BLASTOMYCOSIS

BLASTOMYCOSIS - William G.Gardner, MD, MACP
BASICS
DESCRIPTION
• An uncommon, systemic infection caused by the dimorphic fungus Blastomyces dermatitidis
• System(s) Affected: Pulmonary; Skin/subcutaneous; Bone/joint; Genitourinary; Central nervous system (CNS)
• Synonym(s): North American blastomycosis
ALERT
Geriatric Considerations
Prognosis is worse in elderly patients with significant underlying pulmonary or renal disease.
Pediatric Considerations
Uncommon in children
Pregnancy Considerations
• Amphotericin B is drug of choice
• Azoles should not be used during pregnancy.
GENERAL PREVENTION
• Unknown
• Condoms for sexual encounters
EPIDEMIOLOGY
• Incompletely understood
• Predominant age: Adults, but 10-20% of cases in children in endemic areas
• Predominant sex: Male > Female
Incidence
Ranges from 0.3-1.5 cases per 100,000 population per year
Prevalence
Higher prevalence in endemic areas
• Midwestern, Southcentral US, Great Lakes region of US and Canada
• Large outbreak occurred in Wisconsin
• Sporadic cases around the world
RISK FACTORS
• Occupational or recreational exposure to soil containing spores of Blastomyces dermatitidis
• Residence in endemic areas
• HIV/AIDS or other immunocompromised states (corticosteroids, blood malignancies)
Genetics
No genetic predisposition known
ETIOLOGY
• Infection acquired by respiratory route
• Inhalation of spores of Blastomyces dermatitidis into lungs with lymphohematogenous dissemination to other organ systems
• Primary inoculation of skin may occur rarely.
• Female infection results from sexual contact.
• Reactivation of latent infection or reinfection may occur in immunocompromised patients
ASSOCIATED CONDITIONS
• Most infected persons have no predisposing conditions
• Occasionally occurs in HIV-infected or immunocompromised persons


DIAGNOSIS
SIGNS AND SYMPTOMS
• Acute pulmonary infection
- Onset may be abrupt or insidious
- Incubation period 30-45 days
- Presents as a non-specific flu-like illness
- Fever, chills, myalgias, arthralgias
- Cough nonproductive
- Often self-limiting
- Severe disease and respiratory failure occurs in 10% of cases
• Chronic pulmonary infection
- Chronic pneumonia, indolent onset
- Weight loss, fever, night sweats
- Productive cough, purulent sputum
- Hemoptysis uncommon
- May mimic tuberculosis, other fungal pneumonias, and cancer
• Cutaneous blastomycosis
- Most common extrapulmonary type: 80%
- May occur with or without pulmonary disease
- 2 types of lesions
 Verrucous lesions begin as small papulopustular lesions, become crusted, and have sharp borders, central clearing, scar formation, depigmentation, and microabscesses at periphery.
 Ulcerative lesions (initially pustules) form shallow ulcers with raised edges and granulating base.
- May be mistaken for pyoderma gangrenosum, squamous cell carcinoma, and other chronic infectious lesions (e.g., Sporotrichosis, atypical mycobacteria)
- SC nodules may suppurate forming chronic ulcers.
- Regional adenopathy (uncommon)
• Skeletal blastomycosis
- 10-50% of extrapulmonary cases
- Long bones, vertebrae, ribs, cranium most commonly involved
- Well-circumscribed osteolytic lesions
- May present with contiguous soft tissue abscesses and/or sinus tracts
- Paraspinous abscess in vertebral disease
- Acute or chronic arthritis may result from joint involvement, usually large joints.
• Genitourinary blastomycosis
- Occurs in 10-30% of cases
- Involves prostate, epididymis, and testes
- Enlarged, tender prostate
- May cause outflow obstruction
- Involvement of female genitalia uncommon but can be acquired through sexual contact
• Other
- CNS involvement with acute or chronic meningitis, epidural or cerebral abscesses: More common in AIDS
- Liver, spleen, pericardium, thyroid, gastrointestinal tract, and adrenal gland involved
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
Lab
• Culture of Blastomyces dermatitidis from tissue or body secretions on Sabouraud's media
- Slow growing
- Identify by highly specific DNA probes
• Yeast forms (5-15 um in diameter, with refractile cell wall, broad-based budding, and no capsule) in tissue or secretions by wet mount
• In pulmonary disease, potassium hydroxide prep of sputum reveals organism in >50%
• Serologic tests have variable sensitivity and low specificity and are not helpful in the diagnosis.
• Skin testing with Blastomycin is not useful.
• Disorders that alter lab results: Lidocaine inhibits growth in bronchoscopic cultures.
Imaging
• CT scan of head for CNS lesions
• CT scan or MRI of spine for vertebral lesions
• Bone scan for skeletal lesions
• Chest x-ray
- Acute pulmonary disease
 Alveolar or interstitial infiltrates
- Chronic pulmonary disease
 Upper lobe fibronodular infiltrates in 50%
 Mass lesions in 30%
 Pulmonary nodules  without cavitation
 Pleural effusion in 10%
 Mediastinal adenopathy in 20%
Diagnostic Procedures/Surgery
• Aspiration of abscess for wet mount and culture
• Needle or surgical biopsy of involved tissue for histology and culture
Pathological Findings
• Early 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.
