Causes Of Eosinophilia Research Articles

Redefinition of Hypereosinophilic Disorders Based on an Analysis of 28 Cases of FIP1 L1-PDGFRA Negative Persistent Unexplained Eosinophilia (PUE) with Eosinophil End-Organ Damage (EEOD).

In 1997 the term eosinophil end-organ damage(EEOD) was introduced to facilitate management of patients with high eosinophil counts in whom damage to organs such as heart, lungs, and skin by eosinophils was associated with persistent unexplained eosinophilia (no obvious cause for eosinophilia was identified). In 2003 Cools et al identified the presence of the FIP1L1-PDGFRA gene as the causation of eosinophilia in 50% of cases of hypereosinophilic syndromes with end organ damage. Cases which are negative for this gene and a Tcell clone appear to form a distinctive group whose aetiopathogenesis and clinical significance are different. In order to identify the extent of end organ damage in FIP1L1-PDGFRA negative cases and/or identify rarer causes of unexplained eosinophilia in all cases of eosinophilia presenting from 14.06.2002 to 14.06.2006, we looked at all patients who had persistent eosinophilia present on two separate blood tests done I month apart with eosinophil counts greater than 1–1.5 x 10 9/l. All cases of unexplained eosinophilia (Eosinophil count greater than 1– 1.5 x 10 9/L) seen at our institution in a 4 year period in whom no obvious cause of eosinophilia was found were evaluated for the presence of the FIP1L1-PDGFRA gene, TEL-PDGFRB and variant BCR-ABL gene. Of 40 cases seen 2 men were FIP1L1-PDGFRA positive, 3 others (2 men and 1 woman) had myeloproliferative diseases, I man had clozapine induced eosinophilia, one woman Kimura Weils disease and 1 man had cutaneous mastocytosis . There were 28 cases (14 women, 2 children,12 men) who were FIP1L1 -PDGFRA negative and had persistent unexplained eosinophilia without clonal T cells. These cases were followed up over a 4 year period and tested serially for damage to end organs by eosinophils. FIP1L1-PDGFRA was tested and found negative on two separate occasions. Ig E levels had to be less then 500 iu/l to exclude allergy and a therapeutic trial of mebendazole 100mg daily for three days was given in all cases even if parasite testing did not identify a parasitic infestation. There were 28 cases (14 women, 2 children,12 men) who were FIP1L1-PDGFRA negative which contrasts with the Male Female ratio seen in FIP1 L1-PDGFRA positive cases in which males predominate. The age ranged from 9–80. Four year follow up identified a chronic illness in these cases with no damage to vital organs. Clinical symptoms complained of included fatigue(28), joint and muscle pains(28), skin rashes(10), blackouts(1), thrombotic events(2), diarrhoea(2), fasciitis(2), gastroenteritis(2), cough(2), and breathlessness(2). No organomegaly was seen. In one clonal T cells were identified on serial testing after 1 year of follow up. We conclude that cases of FIP1L1-PDGFRA negative hypereosinophilia are a distinct group with a chronic illness mainly affecting skin and joints who respond well to symptomatic treatment, oral steroids, or hydroxyurea. We believe that hypereosinophilic diorders need to be redined as PUEand EEOD. When both PUE and EEOD are present the diagnosis is HES.

Idiopathic Hypereosinophilic Syndrome in a Child.

