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Blastomycosis
OVERVIEW: An uncommon, systemic, fungal infection with a broad range of manifestations including pulmonary, skin, bone and genitourinary involvement
System(s) affected: Skin/Exocrine, Pulmonary, Musculoskeletal, Renal/Urologic, Endocrine/Metabolic
Genetics: N/A
Incidence/Prevalence in USA: Ranges from 0.4-4 cases per 100,000 population per year. Higher prevalence in states bordering the Mississippi and Ohio Rivers. Sporadic cases occurring in other areas.
Predominant age: Adults, but 10-20% of cases occur in children
Predominant sex: Male > Female
SIGNS AND SYMPTOMS: • Acute infection
• Onset may be abrupt or insidious
• May be asymptomatic and self-limiting
• Incubation period 30-45 days
• Fever, chills, myalgias, arthralgias
• Cough initially nonproductive, then productive
• Hemoptysis (common)
• Erythema nodosum
• Pulmonary blastomycosis
• 60-90% of cases
• Three forms - acute, chronic, asymptomatic
• Cough - nonproductive to productive
• Hemoptysis
• Weight loss
• Pleuritic chest pain
• Pleural effusions - 10%
• Respiratory failure in small percentage
• Upper lobe fibronodular infiltrates - 50%
• Mass lesion - 30%
• Diffuse pulmonary infiltrates; cavitation (uncommon)
• Pleural thickening
• Cutaneous blastomycosis
• Most common extrapulmonary manifestation - 40-80%
• May occur with or without pulmonary disease
• Two types of lesions
• Verrucous lesions begin as small papulopustular lesions, slowly spread, become crusted, have sharp borders; central clearing with scar formation and depigmentation; microabscesses noted at periphery of lesion
• Ulcerative lesions (initially pustules) form shallow ulcers with raised edges and granulating base
• Mucosal lesions may occur
• Regional adenopathy (uncommon)
• Subcutaneous nodules - cold abscesses
• Skeletal blastomycosis
• Occurs 25-50% of extrapulmonary cases
• Long bones, vertebrae, ribs most commonly involved
• Well circumscribed osteolytic lesions
• May present with contiguous soft tissue abscesses and/or sinus tracts
• Paraspinous abscess may occur in vertebral disease
• Acute or chronic arthritis may result from extension of contiguous osteomyelitis
• Genitourinary blastomycosis
• Occurs in 10-30% of cases
• Involves prostate most commonly but also epididymis and testes
• Outflow obstruction
• Enlarged tender prostate
• Involvement of female genitalia uncommon and usually acquired through sexual contact
• Other
• Central nervous system involvement with acute or chronic meningitis, epidural or cerebral abscesses
• Liver, spleen, pericardium, thyroid, gastrointestinal tract, adrenal gland may each be involved
CAUSES: • Inhalation of spores of Blastomyces dermatitidis into lung with spread to other organ systems by lymphohematogenous dissemination
• Primary inoculation of skin may rarely occur
• Female genital infection may result from sexual transmission
• Reactivation of previous infection may occur in immunocompromised patients including those with AIDS
RISK FACTORS: • Occupational or recreational exposure to soil containing spores of B. dermatitidis
• Residence in areas of increased disease prevalence
• Rarely associated with AIDS
DIAGNOSIS DIFFERENTIAL DIAGNOSIS: • Pulmonary - acute bacterial pneumonia, tuberculosis, other fungal diseases, bacterial lung abscess, empyema, bronchogenic carcinoma
• Cutaneous - bacterial pyoderma, cutaneous mycobacterial infection, other cutaneous fungal infections (sporotrichosis, histoplasmosis, cryptococcosis), squamous cell carcinoma
• Bone - bacterial osteomyelitis, tuberculosis, neoplastic disease
• Genitourinary - bacterial prostatitis, prostate cancer, other fungal infections, tuberculosis
LABORATORY: • Culture of B. dermatitidis from tissue or body secretions on Sabouraud's or other enriched media
• Demonstration of yeast forms (5-15 micrometers in diameter, with refractile cell wall, broad-based budding and no capsule) in tissue or body secretions by wet mount or special stains
• Serologic tests include complement fixation, enzyme-linked immunoassay, immunodiffusion precipitin antibody tests. All have variable sensitivity and low specificity and are not helpful in diagnosis.
