Systemic fungal infections (endemic mycoses)
Systemic mycoses are infections in which fungi enter through the lungs or skin and disseminate to organs such as brain, bone, skin, lymph nodes and adrenal glands. Many are caused by thermally dimorphic fungi that grow as moulds in the environment and convert to yeast or another tissue form in the host. Severity depends on inoculum, immunity, lung structure, pregnancy, HIV, corticosteroids and delayed diagnosis.
A chronic “TB-like” illness that fails TB treatment, especially after soil, bird/bat or agricultural exposure, should trigger fungal investigation.
Learning objectives
- Explain dimorphism, environmental acquisition and pulmonary-to-disseminated spread.
- Recognise histoplasmosis, blastomycosis, coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and other deep mycoses.
- Interpret microscopy, culture, antigen, serology, imaging and biopsy.
- Plan induction, consolidation, maintenance and surgical management with specialist input.
- Identify severe respiratory, CNS, adrenal, mucocutaneous and bone disease.
Important systemic fungi
| Infection | Exposure/organism | Clinical pattern |
|---|---|---|
| Histoplasmosis | Histoplasma capsulatum; soil enriched with bird/bat droppings | Pneumonia, mediastinal disease, chronic cavitation and disseminated reticuloendothelial infection. |
| Blastomycosis | Blastomyces; soil/decaying wood in endemic areas | Pulmonary disease with verrucous skin, bone and genitourinary dissemination. |
| Coccidioidomycosis | Coccidioides; desert dust | Pneumonia, erythema nodosum, meningitis, bone and disseminated skin disease. |
| Paracoccidioidomycosis | Paracoccidioides; rural soil in Latin America | Chronic pulmonary and mucosal disease, lymphadenopathy and adrenal involvement. |
| Sporotrichosis | Sporothrix; thorn/plant inoculation or zoonotic cat exposure | Lymphocutaneous nodules; pulmonary, osteoarticular or disseminated disease in immune compromise. |
Acquisition and pathogenesis
Inhaled conidia reach alveoli, where macrophages and neutrophils attempt containment. Dimorphic conversion at body temperature enables tissue survival. Granulomas may contain organisms for years; reactivation occurs when cellular immunity falls. Dissemination follows lymphatic or haematogenous spread. The lungs, reticuloendothelial system, skin, bone, CNS and adrenal glands are common targets.
Large inoculum, smoking, chronic lung disease, diabetes, HIV, TNF-inhibitor or corticosteroid therapy, transplant, malignancy, malnutrition and pregnancy can shift a mild pulmonary syndrome toward progressive or disseminated disease.
Clinical presentation
Acute pulmonary disease
Fever, dry cough, dyspnoea, chest pain, myalgia, headache and fatigue may follow a shared soil or dust exposure. Chest imaging can show diffuse infiltrates, nodules, hilar/mediastinal adenopathy or focal consolidation.
Chronic pulmonary disease
Weeks to months of cough, weight loss, night sweats, fever, haemoptysis and progressive dyspnoea can mimic tuberculosis, malignancy or bacterial bronchiectasis. Cavities may develop.
Disseminated disease
- Persistent fever, weight loss, hepatosplenomegaly and lymphadenopathy.
- Mucocutaneous ulcers, papules, plaques or verrucous lesions.
- Adrenal insufficiency with postural hypotension, hyperpigmentation, hyponatraemia and hyperkalaemia.
- Osteomyelitis, arthritis, genitourinary disease or CNS infection.
- Sepsis, respiratory failure and multiorgan dysfunction in severe cases.
History and examination
Ask about soil, caves, poultry houses, bat/bird droppings, construction, farming, mining, desert travel, decaying wood, cat scratches/bites, chronic lung disease, HIV, steroids, transplant and anti-TNF therapy. Examine temperature, weight, respiratory effort, oxygen saturation, lymph nodes, liver/spleen, skin/mucosa, bones/joints, neurological status and signs of adrenal insufficiency.