The idiopathic hypereosinophilic syndrome (HSE) is a new heterogeneus disorder characterized by persistent unxplained hypereosinophilia (eosinophil count > 1.5 x 10 9 /L) persisting at least 6 months with possibile organ involvment. The diagnosis of HSE is based on exclusion criteria of other causes of eosinophilia. We reporte a case of an atopic 3 year-old male child with a history of eczema since first years of life and hypereosinophilia. At admission he showed severe generalized eczema with pruritus pain in the jonts, fever, several athsma, mild hepatosplenomegaly and lymphoadenomegaly. Biological findings included mild hypochromic microcytic anemia (Hb 10.5 g/dl, MCV 65 μ3, MCH 23 pg) due to heterozygous α thalassemia -delection (α) −37-, hyperleukocitosis (WBC 45.5 x 10 3 / μL) and hypereosynophilia (20.9 x 10 3 / μL). Bone marrow aspiration revealed absence of blast cells, mild reduction of myeloid (40%) and erythroid cells (10%) with increased M/E ratio 6/1. The eosynophilic cells represented 35%. Some of these cells presented cytoplasmatic atypia. Blood lymphocyte immunophenotypical analysis showed increased values of T lymphocytes CD3+, B lymphocytes CD19+ and T helper lymphocytes CD3+CD4+ Serum IgE levels were increased. Cytokines serum levels were undectable. Karyotype was 46XY. Non cytogenetic abnormalities were found in myeloid cells. Specific viral antibodies as well as autoantibodies and parasitologic assessements were negative. Corticosteroids were used with mild clinical improvement, followed by worsenings when the drug was stopped. The absence of blast cells or cytogenetic abnormality favor the diagnosis of HSE. However some patients in whom a diagnosis of idiopathic HSE appears appropiate may subsequently develope malignancies. A systematic survey of a large group of patients with otherwise unexplained eosinophilia is needed as well as a prolonged follow up of patients to early evaluate in each case neoplastic risk.

Infliximab as a Therapy for Idiopathic Hypereosinophilic Syndrome

A 77-year-old woman from Guyana presented with a 3-year history of a generalized, pruritic eruption associated with chronic chills, fatigue, generalized malaise, and a 14-kg weight loss over a 9-month period (Figure 1). Her medical history was significant for hypertension and diabetes, and her medications included glucophage, atenolol, and lisinopril. She had no personal or family history of atopy. Her physical examination findings were remarkable for exfoliative erythroderma and keratoderma associated with generalized lymphadenopathy (Figure 1). Complete blood cell counts were normal except for a persistently elevated absolute eosinophil count (1500-3000/ μL) for more than 8 months. Positron emission tomographic scans detected enhanced fludeoxyglucose F 18 uptake bilaterally in the supraclavicular, axillary (largest node measuring 2.5 cm), and inguinal nodes (largest node measuring 2 cm). A left inguinal lymph node biopsy specimen revealed dermatopathic lymphadenitis and no evidence of a lymphoproliferative disorder. Histopathologic examination of a skin sample revealed parakeratosis, hypogranulosis, psoriasiform epidermal hyperplasia, mild spongiosis, a mild superficial perivascular lymphocytic infiltrate with occasional plasma cells and rare eosinophils, and numerous melanophages. Flow cytometry and skin and bone marrow biopsy specimens revealed no evidence of a clonal Tor B-cell population on immunophenotyping or molecular genetic analysis, and FIP1L1-PDGFRA gene fusion was not detected. Extensive studies were performed to rule out infectious, allergic, vasculitic, rheumatic, and malignant causes of eosinophilia. A transthoracic echocardiogram, which was obtained to rule out heart failure or mural thrombus in the setting of chronic hypereosinophilia, demonstrated no abnormalities.

Diltiazem‐Induced Eosinophilic Pleural Effusion

A 68-year-old woman developed eosinophilic pleural effusion and systemic eosinophilia 2 months after starting antihypertensive therapy with diltiazem. Several drugs are known to cause this disorder; however, the only other drug the patient had been taking was clonidine, which she had taken for the past 3-4 years. She was evaluated for all other possible causes of eosinophilia and eosinophilic pleural effusion, including malignancy, infection, and autoimmune disorders. Her symptoms resolved after diltiazem was discontinued, and no recurrence was noted on follow-up. To our knowledge, this is the first case report of eosinophilic pleural effusion caused by diltiazem. According to the Naranjo adverse drug reaction probability scale, a probable relationship existed between diltiazem and the patient's eosinophilia and pleural effusion. Although numerous drugs have been associated with eosinophilia and eosinophilic pleural effusion, the spectrum may actually be wider than is commonly thought and may include such unrecognized agents as diltiazem.

