Eosinophilic Disorders

Figure 1 Jean-François Cordier, M.D. Roland M. du Bois, M.D.

Other than parasitic pulmonary eosinophilia, the worldwide prevalence of which has not been evaluated, the disorders characterized by pulmonary eosinophilia covered by this issue are rare and mostly orphan conditions. However, all chest physicians will encounter some during their career and then often have difficulty in setting out a realistic differential diagnosis and in evaluating the possible systemic manifestations related to eosinophilic infiltration of the extrathoracic organs. A reference document such as this aims, therefore, to palliate the general lack of clinical experience in the field. This is the main objective of this issue of Seminars in Respiratory and Critical Care Medicine.

Pulmonary eosinophilia is defined by the infiltration of the lung by eosinophils. Its diagnosis may be obtained by lung biopsy, especially surgical (seldom done), bronchoalveolar lavage (a good surrogate for lung biopsy), or the finding of imaging features compatible with an eosinophilic pulmonary disorder and associated with blood eosinophilia. The levels of blood and bronchoalveolar lavage eosinophils that allow a diagnosis of pulmonary eosinophilia have not been defined unequivocally, but values greater than 1.5 cells × 10⁹/L and greater than 25% or more respectively at differential cell count are clinically recognized thresholds. However, blood and bronchoalveolar lavage eosinophil levels may not necessarily be concordant (e.g., acute eosinophilic pneumonia in which blood eosinophilia is usually absent despite high percentages of eosinophils at bronchoalveolar lavage). Once pulmonary eosinophilia is established, the search for etiology is of major importance. Drugs and parasites (for patients who have visited countries where specific parasites are endemic) must be excluded. However, the search for causation is most often disappointing in the Western hemisphere, as a large proportion of pulmonary eosinophilia in Western countries is of unknown cause (idiopathic/cryptogenic). Some disorders are limited to the lung (such as the idiopathic eosinophilic pneumonias), whereas others occur as part of a systemic disease, such as Churg-Strauss syndrome, which belongs to the vasculitis family of diseases, and the idiopathic hypereosinophilic syndrome of which two variants have been individualized-hematological lymphoid and myeloproliferative disorders. In established or suspected systemic eosinophilic disease, a complete evaluation is necessary, directed by clinical manifestations or specifically targeted to the heart and the kidney, where severe functional failure often develops insidiously. Pulmonary eosinophilia is thus a paradigm of the unique directing role of the chest physician in internal medicine.

In this issue of Seminars in Respiratory and Critical Care Medicine, Kariyawasam and Robinson set out the considerable armamentarium of the eosinophil and highlight its potency as an effector cell. The chapter outlines the biology of the eosinophil and its involvement in host defense and immune modulation.

Scott and Wardlaw illustrate the overlapping features that occur in the chronically inflamed airways of asthma and chronic bronchitis and describe the relatively novel entity of eosinophilic bronchitis. They dissect out those features that distinguish the different entities, highlighting the variable patterns of cellular infiltration.

Idiopathic chronic eosinophilic pneumonia, as Marchand and Cordier describe it, is a very characteristic disorder. It may complicate or be contemporaneous with or followed by asthma. The patchy bilateral, possibly migratory opacities on chest imaging with high blood and bronchoalveolar lavage eosinophil levels make the diagnosis secure, once definite causes of pulmonary eosinophilia and systemic eosinophilic disorders have been excluded. The response to corticosteroids is extremely rapid, and one of the most spectacular in medicine. However, relapses are common after decreasing or stopping treatment, thus making prolonged corticosteroid treatment often necessary.

Acute eosinophilic pneumonia, described by Allen, develops within a few days, often progressing to a febrile acute lung injury or respiratory distress syndrome. Diagnosis is obtained by bronchoalveolar lavage showing high levels of eosinophils contrasting with usually normal blood eosinophils levels at the onset of the pulmonary manifestations. There is no association with asthma, and in general, complete recovery without relapse follows corticosteroid treatment. The disorder is idiopathic in most cases, but a recent starting of cigarette smoking seems to be a recognized trigger.

Keogh and Specks define the eosinophilic vasculitis, Churg Strauss syndrome, in the context of the vasculitic diseases and outline the logical approach to investigation and current, including more novel treatment strategies in this complex systemic disease.

The idiopathic hypereosinophilic syndrome can be subset into two variants as Roufosse, Goldman, and Cogan explain. This has been the outcome of careful cellular and molecular biology studies. The myeloproliferative variant is associated with the FIP1L1-PDGFRα fusion tyrosine kinase gene and has led to the logical introduction of treatment with the tyrosine kinase inhibitor, imatinib mesylate. The lymphoproliferative variant is the consequence of interleukin 5 production by abnormal T cells. The two variants carry a strong risk of developing acute myelogenous (eosinophilic) leukemia and T-cell lymphoma, respectively.

Chitkara and Krishna illustrate the importance of excluding parasitic infection, set out a schema for recognizing the different forms of parasitic diseases, and compare three of the commoner clinical manifestations, Löffler's syndrome, visceral larva migrans, and tropical pulmonary eosinophilia.

Gibson describes allergic bronchopulmonary aspergillosis, which occurs in asthmatic patients, the airways of whom are colonized and sensitized to Aspergillus fumigatus. The allergic, immune, and inflammatory reactions lead to tissue damage and remodeling and bronchiectasis. The treatment requires a combination of corticosteroids and antifungal azoles to obtain the control of the disease and its exacerbations.

Solomon and Schwarz review the drug and less common toxin causes of pulmonary eosinophilia. Nonsteroidal antiinflammatory drugs and antibiotics are top of the list of suspects. Toxins and radiation therapy to the breast are less common definite causes of pulmonary eosinophilia. Finding possible extrinsic causes has an immediate advantage, as their removal provides both the diagnostic test and first-line treatment of these forms of pulmonary eosinophilia.

This issue of Seminars aims to provide a valuable resource for clinicians providing care for patients with eosinophilic lung disease. We believe the information presented here will be instructive and of practical value to our readers.