Yeast-Associated Infections

Diagnosis

Indications for Testing

• At-risk patients with suspected yeast-associated disease

Laboratory Testing

Respiratory – acute primary infection

Respiratory – Acute Primary Infection
Histoplasma	Sputum fungal stain Histoplasma EIA serum and/or urine Tissue culture
Cryptococcus	Fungal stain Serum Cryptococcus antigen Culture
Candida	Tissue biopsy specimen showing invasion Tissue culture
Coccidioides	Sputum fungal stain Tissue culture Serum ID
Blastomyces	Sputum fungal stain Serum ID, CF, EIA Tissue culture Antigen (serum, urine) as secondary test
Trichosporon or Rhodotorula	N/A

Respiratory – chronic pulmonary disease

Respiratory – Chronic Pulmonary Disease
Histoplasma	EIA serum or urine Tissue culture Antibody detection
Cryptococcus	CF antibodies
Candida	N/A
Coccidioides	N/A
Blastomyces	Serum CF, ID, EIA
Trichosporon or Rhodotorula	N/A

Central nervous system

Central Nervous System
Histoplasma	Cerebral spinal fluid (CSF) stain and culture Serum Histoplasma antigen
Cryptococcus	India ink Serum Cryptococcus antigen CSF Cryptococcus antigen Culture
Candida	Culture Fungal stain (1-3) beta-D-glucan
Coccidioides	CSF stain and culture CF, ID, and ELISA antibodies
Blastomyces	CSF stain and culture CF and ID antibodies, EIA
Trichosporon or Rhodotorula	N/A

Ophthalmologic

Ophthalmologic
Histoplasma	Culture Serum Histoplasma antigen and antibody
Cryptococcus	Culture Serum Cryptococcus antigen
Candida	Culture (vitreous fluid) Blood culture (1-3) beta-D-glucan
Coccidioides	N/A
Blastomyces	N/A
Trichosporon or Rhodotorula	N/A

Otorhinolaryngologic

Otorhinolaryngologic
Histoplasma	N/A
Cryptococcus	Fungal stain Serum Cryptococcus antigen Culture
Candida	Culture Fungal stain
Coccidioides	N/A
Blastomyces	N/A
Trichosporon or Rhodotorula	N/A

Hepatosplenic or gastrointestinal

Hepatosplenic or Gastrointestinal
Histoplasma	Serum Histoplasma antigen
Cryptococcus	Blood culture Serum Cryptococcus antigen Tissue biopsy
Candida	(1-3) beta-D-glucan
Coccidioides	N/A
Blastomyces	N/A
Trichosporon or Rhodotorula	N/A

Dermatologic

Dermatologic
Histoplasma	Culture and histology of skin biopsy Serum Histoplasma antigen
Cryptococcus	Culture of purulent material/fluid Serum antigen
Candida	Fungal stain Culture Vaginal pathogens (DNA probe)
Coccidioides	Fungal stain of purulent material CF, ID, and ELISA antibodies
Blastomyces	Fungal stain of purulent material CF and ID antibodies, EIA
Trichosporon or Rhodotorula	Culture

Bone

Bone
Histoplasma	Bone marrow culture Serum Histoplasma antigen
Cryptococcus	Bone marrow culture Cryptococcus antigen
Candida	Bone marrow culture (1-3) beta-D-glucan
Coccidioides	Bone marrow culture CF, ID, and ELISA antibodies
Blastomyces	Bone marrow culture CF and ID antibodies, EIA
Trichosporon or Rhodotorula	N/A

Genitourinary

Genitourinary
Histoplasma	Urine and serum Histoplasma antigen, and CF and ID antibodies Tissue biopsy (focal lesion) Disseminated disease – order fungal blood culture
Cryptococcus	Serum Cryptococcus antigen Tissue biopsy (focal lesion)
Candida	Fungal stain Culture (1-3) beta-D-glucan
Coccidioides	N/A
Blastomyces	Urine culture after prostatic massage CF and ID antibodies, EIA Tissue biopsy (focal lesion)
Trichosporon or Rhodotorula	Urine culture (Trichosporon only)

Clinical Background

Yeasts cause a spectrum of diseases that range from colonization to uniformly fatal invasive disease.