Eosinophilic Enteritis Presenting as Intussusception in Adult

Eosinophilic gastroenteritis is defined as a disorder that selectively affects the gastrointestinal tract with eosinophil-rich inflammation in the absence of any known causes for eosinophilia. The clinical manifestations vary according to the site of the eosinophilic infiltrated layer of the bowel wall. Eosinophilic enteritis presenting as intussusception in adult has not been previously reported in the literature. Especially, making the diagnosis of intussusception in adults is often difficult due to the variable clinical findings. In our case, the correct diagnosis of intussusception due to eosinophilic enteritis was arrived at rather easily based on the ultrasonography and endoscopic biopsy. The patient was treated with oral prednisolone at 30 mg/day for 7 days, and then the drug was tapered off for 2 months; we didn't perform surgery. He has been asymptomatic for about 1 year after discharge without disease recurrence.

Steroid-Sparing Effects of Anti-IL-5 Monoclonal Antibody (Mepolizumab) Therapy in Patients with HES: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

An international, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial has evaluated the effects of mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, on therapeutic prednisone dose requirements, eosinophil levels, signs and symptoms of disease in patients with hypereosinophilic syndrome (HES). The trial enrolled 85 patients (mean age 48.1 years) with HES (blood eosinophil count >1500/μl with evidence of eosinophil-related organ involvement or dysfunction and no known cause of eosinophilia), who tested negative for the FIP1L1-PDGFRα gene rearrangement and required 20–60 mg/day prednisone monotherapy to maintain blood eosinophils at <1000 cells/μL during a run-in period of ≤6 weeks. Patients were randomized to treatment with intravenous mepolizumab 750 mg (n=43) or saline (placebo; n=42) every 4 weeks for 36 weeks (final infusion at Week 32). The prednisone dose was tapered at weekly intervals following the first infusion according to a predefined algorithm based on blood eosinophil counts and HES clinical activity criteria. A total of 84% of patients in the mepolizumab group vs 43% in the placebo group (P<0.001) achieved the primary endpoint (≤10 mg/day prednisone for ≥8 consecutive weeks within the 36-week treatment period). Time to achievement of the primary endpoint, a post-hoc analysis, was significantly shorter in mepolizumab- vs placebo-treated patients (P=0.002). Significantly higher proportions of patients on mepolizumab achieved pre-defined secondary steroid-sparing and eosinophil endpoints vs placebo (Table). Initial assessments of cutaneous disease (based on pruritus visual analog scales and erythema/edema scores) did not differ between the treatment groups. This study, the largest placebo-controlled trial to be conducted in patients with HES to date, has shown that mepolizumab is more effective than placebo at reducing therapeutic prednisone use and stabilizing eosinophil counts in patients with HES. Importantly, a significantly higher proportion of HES patients treated with mepolizumab than placebo achieved the primary endpoint and required ≤10 mg/day prednisone for at least 8 consecutive weeks. These findings indicate that mepolizumab will be an effective therapy for FIP1L1-PDGFRα negative patients with HES.Primary and secondary endpointsEndpointPlacebo (n=42)Mepolizumab (n=43)P-value (95% CI)Patients on ≤10 mg/day prednisone for ≥8 weeks (primary endpoint), %43%84%<0.001 (2.69, 23.78)Patients with eosinophils <600 μL for ≥8 weeks, %45%95%<0.001 (4.74, 75.17)Primary endpoint in patients on ≤30 mg/day prednisone at baseline, %57% (n=30)87% (n=30)0.011 (1.39, 17.82)Primary endpoint in patients on >30 mg/day prednisone at baseline, %8% (n=12)77% (n=13)<0.001 (3.26, 412.26)Patients achieving ≤7.5 mg/day prednisone during the treatment period, %50%86%<0.001 (2.04, 15.00)Mean (±SE) prednisone dose at Week 36 (adjusted), mg/day21.8±1.926.2±1.87<0.001

