Clinical Background
Molds may cause human disease that ranges in spectrum from colonization to uniformly fatal. Molds may also cause hypersensitivity reactions.
- Invasive fungal disease occurs most commonly in immunocompromised patients
- Molds most often associated with significant disease include:
- Hyaline molds such as:
- Aspergillus fumigatus
- Fusarium spp
- Scedosporium spp
- Zygomycetes
- Hallmarks of Zygomycetes infection are vascular invasion and tissue necrosis (presence of black tissue)
- Dematiaceous molds
| Mold-Associated Respiratory Signs and Symptoms |
| | Hyaline molds
A - Aspergillus fumigatus
F - Fusarium
S - Scedosporium | Zygomycetes | Dematiaceous
Phaehyphomycosis
Chromoblastomycosi
Mycetoma |
| At risk | All immunocompromised patients
Special risk - patients with acute leukemia or organ transplant (prolonged neutropenia) | All immunocompromised patients
Special risk - organ transplant recipients and patients with a propensity to be acidotic (diabetes, renal insufficiency) and patients treated with deferoxamine for iron overload | All immunocompromised patients |
| Pneumonia | Acute respiratory distress syndrome (ARDS)
Chronic inflammatory process in colonized cystic fibrosis patients (A,S)
Necrotizing pneumonias (halo and crescent signs) (A) Pulmonary mycetoma (S) Rapidly progressive consolidation; also have tracheobronchitis in lung transplantation (A,S) | Infiltrate or cavity on X-ray
Hemoptysis Necrotizing pneumonias Mycotic pulmonary aneurysms | Rare pulmonary chromoblastomycosis |
| Hypersensitivity | Endobronchial saprophytic Scedosporium and aspergillus (fungal balls) (A,S)
Allergic bronchopulmonary aspergillosis (ABPA) and Scedosporium pneumonia (A,S) Asthma (A) | | |
| Mold-AssociatedSigns and Symptoms- Sites Other Than Pulmonary |
| | Hyaline molds
A - Aspergillus fumigatus
F - Fusarium
S - Scedosporium | Zygomycetes | Dematiaceous
Phaeohyphomycosis
Chromoblastomycosis
Mycetoma |
| Ophthalmic | Endophthalmitis (A,S)
Keratitis (A,F) | | |
| Otorhinolaryngologic | Otomycosis - growth on cerumen and detritus in ear canal (A,F,S)
Sinus (A,F,S)
- Ball of hyphae with obstruction
- Acute invasive rhinosinusitis
- Chronic fibrosing granulomatous inflammation with tissue invasion
| Orbital cellulitis
Cranial nerve palsies Cavernous sinus and internal artery thromboses Invasive rhinosinusitis | Phaeohyphomycoses (allergic)
Fungal sinusitis
Acute invasive rhinosinusitis |
| Central nervous system | Brain abscess (A,F,S)
Meningitis (rare) (A,F,S)
Vascular infarcts in brain (A) | Brain abscesses (generally invasive from sinuses)
Meningitis (rare) | Chromomycosis - rare CNS dissemination
Phaeohyphomycoses - brain abscess, meningitis |
| Cardiac/mediastinum | Endocarditis (A,F,S)
Pericarditis (A,F,S) | Endocarditis | |
| Hepatosplenic or gastrointestinal (GI) system involvement | | All portions of GI tract with ulcers (stomach most commonly affected) | |
| Dermatologic | Onychomycosis (A,F,S)
Invasion of catheters (A,F)
Burns (A)
Necrotic skin lesions (S)
Papules, nodules (tender) (F) | Ulcers
Necrosis | Chromomycosis
Blastomycosis nodules turn into verrucous lesions and plaques
Mycetoma - usually lower extremity nodule with draining sinus tract and extrusion of granules
Phaeohyphomycoses - single red nodule on extremity
Chronic chromomycosis may lead to squamous cell carcinoma |
| Bone | Vertebral (A,S; most common for A)
Long bones and joints (S) | Rare bone necrosis | |
See Also
Diagnosis
| Diagnosis of Mold-Associated Syndromes |
| | Hyaline molds
A - Aspergillus fumigatus
F - Fusarium
S - Scedosporium | Zygomycetes | Dematiaceous |
