Blastomycosis
Also known as: Blastomyces Infection, North American Blastomycosis, Gilchrist Disease
Blastomycosis is a systemic infection caused by thermally dimorphic fungi of the genus Blastomyces, acquired by inhalation of conidia from moist soil and decaying wood. Unlike other endemic mycoses, most cases occur in people with normal immunity, and disease is symptomatic in about half of those infected. The lung is the portal of entry, and spread to skin, bone, genitourinary tract, and brain follows. Blastomycosis is commonly mistaken for bacterial pneumonia, tuberculosis, or cancer, and delays in diagnosis are frequent.
| Feature | Description |
|---|---|
| Species | Blastomyces dermatitidis and Blastomyces gilchristii (North America, the commonest), Blastomyces percursus (Africa and Middle East), Blastomyces helicus and Blastomyces parvus (formerly Emmonsia; western North America, with immunocompromised hosts and adiaspore like forms) |
| Mould phase | At 25 to 30 degrees Celsius, white to tan colonies of hyaline septate hyphae with small round to oval conidia (2 to 10 micrometres) on conidiophores (the infectious form) |
| Yeast phase | At 37 degrees Celsius and in tissue, round thick walled, double contoured yeasts 8 to 15 micrometres (up to 30), each with a single broad based bud (the isthmus is as wide as the diameter of the bud), and multinucleate with no capsule |
| Culture | Slow (1 to 4 weeks, up to 6); enriched media at 37 degrees Celsius gives rough, wrinkled, cream to tan yeast colonies |
| Identification | Microscopy of yeast morphology, DNA probe, sequencing, and mass spectrometry; the mould phase is hazardous in the laboratory |
| Aspect | Details |
|---|---|
| Geography | The Ohio and Mississippi river basins, the Great Lakes region, the Canadian provinces of Ontario, Manitoba, and Quebec, and the Saint Lawrence Seaway; rare reports from Africa, India, the Middle East; most cases are in Wisconsin, Minnesota, Michigan, Illinois, Arkansas, Louisiana, Mississippi, and Kentucky |
| Incidence | About 1 to 2 cases per 100 000 in endemic areas, and over 40 per 100 000 in hyperendemic regions (for example northern Wisconsin) |
| Reservoir | Moist, acidic, organic soil near waterways, decaying wood, beaver dams, and rotting vegetation |
| Exposure | Fishing, hunting, camping, forestry, excavation, and construction near water; outbreaks follow soil disturbance (including a paper mill outbreak in Michigan in 2023) |
| Host | Men more than women, and the disease is described in outdoor workers; occasionally in children, pregnant women, and in the immunosuppressed; dogs are sentinels, with a high incidence in endemic regions |
| Incubation | 3 to 15 weeks (mean about 45 days) |
| Transmission | Inhalation; direct cutaneous inoculation (laboratory or animal bite) rarely |
| Stage | Details |
|---|---|
| Inhalation and conversion | Conidia reach the alveoli and convert to yeasts at 37 degrees Celsius |
| Virulence | The surface adhesin BAD-1 (Blastomyces adhesin 1, also called WI-1) binds host cells and complement receptors, suppresses tumour necrosis factor alpha, and mediates immune evasion; alpha 1,3 glucan masks the beta glucan |
| Immune response | Neutrophils and macrophages, then T helper 1 and T helper 17 responses with interferon gamma, interleukin 17, and granuloma formation; a pyogranulomatous pattern (suppuration and granuloma) is typical |
| Dissemination | Lymphohaematogenous spread to skin, bone, prostate, and central nervous system |
| Immune compromise | Increased severity and dissemination, but less than in histoplasmosis |
| Form | Features |
|---|---|
| Asymptomatic or mild infection | About 50 percent |
| Acute pulmonary blastomycosis | A flu like or pneumonia like illness with fever, cough, pleuritic pain, myalgia, and dyspnoea, with lobar or segmental consolidation, which does not respond to antibacterials; a pattern that mimics bacterial pneumonia |
| Chronic pulmonary blastomycosis | Weeks to months of cough, sputum, haemoptysis, weight loss, and night sweats, with mass like infiltrates, nodules, and cavities that mimic tuberculosis or lung cancer |
| Acute respiratory distress syndrome | Fulminant disease with diffuse alveolar infiltrates, hypoxaemia, and shock; mortality 50 to 89 percent |
| Cutaneous | The commonest extrapulmonary site (40 to 80 percent): verrucous (warty) lesions with an irregular border and microabscesses at the edge, ulcerative lesions with heaped up borders, nodules, and plaques; healing with scarring; usually on exposed areas |
| Osteoarticular | 10 to 60 percent: lytic lesions of vertebrae, ribs, skull, and long bones; osteomyelitis, adjacent abscesses, and septic arthritis |
| Genitourinary | Prostatitis and epididymo orchitis (in about 10 to 30 percent of extrapulmonary cases), with a sterile pyuria |
| Central nervous system | 5 to 10 percent: meningitis, brain abscess, and epidural abscess; higher in the immunosuppressed |
| Others | Laryngeal disease (hoarseness, a mass resembling carcinoma), eye, adrenal, liver, and rarely pericardium |
| Immunocompromised hosts | Disseminated disease with a mortality of 30 to 50 percent |
| Pregnancy | Severe disease and rare vertical transmission, with a risk to the neonate |
| Pattern | Notes |
|---|---|
| Alveolar consolidation (lobar or segmental) | The commonest |
| Mass like lesions | Resemble cancer |
| Nodules and cavities | In chronic disease |
