montelukast and Eosinophilia

Eosinophilic gastrointestinal disorders, also known as eosinophilic gastroenteritis, are rare inflammatory conditions characterized by eosinophilic infiltration of different parts of the gastrointestinal tract, along with peripheral eosinophilia in most cases. Other known causes for gut eosinophilic infiltration must be excluded to confirm the diagnosis of eosinophilic gastroenteritis. Symptoms of the disorder depend on the affected gastrointestinal tract segment and depth of involvement. Treatment includes systemic glucocorticoids and/or dietary therapy with an empiric elimination diet. Second line therapies include the leukotriene receptor antagonist montelukast, and other anti-allergy drugs such as mast cell stabilizers (including cromolyn and the H1-antihistamine ketotifen), suplatast tosilate which is a selective Th-2 cytokines (IL-4 and IL-5) inhibitor, and the monoclonal anti-IgE antibody omalizumab. We report a case of eosinophilic gastroenteritis who was successfully treated and achieved remission with montelukast as an initial monotherapy. Upon extensive literature review, this represents the second reported adult case of eosinophilic gastroenteritis who responds to montelukast alone as a first line therapy.. A 49-year-old female presented with recurrent abdominal pain, vomiting, diarrhea and unexplained eosinophilia. She was diagnosed with eosinophilic gastroenteritis and was successfully treated with montelukast monotherapy. After 7 days of therapy, the patient responded well and had complete resolution of her gastrointestinal symptoms and peripheral eosinophilia. Patient remained in remission on follow-up after 12 months. We reviewed the literature for leukotriene antagonist use in the treatment of eosinophilic gastroenteritis and included the cases treated with the leukotriene antagonist montelukast as an initial therapy or as a second line therapy for refractory disease.. Montelukast may be an effective treatment for eosinophilic gastroenteritis, either alone or in combination with systemic steroids or ketotifen. Our patient is the second reported adult case of eosinophilic gastroenteritis who responded to montelukast alone as a first line therapy. Further studies and clinical trials are required to confirm efficacy compared to standard therapy.

Topics: Acetates; Adult; Cyclopropanes; Enteritis; Eosinophilia; Female; Gastritis; Gastroenteritis; Humans; Middle Aged; Quinolines; Sulfides

Eosinophilic esophagitis (EE) is a disease that is being recognized with increasing frequency. In children it is responsible for feeding disorders, vomiting, reflux symptoms and abdominal pain and in adults it causes dysphagia and esophageal food impactions. The diagnosis requires the histologic finding of > 20 eosinophils per high powered field in esophageal squamous mucosa. The most common treatment regimens in children and adults involve the ingestion of topical corticosteroids. Symptomatic relapse after one treatment course is common, and many patients require repeated courses of treatment. The long-term prognosis of EE is largely unknown.

Topics: Acetates; Adrenal Cortex Hormones; Allergens; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Catheterization; Cyclopropanes; Diet; Eosinophilia; Esophagitis; Food Hypersensitivity; Humans; Leukotriene Antagonists; Prognosis; Quinolines; Sulfides

Eosinophilic esophagitis (EE) is a relatively new, chronic, TH 2-type allergic inflammation of the esophagus. EE occurs more frequently in men. Allergic diseases such as asthma or atopic dermatitis are present in 50-70 % of patients or their relatives. In adults, the most common presenting symptom of EE is dysphagia, with or without food bolus impaction. Endoscopic findings of EE include mucosal furrows, corrugated or concentric rings or ridges in the esophagus ("feline esophagus"), with or without tiny whitish exudates. The diagnosis is confirmed by the observation of high counts of eosinophils in the esophageal epithelium (at least 24 /HPF). The cornerstones of medical therapy are either topical or systemic corticosteroids. Additional therapies included leukotriene receptor antagonists (montelukast) and IL-5 blockers (Mepolizumab). Complications of EE such as esophageal strictures should be carefully dilated using either bougies or a balloon. Currently it is still not known whether the late complications of EE can be prevented by the use of anti-inflammatory agents and this can only be demonstrated through further long-term follow-up studies.

Topics: Acetates; Adrenal Cortex Hormones; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bezoars; Catheterization; Cyclopropanes; Deglutition Disorders; Eosinophilia; Eosinophils; Esophagitis; Esophagoscopy; Humans; Leukocyte Count; Quinolines; Sulfides; Th2 Cells

Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Asthma; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Eosinophilia; Female; Humans; Male; Poland; Prospective Studies; Quinolines; Seasons; Spirometry; Sputum; Sulfides