| Pneumonia | Tracheal lavage with fungal stain Galactomannan tissue culture | Tissue culture | Not applicable |
| Hypersensitivity | Clinical deterioration (increased cough, wheezing, exercise intolerance, exercise-induced asthma, increased sputum, decrease in pulmonary function)
- Immediate cutaneous reactivity to Aspergillus or presence of IgE to A. fumigatus
- Total serum IgE concentration >500 IU/mL (>1200 ng/mL)
- One of the following:
Precipitins (or IgG) to A. fumigatus, new or recent abnormalities on computed tomography (bronchiectasis) or chest radiograph (mucus plugging/infiltrates)
Fungal balls: sputum culture+ Aspergillus antibodies CF, ID | Not applicable | Not applicable |
| Ophthalmic | Culture | Not applicable | Not applicable |
| Otorhinolaryngologic | Ball of hyphae with obstruction Acute invasive rhinosinusitis associated with invasive disease
- CT scan and tissue culture
- Chronic fibrosing granulomatous inflammation with tissue invasion
| Tissue culture | Allergic - CT with lack of invasion
Acute invasion - CT scan and tissue culture |
| Central nervous system | Cerebral spinal fluid (CSF) stain and culture | Tissue culture | Chromomycosis - culture
Phaeohyphomycoses - culture |
| Cardiac/mediastinum | Blood culture
Galactomannan
Antigen | Blood culture | |
| Hepatosplenic or gastrointestinal (GI) system involvement | | Tissue culture | |
| Dermatologic | Fungal stain and culture of pus | KOH/Calcofluor White Stain and culture | Chromomycosis - fungal stain |
| Bone | Bone marrow culture | Bone marrow culture | Mycetoma - stain of pus |
| Disseminated/invasive | Blood culture
Galactomannan
Antigen | Blood culture | |
| Tests |  |
Tests generally appear in the order most useful for common clinical situations
| Test name: Aspergillus Antibodies by CF & ID
|
| ARUP #: 0050101 |
| Methodology: Complement Fixation/Immunodiffusion
|
| Use: Detect presence of Aspergillus antibodies |
| Limitations: |
| Follow-up:
|
| Test name: Aspergillus Niger IgE
|
| ARUP #: 0092598 |
| Methodology: ImmunoCAP
|
| Use: Use to measure IgE |
| Limitations: |
| Follow-up:
|
| Test name: Aspergillus Galactomannan Antigen by EIA
|
| ARUP #: 0060068 |
| Methodology: Enzyme Immunoassay
|
| Use: Diagnose Aspergillus infection |
| Limitations: Negative results do not exclude the diagnosis of invasive aspergillosis; a single positive test result (index equal to or greater than 0.5) should be confirmed by testing a separate serum specimen because many agents (e.g. food, antibiotics) may cross-react with the assay |
| Follow-up: If invasive aspergillosis is suspected in high-risk patients, serial sampling is recommended |
| Test name: Fungal (Mould) Identification
|
| ARUP #: 0060163 |
| Methodology: Standard reference procedures for mould identification
|
| Use: Identify fungal agent |
| Limitations: |
| Follow-up:
|
| Test name: Fungal Culture
|
| ARUP #: 0060149 |
| Methodology: Standard reference procedures for fungal culture and identification of mould/yeast. DNA probes available for Histoplasma, Coccidioides, and Blastomyces
|
| Use: Gold standard test for diagnosing fungi as agent of infection in pus, sputum, tissue or urine |
| Limitations: |
| Follow-up:
|
| Test name: Fungal Stain - KOH with Calcofluor White
|
| ARUP #: 0060161 |
| Methodology: KOH with Calcofluor White/Microscopic Exam
|
| Use: Identify fungus from fungal smear |
Limitations: Difficult to identify type of fungus from a smear |
| Test name: Blood Culture, Fungal
|
| ARUP #: 0060070 |
| Methodology: Bactec® 9240, continuous monitoring systems. Standard reference procedures for identification of positive cultures.
