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The abnormal eosinophils are part of the leukemic cell population in acute myelomonocytic leukemia with abnormal eosinophils (AML M4Eo) and carry the pericentric inversion 16: a combination of May-Grünwald-Giemsa staining and fluorescence in situ hybridization.

The French-American-British subtype acute myelomonocytic leukemia with abnormal eosinophils (FAB AML M4Eo) with pericentric inversion of chromosome 16 is cytomorphologically defined by a myelomonoblastic blast population and abnormal eosinophils. Until now, it remained an open question whether these abnormal eosinophils are part of the malignant clone or an epiphenomenon. We analyzed five cases of AML M4Eo with inv(16) and combined May-Grünwald-Giemsa staining with fluorescence in situ hybridization using yeast artificial chromosome clone 854E2, which spans the inv(16) breakpoint on 16p. In the case of inv(16), three instead of the normal two hybridization signals can be observed both on metaphase spreads and in interphase cells. With this approach, we were able to show inversion 16 in abnormal eosinophils and, therefore, identified them as a part of the leukemic cell population.

Adult↗

Potent induction of a neutrophil and eosinophil-rich infiltrate in vivo by human mast cell tryptase: selective enhancement of eosinophil recruitment by histamine.

Tryptase is the most abundant protein constituent of the secretory granules of human mast cells, but little is known of the contribution of this serine proteinase in acute allergic reactions. We have purified tryptase from human lung tissue by immunoaffinity procedures, and have investigated its potential to provoke an inflammatory infiltrate in vivo. Within 6 h of injection into the skin of guinea pigs, the accumulation of large numbers of neutrophils and eosinophils was observed, and those eosinophils closest to the injection site were partially degranulated. Similarly, injection of tryptase into the peritoneum of mice, even in quantities as low as 5 ng, stimulated the ingress of neutrophils. The response was dose dependent at 3, 6, and 16 h, with increases in median numbers of up to 400-fold. At the later time points eosinophil numbers were increased by up to 10-fold, and there were elevations also in the numbers of lymphocytes and macrophages. In both models, the actions of tryptase appeared to be dependent on an intact catalytic site. Coinjection of heparin with tryptase had relatively little effect on tryptase-induced responses. On the other hand, although histamine did not itself stimulate cell accumulation, over a range of concentrations it altered the cellular composition of the infiltrate induced by tryptase. Addition of histamine to tryptase provoked selective increases in eosinophil numbers of up to fivefold in the mouse peritoneum. Tryptase may provide an important stimulus for granulocyte recruitment in allergic disease.

Adjuvants, Immunologic↗

[Evaluation of eosinophilic cationic protein levels in patients with eosinophilic pneumonia].

We investigated the significance of eosinophilic cationic protein (ECP) as a biological indicator of disease activity in patients with eosinophilic pneumonia (EP). ECP levels were measured in serum and bronchoalveolar lavage fluid (BALF) samples from patients with EP or other diffuse interstitial lung diseases and from healthy subjects. Also we performed immunohistochemical staining of lung tissue sections from patients with EP using anti-EG 2 antibody, and computed the correlation between the number of EG 2-positive cells in lung tissues and ECP levels in serum and BALF from patients with EP. Levels of ECP in serum and BALF samples from patients with EP were significantly elevated compared to the levels in samples from other interstitial lung-disease patients and healthy subjects. Additionally, changes in serum ECP levels reflected the clinical courses for EP patients. Approximately 90 percent of the infiltrated eosinophils in tissue sections from patients with EP were EG 2-positive and activated. The number of EG 2-positive cells in lung tissues correlated significantly with levels of ECP in serum and BALF samples from patients with EP. These findings suggested that ECP levels in serum and BALF reflect the degree of eosinophil activation in lung tissues and the degree of disease activity in patients with EP. We concluded that ECP may serve as a useful biological indicator in EP.

Biomarkers↗

Eosinophils and mediators of anaphylaxis. Histamine and imidazole acetic acid as chemotactic agents for human eosinophil leucocytes.

