Hypereosinophilic syndrome

Daniel Norman, MSIV; Roham T Zamanian, MD; Thomas T Vovan, MD--UCI Medical Center, Department of Pulmonary and Critical Care, Irvine, California, USA

Introduction: Pulmonary infiltrates with eosinophilia (PIE) syndromes are a heterogeneous group of disorders that are characterized by the presence of peripheral eosinophilia and chest x-ray infiltrates. Davis et al attempted to classify the primary pulmonary eosinophilias into several causes. Simple Pulmonary Eosinophilia, Acute and Chronic Eosinophilic Pneumonias, Churg-Strauss Syndrome, Idiopathic Hypereosinophilic Sydrome, Asthma, Allergic Bronchopuhnonarv Aspergillosis, Bronchocentic Granulomatosis, certain parasitic infections, and certain drug reactions. There exists another group of pulmonary eosinophilias, however, in which the eosinophilia is thought to represent only a minor component of the illness. These "secondary pulmonary eosinophilias" include sarcoidosis, non-parasitic lung infections, rheumatoid arthritis, and a variety of thoracic malignancies. While both primary and secondary lung cancers have been associated with peripheral eosinophilia, we report what we believe to be the first ease of a patient with pulmonary infiltrates and peripheral eosinophilia associated with bronchoalveolar carcinoma (BAC).

Case Presentation: A 68-year old Hispanic woman with no previous history of pulmonary disease presented with a two-month history of progressive shortness of breath associated with a cough initially productive of blood-streaked sputum, which changed to thick-yellow over the 2 weeks prior to admission. She had been in good health until the onset of the illness. She denied any history of fever, chills, night-sweats, orthopnea, arthralgias, GI complaints, chest pain, or ill contacts, but did report an approximate 20 lbs weight loss over the past two months. Her past medical history was significant only for hypertension, for which she had been taking various antihypertensive medications over the past 20-30 years. Her social history revealed that she was a homemaker residing in a city in Mexico, married to a farmer, with three adult sons, and migrated to America for treatment 1 week prior to admission. She had acquired two pet birds two months prior to the onset of her symptoms. There was no history of tobacco, alcohol, or drug abuse. On presentation to the hospital, she was afebrile at 36.8 [degrees] C, tachycardic at 109 beats/min; normotensive at 125/92 mm Hg, and slightly tachypnic at 26 breaths/min with an arterial oxygen saturation of 80% on a 50% mask and 90% on a 100% non-rebreather mask. The physical examination revealed a well-developed, well-nourished female in mild to moderate respiratory distress speaking in abbreviated sentences. The rest of her exam was normal and only notable for bi-basilar crackles (without wheezing or egophony) on chest auscultation. The initial laboratory work up revealed a white blood cell count of 31,000/ml with 59% neutrophils, 7% lymphocytes, and 31% eosinophils. Initial hemoglobin was 14.2 g/dL and a platelet count of 285,000/mL. While on 100% non-rebreather face mask, an arterial blood gas analysis revealed a pH of 7.43, pCO2 of 32 mm Hg, pO2 of 44 mm Hg, serum bicarbonate of 21 mmpol/L, and an arterial saturation of 82%. Chest radiographs demonstrated extensive bilateral airspace disease which obscured the cardio-mediastinal borders of all lung fields. Computed tomography of the chest revealed bilateral diffuse nodular consolidations, measuring at least 5 mm across, that were partially confluent and formed conglomerates of up to several centimeters in diameter, with no evidence of pleural or pericardial effusion. At this point, work-up of peripheral eosinophilia with pulmonary infiltrates was initiated. Sputum viral, fungal, and bacterial cultures were negative, as were sputum acid-fast stains, and direct fluorescent antibody examinations for pneumocystis carnii and legionella pneumophila. The patient's hospital course was marked by worsening dyspnea and hypoxemia, for which the patient was eventually intubated and mechanically ventilated. Open lung biopsy was performed for definitive diagnosis, revealing a multinodular-appearing, firm and fibrotic lung parenchyma. Pathologic results of lung biopsies were consistent with BAC, with malignant cells diffusely replacing normal lung parenchyma along the alveolar septae, and occasionally forming papillary structures and mitotic figures. Acid-fast and parasite trichrome stains of lung biopsy specimens were negative, as were direct fluorescent antibody stains for legionella and pneumocystis carinii. Bacterial culture of biopsy specimens grew few coagulase negative staphylococci (which are thought to be contaminants), while fungal, viral, and legionella cultures of the specimens were all negative. After reviewing the prognosis, the patient's family requested not to pursue aggressive therapy and the patient eventually succumbed to cardiac arrest secondary to respiratory failure.

Discussion: Based on the history, physical examination, laboratory, radiographic, and pathology, we believe that this is an unusual case of BAC presenting as an ARDS picture and peripheral eosinophilia. While many malignancies have been known to present with peripheral eosinophilia, to our knowledge this is the first reported ease of BAC presenting in this manner. Large cell carcinomas are the bronchial neoplasms most commonly associated with peripheral eosinophilia, but it has also been described with squamous cell, undifferentiated, and adenocarcinomas of the lung, and in other tumors with lung metastases. The mechanism of the peripheral eosinophilia in these cases is not fully understood, but some have suggested that tumor-cell induced granulocyte colony-stimulating activity, IgE, IL-5, or other heinatopoietie growth factors may play a role. While the function of tumor-associated eosinophilia in these cases is not known, a number of possible roles have been suggested, including stimulation of angiogenesis or participation in the anti-tumor response. Some studies have suggested that it may be linked with increased survival times, but the prognostic significance, if any, of tumor-associated eosinophilia has yet to be determined.

Conclusion: In this report, we describe an unusual case where BAC is a surprise finding in a patient with ARDS physiology and eosinophilia. Based on our findings, we initially considered acute interstitial fibrotic diseases, ARDS or hypersensitivity pneumonitis but could not explain the eosinophilia. Given the acute presentation, we felt that going directly to an open lung biopsy helped us tremendously with the diagnosis. We surprised by the finding of BAG on lung biopsy.

COPYRIGHT 2000 American College of Chest Physicians
COPYRIGHT 2001 Gale Group