|
| Use: Gold standard test for diagnosing fungi as agent of infection in blood |
| Limitations: Poor sensitivity for Aspergillus spp, Zygomycetes and Dematiaceous molds |
| Test name: Fungal Culture, Skin, Hair or Nails
|
| ARUP #: 0060728 |
| Methodology: Standard reference procedures for fungal culture and identification of mould/yeast.
|
| Use: Gold standard test for diagnosing fungi (dermatophytes, etc.) as agent of infection in skin, hair or nails |
| Limitations: |
| Follow-up:
|
| Test name: Aspergillus fumigatus Antibody, IgG by ELISA
|
| ARUP #: 0097771 |
| Methodology: Enzyme-Linked Immunoassay
|
| Use: Diagnose antibody response to Aspergillus fumigatus |
Additional Tests Available
| Test name: Fungal Antibodies by ID
|
| ARUP #: 0050164 |
| Methodology: Immunodiffusion
|
| Comments: |
| Test name: Aspergillus Antibody by CF
|
| ARUP #: 0050100 |
| Methodology: Complement Fixation
|
| Comments: Use with paired sera taken 3 weeks apart to detect a rise in titer against a single antigen |
| Test name: Aspergillus Antibody by ID
|
| ARUP #: 0050171 |
| Methodology: Immunodiffusion
|
| Comments: Use to measure IgG and precipitins |
| Test name: (1-3) Beta-D Glucan Assay |
| ARUP #: |
| Methodology: |
| Comments: |
| Test name: Fungal Antibodies by CF, CSF
|
| ARUP #: 0050750 |
| Methodology: Complement Fixation
|
| Comments: |
| Test name: Fungal Antibodies by CF, Serum
|
| ARUP #: 0050605 |
| Methodology: Complement Fixation
|
| Comments: |
Additional Information
Refer to Mold-Associated Syndromes at www.arupconsult.com
Refer to Mold-Associated Syndromes at www.arupconsult.com
References
Guidelines
Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect
Dis.
2008;
46(
3):
327-360.
General References
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References from the ARUP Institute for Clinical and Experimental Pathology Research®
Blaschke AJ, Bender J, Byington CL, Korgenski K, Daly J, Petti CA, Pavia AT, Ampofo K. Gordonia species: emerging pathogens in pediatric patients that are identified by 16S ribosomal RNA gene sequencing. Clin Infect Dis.
2007;
45(
4):
483-486.
Pickering JW, Sant HW, Bowles CA, Roberts WL, Woods GL. Evaluation of a (1->3)-beta-D-glucan assay for diagnosis of invasive fungal infections. J Clin Microbiol.
2005;
43(
12):
5957-5962.
Pounder JI, Hansen D, Woods GL. Identification of Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species by repetitive-sequence-based PCR. J Clin Microbiol.
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8):
2977-2982.
Pounder JI, Simmon KE, Barton CA, Hohmann SL, Brandt ME, Petti CA. Discovering potential pathogens among fungi identified as nonsporulating molds. J Clin Microbiol.
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45(
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Pounder JI, Williams S, Hansen D, Healy M, Reece K, Woods GL. Repetitive-sequence-PCR-based DNA fingerprinting using the Diversilab system for identification of commonly encountered dermatophytes. J Clin Microbiol.
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Medical Reviewers
Carney, Heather, M.D. Assistant Medical Director, Transfusion Services at ARUP Laboratories; Pathology, University of Utah
Petti, Cathy A., M.D. Medical Director, Infectious Diseases at ARUP Laboratories; Assistant Professor, Pathology and Medicine, University of Utah
Comprehensive Review: May 2008
Last Update: July 2008
