Aspergillosis

188. ASPERGILLOSIS

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Causes intermittent episodes of wheezing, pulmonary infiltrates from transient bronchial plugging, sputum and blood eosinophilia, low grade fever , and brownish or greenish flecks in the sputum.

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Flecks: contain Aspergillus hyphae, thick mucus, eosinophils and Charcoat Leyden crystals.

Etiologic Agents: Aspergillus fumigatus , others: A. flavus, A. niger, A.nidulans, A. terreus Aspergillus – mold with septate branching hyphae (2-4 um in diameter), identified by its gross and microscopic appearance in culture. PATHOGENESIS AND PATHOLOGY: -

ubiquitous in the environment, growing on dead leaves, stored grain, compost piles, hay and other decaying vegetation. Fungus can be isolated from potable water. Inhalation of spores is common Invasion of lung tissue is confined almost entirely to immunocomrpmised px (90% of whom 2 of the ff. 3 conditions are operative: a) b) c)

granulocyte count in peripheral blood of <500/uL tx with supraphysiologic doses of adrenal glucocorticoids history of tx with other immunosuppressive drugs such as cyclosporine.

1.Invasive Aspergillosis – an occasional complication of AIDS. 2.Aspergillosis infn in neutropenic px -Hyphal invasion of blood vessels, thrombosis, necrosis and hemorrhagic infarction. 3.Invasive Pulmonary aspergillosis - from a chronic granulomatous disease of childhood.

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Some px with repeated exacerbations develop central bronchiectasis and progressive loss of pulmonary function.

2. Endobronchial Sparophytic Pulmonary Aspergillosis - Chronic productive cough,often with hemoptysis, in a px with prior chronic lung disease, such as TB, Sarcoidosis, Bronchiectasis and Histoplasmosis. 3. Necrotizing Aspergillus Pneumonia. - Aspergillus may spread from its endocavitary or endobronchial site to the pleura. - px have had saprophytic endobronchial colonization, with or w/o superimposed bacterial infxns. 4. Invasive Aspergillosis in the Immunocompromised hosts - acute, rapidly progressive, densely consolidated pulmonary infiltrate. - most common in px with acute leukemia and recipients of tissue transplants. - infxn progresses  direct extension across tissue planes and hema dissemination to the lung, brain and other organs. Prognosis: very poor -CT – one or more small pulmonary nodules.

4. Pneumonitis – acute, diffuse and self-limited - massive inhalation of spores by healthy persons - epitheloid granulomas with giant cells and central pyogenic areas containing hyphae - px shd be tested for underlying chronic granulomatous disease

As nodule enlarges, the dense central core of infracted tissue becomes surrounded by edema or hemorrhage, forming a hazy rim called “HALO SIGN” (disappears in few daysas the dense core enlarges)

5. Aspergilloma (balls of hyphe within cysts or cavities), usually in the upper lobe may reach several cm in diameter and may be visible on CXR.

When bone marrow fxn recovers, the infracted central core cavitates, creating the “CRESCENT SIGN”

CLINICAL MANIFESTATIONS:

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Allergic bronchopulmonary aspergillosis in px with pre-existing asthma (glucocorticoid dependent asthma) or cystic fibrosis.

4. Aspergillus sinusitis 3 forms: a) a chronically obstructed paranasal sinus forms a ball of hyphae , without tissue invasion. b) a chronic fibrosing granulomatous inflammation assoc with Aspergillus hyphae

within tissue may begin in the sinus  spread slowly to the orbit and the brain. healthy , presenting with painless proptosis, nasal obstruction or dull aching pain. CT or MRI – soild soft tissue mass pushing out the lateral wall of the ethmoid sinus or the medial wall of the maxillary sinus. Sinus exploration : mucosa is thickened and inflamed but intact. Within the cavity, sticky mucopus with strands of neutrophils, eos and Charcoat Leyden crystals, and occasional hyphae are found. 5. ASPERGILLOSIS IN HIV INFECTED PX - most commonly involves the LUNG (well localized, white necrotic pseudomembranes full of hyphae or ulcers may dev in the trachea or major bronchi) - fever, cough and dyspnea - CD4+ cell count is <50/uL (allergic form even if >50/uL) - half of px: neutropenic or have been treated with Glucocorticoids RADIO: bilateral diffuse or focal pulmonary infiltrates with a tendency to cavitate -progression of bronchitis  pneumonia 6. OTOMYCOSIS - the growth of Aspergillus on cerumen and detritus within the external auditory canal 7. ASPERGILLUS KERATITIS - Trauma to the cornea

Allergic bronchopulmonary aspergillosis Invasive aspergillosis

DIAGNOSIS: 1. Endcobronchial colonization or infection -Repeated isolation of Aspergillus from sputum or the demonstration of hyphae in sputum or bronchoalveolar lavage fluid 2. Invasive Aspergillosis - even with a single isolation of Aspergillus from the sputum of a neutropenic px or a hematopoietic stem cell transplant recipient with pneumonia, particularly a child or a non smoker. 3. Patients with advanced AIDS, fever and cough - isolation of Aspergillus from respiratory secretions , prompt bronchocopy - Fungus ball of the lungs – CXR - IgG Antibody to Aspergillus antigens in the serum of colonized px and in px with fungus ball. (serum IgG conc: > 1000 ng/mL) 4. Biopsy for the dx of Aspergillosis of the lung mose and paranasal sinus, bronchi, or sites of dissemination. 5. Blood cultures are rarely positive, even in px with infected heart valves (native or prosthetic) - detection of galactomannan antigen in serum suggest the dx 6. Histology – Aspergillus hyphae

8. ASPERGILLUS ENDOPHTHALMITIS -Introduction of Aspergillus into the globe by trauma or surgery TREATMENT: Table 188-1 page 1189 TYPE OF DISEASE Fungus ball of the lungs

c) Allergic fungal sinusitis – (more common cause:Curvularia, Alternaria) - Px with a history of chronic allergic rhinitis, sometimes with nasal polyps, but are otherwise 9. Aspergillus may infect intracardiac or intravascular prosthesis.

7. Culture – distinguish aspergillosis from pseudallescheriasis

PREFFERED TREATMENT Surgical resection (lobectomy if with severe hemoptysis) Short courses of Glucocorticoids (200mg twice daily) Voriconazole (6mg/kg twice daily for 2 doses; for later oral admi, 200mg twice daily), liposomal (5mg/kg daily)or conventional Amphotericin B (1-1.5mg/kg daily)

ALTERNATIVES Bead embolization for hemoptysis Itraconazole prophylaxis (to treat exacerbations) Amphotericin B colloidal dispersion (6mg/kg daily) or lipid complex (5mg/kg daily), IV Itraconazole (200 mg twice daily for 4 doses, then 200 mg daily) or IV Caspofungin ( 70 mg once, then 50 mg daily)

Addtnal notes: -Amphotericin B colloidal dispersion – shows equivalent efficacy with Conventional Amphotericin B, it is less nephrotoxic and more often causes infusion-related chills and fever.

-IV Itraconazole – contraindicated in px with CREA clearance of <30mL/min -IV Capsufungin - for patients in whom therapy with other drug fails

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