Pulmonary eosinophilic infiltrates

Pulmonary eosinophilic infiltrates include an heterogeneous group of disorders characterized by the presence of eosinophils in the lungs as detected by bronchoalveolar lavage or tissue biopsy, with or without blood eosinophilia. The disease can be idiopathic (simple pulmonary eosinophilia, acute and chronic eosinophilic pneumonia, hypereosinophilic syndrome), secondary (to drugs, parasites, fungal and mycobacterial infection, irradiation, toxic products) or associated with diffuse lung diseases (connective tissue diseases and some neoplasms). Pathologists faced with eosinophils in the lungs (either on cytology or biopsy) should keep in mind several possibilities, although a diagnosis of certainty is rarely based on morphology alone. Correlation with laboratory tests, imaging studies and clinical presentation has a key role, even if some pulmonary eosinophilic diseases are sufficiently characteristic on clinico-radiologic ground to not require a biopsy (e.g. some drug reactions, parasitic infections, idiopathic hypereosinophilic syndrome, allergic bronchopulmonary aspergillosis). Nevertheless, pathologists can play a central role because they can be the first to note eosinophils in the lungs of a very sick patient. Knowledge of histologic features and a striking collaboration with other physicians are necessary to achieve correct diagnosis and to establish adequate treatments.     

Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes

Eosinophilia is an important indicator of various neoplastic and nonneoplastic conditions. Depending on the underlying disease and mechanisms, eosinophil infiltration can lead to organ dysfunction, clinical symptoms, or both. During the past 2 decades, several different classifications of eosinophilic disorders and related syndromes have been proposed in various fields of medicine. Although criteria and definitions are, in part, overlapping, no global consensus has been presented to date. The Year 2011 Working Conference on Eosinophil Disorders and Syndromes was organized to update and refine the criteria and definitions for eosinophilic disorders and to merge prior classifications in a contemporary multidisciplinary schema. A?panel of experts from the fields of immunology, allergy, hematology, and pathology contributed to this project. The expert group agreed on unifying terminologies and criteria and a classification that delineates various forms of hypereosinophilia, including primary and secondary variants based on specific hematologic and immunologic conditions, and various forms of the hypereosinophilic syndrome. For patients in whom no underlying disease or hypereosinophilic syndrome is found, the term hypereosinophilia of undetermined significance is introduced. The proposed novel criteria, definitions, and terminologies should assist in daily practice, as well as in the preparation and conduct of clinical trials.     

Pulmonary eosinophilic response to respiratory syncytial virus infection in mice sensitized to the major surface glycoprotein G.

To investigate the contribution of immunity to individual respiratory syncytial (RS) virus proteins to the augmentation of pulmonary pathology, mice were scarified with recombinant vaccinia viruses (rVV) expressing individual RS virus proteins. The pulmonary response to infection with RS virus was monitored by bronchoalveolar lavage (BAL). In mice vaccinated with the major surface glycoprotein (G), 14-25% of BAL cells were eosinophils; these comprised less than 3% of BAL cells from other groups of mice after RS virus challenge. Mice sensitized to the G or fusion (F) proteins developed lung haemorrhage and those sensitized to G, F or nucleoprotein (N) showed pulmonary polymorphonucleocyte efflux. To investigate the concomitant changes in local T-cell subsets, BAL cells were stained with mAbs to CD4, CD8, CD45RB, alpha beta and gamma delta T cell receptor (TCR) proteins. Three colour flow cytometry showed that most cells were CD3+CD4+ alpha beta+gamma delta+ or CD3+CD8+ alpha beta+gamma delta-, although some CD4-CD8-SIg- cells were also identified. Most of these 'null' cells lacked CD3, but CD3+ null cells from rVV-G or -F primed mice bore either alpha beta and gamma delta TCR in approximately equal numbers. The intensity of staining for CD45RB declined rapidly after infection with RS virus on both CD4 and CD8 cells. The rate of loss of CD45RB on CD4 T cells was accelerated by prior sensitization with rVV-G, consistent with conversion to helper T cell subsets producing eosinophil-promoting cytokines. The eosinophilic reaction to RS virus infection therefore specifically reflects sensitization to G protein, but sensitization to other proteins can also cause distinct pathological effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Non-allergic eosinophilic inflammation