Histamine and one of its major catabolites, imidazole acetic acid (ImAA), were selectively chemotactic for human eosinophils, whereas L-histidine and other histamine catabolites including 1,4-methylhistamine, 1-methyl-4-imidazole acetic acid and N-acetylhistamine were inactive in eosinophilotaxis over a large dose range. The dose response for histamine was dependent on the chemotaxis incubation time and the source of eosinophils, although the latter was not clearly associated with particular disease states. When histamine and ImAA were combined the chemotactic response was similar to that obtained when one agent was assayed alone, no additive or synergistic effects being observed. There was cross-deactivation between histamine and ImAA. These experiments suggest that histamine and ImAA activate the same chemotactic recognition mechanism for eosinophils. Thus ImAA joins histamine and the tetrapeptides (ECF-A) as anaphylaxis-associated selective chemoattractants for human eosinophils

Anaphylaxis↗

Indirect assessment of eosinophiluria in urinary schistosomiasis using eosinophil cationic protein (ECP) and eosinophil protein X (EPX).

The pre- and post-treatment level of eosinophiluria, as measured indirectly by the amount of free or cell bound eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in urine from Schistosoma haematobium-infected Kenyan school children, were measured and compared with intensity of infection (eggs/10 ml of urine), albuminuria and pathological changes as detected by ultrasonography. ECP and EPX were determined by means of specific ELISA methods and levels were determined in both urine supernatants and extracted urine deposits (cells and cell debris). The level of ECP was significantly raised in urine supernatants from infected children compared to controls, whereas high amounts of EPX were found in urine supernatants from infected children as well as from controls. However, the amounts of cell bound ECP and EPX were significantly raised in infected children. In pre-treatment observations significant correlations were demonstrated between egg counts, albuminuria and eosinophiluria as measured by the amount of cell bound ECP and EPX, or ECP in urine supernatants. No such correlations were demonstrated with the amount of EPX in the urine supernatants. Comparable amounts of ECP and EPX could be extracted from the urine deposits from infected children, but due to the high amounts of EPX in urine deposit extracts from controls, extracted ECP gave the best discrimination between infected and non-infected children. While albuminuria disappeared in most children at the 6 week post-treatment follow-up, eosinophiluria persisted in a significant proportion of the treated children indicating continued eosinophil activity in the bladder wall. Detection and quantification of early acute inflammatory reactions using ECP/eosinophils in combination with detection of later stages of bladder pathology using ultrasound may allow for a dynamic evaluation of the pathological process, the morbidity development and post treatment pathological changes in S. haematobium infections.

Adolescent↗

Structure and chromosome localization of the human eosinophil-derived neurotoxin and eosinophil cationic protein genes: evidence for intronless coding sequences in the ribonuclease gene superfamily.

Human genomic DNAs for the eosinophil granule proteins, eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP), were isolated from genomic libraries. Alignment of EDN (RNS2) and ECP (RNS3) gene sequences demonstrated remarkable nucleotide similarities in noncoding sequences, introns, and flanking regions, as well as in the previously known coding regions. Detailed examination of the 5'-noncoding regions yielded putative TATA and CAAT boxes, as well as similarities to promoter motifs from unrelated genes. A single intron of 230 bases was found in the 5' untranslated region and we suggest that a single intron in this region and an intronless coding region are features common to many members of the RNase gene superfamily. The RNS2 and RNS3 genes were localized to the q24-q31 region of human chromosome 14. It is likely that these two genes arose as a consequence of a gene duplication event that took place approximately 25-40 million years ago and that a subset of anthropoid primates possess both of these genes or closely related genes.

Animals↗

Serum eosinophil derived neurotoxin may reflect more strongly disease severity in childhood atopic dermatitis than eosinophil cationic protein.

Serum levels of eosinophil cationic protein (ECP) have been shown to be a good parameter of the disease severity of patients with atopic dermatitis (AD). However, the relationship between the disease severity and the eosinophil derived neurotoxin (EDN) has not been established in AD patients. The purpose of this study is to examine serum ECP and EDN levels in relation to the disease severity in AD children. Serum ECP and EDN levels were assessed in relation to the skin scores in 34 AD children (18 boys and 16 girls; age 0.6 to 7years: mean+/-S.D. 2.2+/-1.9) and six non-atopic control children (three boys and three girls; age 1 to 3years: mean+/-S.D. 1.7+/-0.9). Serum ECP and EDN levels of the patients with AD were significantly increased compared with the non-atopic controls. Serum EDN levels of the patients were also related to the disease severity. The skin scores were more significantly correlated with serum EDN levels than ECP levels. We concluded that serum EDN may reflect more strongly disease severity as eosinophilic activation in AD children than serum ECP.

Biomarkers↗

Expression on human eosinophils of CD148: a membrane tyrosine phosphatase. Implications in the effector function of eosinophils.

