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Blastomycosis

Description of Medical Condition

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

Blastomycosis

Medical Symptoms and Signs of Disease

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

  • Three forms — acute, chronic, asymptomatic
  • Acute form presents as nonspecific, flu-like illness
  • Chronic pneumonia in 60-90% of patients with proven disease
  • 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%
  • Cavitary lesions, nodular infiltrates, mass-like lesions are frequent in chronic pulmonary disease
  • 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
  • May be mistaken for pyoderma gangrenosum or squamous cell carcinoma
  • Mucosal lesions may occur
  • Regional adenopathy (uncommon)
  • Subcutaneous nodules — cold abscesses

Skeletal blastomycosis

  • Occurs in 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
  • Joint involvement (usually large joints) — knees, ankles, hips

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: more common in AIDS
  • Liver, spleen, pericardium, thyroid, gastrointestinal tract, adrenal gland may each be involved

What Causes Disease?

  • 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 im-munocompromised 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
  • Long-term corticosteroids, hematologic malignancies

Diagnosis of Disease

Differential Diagnosis

  • Pulmonary — acute bacterial pneumonia, tuberculosis, other fungal diseases, bacterial lung abscess, empy-ema, bronchogenic carcinoma
  • Cutaneous — bacterial pyoderma, cutaneous mycobac-terial infection, other cutaneous fungal infections (spo-rotrichosis, 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 retractile cell wall, broad-based budding and no capsule) in tissue or body secretions by wet mount or special stains
  • In pulmonary disease, KOH prep of sputum reveals organism 50-70% of time
  • 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 (Medical Therapy)

Appropriate Health Care

  • Acute non-life-threatening pulmonary infection may be treated with oral itraconazole as an outpatient
  • Severe life threatening infection, central nervous system 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 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 (Drugs, Medicines)

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
  • CNS disease
    • Amphotericin B: total dose 2 gm
    • Alternative to amphotericin B — fluconazole 800 mg/d because of good CNS penetration

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 /jmol/L) or greater, dosage interval should be changed to 48 hours
  • Watch for phlebitis at infusion site
  • Consider peripherally inserted central catheter (PICC) 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

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

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 / 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

Pregnancy

  • Amphotericin B is drug of choice
  • Azoles should not be used in pregnancy

Synonyms

North American blastomycosis

International Classification of Diseases

116.0 Blastomycosis

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