Molecular Diagnosis of Disseminated Adiaspiromycosis Due toEmmonsia crescens

Abstract

Emmonsia crescens is a saprophytic fungus that is distributed worldwide, causing diseases mostly in rodents. It has also been described, though rarely, as an etiologic agent of pulmonary pathology in humans, potentially leading to death. A case of pulmonary adiaspiromycosis is reported in a 30-year-old immunocompetent man. The patient presented with a history of several weeks of weakness, cough, fever, and weight loss of 10 kg. Clinical and radiographic findings showed pulmonary lesions consistent with tuberculosis or histoplasmosis, but no pathogen was found with classical microbiological procedures. The diagnosis of adiaspiromycosis due to Emmonsia crescens was initially made using molecular biology techniques. Histological observations subsequently confirmed the presence of adiaspores in granulomas. To our knowledge, this is the first case of adiaspiromycosis diagnosed by PCR and sequencing. The patient was treated with itraconazole and was seen at 1 month with symptomatic improvement. Here we will discuss this rare fungal infection and its difficult treatment and diagnosis. As represented in this case, molecular biology is a powerful method to optimize diagnostic tests and therefore improve the care of the infected patient. CASE REPORTA 30-year-old man was admitted to the Hospital of Metz on 21 May 2008 with a 2-week history of unproductive cough, fever at 39°C, progressive dyspnea, thoracic pain, generalized weakness, and weight loss of 10 kg in 1 month. The chest radiography revealed diffuse bilateral interstitial pneumonia with a micronodular pattern (Fig. 1). Computerized tomography of the chest (high resolution) showed disseminated pulmonary nodules (Fig. 2). The peripheral blood leukocyte count was 12 g/liter with 76% neutrophils and 14% lymphocytes. Bronchoalveolar lavage (BAL) showed 13,330 leukocytes/l with 1,333 lymphocytes (CD4/CD8 ϭ 1.25). The CRP was increased to 287 mg/liter, but no other abnormalities were found.Based on the clinical symptoms and radiological features, the main differential diagnosis was tuberculosis or histoplasmosis as the patient had traveled several months and years earlier in areas where these diseases were endemic. Other noninfectious hypotheses, such as lymphoma or sarcoidosis, were also suspected based on the clinical and biological features with an important alteration of the patient status associated with polyadenopathies. All of these hypotheses were then excluded by corresponding analyses.Diagnostic procedures. Direct examination and bacterial and mycological cultures of a BAL sample were negative. Serological tests for Histoplasma capsulatum were performed at the Pasteur Institute of Paris and revealed negative immunodiffusion. The BAL sample was sent to the Mycology Unit of the Nancy Hospital for further investigation.The BAL was microscopically reexamined with chlorazole black, and any fungal elements were visualized. Cultures of the sample on Sabouraud agar containing cycloheximide (0.5 mg/ ml) at 30°C and 37°C yielded no growth.Molecular biology studies. In or...

Adiaspiromycosis Causing Respiratory Failure and a Review of Human Infections Due to Emmonsia and Chrysosporium spp

“…Approximately 67 probable cases of human pulmonary adiaspiromycosis due to E. crescens have been described in the literature. England and Hochholzer, in their 1993 case series and review (21), identified 46 cases; there have been 20 other cases reported since that time or that were omitted from the England and Hochholzer review (6,11,13,15,31,32,36,37,38,40,50,51,52,56,60,62) (Table 1). Adiaspiromycosis may be discovered incidentally after histopathologic exam of the lung for other conditions.…”

Epidemiology of Emerging Fungi and Fungi-like Organisms

“…Three forms of disease have been described: solitary granuloma; localized granulomatous disease; and diffuse, disseminated granulomatous disease [43]. There have been case reports describing lone cutaneous infection or organ involvement, including bone, peritoneum, and eyes [43][44][45]. In patients with localized disease, infection may be asymptomatic and often is an incidental finding, but symptoms of disseminated disease may include fever, cough, and dyspnea, which may progress to respiratory failure [43].…”

“…Infection occurs via inhalation of conidia, which then transform into spherical adiaconidia and subsequently undergo massive enlargement [43]. Germination in the lung does not appear to occur [43,44].…”

“…E. crescens is widespread through Europe, whereas E. parva is found mainly in exothermic regions, including Central and South America, Central Asia, and Africa [43,44]. It appears that rodents may serve as a zoonotic reservoir for disease, but infection in other mammals also has been described [44].…”

Histopathologic Diagnosis of Fungal Infections in the 21st Century

“…Alternative testing for rhinosporidiosis does not exist. Molecular diagnosis with fresh tissues has been used for several of these infections, using either specific primers for these fungi or panfungal primers (23,45,83).…”