Disseminated blastomycosis is a systemic pyogranulomatous infection caused by the dimorphic fungus Blastomyces dermatitidis (and related species), occurring when pulmonary infection spreads hematogenously to extrapulmonary sites — most commonly skin, bones/joints, genitourinary tract, and CNS. [1-3] It affects 25–40% of infected individuals and occurs in both immunocompetent and immunocompromised hosts. [3-4]
1. History
- Key HPI questions: Cough (productive or dry), dyspnea, chest pain, fevers, night sweats, weight loss, skin lesions (nodular, verrucous, or ulcerative), bone/joint pain, dysuria, headache, confusion
- Timing: Incubation period 30–45 days after exposure; chronic presentations may evolve over weeks to months [3]
- Triggers: Occupational or recreational exposure to moist soil, decaying vegetation near waterways (rivers, lakes) [3]
- Progression: Pulmonary symptoms often precede extrapulmonary manifestations; skin lesions may evolve from pustules to verrucous plaques [5]
- Important negatives: No response to empiric antibiotics for CAP is a critical clue — diagnostic delays are common and often exceed 1 month [6]
2. Alarm Features
- Hypoxic respiratory failure / ARDS — mortality 40–75% when mechanical ventilation is required [7-8]
- CNS involvement: Headache, confusion, focal neurological deficits, seizures (occurs in <5% of immunocompetent but up to 40% of AIDS patients) [3][9]
- Rapidly progressive multilobar pneumonia with diffuse infiltrates
- Hemodynamic instability requiring vasopressors (84% of ARDS cases in one series) [10]
- Immunocompromised state (SOT recipients, HIV/AIDS) — associated with significantly higher severity, respiratory failure, and mortality [4]
- Renal failure requiring RRT — independently associated with in-hospital mortality [11]
3. Medications
- Severe/disseminated disease (IDSA):
- Liposomal amphotericin B (L-AmB) 3–5 mg/kg/dayitraconazole 200 mg TID × 3 days → 200 mg BID[3]
- Mild-to-moderate disseminated disease (non-CNS):
- Itraconazole 200 mg TID × 3 days → 200 mg daily-BID[3]
- CNS blastomycosis:
- L-AmB 5 mg/kg/day × 4–6 weeks, then oral azole (fluconazole 800 mg/day, voriconazole 200–400 mg BID, or itraconazole 200 mg BID-TID) for ≥12 months until CSF normalization [3][9]
- Voriconazole preferred for step-down given superior CNS penetration and intrinsic activity [9][12]
- Alternatives for itraconazole intolerance: Fluconazole 400–800 mg/day (less effective), voriconazole, posaconazole, isavuconazole (limited data) [3][13]
- Contraindicated/cautions: Ketoconazole (more toxic, rarely used); monitor itraconazole serum levels at 2 weeks to ensure adequate exposure; significant drug interactions with itraconazole (CYP3A4) [3]
- ARDS: L-AmB is mainstay; corticosteroids used at some centers but no evidence of benefit; consider AmB deoxycholate continuous infusion if poor response to L-AmB; ECMO for refractory cases [10][14]
4. Diet
- No specific dietary triggers or restrictions
- Ensure adequate hydration and nutrition, particularly during prolonged antifungal therapy
- Monitor for hepatotoxicity with azole therapy — avoid excessive alcohol
5. Review of Systems
- Pulmonary: Cough, hemoptysis, dyspnea, pleuritic chest pain
- Dermatologic: New skin nodules, verrucous or ulcerative plaques, draining lesions (especially face, extremities)
- Musculoskeletal: Bone pain, joint swelling, back pain (vertebral involvement)
- Genitourinary: Dysuria, urinary retention, scrotal swelling/pain (prostatitis, epididymitis) [15-17]
- Neurologic: Headache, confusion, vision changes, focal deficits, seizures
- Constitutional: Fevers, night sweats, weight loss, fatigue
6. Collateral History and Family History
- Geographic exposure: Residence in or travel to endemic areas — Great Lakes region, Ohio/Mississippi River valleys, southeastern US, parts of Canada [3]
- Occupational/recreational history: Farming, construction, excavation, hunting, fishing, camping near waterways [3]
- Animal exposure: Dogs are commonly co-infected and may serve as sentinel hosts
- Household contacts: Point-source outbreaks have been documented (e.g., paper mill outbreak with 131 cases) [18]
- No hereditary predisposition — blastomycosis is not a familial condition
7. Risk Factors
- Geographic: Endemic regions (midwestern, southeastern, south central US; Canadian Great Lakes provinces) [3]
- Environmental: Exposure to moist soil, decaying vegetation near waterways [3]
- Immunosuppression: SOT recipients (18-fold higher incidence), HIV/AIDS, malignancy, immunosuppressive medications [4]
- Diabetes mellitus — associated with increased hospitalization risk [18]
- Male sex — more commonly affected due to occupational exposures [19]
- Age: Advanced age associated with increased mortality [3]
- Comorbidities: COPD, cancer, African American ethnicity associated with increased mortality [3]
8. Differential Diagnosis
Blastomycosis is called "the great mimicker": [19]
- Bacterial community-acquired pneumonia — most common initial misdiagnosis; failure to improve on antibiotics is a key distinguishing feature [6]
- Tuberculosis — chronic cough, upper lobe cavitary disease, weight loss; AFB smear/culture and TB PCR differentiate [19-20]
- Lung malignancy — mass-like consolidations on imaging can mimic bronchogenic carcinoma; PET may show hypermetabolic lesions in both [21-22]
- Other endemic mycoses: Histoplasmosis (smaller yeast, more lymphadenopathy), coccidioidomycosis (geographic distinction), paracoccidioidomycosis (pilot-wheel yeast)
- Cutaneous malignancy — verrucous skin lesions can mimic squamous cell carcinoma [19]
- Sarcoidosis — granulomatous disease with multiorgan involvement
- Nocardiosis — pulmonary + skin + CNS involvement in immunocompromised
9. Past Medical History
- Prior blastomycosis episodes (relapse rate 5–8%) [4]
- Immunosuppressive conditions: SOT, HIV/AIDS, hematologic malignancy, chronic corticosteroid use
- Diabetes mellitus
- COPD
- Prior residence in or travel to endemic areas
10. Physical Exam
- Vitals: Fever, tachycardia, tachypnea, hypoxia (SpO₂ monitoring critical)
- Pulmonary: Crackles, decreased breath sounds, signs of consolidation or effusion (effusion is uncommon) [22-23]
- Skin: Verrucous plaques, papulopustular lesions, ulcerative nodules — often on face and extremities; may mimic malignancy [5][19]
- Musculoskeletal: Joint effusion, tenderness over affected bones (vertebrae, ribs, long bones) [24]
- Neurologic: Meningismus, focal deficits, altered mental status (if CNS involvement)
- GU (males): Tender/boggy prostate on DRE, epididymal swelling [16-17]
- Lymphadenopathy: Uncommon in blastomycosis (unlike histoplasmosis)
11. Lab Studies
- Blastomyces urine antigen — sensitivity ~76–93%, preferred specimen; cross-reacts with histoplasmosis [25]
- Serum Blastomyces antigen — sensitivity ~56%; useful adjunct [25]
- Serum BAD-1 IgG antibody (EIA) — sensitivity 50% overall (80% in chronic non-immunocompromised); lower in acute disease and immunocompromised [26]
- Fungal culture — gold standard; sputum sensitivity ~86%, bronchial washings ~100%; takes up to 6 weeks [3][13]
- Direct visualization — KOH prep or calcofluor white showing large (8–15 μm) thick-walled yeast with broad-based budding is pathognomonic; sensitivity 50–90% [1][3]
- Histopathology — GMS or PAS staining of tissue biopsies (skin, bone, lung)
- Baseline labs: CBC, CMP (renal/hepatic function for antifungal dosing), LFTs, HIV testing
- CSF analysis if CNS involvement suspected — cell count, protein, glucose, fungal culture, antigen
- Itraconazole serum levels — check at ≥2 weeks; target trough >1 μg/mL [3]
The ATS recommends using more than one diagnostic test given that no single test has sufficient sensitivity in isolation. [25]
12. Imaging
- Chest radiograph — required for all patients; findings include alveolar infiltrates, mass-like consolidations, fibronodular infiltrates, miliary pattern [13][22]
- CT chest — better characterizes extent; upper lobe nodules with airspace consolidation raise suspicion for fungal disease; cavitation possible; lymphadenopathy and calcification are uncommon [22]
- MRI brain — superior to CT for CNS blastomycosis; may show mass lesions, abscesses, meningeal enhancement [9][12][27]
- Bone imaging — CT or MRI for suspected osteoarticular disease (vertebrae, ribs, long bones)
- FDG-PET/CT — emerging role for staging disseminated disease; can identify clinically unsuspected foci of infection but may mimic metastatic malignancy [21][28]
- Imaging is unnecessary for isolated mild pulmonary disease that has already resolved clinically
13. Special Tests
- Bronchoscopy with BAL — indicated when sputum is non-diagnostic; culture and cytology; antigen testing on BAL fluid [25]
- Skin biopsy — high diagnostic yield for cutaneous lesions; send for culture, GMS/PAS staining [24]
- Bone/joint aspiration — culture of synovial fluid or bone biopsy for osteoarticular disease
- Lumbar puncture — if CNS involvement suspected; CSF fungal culture, antigen, cell count
- PCR for Blastomyces — emerging but not yet widely available [25]
- No validated clinical scoring system specific to blastomycosis severity
14. ECG
- Not routinely indicated unless hemodynamically unstable or septic
- Monitor for QTc prolongation with azole antifungals (particularly voriconazole, fluconazole)
- Baseline ECG recommended before initiating azole therapy in patients with cardiac risk factors
15. Assessment
- Overall pooled mortality: ~6.6%; rises to 37% in immunocompromised and 75% with ARDS [8]
- Mechanical ventilation mortality: ~40% (16-fold higher than non-ventilated patients) [7]
- ICU admission rate: ~35% among hospitalized patients [11]
- Case fatality rate: 4.3–6.4% overall; 33–38% in SOT recipients [23]
- Dissemination rate is similar across immunologic spectrum (~25–40%), suggesting pathogen-related factors drive dissemination more than host immunity [4]
- Diagnostic delays are common and contribute to morbidity — median delay often exceeds 1 month [6]
- Osteoarticular disease is more difficult to treat and more prone to relapse [3]
16. Treatment Plan
Initial stabilization (ED/ICU)
- ABCs, supplemental O₂, IV access, hemodynamic monitoring
- For severe disease/ARDS: intubation and lung-protective ventilation as needed; vasopressors for shock
Antifungal therapy (per IDSA guidelines): [3]
Additional considerations
- Corticosteroids for ARDS: used at some centers but no proven mortality benefit; clinical judgment should guide use [10][13]
- ECMO: consider for refractory ARDS — all 4 patients treated with ECMO survived in one series [10]
- AmB deoxycholate continuous infusion: consider if poor response to L-AmB [14]
17. Disposition
- Admit (ICU): ARDS, respiratory failure, hemodynamic instability, CNS involvement, multiorgan dysfunction
- Admit (floor): Moderate-severe disseminated disease requiring IV amphotericin B, significant hypoxia, inability to tolerate oral medications
- Observation: Mild disseminated disease with stable vitals pending diagnostic confirmation
- Outpatient management: Mild-to-moderate disease in stable, reliable patients who can tolerate oral itraconazole with close follow-up
- Infectious disease consultation — recommended for all cases of disseminated blastomycosis [3]
- Neurosurgery consultation — for CNS mass lesions or epidural abscesses requiring drainage [3]
18. Follow Up / Return Precautions
- Follow-up timing: Infectious disease follow-up within 1–2 weeks of discharge; itraconazole serum level at ≥2 weeks [3]
- Monitoring: Serial urine antigen levels to assess treatment response; LFTs every 1–3 months on azole therapy; chest imaging to document resolution
- Treatment duration: Continue therapy for several months beyond clinical and radiographic resolution [3]
- Relapse rate: 5–8% overall; higher with osteoarticular and CNS disease [3-4]
- Return precautions — instruct patients to return immediately for:
- Worsening shortness of breath or new oxygen requirement
- New or worsening skin lesions
- Headache, confusion, vision changes, or focal weakness
- New bone/joint pain or swelling
- Fever not improving after 48–72 hours of therapy
- Expected recovery: Clinical improvement typically within 1–2 weeks of appropriate antifungal therapy; skin lesions may take weeks to months to resolve; complete treatment course is essential to prevent relapse
References
1. Blastomycosis. — Zhou S, Kauffman CA, Miceli MH. Infectious Disease Clinics of North America. 2025.
2. Blastomycosis. — Schwartz IS, Kauffman CA. Seminars in Respiratory and Critical Care Medicine. 2020.
3. Clinical Practice Guidelines for the Management of Blastomycosis: 2008 Update by the Infectious Diseases Society of America. — Chapman SW, Dismukes WE, Proia LA, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2008.
4. Clinical Manifestations and Outcomes in Immunocompetent and Immunocompromised Patients With Blastomycosis. — McBride JA, Sterkel AK, Matkovic E, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2021.
5. Disseminated Blastomycosis in an Immunocompetent Patient. — Cheng C, Blackburn R. Journal of General Internal Medicine. 2024.
6. Blastomycosis, Histoplasmosis, and Coccidioidomycosis in Outpatient Community-Acquired Pneumonia. — Benedict K, Thompson GR, Ampel NM, et al. JAMA Network Open. 2026.
7. Outcomes With Severe Blastomycosis and Respiratory Failure in the United States. — Rush B, Lother S, Paunovic B, Mooney O, Kumar A. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2021.