No studies have directly compared the effects of immunotherapy and antileukotrienes due to the long time required to appreciate the clinical effects of immunotherapy. We compared the effect of montelukast (MK) and SLIT added to standard therapy in moderate asthma over 5 years.. Open randomized controlled trial. Patients with moderate asthma (and rhinitis) solely due to birch pollen were randomized to receive either MK (10 mg/d) or birch sublingual immunotherapy (SLIT) in the pollen seasons, in addition to formoterol/fluticasone. All the patients also received salbutamol and cetirizine as rescue medications. Asthma and rhinitis symptoms were recorded on diary cards from February to May at baseline and after 3 and 5 years of study. In-season nasal eosinophils and bronchial hyperresponsiveness were also evaluated.. Thirty-three adult patients were enrolled and 29 completed the study. The groups were homogeneous at baseline. Bronchial and nasal symptom scores were lower at 3 and 5 years compared to baseline in the SLIT group. Bronchial hyperresponsiveness and bronchodilator use decreased significantly in both groups at 5 years, but only in the SLIT group at 3 years. In the SLIT group there was a significant decrease in nasal eosinophils compared to baseline and to the MK group.. In patients with birch pollen-induced moderate asthma and rhinitis, the addition of SLIT provides a greater clinical benefit than that of MK.

Topics: Acetates; Administration, Sublingual; Adolescent; Adult; Aged; Antigens, Plant; Asthma; Betula; Cell Count; Cyclopropanes; Desensitization, Immunologic; Disease Progression; Eosinophilia; Female; Follow-Up Studies; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Obstruction; Quinolines; Rhinitis, Allergic, Seasonal; Sulfides

Airway inflammation is a key pathological feature of asthma which underlies its clinical presentation.. To examine whether adding a leukotriene modifier to an inhaled corticosteroid produces further clinical and/or anti-inflammatory benefits in patients symptomatic on short-acting beta(2)-agonists.. Patients uncontrolled on short-acting beta(2)-agonists were treated for 12 weeks with either fluticasone propionate (100mcg BD) or fluticasone propionate (100mcg BD) and montelukast (10mg QD) in a randomized, double-blind, parallel group study. Bronchoscopy with endobronchial biopsy and bronchoalveolar lavage (BAL) was performed before and after treatment to compare effects on airway inflammation.. Of 103 subjects enrolled, 89 subjects completed treatment and 82 subjects had matched pair biopsy samples. Submucosal eosinophil counts, the primary endpoint, and asthma control improved to similar extents after both treatments (p

Topics: Acetates; Administration, Inhalation; Adult; Androstadienes; Asthma; Bronchi; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Eosinophilia; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Quinolines; Sulfides; Treatment Outcome

We have previously demonstrated the clinical efficacy of montelukast in a randomized double-blind controlled cross-over trial in patients with dyspepsia in association with duodenal eosinophilia. The mechanism of this clinical response is unknown but could involve a decrease in eosinophil density or activation.. Twenty-four dyspeptic patients 8-17 years of age underwent initial blood sampling and endoscopy with biopsy. Eighteen of these patients had elevated duodenal eosinophil density and underwent repeat blood sampling and endoscopy following 21 days of therapy with montelukast (10 mg/day). The following were determined: global clinical response on a 5-point Lickert-type scale, eosinophil density utilizing H & E staining, eosinophil activation determined by degranulation indices on electron microscopy, and serum cytokine concentrations. On day 21, pharmacokinetics and duodenal mucosal drug concentrations were determined.. Eighty-three percent of the patients had a positive clinical response to montelukast with regard to relief of pain with 50% having a complete or nearly complete clinical response. The response was unrelated to systemic drug exposure or to mucosal drug concentration. Other than a mild decrease in eosinophil density in the second portion of the duodenum, there were no significant changes in eosinophil density, eosinophil activation, or serum cytokine concentrations following treatment with montelukast. Pre-treatment TNF-alpha concentration was negatively correlated with clinical response.. The short-term clinical response to montelukast does not appear to result from changes in eosinophil density or activation. Whether the effect is mediated through specific mediators or non-inflammatory cells such as enteric nerves remains to be determined.. ClinicalTrials.gov; NCT00148603.

Topics: Acetates; Adolescent; Biopsy; Cell Count; Child; Cyclopropanes; Cytokines; Dose-Response Relationship, Drug; Duodenum; Dyspepsia; Eosinophilia; Eosinophils; Female; Humans; Intestinal Mucosa; Leukotriene Antagonists; Male; Quinolines; Sulfides; Treatment Outcome

