Aspergillosis disseminated B44.9

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

(e) Disseminated aspergillosis; (e) Pulmonary aspergillosis; Invasive aspergillosis

Definition
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Opportunistic, systemic fungal disease with a poor prognosis, occurring mainly in immunocompromised and neutropenic patients.

Pathogen
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Fungi of the genus Aspergillus ( Aspergillus fumigatus, Aspergillus flavus).

Manifestation
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The entry point is usually the lungs through inhalation of mould spores. However, these can also enter via open wounds.

The skin is only affected in 11% of cases (site of manifestation of secondary disseminated aspergillosis).

Clinical features
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The first symptom is a long lasting antibiotic resistant fever.

Lungs: In 80-90% of patients the lungs are affected (interstitial pneumonia).

NNH and CNS: Infections of the paranasal sinuses and CNS are observed in 5-10% of patients.

Skin infection: Different clinical pictures are possible: solitary necrotizing dermal plaques and nodules, subcutaneous granulomas or abscesses, persistent spotted or papular lesions, volatile erythema or generalized exanthema, progressive confluent granulomas (only in immunocompetent patients).

In leukaemic children, primary skin infestation with solitary necrotizing skin ulcerations covered by black scab has also been described, especially at the inoculation site, e.g. entry sites of indwelling venous catheters.

Histology
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Skin biopsy: Panniculitis with isolated fat cell necrosis, low lymphocytic inflammatory response. In small vessels thrombosed fungal mycelia were found due to secondary fibrin deposits, some of which penetrated the arterial wall. Staining of the polymycecilia with PAS and Grocott.

Diagnosis
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Also perform aspergillus exclusion diagnostics in case of unspecific chest x-ray under immunosuppression. Culture from biopsy, possibly frozen section (PAS staining). Detection of Aspergillus precipitins in serum or sputum culture may be negative.

Therapy
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  • Early 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/day/kg bw i.v., if necessary gradually increasing to 3 mg/kg bw/day i.v. Possibly combination with Flucytosin (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. In case of failure of all the above mentioned therapies, try caspofungin (e.g. Cancidas) initially 70 mg/day i.v. up to and including 7 days after the symptoms have subsided or voriconazole up to and including 7 days after remission.
  • Posaconazole: resistance to therapy or patients with intolerance to other systemic antifungal drugs: 2 times/day 400 mg (10 ml) p.o. (daily dose 800 mg) or 4 times/day 200 mg (5 ml) p.o. The duration of therapy depends on the severity of the disease, if necessary recovery from immunosuppression and clinical response.

Progression/forecast
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Badly. Frequently septicaemic, usually fatal course with infestation of lungs, heart, liver, kidneys and CNS.

Literature
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  1. Darr-Foit S (2017) Primary cutaneous aspergillosis - a rare opportunistic infection a case report with literature review. J Dtsch Dermatol Ges 15: 839-841
  2. Marr KA et al (2002) Aspergillosis. Pathogenesis, clinical manifestations, and therapy. Infect Dis Clin North Am 16: 875-894
  3. Petraitis V et al (2003) Combination Therapy in Treatment of Experimental Pulmonary Aspergillosis: Synergistic Interaction between an Antifungal Triazole and an Echinocandin. J Infect Dis 187: 1834-1843
  4. Warris A (2001) Invasive pulmonary aspergillosis associated with infliximab therapy. N Engl J Med 344: 1099-1100
  5. Warris A et al (2002) Multidrug resistance in Aspergillus fumigatus. N Engl J Med 347: 2173-217

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Last updated on: 29.10.2020