Synopsis
Differentiate allergic, chronic, fungal-ball and invasive Aspergillus syndromes, combine imaging with organism-specific biomarkers and tissue diagnosis, and deliver early phenotype-appropriate antifungal and procedural care.
- Aspergillus causes distinct syndromes: allergic bronchopulmonary aspergillosis, aspergilloma, chronic pulmonary aspergillosis and invasive disease; a positive respiratory culture must be interpreted within that phenotype.
- Invasive pulmonary aspergillosis is especially associated with prolonged neutropenia, acute leukaemia, allogeneic transplantation, solid-organ transplantation, corticosteroids, chronic granulomatous disease and severe influenza or COVID-19 critical illness.
- First-line imaging for suspected invasive pulmonary disease is urgent thin-section CT chest; nodules, surrounding ground-glass halo, wedge infarcts or cavitation support but do not independently prove infection.
- Serum and bronchoalveolar-lavage galactomannan plus Aspergillus PCR support diagnosis in the right host; 1,3-beta-D-glucan is a pan-fungal marker and is not Aspergillus specific.
- Reference-standard confirmation is compatible histopathological tissue invasion with culture or molecular identification, but treatment must not wait when invasive disease is strongly suspected.
- First-line treatment of invasive aspergillosis is voriconazole, commonly 6 mg/kg intravenously every 12 hours for two doses then 4 mg/kg every 12 hours, with therapeutic drug monitoring.
- Isavuconazole or liposomal amphotericin B is an alternative when toxicity, interaction, resistance, pregnancy or possible Mucorales changes the risk-benefit balance.
- Chronic pulmonary disease uses symptoms for at least three months, progressive cavities or nodules and Aspergillus IgG or microbiological evidence; long-term oral triazole therapy belongs with a specialist service.
Key red flags
Massive or recurrent haemoptysis with an aspergilloma or chronic cavitary disease requires emergency airway, interventional-radiology and thoracic-surgical assessment.
Focal neurological deficit, seizure, confusion or severe headache may reflect cerebral infarction, abscess or haemorrhage from angioinvasive spread.
Black nasal eschar, facial pain, ophthalmoplegia or visual loss in an immunocompromised patient suggests invasive fungal sinusitis and needs immediate ENT and surgical review.
Persistent fever with pulmonary nodules during prolonged neutropenia demands urgent mould investigation even when chest radiography is normal.
Breakthrough disease during mould-active prophylaxis raises non-adherence, low exposure, azole-resistant Aspergillus or a non-Aspergillus mould and should trigger a class change plus tissue diagnosis.
Pregnancy, liver failure, major QT risk and interacting transplant or oncology medicines can make standard triazole therapy unsafe without specialist pharmacy input.
Persistent fever, dry cough, pleuritic chest pain, dyspnoea or haemoptysis occurs in an immunocompromised host, sometimes with few auscultatory findings.
Sinus pain, cranial neuropathy, skin nodules, visual change, embolic phenomena or neurological deficits may reflect direct extension or haematogenous dissemination.
Investigation priorities
Detect early nodules, infarct-shaped lesions, halo sign, consolidation, cavitation, air-crescent change and chronic structural progression.
Management branches
A high-risk host develops persistent fever, focal chest symptoms, hypoxaemia, nodules or extrapulmonary signs.
- Obtain urgent thin-section CT chest and targeted sinus or brain imaging, then send serum galactomannan, beta-D-glucan and Aspergillus PCR according to local diagnostic policy.
- Collect sputum or BAL for microscopy, fungal culture, galactomannan and PCR before treatment when safe; pursue tissue from a peripheral lesion or involved site if feasible.
- Ask the laboratory for species identification and antifungal susceptibility and tell them about mould-active prophylaxis or prior azole exposure.
- Start mould-active therapy immediately when suspicion is strong; diagnostics refine treatment but should not create a dangerous wait.
Invasive disease is proven, probable or strongly suspected and no overriding contraindication changes drug choice.
- Load intravenous voriconazole at 6 mg/kg every 12 hours for two doses, then give 4 mg/kg every 12 hours; convert to an exposure-guided oral regimen when stable and absorbing.
- Check baseline liver tests, ECG, renal function and interacting medicines, especially calcineurin inhibitors, sirolimus, rifamycins, anticonvulsants and some anticancer agents.