| Miliary and diffuse infiltrates | In acute respiratory distress syndrome |
| Bone | Well demarcated lytic lesions with periosteal reaction |
| Hilar adenopathy and pleural effusion | Uncommon |
| Condition | Points that separate it |
|---|---|
| Community acquired bacterial pneumonia | Failure to respond to antibacterials, cultures, and antigen |
| Tuberculosis | Acid fast bacilli; skin lesions with abscess formation |
| Lung cancer, lymphoma, and cutaneous carcinoma | Histology |
| Histoplasmosis, coccidioidomycosis, and other mycoses | Yeast morphology and culture |
| Sporotrichosis, chromoblastomycosis, and cutaneous tuberculosis | Culture |
| Pyoderma gangrenosum | Histology and culture |
| Granulomatosis with polyangiitis | Autoantibodies |
| Test | Details |
|---|---|
| Direct microscopy | Potassium hydroxide or calcofluor white on sputum, bronchoalveolar lavage, pus, and skin scrapings shows thick walled, broad based budding yeasts 8 to 15 micrometres; sensitivity of about 50 to 90 percent, and the fastest method |
| Histology and cytology | Pyogranulomatous inflammation with yeasts on methenamine silver or periodic acid Schiff stain |
| Culture | The definitive test; positive in 70 to 90 percent but takes 1 to 4 weeks |
| Antigen | Urine and serum Blastomyces galactomannan antigen enzyme immunoassay (about 76 to 93 percent sensitive), with cross reaction with Histoplasma and other endemic fungi (so the antigen test is not species specific) |
| Antibody | Enzyme immunoassay for the BAD-1 antigen is positive in about 85 percent, with an immunodiffusion assay less sensitive |
| Molecular tests | Polymerase chain reaction on tissue and respiratory specimens; sequencing |
| Cerebrospinal fluid | Pleocytosis, high protein, and low glucose; culture low yield, and antibody testing is more sensitive |
| Others | Chest imaging, a search for skin, bone, and genitourinary lesions, and brain imaging in central nervous system disease |
| Form | Regimen |
|---|---|
| Mild to moderate pulmonary disease | Itraconazole 200 mg three times daily for 3 days, then 200 mg once or twice daily for 6 to 12 months |
| Moderately severe to severe pulmonary disease | Liposomal amphotericin B 3 to 5 mg per kg intravenously once daily (or deoxycholate 0.7 to 1 mg per kg once daily) for 1 to 2 weeks or until improvement, then itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily for a total of 6 to 12 months |
| Disseminated disease, mild to moderate | Itraconazole 200 mg three times daily for 3 days, then 200 mg once or twice daily for 6 to 12 months |
| Disseminated disease, moderately severe to severe | Liposomal amphotericin B 3 to 5 mg per kg once daily for 1 to 2 weeks or until improvement, then itraconazole for 6 to 12 months |
| Osteoarticular disease | Itraconazole for at least 12 months, with surgical drainage and debridement as needed |
| Central nervous system disease | Liposomal amphotericin B 5 mg per kg once daily for 4 to 6 weeks, then an oral azole for at least 12 months and until cerebrospinal fluid abnormalities resolve: fluconazole 800 mg daily, itraconazole 200 mg two or three times daily, or voriconazole 200 to 400 mg twice daily (these have better central nervous system penetration than itraconazole) |
| Immunosuppressed patients | Amphotericin B induction for 1 to 2 weeks (or until improvement) then itraconazole for at least 12 months; lifelong suppression with itraconazole 200 mg daily if immunosuppression cannot be reversed or the disease relapses |
| Pregnancy | Liposomal amphotericin B; azoles are avoided in pregnancy, and treatment after delivery is considered |
| Children | Amphotericin B deoxycholate 0.7 to 1 mg per kg daily for 1 to 2 weeks, then itraconazole 10 mg per kg per day (maximum 400 mg per day) in divided doses for 6 to 12 months |
| Acute respiratory distress syndrome | Liposomal amphotericin B, with lung protective ventilation and extracorporeal support in selected cases; the use of corticosteroids has limited evidence |
| Surgery | Drainage of abscesses, debridement of bone, and resection of persistent lesions |
| Monitoring | Itraconazole serum levels (at least 1 microgram per mL, after 2 weeks of therapy), liver tests, and follow up for relapse for at least a year after therapy; antigen and imaging |
Itraconazole is taken as capsules with food and an acidic drink, or as a solution on an empty stomach. Alternatives for intolerance include voriconazole, posaconazole, and isavuconazole, with limited data, and fluconazole 400 to 800 mg daily is less active.
| Group | Outcome |
|---|---|
| Treated immunocompetent hosts | Mortality of about 4 to 8 percent, with a good response in more than 90 percent |
| Acute respiratory distress syndrome | Mortality of 50 to 89 percent |
| Immunosuppressed hosts | Mortality of 30 to 40 percent |
| Central nervous system disease | Mortality up to 40 percent in some series, and relapse is frequent |
| Relapse | Up to 10 to 15 percent when therapy is shorter than recommended, and bone disease needs longer courses |
No vaccine is available. Avoidance of exposure in endemic areas is difficult, and use of respirators during soil excavation and waterway work is reasonable, together with attention to clusters of cases and early recognition in doctors working in endemic regions. Delay of diagnosis is the main modifiable cause of harm, and suspicion arises for pneumonia that does not respond to antibacterials in a person exposed to soil or water in an endemic region.