The role of protein tyrosine phosphatases (PTP) is crucial in regulating the phosphorylation status of cells. CD148 is a recently described membrane-type PTP. In this study, we have demonstrated that this molecule is expressed on human eosinophils and eosinophilic cell line EoL-3. Interestingly, our data also showed that this molecule acts as a transduction molecule on these cells. Thus, the crosslinking of CD148 was able to induce the degranulation and the induction of superoxide anion generation. By using specific inhibitor and by western blotting, we have shown that tyrosine kinase activation is involved in this transduction pathway. In addition, we have shown the presence of a serine/threonine kinase activity associated with CD148. In conclusion, the activation capacity of CD148 on eosinophils suggests a potential role of this molecule on inflammatory diseases, such as allergic and parasitic diseases, associated with eosinophilia.

Blood Proteins↗

Eosinophilic esophagitis: A subset of eosinophilic gastroenteritis.

Eosinophilic gastroenteritis (EG) was first described over 50 years ago. Despite its long history, it remains an ill-defined and poorly understood entity. EG can present in a number of ways, none of which are exclusive to the disorder. EG has features of allergy and immune dysregulation but does not clearly fit into the category of allergic or immune disorder. While EG has been reported to affect all locations and layers of the gastrointestinal tract, the vast majority of reported cases have demonstrated mucosal involvement of the gastric antrum and small intestine in addition to disease activity of other locations of the gastrointestinal tract. Recently, several reports have identified a disease consisting of an isolated esophageal eosinophilia. Eosinophilic esophagitis (EE), also known as primary eosinophilic esophagitis or idiopathic eosinophilic esophagitis, occurs in adults and in children and represents a subset of EG with an isolated severe esophageal eosinophilia. Patients with EE present with symptoms similar to those of gastroesophageal reflux but are unresponsive to antireflux medication. Reports have demonstrated that patients with EE respond to either dietary restriction or corticosteroids.

Adult↗

Eosinophilic cellulitis and eosinophilic pustular folliculitis.

This report describes a patient with a drug reaction and histologic changes of both eosinophilic cellulitis and eosinophilic pustular folliculitis. We propose that some cases of eosinophilic pustular folliculitis, like eosinophilic cellulitis, may occur as a result of a hypersensitivity phenomenon.

Cellulitis↗

A case of T-cell lymphoma accompanying marked eosinophilia, chronic eosinophilic pneumonia and eosinophilic pleural effusion. A case report.

A 57-year-old woman was admitted to our hospital for lumbago, weight loss and weakness of her right lower extremity. Leukocytosis was evident with marked eosinophilia (65.5% = 46,000/mm3), and the chest roentgenogram showed diffuse reticular shadows throughout both lung fields and a left pleural effusion. The pleural effusion contained 22.4% eosinophils with no immature cells. Biopsy of a thumb-sized mass on the chest wall revealed a T-cell lymphoma of pleomorphic type. The diffuse pulmonary shadow was diagnosed as chronic eosinophilic pneumonia by autopsy. This was a relatively rare case of T-cell lymphoma, in which an eosinophilic pneumonia and eosinophilic pleural effusion were observed.

Chronic Disease↗

A case of eosinophilic myocarditis complicated by Kimura's disease (eosinophilic hyperplastic lymphogranuloma) and erythroderma.

This report describes a patient with eosinophilic myocarditis complicated by Kimura's disease (eosinophilic hyperplastic lymphogranuloma) and erythroderma. A 50-year-old man presented with a complaint of precordial pain. However, the only abnormal finding on examinatioin was eosinophilia (1617 eosinophils/microl). Three years later, the patient developed chronic eczema, and was diagnosed with erythroderma posteczematosa. One year later, a tumor was detected in the right auricule, and a diagnosis of Kimura's disease was made, based on the biopsy findings. The patient developed progressive dyspnea 6 months later and was found to have cardiomegaly and a depressed left ventricular ejection fraction (17%). A diagnosis of eosinophilic myocarditis was made based on the results of a right ventricular endomyocardial biopsy. The eosinophilic myocarditis and erythrodrema were treated with steroids with improvement of both the eosinophilia and left ventricular function.

Angiolymphoid Hyperplasia with Eosinophilia↗

Eosinophilic pneumonia with eosinophilic gastroenteritis.