Sputum eosinophilia is a sensitive predictor of benefit from corticosteroid treatment. Montelukast is a cysteinyl leukotriene antagonist, which also reduces sputum and blood eosinophils. The present study examined the possibility that montelukast has an added eosinophil-lowering effect in subjects with asthma who are corticosteroid responsive but relatively corticosteroid resistant. A total of 14 clinically stable adults with asthma requiring minimum treatment with a high-dose inhaled steroid or prednisone, with baseline sputum eosinophilia (> or =5%), were randomised to receive 4 weeks of 10 mg montelukast or placebo daily in a double-blind crossover trial. The primary outcome was the effect of treatment on the percentage of sputum eosinophils. Secondary outcomes were changes in the blood eosinophil count, symptoms, forced expiratory volume in one second, peak expiratory flow and the need for salbutamol. The median (interquartile range, i.e. 75th-25th centile) for sputum eosinophils at baseline was 15.7% (22). The effect of adding montelukast was not significantly different from that of placebo, sputum eosinophils being 9.3% (18.9) after montelukast and 11.3% (22.8) after placebo. No difference was detected on secondary outcomes. No crossover interactions were observed. In conclusion, the addition of montelukast to existing high-dose corticosteroid therapy in subjects with asthma with elevated sputum eosinophils does not provide additional attenuation of airway eosinophilia.

Topics: Acetates; Adult; Aged; Analysis of Variance; Asthma; Cross-Over Studies; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Eosinophilia; Eosinophils; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Prednisone; Probability; Quinolines; Reference Values; Respiratory Function Tests; Risk Assessment; Severity of Illness Index; Sputum; Sulfides; Treatment Failure

Twenty-four consecutive patients with symptomatic nasal polyposis and nonallergic or perennial rhinitis who were undergoing chronic nasal steroid therapy were prospectively evaluated for response to adjunctive oral montelukast sodium therapy.. The patients were undergoing daily intranasal steroid sprays for a minimum of 6 months before being started on montelukast sodium 10 mg by mouth per day for 3 months while intranasal steroids were continued. The patients were given a validated symptom score survey at the start and end of therapy, with a lower score indicating fewer symptoms. The nasal polyps were submitted to biopsy before and after treatment to determine their degree of eosinophilia. Eosinophilia was graded in a blinded fashion by an independent pathologist on a scale of 0 to 3, with 3 being severe. Patients with seasonal allergies were excluded, and the studied patients were treated during the winter season to avoid confounding by potential seasonal allergic responses.. The patients tended to improve on montelukast therapy in terms of their symptom scores and polyp eosinophil counts. The symptoms improved in 17 patients (71%) and remained the same or worsened in 7 patients (29%). The symptom score for the group improved from a pretreatment value of 33.4 (SD, 7.73) to a posttreatment value of 23.3 (SD, 13.73; p < .001). In addition, the eosinophilia score improved from 2.3 (SD, 0.68) to 1.5 (SD, 0.82; p < .01). The improvement was most noticeable in the patients with perennial allergies.. These results suggest that montelukast appears to be beneficial for some patients with nasal polyposis. Patients with perennial allergies and nasal polyposis seem more likely to respond to the treatment than those with nonallergic nasal polyposis.

Topics: Acetates; Administration, Intranasal; Biopsy; Cyclopropanes; Eosinophilia; Humans; Leukotriene Antagonists; Nasal Polyps; Prospective Studies; Quinolines; Sulfides; Treatment Outcome

Montelukast, a competitive cysteinyl leucotriene-1 receptor antagonist, reduces airway eosinophilia in asthmatics. We evaluated the effect of this drug in children with eosinophilic duodenitis, defined histologically as duodenal mucosa with peak eosinophil count of more than 10 eosinophils/hpf.. Forty children and adolescents (6-18 yr) with dyspepsia and duodenal eosinophilia were enrolled in a double blind, randomized, placebo-controlled, cross-over study of monteleukast therapy. Subjects were randomized to receive either 10 mg montelukast or an identical placebo once daily and were evaluated on day 14 for symptomatic and biochemical responses. Subjects were also randomized to one of two blood sampling schemes to evaluate montelukast pharmacokinetics.. Using a post treatment global pain assessment, a positive clinical response was observed in 62.1% of patients receiving montelukast compared with 32.4% on placebo (p < 0.02). Pain assessment score deteriorated in 45% of montelukast responders (5/11) after cross-over to placebo and improved in 62% (8/13) of placebo non-responders on cross-over to montelukast. In patients with peak duodenal eosinophil counts between 20-29/hpf (n=19), a positive pain assessment response was observed in 84% of patients receiving montelukast compared to 42% receiving placebo (p < 0.01). Response rate did not differ by age, gender or histologic findings at baseline. Pharmacokinetic analysis yielded parameter estimates for absorption rate constant (Ka), apparent volume of distribution (Vd/F) and elimination rate constant (Kel) of 0.42 h, 0.19 L/kg and 0.26 h, respectively. The relative extent of systemic drug exposure was comparable to that observed in previous pediatric investigations with similar weight-adjusted montelukast doses. Neither dose nor calculated drug exposure were associated with the level of post treatment pain assessment or the change in biochemical markers.. These data suggest a beneficial role for montelukast in the treatment of pediatric patients with dyspepsia associated with duodenal eosinophilia.

Topics: Acetates; