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Paracoccidioidomycosis Workup

  • Author: Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH; Chief Editor: Mark R Wallace, MD, FACP, FIDSA  more...
 
Updated: Mar 23, 2015
 

Approach Considerations

The diagnosis of paracoccidioidomycosis is most commonly made through the visualization of typical yeast cells in tissue, wet preparations (eg, sputum), or superficial scrapings (eg, skin lesions).[22] Cultures should be obtained, but are limited by low sensitivity. Cerebrospinal fluid (CSF) studies are nonspecific, and mycologic examination (smears and culture) is usually negative. Blood culture results are typically negative, but recovery of P lutzii from blood has recently been reported.[23]

Other laboratory studies

Patients with juvenile paracoccidioidomycosis can have anemia, hypergammaglobulinemia, and eosinophilia.

Pulmonary function tests

These may reveal obstructive abnormalities.

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Microbiology

Wet mount of sputum or lesional material

In more than 90% of patients, potassium hydroxide (KOH) preparation of sputum or lesional material reveals large, multiple budding yeasts (blastoconidia) (2-30 µm in diameter) diagnostic for paracoccidioidomycosis. The typical pathognomonic features are large, thick-walled, spherical yeast cells with multiple peripheral buds encircling the central cell (pilot's wheel or mariner's wheel). This appearance helps to differentiate Paracoccidioides from Blastomyces dermatitidis and all other yeasts. (See the image below.)

Potassium hydroxide (KOH) preparation from pus; no Potassium hydroxide (KOH) preparation from pus; note the multiple budding and variation in cell size with Paracoccidioides.

Histologic findings

Histologic examination reveals a granulomatous reaction with epithelioid and giant cells in association with a severe inflammatory infiltrate. Yeast with the characteristic pilot's wheel configuration may be found within giant cells or free in the inflammatory infiltrate. In skin and mucous membrane lesions, pseudoepitheliomatous hyperplasia with intraepidermal abscesses may be seen. Caseous necrosis is seen within the lymph nodes. A diffuse tissue reaction is typically seen in the juvenile form.

Culture

Paracoccidioides can be recovered on fungal media (eg, Sabouraud dextrose agar) but may require 20-30 days for growth. The fungus grows as a mold at room temperature; conversion to the typical yeast form by growth at 35-37°C is required for confirmation of the diagnosis.

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Serologic Diagnosis

Serologic testing is not available in the United States (or outside endemic areas) and may be negative in patients infected with P lutzii infection.

Immunodiffusion

Double-agar gel immunodiffusion can be used for screening, diagnosis, and treatment follow-up. The most-used test, with a sensitivity of greater than 80% and a specificity of more than 90%, it detects circulating Paracoccidioides antibodies.

Complement fixation test

This test is useful but technically cumbersome. It has a quantitative nature that allows evaluation of patient response to treatment, but it may cross-react with Histoplasma capsulatum antigens.

Counter immunoelectrophoresis

This test is similar to immunodiffusion with regard to sensitivity and specificity. Counter immunoelectrophoresis can be a useful test in endemic areas that are resource poor, as it does not require a power supply or buffers.

Solid-phase immunoassays

These tests (eg, enzyme-linked immunoassay [ELISA]) are used to detect circulating antibodies in the patient's serum. Most ELISA tests detect antibodies to gp43, and newer assays report a sensitivity of 95% and a specificity of 93%. Cross-reactivity is also possible in patients with histoplasmosis or lobomycosis.

Immunoblotting

These tests (eg, Western blot) detect circulating antibodies to gp43 in the serum in 100% of patients and circulating antibodies to gp70 in 96% of patients.

Novel and emerging technologies

Monoclonal antibodies to antigenic compounds of P brasiliensis have increased sensitivity. The antigen gP43 reacts with the sera of almost all patients infected with P brasiliensis, but it also shows positivity in patients with histoplasmosis. Because of specific protocols needed in the development and purification of the antigen, it is typically only used in a research setting or at larger referral centers.[1]

Synthetic peptides mimicking P brasiliensis innate antigens have been studied as cheaper and more sensitive and specific alternatives to current serologic testing. However, they are still under investigation.

Polymerase chain reaction (PCR) diagnosis has been reported in experimental settings and holds the potential for a more sensitive and specific methodology for the diagnosis of paracoccidioidomycosis.

