Blastomyces dermatitidis

From IDWiki
Blastomyces dermatitidis

Background

Microbiology

  • Broad-based dimorphic budding yeast
  • Mold at 25-28ºC and yeast at 37ºC
  • Branching hyphae 2-3 µm in diameter and right-angle conidiophores resembling lollipops
    • Conidia become airborne when disturbed

Epidemiology

Distribution of blastomycosis
  • Present in the Mississippi, Ohio, and St. Lawrence River Valleys, the Great Lakes regions, and western Ontario
  • May also be endemic to Africa and India, though it's unclear whether these are true cases or late reactivation
  • Hosts include humans, dogs, cats, horses, brown bears, and exotic pets like the kinkajou and red ruffed lemur
  • There have been point-source outbreaks associated with occupational and recreational activities, usually along streams or rivers enriched with decaying vegetation
  • Possibly has cold-weather seasonality

Pathophysiology

  • Inhalation of conidia into the lungs
  • Macophages can phagocytize and kill the conidia, and can also slow conversion into yeast form
    • A thick cell wall helps to prevent phagocytosis
  • Some conidia successfully convert to the pathogenic yeast form
  • Major antigens include BAD1 on the cell wall surface and binds CR3 (CD11b/CD18) and CD14
  • Humoral immunity has little effect; rather, immune response relies on cell-mediated immunity

Clinical Manifestations

  • Can be acute pneumonia (followed by either recovery or chronic infection), or asymptomatic (followed by recovery or chronic infection)
    • About 50% overall resolve without treatment
    • About half of symptomatic patients have isolated lung involvement and half are disseminated
  • When symptomatic, may have non-specific and constitutional symptoms
  • Can be primary or reactivation
  • Incubation period 3 weeks to 3 months

Respiratory Blastomycosis

  • Respiratory symptoms are the most common focus
  • Can mimic community-acquired pneumonia or tuberculosis, and may have hemoptysis
    • Less likely cavitary, but possible
  • Can be acute or chronic presentation, or asymptomatic
    • Chronic typically lasts 2 to 6 months, with constitutional symptoms
  • Even if there is non-pulmonary infection, there are often findings on chest x-ray
  • Can also cause ARDS in about 10% of cases, which distinguishes it from histoplasmosis

Extra-Pulmonary Blastomycosis

  • Next most common feature is dissemination to skin
    • Lesions usually either verrucous or ulcerative
    • May be misdiagnosed as pyoderma gangrenosum, keratoacanthoma, BCC, squamous cell carcinoma, or mycosis fungoides
    • Differential also contains NTM, other fungal infections, lupus
  • Osteomyelitis, with or without evidence of lung involvement, is the third most common form
    • There are no specific clinical or radiographical features of blastomycosis
  • Genitourinary involvement, especially prostatitis and epididymo-orchitis, are next most common
    • May be cultured in urine collected after prostate massage
  • Meningitis and cerebritis/abscess are possible
    • Consider screening for it in immunocompromised people
    • Cerebellum more common
    • CSF culture is insenitive, though PCR is better
    • Found in 5-10% of cases of disseminated blasto, but associated with high mortality
    • Can have ocular involvement, as well
    • Differential would involve bacterial and fungal meningitis/abscess (including cryptococcosis), and Nocardia
  • Can also affect larynx, lymphatics or lymph nodes, spleen, and any other organ, though fungemia is rarely found
  • Infection can cause endocrinologic abnormalities including adrenal insufficiency, thyroid infection, hypercalcemia (granulomatous)
    • There are case reports of diabetes insipidus, and hyperprolactinemia
  • Because it can occur in any organ, there are also case reports of breast lesions, tubo-ovarian abscess, otitis media, branchial cleft cyst infection

Pregnancy

  • May be higher risk group, and can transmit it to the newborn

Immunocompromised Patients

Diagnosis

  • Requires a microbiologic diagnosis

Microscopy

  • Can be directly visualized on exudate, sputum, tissue, or really any sample
  • Fairly easy to see with KOH or calcofluor
  • Can be seen on histology of skin lesion biopsy with Gomori methenamine silver (GMS) and periodic acid-Schiff (PAS) stains
  • Thick-walled, multinucleated, broad-based budding

Culture

  • Grows as mycelial (mold) form at 25-30ºC, usually after 1 to 3 weeks, starting as a white mold that slowly turns light brown
    • Grows 5-10 days before they develop conidia, so relatively low risk of infection early on
  • Usually needs a DNA probe to confirm the species
  • Biosafety level 3 pathogen, so needs to be sent to Public Health

Serology

  • Antibody
    • Serology with complement fixation is insensitive
    • A antigen antibodies is better (Sn 65-80%, Sp 100%)
    • BAD1 antigen antibodies is 85% sensitive but not yet used
  • Urinary antigen has 93% sens and 80% spec
    • It cross-reacts with other dimorphic fungi, especially histoplasmosis
    • Can be trended to monitor response during therapy
  • Can check 1,3-β-d-glucan, but not specific or particularly sensitive

Molecular Methods

  • Not yet well-developed, but theoretically possible to do PCR

Management

  • Chronic blastomycosis doesn't resolve without treatment, and mortality is as high as 60%
  • Although many cases of acute pulmonary blastomycosis self-resolve, it is still recommended to treat, since triazoles are well-tolerated
  • Severity is based on clinical judgement, as there are no validated criteria

Pulmonary Blastomycosis

Disseminated Extrapulmonary Blastomycosis

  • Same as for pulmonary blastomycosis, but treated for at least 12 months if bone involvement

CNS Blastomycosis

Immunocompromised Patients

  • Same as for severe pulmonary blastomycosis, but duration is at least 12 months
  • May be followed by lifelong suppressive itraconazole 200 mg po daily if immunosuppression cannot be decreased and they have relapsed despite appropriate therapy

Pregnant women

Children

Itraconazole

  • Tablet formulation has poorer oral bioavailability than liquid formulation
  • Need to avoid PPIs and H2 blockers, as it needs an acidic stomach environment to get absorbed, especially for tablet formulation
  • Not as good CNS penetration as other triazoles
  • Needs therapeutic drug monitoring after 2 weeks with goal of maintaining serum levels between 1.0 and 10.0 μg/ml

Further Reading