• Delayed hypersensitivity skin testing with blastomycin also has low sensitivity and specificity and not useful in diagnosis
Drugs that may alter lab results: N/A
Disorders that may alter lab results: Histoplasma cross-reacts with serologic tests for blastomycosis
PATHOLOGICAL FINDINGS: • Early inflammatory response with polymorphonuclear leukocytes followed by granuloma formation with lymphocytes and macrophages
• Granulomas do not show caseation necrosis
• Yeast is often found attached to or inside monocytes, macrophages and giant cells
SPECIAL TESTS: • Special staining of tissue with Gomori methenamine silver stain
• Periodic acid-Schiff's stain colors cell wall pink or red
• Mucicarmine stain helps differentiate from encapsulated Cryptococcus
IMAGING: • CT scan of head for CNS lesions
• CT scan of spine for vertebral lesions
• Bone scan for skeletal lesions
• Chest x-ray may show upper lobe fibronodular infiltrates, consolidation, diffuse alveolar infiltrates, mass lesions or pleural thickening
DIAGNOSTIC PROCEDURES: • Aspiration of abscess contents for wet mount and culture
• Needle or surgical biopsy of involved tissue
TREATMENT APPROPRIATE HEALTH CARE: • Acute pulmonary blastomycosis may be treated with oral itraconazole as an outpatient
• Chronic blastomycosis, overwhelming pneumonia, or extrapulmonary disease should be treated initially with intravenous amphotericin B as a hospital patient
GENERAL MEASURES: • Systemic antifungal therapy is indicated for all cases of extrapulmonary blastomycosis
• Systemic antifungal therapy is indicated for all but the very mild or asymptomatic pulmonary cases in which a trial of observation may be appropriate
SURGICAL MEASURES: • Surgical debridement of bone lesions if there are areas of devitalized bone
• Surgical drainage of large cutaneous abscesses or pleural empyemas
ACTIVITY: No restrictions, once patient is released from hospital
DIET: No special dietary requirement
PATIENT EDUCATION: Counsel patient and family on potential adverse effects associated with antifungal therapy, duration of therapy required and potential for relapse or chronic infection
MEDICATIONS DRUG(S) OF CHOICE: • Milder forms
• Itraconazole (Sporanox) 200 mg po twice a day for at least 6 months
• Bioavailability enhanced when taken with food
• Antacids or H2 blockers result in lower serum level
• Very little drug excreted in urine; GU disease more resistant to therapy
• Severe forms
• Amphotericin B (Fungizone): 0.5-0.8 mg/kg IV over 4-6 hours daily for a cumulative dose of 1.5-2 gm
• First dose of amphotericin B is given as a test dose of 1 mg in 200 mL dextrose 5% in sterile water intravenously over 2-4 hours
• Dose is increased by 10 mg daily until a maintenance dose of 0.5 mg-0.8 mg per kg per day is reached. Slow escalation is not appropriate for severe blastomycosis. Full dose can be given on 1st or 2nd day of treatment.
• Rigors can be prevented by pre-infusion dose of meperidine 50 mg
• To reduce infusion-related fever, pre-infusion acetaminophen and diphenhydramine
Contraindications: Life threatening intolerance to amphotericin such as anaphylaxis
Precautions:
• Monitor for hypotension during the infusion
• Monitor renal function, serum sodium, potassium and magnesium, and CBC twice weekly during therapy
• Replace potassium and magnesium as indicated
• When serum creatinine rises to 1.6 mg/dL (141 µmol/L) or greater, dosage interval should be changed to 48 hours
• Watch for phlebitis at infusion site
Significant possible interactions:
• Avoid use of potentially nephrotoxic drugs such as aminoglycosides which may potentiate nephrotoxicity of amphotericin B
• Itraconazole - concurrent use of rifampin, phenytoin or carbamazepine may increase hepatic metabolism resulting in lower serum drug levels and treatment failure
ALTERNATIVE DRUGS: Efficacy of alternate regimens not well established by controlled studies
• Fluconazole 400 mg daily for 6 months for non-life-threatening blastomycosis
• Ketoconazole (Nizoral): 400-800 mg po daily for 6 months
• Lipid preparations of amphotericin B have not been adequately evaluated in human blastomycosis; they may provide an alternative for selected patients unable to tolerate standard amphotericin B
FOLLOW UP PATIENT MONITORING: • Monitor closely during early therapy
• Frequency of followup depends on severity of disease
• Monitor serum electrolytes, creatinine and CBC twice weekly during amphotericin B therapy
• Post-therapy followup every 3 months for 2 years then twice yearly
PREVENTION/AVOIDANCE: • Unknown
• Condoms for sexual encounters
POSSIBLE COMPLICATIONS: Treatment-induced nephrotoxicity, electrolyte imbalance, anemia
EXPECTED COURSE AND PROGNOSIS: • Cure in over 90% with appropriate therapy
• Relapse in less than 10% of cases
• Relapse rate higher with ketoconazole therapy
• Adverse reactions with amphotericin B are frequent and significant
MISCELLANEOUS ASSOCIATED CONDITIONS: N/A
AGE-RELATED FACTORS:
Pediatric: Uncommon in children
Geriatric: Prognosis is worse in elderly patients with significant underlying pulmonary or renal disease
Others: N/A
PREGNANCY: Safety of amphotericin B and ketoconazole in pregnancy has not been established
SYNONYMS: North American blastomycosis
ICD-9-CM: 116.0 Blastomycosis
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