Diagnosis
| Method | Use | Interpretive caution |
|---|---|---|
| Direct microscopy/histopathology | Yeast, spherules, broad-based budding or characteristic tissue forms | Organism burden varies; morphology requires expertise. |
| Fungal culture | Species confirmation and susceptibility | May take weeks; laboratory biosafety is essential. |
| Antigen tests | Histoplasma urine/serum antigen and other assays | Cross-reactivity occurs; test availability varies. |
| Serology | Exposure/support for coccidioides, histoplasma and paracoccidioides | May be negative early or in immunosuppression; antibodies can persist. |
| Imaging | Chest X-ray/CT, ultrasound, MRI brain/bone/adrenal | Findings overlap TB, malignancy and bacterial infection. |
Send sputum, bronchoalveolar lavage, blood, marrow, skin lesion, lymph node, CSF or tissue according to the syndrome. Always alert the laboratory when a dimorphic fungus is suspected because mould cultures may pose an aerosol risk.
Differential diagnoses
Tuberculosis, bacterial pneumonia, nocardiosis, lung cancer, sarcoidosis, vasculitis, leishmaniasis, lymphoma, HIV-related opportunistic infection and chronic melioidosis. Disseminated fungal disease and TB can coexist; a negative TB test does not prove fungus, and a positive fungal antigen may require confirmation.
Management principles
Mild-to-moderate pulmonary disease
Use an oral azole such as itraconazole or another guideline-recommended agent after species and severity assessment. Ensure absorption, adherence, drug-interaction review and liver monitoring.
Severe or disseminated disease
Hospitalise and use liposomal amphotericin B or another recommended induction regimen, then step down to prolonged oral azole consolidation. Monitor renal function, potassium, magnesium, FBC and infusion reactions.
CNS, bone or adrenal disease
Obtain specialist infectious-disease input; treatment is longer and may require CNS-penetrating azole, amphotericin induction, surgery or endocrine replacement.
- Assess oxygenation, sepsis, renal function and drug interactions before therapy.
- Itraconazole absorption depends on formulation and gastric conditions; verify administration and levels where available.
- Azoles inhibit CYP enzymes and interact with rifampicin, some antiretrovirals, anticoagulants and anticonvulsants.
- Therapy often lasts months; premature cessation causes relapse.
Organ-specific emergencies
- Respiratory failure: oxygen, ventilatory support, sepsis management and urgent antifungal induction.
- Meningitis: lumbar puncture when safe, brain imaging, CNS-active therapy and intracranial-pressure management.
- Adrenal crisis: immediate hydrocortisone and isotonic saline, then endocrine evaluation.
- Spinal/bone disease: MRI, prolonged therapy and surgical stabilisation/drainage when required.
- Massive haemoptysis: airway protection, imaging, bronchoscopy/interventional support and treatment of the cavity.
Follow-up and prevention
- Review symptoms, weight, oxygenation, imaging, inflammatory markers and organ function.
- Monitor azole levels or interactions where available and check liver tests.
- Follow disseminated disease for relapse after completing therapy.
- Reduce exposure to bird/bat droppings, disturbed desert soil and decaying vegetation; use masks and wet-cleaning during high-risk work.
- Optimise HIV treatment, nutrition and immunosuppression decisions.
Exam pearls
- Dimorphic fungi are moulds in the environment and tissue forms at body temperature.
- Chronic cavitary disease can mimic TB; tissue, culture and antigen testing may be decisive.
- Disseminated histoplasmosis commonly involves reticuloendothelial organs and is strongly associated with advanced HIV.
- Amphotericin B is potent but nephrotoxic; azoles require interaction and liver monitoring.
References
- SlideShare: Systemic mycoses.
- WHO and national guidance for endemic mycoses and HIV-associated fungal disease.
- Current Uganda Clinical Guidelines and specialist infectious-disease protocols.
Safety note: Systemic antifungals are specialist medicines. Confirm species, severity, pregnancy status, organ function and interactions before prescribing.