Safety and Tolerability of Anti-IL-5 Monoclonal Antibody (Mepolizumab) Therapy in Patients with HES: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Mepolizumab is a fully humanized monoclonal IgG antibody which binds to interleukin 5 (IL-5) with high affinity and specificity, preventing it from binding to IL-5 receptors on the eosinophil cell surface. Since IL-5 is central in eosinophil proliferation, differentiation, mobilization, activation, and survival, yet has limited effects on other cell types, IL-5 inhibition should inhibit the production and activity of eosinophils without affecting the function of other immune cells. Reducing the blood eosinophil count is a critical therapeutic objective in patients with eosinophil-driven diseases, such as hypereosinophilic syndrome (HES). The safety and tolerability of mepolizumab has been evaluated, as a secondary endpoint, in a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. The trial enrolled 85 patients with HES (blood eosinophil count >1500/μl for ≥6 months with documented eosinophilia-related organ involvement or dysfunction and no known cause of eosinophilia), who were negative for the FIP1L1-PDGFRα gene rearrangement. Blood eosinophil levels were stabilized at <1000 cells/μL on 20–60 mg/day prednisone monotherapy during a run-in period of up to 6 weeks, then patients were randomized to intravenous mepolizumab 750 mg (n=43) or saline (placebo; n=42) every 4 weeks for 36 weeks (final infusion at Week 32). Overall, 98% of placebo-treated and 93% of mepolizumab-treated patients reported an adverse event during treatment. The most common of these were fatigue (26% on placebo vs 30% on mepolizumab), pruritus (21% vs 28%), headache (21% vs 23%), and arthralgia (17% vs 21%). The only significant differences between the treatment groups were in pharyngolaryngeal pain (14% on placebo vs 2% on mepolizumab; P=0.027) and pain in extremity (12% on placebo vs 2% on mepolizumab; P=0.047); none of the adverse events was significantly more frequent with mepolizumab than with placebo. A greater than 8% difference in adverse event reporting for the mepolizumab vs placebo arms was noted for upper respiratory tract infections, myalgia, rhinitis, bronchitis, and urticaria. Serious adverse events were reported in 5 patients on placebo (7 events) and 7 patients on mepolizumab (14 events, including 1 death due to a cardiac arrest), but none was considered treatment related. Withdrawals due to adverse events (4 patients on placebo; 1 patient on mepolizumab) were also considered unrelated to treatment. Laboratory tests (hematology, clinical chemistry, and urinalysis), vital signs, and ECG findings did not raise any major safety concerns. In conclusion, this study, which is currently the largest placebo-controlled trial involving exclusively patients with HES, indicates that mepolizumab is safe and well tolerated in this patient population.

Baseline Demographics and Disease Characteristics of Patients with Hypereosinophilic Syndrome in a Placebo-Controlled Trial Evaluating the Steroid-Sparing Effects of the Anti-IL-5 Monoclonal Antibody, Mepolizumab.

Mepolizumab is a humanized anti-IL-5 monoclonal antibody that blocks the actions of IL-5, the hematopoietin most responsible for eosinophil production, differentiation, and survival. Clinical experience in small numbers of patients with hypereosinophilic syndrome (HES), asthma, and atopic dermatitis indicated that intravenous (IV) mepolizumab therapy was associated with a reduction in blood eosinophils and was well-tolerated. A multicenter (26 sites worldwide), randomized, double-blind, placebo-controlled, and parallel-group trial has been conducted to evaluate the steroid-sparing effects of mepolizumab in patients with HES, and its efficacy and safety in controlling the signs and symptoms of this disease. The trial recruited patients 18–85 years of age with HES (blood eosinophil count >1500/μl for ≥6 months with evidence of eosinophilia-related organ involvement or dysfunction, without any known cause of eosinophilia), who tested negative for the FIP1L1-PDGFRα gene rearrangement and required 20–60 mg/day prednisone (monotherapy) to maintain blood eosinophils at <1000 cells/μL during a stabilization period of up to 6 weeks. The primary endpoint was the proportion of patients with disease control on ≤ 10 mg/day prednisone for ≥8 consecutive weeks during the 36-week treatment period. Here we report the baseline demographic and clinical characteristics of trial participants who comprise the largest HES population without the FIP1L1-PDGFRα mutation evaluated to date. Moreover, the clinical spectrum of HES in this population encompassed the multiple varieties of HES currently recognized. Of 107 patients screened, 85 were enrolled, 43 were randomized to mepolizumab (750 mg IV every 4 weeks), and 42 to placebo (saline IV every 4 weeks). No major differences in demographic and disease characteristics were observed between the treatment groups (Table). Many patients (60%) had previously tried and discontinued an HES therapy, notably imatinib mesylate (38%), interferon-α (21%), or hydroxyurea (21%). The most prevalent HES-related medical conditions at baseline were skin (47%) and respiratory (41%) disorders. The primary endpoint was significant in favor of mepolizumab treatment, thus providing evidence that this agent will offer clinical benefits in terms of steroid reduction/sparing in HES.Patient demographicsPlacebo (n=42)Mepolizumab (n=43)Total (n=85)Age, y (mean±SD)49.1±14.447.0±16.248.1±15.3Men, %17 (40%)26 (60%)43 (51%)Caucasian, %34 (81%)38 (88%)72 (85%)Weight, kg (mean±SD)79.7±18.380.9±22.280.3±20.3BMI, kg/m2 (mean±SD)27.8±5.827.0±6.427.4±6.1Baseline prednisone≤30 mg, n (%)30 (71%)30 (70%)60 (71%)Baseline prednisone >30 mg, n (%)12 (29%)13 (30%)25 (29%)Previously treated for HES, n (%)40 (95%)41 (95%)81 (95%)HES duration, y (mean±SD)6.5±9.54.3±5.65.4±7.8Age at HES onset, y (mean±SD)42.7±16.242.7±17.742.7±16.9