A 48-year-old man was admitted to our hospital with cough, fever and dysphagia. He had a past history of bronchial asthma and surgery for nasal polyp. Chest radiograph and computed tomography showed atelectasis in the right lower field and infiltrative shadow in the left lower field and overall thickening of the esophageal wall. Transbronchial lung biopsy (TBLB) specimens revealed infiltration of eosinophils and lymphocytes under the bronchial mucosa. Gastrointestinal tract biopsy specimens showed submucosal infiltration of eosinophils. These findings led to a definite diagnosis of eosinophilic pneumonia associated with eosinophilic gastroenteritis, a disease which has been rarely reported.

Asthma↗

Eosinophilic neuritis and eosinophilic panniculitis in a patient with advanced acquired immunodeficiency syndrome.

The pruritic, papular eruption of human immunodeficiency virus with associated peripheral eosinophilia is well documented. We describe a 32-year-old African American man with advanced acquired immunodeficiency syndrome; a generalized painful, pruritic, papular rash; peripheral blood eosinophilia; and perineural eosinophilic infiltrates with eosinophilic panniculitis. To our knowledge, the latter 2 features have not been previously described in the literature on human immunodeficiency virus dermatoses. We propose that eosinophilic neuritis and eosinophilic panniculitis may represent additional findings in the spectrum of cutaneous disease seen in patients with advanced acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Eosinophilic dermatitis with edema in nine dogs, compared with eosinophilic cellulitis in humans.

A unique eosinophilic dermatitis with edema in dogs is characterized by extremely erythematous coalescing macules and plaques with associated edema, and is similar to eosinophilic cellulitis (Wells' syndrome) in humans. Histopathologic features include a profound eosinophilic dermal infiltrate, focal areas of collagen fiber degeneration surrounded by eosinophils (flame figures), dilated vessels, and dermal edema. Etiopathogenesis is unknown, but a hypersensitivity reaction to medications, arthropod bites, or other foreign antigens is suspected.

Animals↗

Dense eosinophilic infiltration of the mucosa preceding ulcerative colitis and mimicking eosinophilic colitis: report of two cases.

There is increasing evidence about the involvement of eosinophils in the pathogenesis of inflammatory bowel disease. We report here two patients with ulcerative colitis who were initially diagnosed as eosinophilic colitis based on histopathological examination during their first attacks. They had symptomatic improvement with ketotifen and metronidazole during their first attacks. However, subsequent attacks which were histopathologically diagnosed as ulcerative colitis did not resolve with the above-mentioned treatment and necessitated a treatment with 5-ASA agents plus corticosteroids. Azathioprine also had to be added in the treatment of the second patient. Dense eosinophilic infiltration in these cases may suggest a role of eosinophils in the initiation of attacks in some ulcerative colitis patients.

Adolescent↗

[A case of eosinophilic bronchiolitis complicated with eosinophilic sinusitis].

A 42-year-old man was admitted to our hospital, complaining of dyspnea and cough for six months. Chest CT demonstrated thickening of the bronchial walls and some centrilobular nodules. From the laboratory data and the clinical course, he was first suspected to have bronchial asthma. However, it was necessary to rule out bronchiolitis due to other causes, because he had no previous asthma history and also because of the CT findings. We performed surgical lung biopsy to make a definite diagnosis. The pathological findings revealed eosinophilic bronchiolitis. While dyspnea and the eosinophilic nasal polyp improved by treatment with oral steroid therapy, the eosionophilic sinusitis and bronchiolitis relapsed after steroid tapering. Improvement and relapse of nasal and lower airway symptoms were synchronously observed. Eosinophilic bronchiolitis and eosionophilic sinusitis in this case may be considered to be a category of airway eosinophilic inflammation.

Adult↗

Eosinophilic gastroenteritis with eosinophilic ascites: report of a case.

Eosinophilic gastroenteritis is a relatively uncommon disease of unknown etiology. Eosinophilic ascites resulting from significant serosal involvement is the rarest clinical subtype. The case reported here is of a 30-year-old male presenting with abdominal pain, diarrhea, and ascites. His personal history included childhood asthma, allergic rhinitis, and recurrent urticaria. The clinical picture was characterized by peripheral eosinophilia and eosinophilic infiltrates of the stomach and small bowel. Computed tomogram (CT) of the abdomen showed generalized thickening of the gastric and small bowel wall. Paracentesis revealed exudative ascites rich in eosinophils. The patient experienced an impressive response to steroid therapy.

Adult↗