle and lower lobes. Interstitial lesions may have miliary (as in this case), nodular or fibronodular patterns. Other patterns observed in these patients are hilar and mediastinal lymph node enlargement, cavities, and calcified lesions. Extrapulmonary disease is found in over 70% of cases and may involve skin, mucous membranes, lymph nodes, adrenals, abdominal organs and CNS (in 9-25%). The most notable clinical findings in this patient are the long latency period from possible infection to development of symptoms; lack of oral involvement; presence of cavitary lesions and the prominent laryngeal involvement. A long latent period is characteristic of paracoccidioidomycosis, reports of decades of latency among expatriates are well known [Mycoses. 2003;46(9-10):407-11]. Cavitary lesions are not common but have been reported, unilateral or bilateral cavities may occur. In all these cases tuberculosis and other conditions were ruled out [Eur J Radiol 2018]. The larynx may be involved either by the hematogenous route or from extension of lesions in the oral cavity, and its involvement was recognized early on by the discoverers of the disease back in 1908. The absence of oral lesions in this case argues against extension from the oral cavity and favors hematogenous dissemination. Laryngeal involvement is reported in 22-43% of patients [Medical Mycology 2006;44:219-25]. The whole larynx may be involved, including the vocal cords, epiglottis and infraglottic [Arch Otolaryngol Head Neck Surg 1999;125:1375-8]. It classically presents in middle-aged males with dysphonia, dyspnea and cough. Laryngeal examination reveals ulcerative and vegetative lesions. The accurate diagnosis requires obtaining tissue to be sent for culture and histopathology. Classical pathological findings include a dense inflammatory reaction, multinucleated giant cells and yeast cells of different sizes with multiple peripheral budding, as in this case. The differential diagnosis is broad and includes tuberculosis, leishmaniasis, histoplasmosis, actinomycosis, syphilis, sarcoidosis, cancer and vasculitis [Eur Arch Otorhinolaryngol 2008]. Important sequelae such as hoarseness, glottal and tracheal stenosis and dysphonia may occur. Treatment in addition to antifungals requires the use of steroids [Medical Mycology 2012]. Tracheal stenosis and asphyxia as a result of an intense inflammatory reaction induced by the release of antigens from the dying fungi during treatment with antifungals have been reported. Prednisone at 1 mg/kg or its equivalents is recommended for 10 days with progressive tapering over the next 4 weeks [Med Mycol 2012]. Some experts recommend starting steroids a few days before antifungal treatment to minimize obstructive complications. This recommendation is based on experience with laryngeal involvement in tuberculosis and leishmaniasis. There is no other indication for using systemic steroids in paracoccidioidomycosis. Our patient was started on dexamethasone 7 days prior to initiating oral itraconazole. The extensive laryngeal involvement and the high risk for airway obstruction argued against starting amphotericin B. Itraconazole is going to be offered for at least one year with serum drug level monitoring and clinical-microbiological follow-up. A new laryngoscopic examination will be performed after one month of therapy and subsequently based on clinical evolution. |