Potential of Blood Eosinophils, Eosinophil-Derived Neurotoxin, and Eotaxin-3 as Biomarkers of Eosinophilic Esophagitis

Eosinophilic esophagitis (EE) is an increasingly recognized disorder characterized by eosinophilic inflammation of the esophageal mucosa, and typically requires serial invasive endoscopic biopsy examinations to document the characteristic histologic features of the disorder. The aim of this study was to identify noninvasive biomarkers that correlated with disease activity and response to treatment as measured by esophageal eosinophilia. A prospective, cross-sectional analysis was performed on 47 pediatric patients undergoing endoscopic evaluation of possible EE. Blood samples were collected for measurement of peripheral blood absolute eosinophil count (AEC) and levels of eosinophil-derived neurotoxin (EDN), eotaxin-1, -2, and -3, and interleukin-5. Stool samples were collected for measurement of EDN. Biomarker levels were correlated with esophageal eosinophil density, and differences in biomarker levels based on disease activity and treatment were determined. AEC, plasma EDN levels, and eotaxin-3 levels significantly correlated with esophageal eosinophil density (AEC: r = 0.56, P < .0001; EDN: r = 0.54, P < .0001; eotaxin-3: r = 0.32, P = .04), and were increased in patients with active EE vs controls (AEC: 440 vs 140 eosinophils/muL, P < .05; EDN: 50.3 vs 31.1 ng/mL, P = .01; eotaxin-3: 37.7 vs 11.5 pg/mL, P = .01). Cut-off values were established to maximize the sensitivity, specificity, and predictive values of these biomarkers alone and in combination. Eotaxin-1, eotaxin-2, interleukin-5, and fecal EDN levels did not correlate with esophageal eosinophil density, and were not increased in active EE vs controls or those with inactive EE. These data show that blood levels of AEC, EDN, and eotaxin-3 may have value as noninvasive biomarkers for monitoring EE.

