View source for Blastomyces dermatitidis

= ''Blastomyces dermatitidis'' =

== 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 ==

* Present in the Mississippi, Ohio, and St. Lawrence River Valleys, the Great Lakes regions, and western Ontario

![Map of fungi in North America](Map of fungi in North America.png)

* 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 Presentation ==

* 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

=== Immunocompromise ===

* Not as commonly described as an opportunistic infection as the other endemic fungi
* Few cases with AIDS, but possible
* Sarcoidosis, transplantation, and steroid use are all risk factors
* Infliximab and etanercept are higher risk

== 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 blasto doesn't resolve without treatment, and mortality is as high as 60%
* Although many cases of acute pulmonary blasto self-resolve, it is still recommended to treat, since azoles are well-tolerated
* Severity is based on clinical judgement, as there are no validated criteria
* Pulmonary blastomycosis
** Mild-to-moderate: itraconazole 200 mg po tid for 3 days followed by bid for 6-12 months
** Moderate severe-to-severe: liposomal amphotericin B 3-5 mg/kg per day for 1-2 weeks or until improvement, followed by itraconazole 200 mg po tid for 3 days, followed by itraconazole 200 mg po bid, for a total of 6 to 12 months
*** May need 6 to 8 weeks of induction
** Monitor serum itraconazole after 2 weeks
* Disseminated extrapulmonary blastomycosis
** Same as for pulmonary blastomycosis
** 12 months for bone and CNS involvement
* CNS blastomycosis
** Amphotericin 5 mg/kg per day for 4-6 weeks followed by an azole for at least 12 months and until resolution of CSF abnormalities
** Azoles include fluconazole 800 mg daily, itraconazole 200 mg bid or tid, or voriconazole 200-300 mg bid
*** Vori ''may'' be better for CNS disease
* Immunosuppressed patients with blastomycosis, including AIDS
** 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
* Blastomycosis in pregnant women
** Use liposomal amphotericin 3-5 mg/kg per day
** Avoid azoles for risk of teratogenicity
* Blastomycosis in newborns: AmB deoxycholate 1 mg/kg per day
* Blastomycosis in children
** Mild-to-moderate: itraconazole 10 mg/kg po per day (up to 400 mg) for 6 to 12 months
** Severe blastomycosis: AmB deoxycholate 0.7-1 mg/kg per day or liposomal AmB at 3-5 mg/kg per day, followed by itraconazole 10 mg/kg po per day (up to 400 mg), for a total of 12 months
** Monitor serum levels after 2 weeks

=== Itraconazole ===

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

== Further Reading ==

* Chapman SW ''et al.'' [https://doi.org/10.1086/588300 Clinical Practice Guidelines for the Management of Blastomycosis: 2008 Update by the Infectious Diseases Society of America]. ''Clin Infect Dis''. 2008 46(12):1801-1812.