DIFFERENTIAL DIAGNOSIS
• Pulmonary
- Acute bacterial pneumonia
- Tuberculosis
- Other fungal diseases
- Bacterial lung abscess
- Empyema
- Bronchogenic carcinoma
• Cutaneous
- Pyoderma gangrenosum
- Bacterial pyoderma
- Cutaneous mycobacterial infection
- Other cutaneous fungal infections (sporotrichosis, histoplasmosis, or ocryptococcosis)
- Squamous cell carcinoma
• Bone
- Bacterial osteomyelitis
- Tuberculosis
- Neoplastic disease
• Genitourinary
- Bacterial prostatitis
- Prostate cancer
- Other fungal infections
- Tuberculosis
TREATMENT
STABILIZATION
• Acute non-life-threatening pulmonary infection may be treated with itraconazole as an outpatient.
• Severe life-threatening infection, CNS disease, or disease in immunocompromised host should be treated initially with intravenous amphotericin B in the hospital.
GENERAL MEASURES
• Systemic antifungal therapy is indicated for all cases of extrapulmonary blastomycosis.
• Systemic antifungal therapy is indicated for all but very mild or asymptomatic pulmonary cases, in which a trial of observation may be appropriate.
Activity
No restrictions after patient is released from hospital
Nursing
Routine care
MEDICATION (DRUGS)
First Line
• Milder forms
- Itraconazole (Sporanox): 200 mg PO b.i.d. for at least 6 months. Take with food; antacids or hydrogen blockers result in lower serum levels. Little drug is excreted in urine; thus genitourinary disease is more resistant to therapy.
- Pediatrics: Non-life-threatening disease treat with itraconazole 5-7 mg/kg/d. Life-threatening or CNS disease treat with amphotericin B.
• Severe forms
- Amphotericin B (Fungizone): 0.5-0.8 mg/kg IV over 4-6 hours daily for a cumulative dose of 1.5-2.5 g (1st dose of amphotericin B is given as a test dose of 1 mg in 200 mL 5% dextrose in sterile water IV over 2-4 hours). If tolerated, give maintenance dose of 0.5-0.8 mg/kg/d. Rigors can be prevented by preinfusion dose of meperidine 50 mg. To reduce infusion-related fever, preinfusion acetaminophen and diphenhydramine.
• Contraindications
- Life-threatening intolerance to amphotericin such as anaphylaxis
- CNS disease: Amphotericin B (total dose 2 g); alternative fluconazole 800 mg/d because of good CNS penetration
• Precautions
- Monitor for hypotension during the infusion.
- Monitor renal function, serum sodium, potassium, and magnesium, complete blood count twice weekly
- Replace potassium and magnesium prn.
- When serum creatinine rises to 1.6 mg/dL (141 umol/L) or greater, dosage interval should be changed to 48 hours.
- Watch for phlebitis at infusion site.
- Consider peripherally inserted central catheter for infusion.
• 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.
Second Line
• Efficacy of alternative 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 provide an alternative for patients unable to tolerate amphotericin B.
SURGERY
• Surgical debridement of bone lesions if there are areas of devitalized bone
• Surgical drainage of contiguous abscesses, cutaneous abscesses, or pleural empyema
FOLLOW-UP
DISPOSITION
Specialty referral
• Immunocompromised or HIV patients
• Severe pulmonary disease
• Deep abscesses
• Children
Admission Criteria
• Severe pulmonary disease
• Immunocompromised or AIDS patient with severe disease
Discharge Criteria
Clinically stable and responding to therapy
Issues for Referral
Follow-up with infectious diseases physician and primary care physician.
PROGNOSIS
• Cure in >90% with appropriate therapy
• Relapse in 10% of cases
• Immunocompromised and AIDS patients have a poorer prognosis
COMPLICATIONS
• Adverse reactions with amphotericin B are frequent and significant.
• Treatment-induced nephrotoxicity, electrolyte imbalance, and anemia
PATIENT MONITORING
• Monitor closely during early therapy.
• Monitor serum electrolytes, creatinine, and CBC twice weekly during amphotericin B therapy.
• Post-therapy follow-up every 3 months for 2 years, then twice yearly
REFERENCES
1. Chapman SW, et al. Practice guidelines for the management of patients with blastomycosis. Clin Infect Dis. 2000;30:679-683.
2. Pappas PG. Blastomycosis. Sem Resp Crit Care M. 2004;25:113-120.
3. Patel RG, et al. Clinical presentation, radiographic findings, and diagnostic methods of pulmonary blastomycosis: A review of 100 consecutive cases. South Med J. 1999;92:289-295.
4. Crampton TL, et al. Epidemiology and clinical spectrum of blastomycosis diagnosed at Manitoba hospitals. Clin Infect Dis. 2002;34:1310-1316.