Aspergillosis B44.9

Mould infection mostly caused by Aspergillus spp.

Aspergillus species, e.g. Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus (see also moulds).

The main reservoir of Aspergillus spp. is long-term stored plant material (hay, compost, potting soil). Aspergillus is found ubiquitously. Frequently occurring as lung and CNS complications in immunocompromised patients.

Weakness of the immune system, malignant tumours, 15% in patients with cystic fibrosis (E84.8), long-term therapy with glucocorticoids, cytostatics, after X-ray radiation; in patients with stem cell transplantation.

Local infections:

• Infestation of skin, mucous membranes and nails see below. Onychomycosis(primary cutaneous or mucous aspergillosis). In skin infestation by aspergilli, different clinical pictures are possible: solitary necrotizing dermal plaques and nodules, subcutaneous granulomas or abscesses, persistent patchy or papular lesions, transient, also generalized exanthema, progressive confluent granulomas (only in immunocompetent patients) (Darr-Foit S 2017). In leukemic (immunocompromised) children and in HIV-infected patients, primary skin involvement with solitary, necrotizing skin ulcerations covered with black eschar has also been described, especially at the site of inoculation, e.g., entry sites of indwelling venous catheters.
• Furthermore, local infestation of the auditory canal, ear and paranasal sinuses is possible.
• Primary cutaneous neonatal aspergillosis in premature infants: rare but increasing disease observed mainly in immature infants. Causes are small local injuries and insufficient keratinization of the immature organism. Clinically, 1 or more derb consistent, surface smooth, reddish papules are found.

Systemic infections:

• In systemic infestation, infection occurs by inhalation of the spores. In this case, the lungs are primarily affected:
  • Aspergilloma (fungal ball) spreading in a cavity of the lung.
  • Invasive pulmonary aspergillosis and Aspergillus pneumonia.
  • "Allergic bronchopulmonary aspergillosis (ABPA)" with bronchial asthma is considered a hypersensitivity reaction. It can occur in rare cases combined with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) (Ren S 2013).
• In cases of pronounced polyetiologic immunodeficiency (e.g., AIDS, organ transplantation), hematogenous dissemination can occur with involvement of multiple internal organs, pyemic-septic course with metastasis primarily to the myocardium, endocardium, central nervous system, and kidneys.

Pathogen detection microscopically and culturally in tissue samples.

Detection of Aspergillus antibodies in the Aspergillus/Galactomann antigen test from serum, bronchial secretions or cerebrospinal fluid.

In case of organ infestation: X-ray, spiral CT, Ak detection, brocnhoscopy with detection of Aspergillus in bronchial secretions.

Histological detection in biopsies.

For these balls of fungus spreading in lung caverns, purely drug-based therapy is ineffective. Surgical removal of aspergillomas if present.

Broad-spectrum antifungals, e.g. Ciclopiroxalamine (e.g. Batrafen cream) or Clotrimazole tincture 2% or Tolnaftat (e.g. Tinatox cream, Tonoftal cream)

For systemic invasive aspergillosis:

• Therapy of the 1st choice is voriconazole (adults and children > 12 years). 2 times/day (every 12 hours) 6 mg/kg bw. Maintenance dose from day 2: 2 times/day 4 mg/kg bw i.v. ).
• Alternatively: Amphotericin B (e.g. Ampho-Moronal 100 mg) 4 times/day 1 tbl. for 2-4 weeks or liposomal amphotericin B (e.g. AmBisome®) initial 1 mg/kg bw i.v., if necessary gradually increasing to 3 mg/kg bw i.v.). Possibly combination with flucytosine (e.g. Ancotil®: 150-200 mg/kg bw/day i.v. for 3-4 weeks in 4 single doses over 20-40 minutes each).
• Alternatively: Itraconazole (e.g. Sempera) 2 times/day 2 Kps. p.o. for 2-5 months.
• Alternative: In case of failure of all above mentioned therapies, try caspofungin (e.g. Cancidas®: initial 70 mg/day i.v. up to 7 days after the symptoms have subsided).

Posaconazole is used prophylactically in severely immunocompromised patients.

There is increasing evidence of azole resistance in Aspergillus species (Dabas Y et al. 2018).

1. Dabas Y et al. (2018) "Emergence of azole resistant Aspergillus fumigatus from immunocompromised hosts
2. in India". Antimicrob Agents Chemother pii: AAC.02264-17.
3. Helmi M (2003) Aspergillus infection in lung transplant recipients with cystic fibrosis: risk factors and outcomes comparison to other types of transplant recipients. Chest 123: 800-808.
4. Klotz D et al (2013) Primary cuntaneous aspergillosis in an extremely immature preterm infant. Dermatologist 64: 664-665.
5. Ren S (2013) Combined Churg-Strauss syndrome and allergic bronchopulmonary aspergillosis - case report and review of the literature. Clin Respir J 7:e6-10.
6. Tarrand JJ et al (2003) Diagnosis of invasive septate mold infections. A correlation of microbiological culture and histologic or cytologic examination. Am J Clin Pathol 119: 854-858.

7. Van Burik JAH (1998) Cutaneous aspergillosis Journal of Clinical Microbiology 36: 3115-3121.