Pediatric Hypereosinophilic Syndrome (HES) Differs From Adult HES

Purpose of the Study. To highlight specific differences between pediatric and adult patients with hypereosinophilic syndrome (HES). Study Population. The case report involved a 15-year-old male who presented with abdominal pain, diarrhea, and a 10-lb weight loss. Colonoscopy revealed colitis. A nonproductive cough, night sweats, and a diffuse pruritic, papular rash developed. His initial absolute eosinophil count was 1890/mm3 (reference: &amp;lt;400/mm3), which increased to 52 000/mm3. Additional laboratory studies included: immunoglobulin E, 8561 U/mL (7–110 U/mL); alkaline phosphatase, 1149 U/mL (reference: 50–280 U/mL); γ-glutamyl transpeptidase, 193 (reference: 0–50 U/mL); and serum tryptase, 4.7 μg/L (reference: 1.9–13.5 μg/L). Ultrasound of the liver revealed an abnormal parenchymal pattern with dilated bile ducts. Molecular analysis of the patient’s peripheral blood for the Fip1-like-1 platelet-derived growth factor receptor α chain (FIP1L1-PDGFRA) fusion tyrosine kinase associated with HES in adults was negative. Open lung biopsy revealed patchy interstitial and intra-alveolar inflammation with a predominance of eosinophils. A skin biopsy showed acute neutrophilic folliculitis with perivascular dermatitis with eosinophils. Bone marrow biopsy demonstrated a hypercellular marrow with predominantly eosinophils, which is consistent with idiopathic HES. Methods. The investigators compared this case report of pediatric HES and additional published cases of pediatric and adult patients with HES. Results. Pediatric HES has only a slight male predominance (55.3% male vs 44.7% female), whereas adult HES is reported to be more common among males than females, with a ratio of 9 to 1. In adults, the frequencies of symptoms found on presentation are: fatigue (26%), cough (24%), dyspnea (16%), rash (12%), and fever (12%). Fever (58.8%), arthralgias (23%), and rash (23.5%) were more common in pediatric cases. As with adults, involvement of the cardiovascular system is the major source of morbidity and mortality. Pediatric HES is commonly associated with chromosomal abnormalities, and in ∼40% of the cases, it has been associated with acute leukemia. As opposed to the vast majority of adult HES cases, no pediatric case with the FIP1L1-PDGFRA fusion gene has been reported. Conclusion. There are several distinct features of pediatric, compared with adult, HES. Reviewer Comments. Most of the published information on the HES has focused on adult patients. This report compares a pediatric case report of HES and a review of published pediatric cases of this condition to adult patients with this syndrome. This is an insightful clinical report that should be useful in the overall workup of pediatric patients who present with dramatic eosinophilia (&amp;gt;1500/mm3) for &amp;gt;6 months’ duration without other known causes of eosinophilia and who have evidence of organ involvement that might be attributable to HES.

Eosinophilie mit Hepatopathie: Ein Fallbericht

We present the case of a 70-year old Patient with diffuse abdominal pain, severe eosinophilia, and increased liver parameters hospitalized for further evaluation. An idiopathic hypereosinophilic syndrome was postulated and the patient was treated with highdose methylprednisolone with rapid normalisation of the eosinophil numbers and decrease of the liver parameters. Later on strongyloidosis could be diagnosed (positive ELISA Test) as the cause of eosinophilia, and the patient was successfully treated with mebendazole. Blood eosionophilia most commonly reflects an allergic, infectious or neoplastic process; increased blood and/or tissue eosinophilia range in severity from self-limited to life-threatening conditions. Strongyloides infection can persist for years without prominent symptoms and should be suspected in any patient with unexplained eosinophilia.

The prevalence and diagnostic value of toxocariasis in unknown eosinophilia

Toxocariasis is one of the causes of eosinophilia in peripheral blood and provokes eosinophilic infiltration in internal organs. Extended studies on the prevalence and clinical characteristics of toxocariasis have been rare. The aim of this study is to evaluate the prevalence of toxocariasis in unknown eosinophilia and to analyze the efficacy of toxocara enzyme-linked immunosorbent assay (ELISA). We evaluated patients presenting with peripheral blood eosinophilia (>500 cells/microl or > or =10% of white blood cell count). After checking drug histories and the presence of allergic diseases and parasitic infections, specific serum IgG antibody to Toxocara canis larval antigen was measured by ELISA. Liver and lung involvement was also evaluated. One-hundred and three patients were evaluated, and the mean age was 50.9 years old. Seventy patients (68.0%) were diagnosed as having toxocariasis. The patients who had a history of raw liver eating had a higher incidence, and the patients with liver involvement had higher serum eosinophil cationic protein values. The eosinophil count was normalized in 7 of 16 treated patients and in 25 of 54 untreated patients. The mean improvement duration was 12 months. We concluded that the prevalence of toxocariasis was high in patients with unknown eosinophilia, and the toxocara ELISA was essential for evaluation of the causes of unknown eosinophilia.