Much is known about the eosinophilic processes associated with antigens, tumors, and infection, yet data on other causes of eosinophilic inflammation are scarce. This paper investigates the locations and causes of other nonrespiratory eosinophilic inflammation. Although eosinophilic inflammation can involve locomotor, urinary, cardiovascular, nervous, gastrointestinal, and other mucosal surfaces, such inflammation also can accompany tissue trauma, foreign-body reactions, and necrotic or granulomatous processes. Despite their cytolytic/histolytic effects, eosinophil leukocytes are a component of tissue remodeling, can be antigen-presenting cells, and have a role in the reproductive system and in blood coagulation. The study of various types of eosinophilic inflammation may increase our understanding of the biological responses of eosinophil leukocytes to different inflammatory stimuli.     

Mepolizumab in eosinophilic disorders

Mepolizumab (Bosatria(?), GlaxoSmithKline) is a biologic agent developed to treat asthma. It represents a humanized monoclonal antibody of IgG1 κ type, which targets human IL-5 and thus prevents its interaction with the α-chain of the IL-5 receptor. To date, it has not been approved for use in any eosinophil-related disorder; however, several studies have suggested some therapeutic benefit across a spectrum of eosinophil-related disorders. This article evaluates the currently available preclinical and clinical studies, and the impact of mepolizumab against a variety of eosinophilic disorders.     

Reactive eosinophilic pleuritis. A sequela of pneumothorax in pulmonary eosinophilic granuloma

Pneumothorax is a frequent complication of pulmonary eosinophilic granuloma (EG) and can be a presenting manifestation of this disorder. Histologically the differential diagnosis of EG in patients presenting with pneumothorax includes reactive eosinophilic pleuritis (REP), a nonspecific inflammatory reaction commonly observed in association with ruptured pleural blebs. The authors present a case in which both EG and REP were found in lung tissue from a patient with recurrent pneumothorax. Immunohistochemical stains for lysozyme and S-100 protein assisted in differentiating these two lesions. Histiocytic cells in areas of EG were S-100 positive and lysozyme negative, whereas mononuclear cells in areas of REP were S-100 negative and lysozyme positive. It is emphasized that the finding of REP and pleural blebs in lung tissue from patients presenting with pneumothorax does not exclude the diagnosis of EG.     

Adult-onset eosinophilic airway diseases

Eosinophilic airway inflammation is one of the cardinal features of allergic airway diseases such as atopic asthma and allergic rhinitis. These childhood-onset conditions are mediated by allergen and allergen-specific IgE and often accompanied by other allergic diseases including food allergy and eczema. They can develop consecutively in the same patient, which is referred to as an allergic march. In contrast, some phenotypes of asthma, nonsteroidal anti-inflammatory drugs-exacerbated airway disease (N-ERD), chronic rhinosinusitis with nasal polyps (CRSwNP)/eosinophilic CRS and allergic bronchopulmonary aspergillosis/mycosis (ABPA/ABPM) are adult-onset airway diseases, which are characterized by prominent peripheral blood eosinophilia. Most of these conditions, except for ABPA/ABPM, are nonatopic, and the coexistence of multiple diseases, including an adult-onset eosinophilic systemic disease, eosinophilic granulomatosis with polyangiitis (EGPA), is common. In this review, we focus on eosinophil biology, genetics and clinical characteristics and the pathophysiology of adult-onset eosinophilic asthma, N-ERD, CRSwNP/eosinophilic CRS, ABPA/ABPM and EGPA, while exploring the common genetic, immunological and pathological conditions among these adult-onset eosinophilic diseases.     

Genetics of eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches.     

Chronic eosinophilic leukemia with eosinophilic granulomas of the lung (author's transl)]

For the first time a report is given on a case of chronic eosinophilic leukemia with occurence of eosinophilic pulmonary granulomas. Even after enucleation of the granulomas eosinophilia remained in the peripheral blood and in the bone marrow, and over a period of 6 years lay at a value of above 50% of the granulocytes. The illness ended with sudden increase in the number of myeloblasts. The autopsy revealed destruction of the bone marrow by myeloblasts, immature and mature eosinophilic granulocytes as well as infiltration of the heart, liver, spleen and kidneys. On the basis of histological, cytological and histochemical examinations of the granulomas, the peripheral blood and the organs after dissection, particularly of the bone marrow, there was good reason to assume common pathogenesis of these changes; it was not however possible to completely exclude an allergically generated cause.