8. Mortality Associated With Blastomyces Dermatitidis Infection: A Systematic Review of the Literature and Meta-Analysis. — Carignan A, Denis M, Abou Chakra CN. Medical Mycology. 2020.
9. Blastomycosis of the Central Nervous System: A Multicenter Review of Diagnosis and Treatment in the Modern Era. — Bariola JR, Perry P, Pappas PG, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2010.
10. Management and Outcomes of Acute Respiratory Distress Syndrome Caused by Blastomycosis: A Retrospective Case Series. — Schwartz IS, Embil JM, Sharma A, Goulet S, Light RB. Medicine. 2016.
11. Intensive Care Unit and Hospital Outcomes of Patients Admitted With Blastomycosis: A 14-Year Retrospective Study. — Ahluwalia V, Almodallal Y, Alkurashi AK, et al. Lung. 2022.
12. Central Nervous System Blastomycosis Clinical Characteristics and Outcomes. — Majdick K, Kaye K, Shorman MA. Medical Mycology. 2021.
13. Global Guideline for the Diagnosis and Management of the Endemic Mycoses: An Initiative of the European Confederation of Medical Mycology in Cooperation With the International Society for Human and Animal Mycology. — Thompson GR, Le T, Chindamporn A, et al. The Lancet. Infectious Diseases. 2021.
14. Radical Treatment for Blastomycosis Following Unsuccessful Liposomal Amphotericin. — Chew C, Thapa N, Ogbuagu H, et al. The Lancet. Infectious Diseases. 2022.
15. Blastomycosis. — Bradsher RW. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 1992.
16. Blastomycosis of the Epididymis and Prostate. — Seo R, Oyasu R, Schaeffer A. Urology. 1997.
17. Blastomycosis of the Genitourinary Tract. — Eickenberg H-U, Amin M, Lich R. The Journal of Urology. 1975.
18. Epidemiological and Clinical Features of a Large Blastomycosis Outbreak at a Paper Mill in Michigan. — Hennessee I, Palmer S, Reik R, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2025.
19. Clinical and Laboratory Update on Blastomycosis. — Saccente M, Woods GL. Clinical Microbiology Reviews. 2010.
20. Disseminated Blastomycosis Mimicking Tuberculosis, China. — Guo C, Pan Y, Yu J, et al. Emerging Infectious Diseases. 2025.
21. Disseminated Blastomycosis Mimicking Metastatic Head and Neck Cancer in a 70-Year-Old Man. — Braman BC, Amin K, Khaja SF. The Laryngoscope. 2023.
22. Imaging Manifestations of Blastomycosis: A Pulmonary Infection With Potential Dissemination. — Fang W, Washington L, Kumar N. Radiographics : A Review Publication of the Radiological Society of North America, Inc. 2007.
23. Disseminated Blastomycosis in a Teenager Presenting With Pleural Effusion and Splenomegaly. — Teijido J, Drendel AL. The Journal of Emergency Medicine. 2019.
24. Cutaneous Clues to a Fungal Culprit: Disseminated Blastomycosis Presenting as Inflammatory Monoarthritis - A Case Report. — Ssentongo P, Akhtar S, Perciuleac Z, et al. Frontiers in Medicine. 2025.
25. Microbiological Laboratory Testing in the Diagnosis of Fungal Infections in Pulmonary and Critical Care Practice. An Official American Thoracic Society Clinical Practice Guideline. — Hage CA, Carmona EM, Epelbaum O, et al. American Journal of Respiratory and Critical Care Medicine. 2019.
26. Role of Blastomyces BAD-1 IgG Enzyme Immunoassay (EIA) for the Diagnosis of Blastomycosis in Persons Residing in an Endemic Area. — Gauthier GM, Hollnagel F, Klein B, et al. Medical Mycology. 2026.
27. Outcomes of Persons With Blastomycosis Involving the Central Nervous System. — Bush JW, Wuerz T, Embil JM, et al. Diagnostic Microbiology and Infectious Disease. 2013.
28. FDG-PET/CT for Effective Staging of Disseminated Blastomycosis. — Lucinian YA, Noorah NB, Maliha PG, Morin MA. Clinical Nuclear Medicine. 2025.
29. Endemic or Regionally Limited Parasitic and Fungal Infections in Haematopoietic Stem-Cell Transplantation Recipients: A Worldwide Network for Blood and Marrow Transplantation (WBMT) Review. — Muhsen IN, Galeano S, Niederwieser D, et al. The Lancet. Haematology. 2023.
30. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. — Constance Benson, John Brooks, Shireesha Dhanireddy, et al Infectious Diseases Society of America; Office of AIDS Research Advisory Council (2025). 2025.