Idiopathic Hypereosinophilic Syndrome: A Rare but Fatal Condition Presenting with Common Symptoms

Idiopathic hypereosinophilic syndrome (IHES) is a leukoproliferative disorder characterized by cytokine-induced overproduction of eosinophils with resultant multiorgan infiltration and damage. The diagnostic criteria includes evidence of end organ damage, exclusion of all other causes of eosinophilia and sustained absolute eosinophil count (AEC) > 1,500 cells/mcl for at least 6 months. An 88-year-old Caucasian female presented with persistent severe chronic cough, weight loss and rhinorrhea unresponsive to various treatments. Her workup during admission revealed absolute eosinophil count of 17,447 and bone marrow biopsy showed eosinophilia with no lymphoproliferative process. After excluding all other causes of eosinophilia, a diagnosis of IHES was made and prednisone was started. Symptoms resolved and her absolute eosinophil count progressively decreased. IHES mimics several other diseases. Mild eosinophilia should be worked up irrespective of age and sex. A high index of suspicion is required for earlier diagnosis and treatment, which could reduce morbidity and mortality.

Eosinophilia: Causes and pathobiology in persons with prior exposures in tropical areas with an emphasis on parasitic infections

Eosinophilia in patients exposed to tropical or subtropical environments is caused most commonly by helminth (worm) infections. Besides a detailed exposure history, the diagnostic approach must consider other infections and noninfectious causes of eosinophilia, as treatments for many of these disorders differ.

Eosinophil function in eosinophil-associated gastrointestinal disorders

Eosinophil-associated gastrointestinal disorders (EGIDs) are characterized by a rich eosinophilic inflammation of the gastrointestinal tract in the absence of known causes for eosinophilia or other gastrointestinal disorders. These disorders include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis, and are being recognized with increasing frequency. Clinical studies suggest that eosinophils have a pathogenic role in EGID; however, the function of eosinophils in these disorders remains an enigma. In this review, we briefly describe the clinical features of EGID of the esophagus, small bowel, and colon. We summarize recent experimental analysis examining the underlying contribution of eosinophils to disease pathogenesis and discuss possible therapeutic approaches for the treatment of these diverse diseases.

Is Primary Biliary Cirrhosis a Rare Cause of Eosinophilia? A Case Report.

INTRODUCTION: Evaluation of eosinophilia involves various medical sybspecialties and the list of diseases, syndromes and inflammatory processes associated with peripheral blood (>300 eosinophils/mm3) and/or tissue eosinophilia, is quite extensive. Little attention, however, has been given to its possible association with primary biliary cirrhosis (PBC).AIMS & METHODS: To identify PBC as a rare cause of eosinophiliaRESULTS: A 59 female patient, complaining of fatigue, referred to us for abnormal liver function tests. She had no prior history of liver disease, alcohol abuse or medication use. The haematological parameters were normal except for eosinophilia: WBC: 7.5 x 109 /lit, eosinophils 1125/mm3 -15% (normal range: 3–5%) and the biochemical abnormalities included an alkaline phosphatase (ALP) of 314 U/L, γ-gt 146 U/L, total bilirubin 2.2 mg/dl (direct 1.6 mg/dl), AST 62 U/L, ALT 88 U/L and cholesterol 302 mg/dl. Eosinophilia was first detected during an initial evaluation for fatigue 20 months before. She had shown a normal serum biochemistry and negative stool examinations for intestinal parasites and ova at that time. Other causes of eosinophilia, such as skin, allergic, pulmonary, collagen, vascular or immunodeficiency disorders and malignancies, had been excluded by history, physical examination, imaging procedures (chest X-ray and abdominal CT scan) and laboratory investigation, including serum protein electrophoresis, quantitative immunoglobulins, serum immunoelectrophoresis, tumor markers and bone marrow aspirate. On admission, both abdominal and ultrasonography examination revealed a mild hepatomegaly. AMA were detected and liver biopsy was performed. After the serological and histological identification of PBC, ursodeoxycholic acid (15 mg/kg daily) was administered. Three months later, her haematological and biochemical profiles were improved (eosinophils 6%, ALP 234 U/L, γ-gt 80 U/L, AST 59 U/L, ALT 72 U/L)CONCLUSIONS: Our case suggests that primary biliary cirrhosis should be contemplated in the differential diagnosis of eosinophilia, when all common causes are excluded. In particular, clinicians should evaluate AMA in cases of otherwise unexplained eosinophilia, even in the absence of symptoms or laboratory findings compatible to PBC.