• Invasive fungal disease occurs in at-risk patient populations
  • Immunocompromised patients
  • Patients on immunomodulatory therapy
  • Patients with indwelling devices
  • Critically ill patients
• Species most likely to cause disease include the following
  • Yeasts – Cryptococcus neoformans, Candida spp
    • Emerging infectious yeast agents such as Rhodotorula spp and Trichosporon spp
  • Dimorphic fungi – Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides immitis
  • See CDC for information on fungal diseases
• Manifestations of infection may occur in one or more body sites
  • Often presents with symptoms related to site of involvement

Yeast-Associated Signs and Symptoms – Pulmonary

• Risk factors for severe pneumonia and disseminated disease

  Risk Factors for Severe Pneumonia and Disseminated Disease
  Histoplasma	Young children HIV
  Cryptococcus	Sarcoidosis Diabetes mellitus HIV Organ transplantation
  Candida	Renal failure Presence of CVC/other vascular-access device TPN administration
  Coccidioides	Pregnancy HIV Ethnicity Filipino Native American African American
  Blastomyces	Pregnancy Organ transplantation HIV
  Trichosporon or Rhodotorula	Severely ill patients (eg, leukemia)

  Acute primary pulmonary infection

  Acute Primary Pulmonary Infection
  Histoplasma	Clinical picture similar to tuberculosis with fever, weight loss, and lymphadenopathy
  Cryptococcus	Fever Chest pain Cough Sputum Weight loss
  Candida	Fever Sputum Pneumonia (rare)
  Coccidioides	Clinical picture similar to tuberculosis with fever, weight loss, and lymphadenopathy
  Blastomyces	Clinical picture similar to influenza
  Trichosporon or Rhodotorula	N/A

  Chronic pulmonary disease

  Chronic Pulmonary Disease
  Histoplasma	Calcified nodes Chronic cavitary disease Mediastinal granuloma Fibrosis
  Cryptococcus	N/A
  Candida	N/A
  Coccidioides	Coin lesions (coccidiomas) Cavitary disease (thin walled) Granulomas
  Blastomyces	Chronic granulomatous disease (Gilchrist disease)
  Trichosporon or Rhodotorula	N/A

Yeast-Associated Signs and Symptoms – Sites Other than Pulmonary

• Ophthalmologic

  Ophthalmologic
  Histoplasma	Uveitis and panophthalmitis Presumed ocular histoplasmosis syndrome  Posterior uveitis with choroidal scars  Neovascularization/loss of central vision
  Cryptococcus	Ocular palsies Papilledema Keratitis Endophthalmitis
  Candida	Fungal keratitis Endophthalmitis
  Coccidioides	N/A
  Blastomyces	N/A
  Trichosporon or Rhodotorula	N/A

  Otorhinolaryngologic

  Otorhinolaryngologic
  Histoplasma	N/A
  Cryptococcus	Gingivitis Sinusitis Salivary gland enlargement
  Candida	Thrush Nasal ulcers Otitis externa
  Coccidioides	N/A
  Blastomyces	N/A
  Trichosporon or Rhodotorula	N/A

  Central nervous system

  Central Nervous System
  Histoplasma	Chronic meningitis Cerebritis and mass lesion
  Cryptococcus	Meningitis Intracranial abscesses Spinal granuloma
  Candida	Meningitis Diffuse microabscesses in the brain
  Coccidioides	Chronic meningitis with indolent course
  Blastomyces	Abscesses Meningitis
  Trichosporon or Rhodotorula	N/A

  Hepatosplenic or gastrointestinal

  Hepatosplenic or Gastrointestinal
  Histoplasma	Hepatosplenomegaly Chronic granulomatous hepatitis
  Cryptococcus	Disseminated yeast infections Hepatitis  Peritonitis  Nodular/ulcerated lesions of colon
  Candida	Disseminated yeast infections Esophagitis Gastrointestinal ulcers Peritonitis Hepatic and splenic abscesses
  Coccidioides	N/A
  Blastomyces	N/A
  Trichosporon or Rhodotorula	N/A

  Dermatologic

  Dermatologic
  Histoplasma	Discrete erythematous skin papules in HIV patients
  Cryptococcus	Papules Subcutaneous abscesses Purpura Bullae Ulcers Draining sinuses
  Candida	Folliculitis (generalized cutaneous form) Disseminated skin infections Intertrigo Paronychia Onychomycosis Diaper rash Vaginitis Chronic mucocutaneous candidiasis
  Coccidioides	Maculopapular to verrucous lesions Subcutaneous abscesses Reactive eruptions (contain no organisms) Erythema nodosum Erythema multiforme Toxic erythema Sweet syndrome
  Blastomyces	Verrucous or ulcerative lesions Subcutaneous nodules
  Trichosporon or Rhodotorula	Red papular lesions (T) Catheter-related fungemia (R)