Skin test

The paracoccidioidin skin test, if available, provides little diagnostic value. A positive skin test result indicates prior exposure, but it does not necessarily indicate current disease. The test may be useful prognostically because the conversion from an anergic result to a positive result is associated with a good prognosis in patients with severe paracoccidioidomycosis. Skin testing may also be an excellent tool for epidemiologic study of this disease.[24]

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Radiology

Juvenile paracoccidioidomycosis

Imaging to evaluate the extent of lymphadenopathy is warranted, and the patient should also be evaluated for possible obstruction or compression of structures secondary to lymphadenopathy. If clinically indicated, bone scanning can be performed to evaluate bone lesions.

Adult paracoccidioidomycosis

Chest radiography and chest CT scanning should be considered. Chronic paracoccidioidomycosis patients without respiratory symptoms may have lung fibrosis. Chest radiography may show a nodular-interstitial, bilateral, and diffuse lung infiltrate in chronic paracoccidioidomycosis.[25] CT scanning may also be useful.

If clinically indicated, CT scanning or magnetic resonance imaging (MRI) of the brain should be obtained to evaluate CNS involvement. Consider imaging suspected affected areas.[26]

Chest radiography

In patients with active paracoccidioidomycosis, chest radiography reveals interstitial infiltrates (in 64% of cases) or mixed lesions with linear and nodular infiltrates. Lesions are frequently bilateral and symmetrical.

Most changes occur in the central and basal portions of the lungs; the apices are usually spared. Cavities are frequent, but hilar adenopathy is rare.

Chronic pulmonary sequelae can present as fibrosis, bullae, and emphysematous areas. Chronic cor pulmonale can cause right ventricular hypertrophy.

CT scanning and MRI

CT scanning of the chest may help delineate disease and rule out coexisting pathology (eg, tuberculosis, malignancy). In CNS disease, features on CT and MRI scans are nonspecific and similar to those seen in other granulomatous diseases (solitary or multifocal parenchymal lesions).[26]

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Contributor Information and Disclosures
Author

Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH Adjunct Professor of Medicine, Department of Medicine, University of Texas Health Science Center at San Antonio

Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, International Society for Infectious Diseases, International Society of Travel Medicine, Medical Mycological Society of the Americas, Armed Forces Infectious Diseases Society, International Society for Human and Animal Mycology, American College of Physicians, American Society for Microbiology, Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Coauthor(s)

Kendall M Egan, MD, FAAD Dermatologist, Veteran's Affairs Medical Center; Dermatologist, Spruce Health, Dermatologist, DermOne

Kendall M Egan, MD, FAAD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists

Disclosure: Nothing to disclose.

Chief Editor

Mark R Wallace, MD, FACP, FIDSA Clinical Professor of Medicine, Florida State University College of Medicine; Clinical Professor of Medicine, University of Central Florida College of Medicine

Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, Florida Infectious Diseases Society

Disclosure: Nothing to disclose.

Acknowledgements

Asgar A Boxwalla, MD Staff Physician, Department of Internal Medicine, Division of Infectious Diseases, St John Detroit Riverview Hospital

Disclosure: Nothing to disclose.

David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Department of Internal Medicine, Director of Infectious Disease Fellowship, Harper Hospital, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Julie E Dixon, MD, FAAD Private Practice, Ironwood Dermatology, Tucson, Arizona

Julie E Dixon, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and American Medical Association

Disclosure: Nothing to disclose.

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Franklin Flowers, MD Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, Affiliate Associate Professor of Pediatrics and Pathology, University of Florida College of Medicine

Franklin Flowers, MD, is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology

Disclosure: Nothing to disclose.

Ronald A Greenfield, MD Professor, Department of Internal Medicine, University of Oklahoma College of Medicine

Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubist Honoraria Speaking and teaching; Forest Pharmaceuticals Speaking and teaching

Norman Levine, MD Private Practice, Tucson, AZ

Norman Levine is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Christina M Schofield, MD Instructor of Medicine, Uniformed Services University of the Health Sciences; Consulting Staff, Department of Infectious Disease, Wilford Hall Medical Center, Lackland Air Force Base

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Acknowledgments

The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of the Navy, Department of the Army, Department of Defense, or the U.S. Government.

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Approximate distribution of paracoccidioidomycosis in North, Central, and South America, based on case reports.
Granulomatous lesion involving the nose in patient with paracoccidioidomycosis; note the resemblance to cutaneous leishmaniasis.
Potassium hydroxide (KOH) preparation from pus; note the multiple budding and variation in cell size with Paracoccidioides.
Crusted plaques over the central part of the face in a man with paracoccidioidomycosis. Courtesy of Rolando Vasquez, MD, Professor of Dermatology, Guatemala.
Ulcerated nodule on the tongue in a man with paracoccidioidomycosis. Courtesy of Heidi Logemann, Professor of Mycology, Universidad de San Carlos, Guatemala.
 
 
 
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