Epicutaneous Antigen Exposure Primes for Experimental Eosinophilic Esophagitis in Mice

Eosinophilic esophagitis (EE) is frequently associated with atopic disease, including dermatitis and asthma. Data are emerging that atopic skin may provide an early entry point for antigen sensitization. We aimed to test the hypothesis that epicutaneous exposure to antigen primes for subsequent respiratory antigen-induced EE. Wild-type and genetically engineered mice were subjected to epicutaneous antigen sensitization and the development of experimental EE, and immune responses were examined. We show that exposure to antigen via the epicutaneous route primes for marked eosinophilic inflammation in the esophagus triggered by a single airway antigen challenge. The development of experimental EE is associated with significant skin eosinophilia, accelerated bone marrow eosinophilopoiesis, blood eosinophilia, and large increases in serum antigen-specific immunoglobulin G1/immunoglobulin E using ovalbumin or Aspergillus fumigatus as the epicutaneous antigen. Mechanistic analysis with gene-targeted mice showed that interleukin-5 was required for esophageal eosinophilia and that interleukin-4, interleukin-13, and STAT6 contributed to a lesser extent. These findings provide the first evidence that epicutaneous exposure to allergens potently primes for EE via a Th2-dependent mechanism.

Akute idiopathische eosinophile Pneumonie

We report the case of a 23-year-old female admitted with high fever and dyspnoea who required intubation shortly afterwards because of severe respiratory failure. In the presence of diffuse bilateral infiltration, severe neutrocytosis and high CRP, bacterial pneumonia was diagnosed and treatment with ceftriaxone and clarithromycin was given. Despite this her condition deteriorated and no bacteria were detected in blood cultures and BAL. After 3 days of antibiotic therapy the leukocytosis was little changed but significant eosinophilia was observed. Under high dose corticosteroids the patient improved rapidly and could be extubated. In the absence of other causes of eosinophilia and pulmonary disease, acute idiopathic eosinophilic pneumonia was diagnosed. The clinical course was typical of this rare disease, which is most commonly observed between the ages of 20 and 40. Initial blood eosinophilia may be absent but may be observed in BAL or indicated by an elevated ECP serum level. The disease responds well to corticosteroid treatment.

Peripheral Blood Eosinophilia: An Unusual Presentation of Bone Marrow Involvement in a Patient with Relapsed Thyroid Papillary Carcinoma

Peripheral blood eosinophilia is a well-known paraneoplastic manifestation, but its underlying mechanism is still unclear. Bone marrow metastasis may be a cause of malignancy-associated eosinophilia. However, there is limited evidence of the relationship between bone marrow metastasis and eosinophilia. Herein, we present a unique case of peripheral blood eosinophilia associated with bone marrow invasion in a patient having a history of papillary thyroid carcinoma. A 68-year old woman showed peripheral blood eosinophilia (91,525/mm 3 ). Since the time she was initially diagnosed as having papillary thyroid carcinoma, eosinophilia had never been found and the other causes of eosinophilia were excluded. A bone marrow study revealed cancer cell infiltration; multiple lymphadenopathies and liver metastasis were also detected. We treated her with steroid; however, her eosinophilia did not respond to steroid and the patient died due to disease progression. Although peripheral blood eosinophilia and bone marrow metastasis are rare findings in patients with papillary thyroid carcinoma, we suggest that eosinophilia might be a sign of the bone marrow metastasis of papillary thyroid carcinoma. (Korean J Hematol 2005;40:274-277.) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Eosinophilia due to osteomyelitis in a dog

A dog with a lesion in the left elbow area and presence of purulent materials was referred to hospital; history, clinical examination, laboratory test and radiological evaluation of the dog proved the presence of osteomyelitis. Eosinophilia was evident by haematologic test. Intensive antibiotic, anti-inflammatory medication, local wound management and restricted physical activity, improved osteomelitis condition and reduced eosinophil number. Therefore it seemed that osteomyelitis was the cause of eosinophilia in this dog.