  Bone

  Bone
  Histoplasma	Osteomyelitis
  Cryptococcus	Osteolytic lesions with soft-tissue abscesses
  Candida	Osteomyelitis (most common in spine, wrist, femur, ribs, scapula, and proximal humerus) Arthritis
  Coccidioides	Osteomyelitis (most common in knees, hands, vertebrae, and long bones) Symmetric arthritis (referred to as desert rheumatism)
  Blastomyces	Osteomyelitis (most common in long bones, vertebrae, and ribs)
  Trichosporon or Rhodotorula	N/A

  Genitourinary

  Genitourinary
  Histoplasma	Epididymitis Testicular and prostatic abscesses (rarely symptomatic)
  Cryptococcus	Prostatitis Renal abscesses Genital lesions
  Candida	Vulvovaginitis Balanitis Papillary necrosis Fungus ball Perinephric abscess
  Coccidioides	N/A
  Blastomyces	Prostatitis Epididymitis
  Trichosporon or Rhodotorula	Hematuria (T) Funguria (T)

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Coccidioides Antibodies, IgG & IgM by ELISA 0050137 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Fungal Antibodies by ID 0050164 Method: Qualitative Immunodiffusion
Fungal Antibodies by CF, Serum 0050605 Method: Semi-Quantitative Complement Fixation
Fungal Identification by ITS rDNA Sequencing 0060756 Method: Sequencing	Identify clinically significant isolates
Antimicrobial Susceptibility - Yeast Susceptibility 0060235 Method: Broth Microdilution	Determine minimum inhibitory antifungal agent concentration to treat identified Candida, Cryptococcus, Geotrichum, and Trichosporon species Agents tested: amphotericin B, anidulafungin, caspofungin, fluconazole, 5-fluorocytosine, itraconazole, micafungin, posaconazole, and voriconazole
Blastomyces Antibody by CF 0050130 Method: Semi-Quantitative Complement Fixation	Use with paired sera taken 3 weeks apart to detect a rise in titer against a single antigen
Blastomyces Antibody by ID 0050172 Method: Qualitative Immunodiffusion	Measure IgG antibodies
Candida Antibody by ID 0055565 Method: Qualitative Immunodiffusion
Candida albicans Antibodies IgA, IgG, and IgM by ELISA 0095200 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay	Measure IgG, IgM and IgA antibodies Best evidence for infection is significant change on two appropriately timed specimens where both tests are done in the same laboratory at the same time; however, low levels of IgM may occasionally persist for >12 months
Coccidioides Antibody by CF 0050170 Method: Semi-Quantitative Complement Fixation	Detect current or past infection Monitor response to therapy Least sensitive in pulmonary cavitary disease
Coccidioides Antibody by ID 0050183 Method: Qualitative Immunodiffusion	Detect current or past infection Monitor response to therapy
Coccidioides Antibody, IgG by ELISA 0050179 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay	Detect current or past infection Negative fungal serology does not rule out possibility of current infection
Coccidioides Antibody, IgM by ELISA 0050178 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay	Detect current or past infection Negative fungal serology does not rule out possibility of current infection For equivocal results, repeat test in 10-14 days
Cryptococcus Antibody 0098947 Method: Semi-Quantitative Immunofluorescence	Detect antibodies to Cryptococcus
Histoplasma Antibodies by CF 0050625 Method: Semi-Quantitative Complement Fixation	Detect current or past Histoplasma infection
Histoplasma Antibodies by CF & ID 0050627 Method: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion	Detect current or past Histoplasma infection Negative fungal serology does not rule out possibility of current infection
Histoplasma Antibody by ID 0050174 Method: Qualitative Immunodiffusion	Identify Histoplasma as causative agent in disease Negative fungal serology does not rule out possibility of current infection
Fungal Antibodies by CF, CSF 0050750 Method: Semi-Quantitative Complement Fixation
Yeast Differentiation by PNA FISH 2004769 Method: Qualitative Peptide Nucleic Acid Fluorescence in situ Hybridization	Presumptive result; definitive identification made from subculture