Chronic Necrotizing Pulmonary Aspergillosis (CNPA)

Introduction: In accordance with the idea that disease caused by aspergillus occurs as a spectrum depending on host and dose factors, CNPA can be viewed as a disease that is more aggressive than aspergilloma and less so than acute, necrotizing pulmonary aspergillosis. CNPA is a slowly progressive, necrotizing pneumonia of more than one month's duration that produces both cavities and scar. Risk factors include chronic lung diseases, especially those that affect the upper lobes and impair clearance or macrophage function, and systemic diseases or treatments that decrease host resistance, especially alcoholism and diabetes, or steroid treatment or chemotherapy [1]. A review of published cases indicated that 9% of patients had no known risk factor [2].

Clinical features: Patients are middle-aged to older individuals (mean age 57 [2]) who present with fever, productive cough, and weight loss that occurs over a period of months. Leukocytosis is usually present [1,2]. Systemic symptoms are more common than in aspergilloma, and hemoptysis is less common [2].

Radiographic changes: Typically, the disease presents as progressive, upper lobe cavitary opacities on one or both sides ± pleural thickening. A fungus ball occurs in about half of patients [2]. There may be related extension to the chest wall or mediastinum [1,3].

Diagnosis: In a review of 59 cases, diagnosis in half of cases was based on histologic demonstration of tissue invasion by culture-proven aspergillus, and in the other half diagnosis was based on isolation of aspergillus from sputum, BAL fluid, or biopsies, and absence of another pathogen. In either case disseminated disease must be excluded, and there must be a response to antifungal therapy [2].

Clinical summary: A 57-year-old man, who had COPD and a myeloproliferative disorder and was being treated with steroids for Sweet's syndrome, was admitted for cough and anorexia. He was emaciated, afebrile, and tachycardic. Oxygen saturation was 88% while he was receiving oxygen via a nasal canula. A chest film showed a RUL opacity, which progressed on antibiotics. Cryptococcus was grown from the blood and aspergillus from the sputum. Amphotericin B was begun. Respiratory failure progressed, and he died of multiorgan failure, one month after admission.

Gross appearance: A slice of postmortem lung shows consolidation of the posterior RUL. The arrows indicate foci of necrosis. Note the emphysema around the consolidation.

Histologic changes: A section shows necrotic debris to the left. It is surrounded by a wall of fibroblasts with chronic inflammatory cells and then by looser granulation tissue. Granulomatous inflammation was absent in all sections. Small collections of aspergillus (seen with a GMS stain) were confined to the areas of necrosis. Cryptococci were absent from the consolidated region, but were found elsewhere in the lung and in the spleen.

Histologic features: Yousem examined the histology of 10 cases of CNPA, six of which were associated with radiographic cavities [4]. All patients had their lesions excised surgically. All were treated postoperatively with amphotericin or itraconazole. Three patterns were described.

In CNPA, the cavitary lesions with or without a fungus ball develop from a necrotizing pneumonia caused by the aspergillus. The fungus ball, if present, is composed of both lung tissue and hyphae--a lung ball--rather than aspergillus colonization of a preformed cavity as in aspergilloma [3].

Differential diagnosis: Tuberculosis, other chronic fungal infections, and cancer are the usual considerations.

Treatment: In this disorder, diagnosis is usually delayed, therapy is toxic, patients are poor operative candidates, and postoperative complications are common [2]. A treatment protocol utilizing primary itraconazole, followed, if necessary, by intravenous amphotericin B or surgical excision or intracavitary amphotericin has been proposed. Mortality is around 40% [2].

References

1. Gefter W. The spectrum of pulmonary aspergillosis. J Thorac Imaging 1992; 7:56-74.

2. Saraceno J, Phelps D, Ferro T, Futerfas R, Schwartz D. Chronic necrotizing pulmonary aspergillosis. Approach to management. Chest 1997; 112:541-548.

3. Binder R, Faling L, Pugatch R, Mahasaen C, Snider G. Chronic necrotizing pulmonary aspergillosis: a discrete clinical entity. Medicine 1982; 61:109-124.

4. Yousem S. The histological spectrum of chronic necrotizing forms of pulmonary aspergillosis. Hum Pathol 1997; 28:650-656.

Clinical summaryDiscussion

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