—  SHORT COURSE #26  —

Lung Biopsy Interpretation

Case 9 - Chronic Eosinophilic Pneumonia

Anna-Luise A. Katzenstein & Jeffrey L. Myers


Clinical History
This 51 year old woman complained of fever and malaise for several weeks. Chest x-ray showed a large infiltrate involving the right upper, middle and lower lobes. She was hospitalized for three weeks during which time she was treated with antibiotics and gradually improved. Eosinophilia ranging from 3 to 11% was noted and a total eosinophil count measured 1320 at one point. One week following discharge she noted recurrence of fever and chills and a chest x-ray showed a new left mid-lung field infiltrate with clearing of the right lung. White blood count was 10.9 with 5% eosinophils.

Microscopic Description


Case 9 - Figure 1 - Low magnification photomicrograph showing combined interstitial and airspace inflammatory infiltrate.
Case 9 - Figure 2 - Higher magnification showing numerous eosinophils and some macrophages within alveolar spaces. There is mild chronic inflammation in alveolar septa and prominent edema in alveolar spaces.
Case 9 - Figure 3 - High magnification view showing cluster of eosinophils in the center of an alveolus with surrounding proteinaceous exudate.

This biopsy shows a combined airspace and interstitial inflammatory process that affects a large proportion of the tissue. The most striking feature is the filling of alveolar spaces by a fibrinous and proteinaceous exudate containing numerous eosinophils. The proteinaceous exudate layers out along alveolar septa in places where it superficially resembles hyaline membranes, but it lacks the smooth, homogeneous staining pattern of those structures. The alveolar septa are mildly thickened as well by edema, scattered fibroblasts, and a scant chronic inflammatory cell infiltrate containing numerous eosinophils. A similar chronic inflammatory cell infiltrate containing numerous eosinophils is present around small arteries. The features are characteristic of eosinophilic pneumonia.

Discussion
The pathologic finding of eosinophilic pneumonia is associated with several clinical syndromes (see Table). The most common, as demonstrated by this patient, is chronic eosinophilic pneumonia. Clinically, chronic eosinophilic pneumonia presents as a subacute illness characterized by a several week to month history of cough, fever, dyspnea, malaise and weight loss. Women are affected about twice as often as men. Asthma is common, being found in as many as one-half of patients in some series, and blood eosinophilia is usually present. Chest x-rays and CT exams show patchy, often peripheral, airspace opacities. Most patients respond rapidly to corticosteroid therapy. Prolonged treatment for several years may be necessary, however, since relapses are common.

Most examples of chronic eosinophilic pneumonia encountered on lung biopsy are idiopathic, but there are also a number of potential etiologies that can cause this picture and should be excluded. Drug toxicity is an important cause, and a large number of drugs have been implicated (see the comprehensive list in the review by Marchand et al), including most commonly sulfonamides, nitrofurantoin and other antibiotics, and cytotoxic agents such as bleomycin. Ingestion of L-tryptophan can also cause eosinophilic pneumonia as can inhalation of crack cocaine or nickel carbonyl vapor. Fungal hypersensitivity is an important additional cause of eosinophilic pneumonia, and the possibility of allergic bronchopulmonary fungal disease should be excluded clinically in all cases, especially when asthma is present. A large number of parasites can be associated with eosinophilic pneumonia, including Strongyloides, Ancylostoma, Ascaris, Toxocara, for example, and laboratory tests should be performed to exclude this possibility.

Eosinophilic pneumonia may also be a manifestation of acute eosinophilic pneumonia. This condition presents as an acute febrile illness usually of less than one week in duration. Most cases are idiopathic although rarely drug reactions and parasites have been implicated. Some authors have suggested a relationship to cigarette smoking, but this association seems unlikely. Bilateral lung infiltrates are seen radiographically, and hypoxemic respiratory failure develops rapidly. Asthma is usually not a feature. The process usually responds dramatically to corticosteroid therapy, and relapses have not been reported.

Tropical eosinophilic pneumonia is another form of eosinophilic pneumonia. As the name implies, it occurs in the tropics. Patients present with an acute febrile illness, high blood eosinophilia and fleeting chest infiltrates. A filarial infestation is thought to be etiologic, and the disease responds to anti-filarial drugs. Biopsy is usually not necessary for diagnosis. Simple eosinophilic pneumonia (Loeffler's syndrome) is a rare, self-limited, and often asymptomatic form of eosinophilic pneumonia that is also usually not biopsied.

Eosinophilic pneumonia sometimes occurs in association with other conditions. It is probably the most common pulmonary manifestation of Churg-Strauss syndrome. This diagnosis can be suspected in patients with high blood eosinophilia (>1500), asthma, and evidence of multi-organ involvement. The P-ANCA test is positive in about 70% of Churg-Strauss cases. An eosinophilic pneumonia-like picture has been associated with coccidioidomycosis, and the latter should be suspected if there are atypical features present such as necrosis or granulomatous change. Small areas resembling eosinophilic pneumonia have been described in otherwise typical examples of UIP. I have also seen eosinophilic pneumonia in parenchyma adjacent to malignancies.

Table. Eosinophilic Pneumonia – Clinical Correlates

• Chronic Eosinophilic Pneumonia
- Idiopathic
- Secondary, due to
Drug Reactions
Inhalants
Fungal Hypersensitivity
Parasites
• Acute Eosinophilic Pneumonia
• Tropical Eosinophilic Pneumonia
• Simple Eosinophilic Pneumonia (Loeffler's Syndrome)
• Eosinophilic Pneumonia Associated with Other Conditions
- Churg-Strauss Syndrome
- Infection (Coccidioidomycosis)
- Usual interstitial pneumonia
- Malignancy

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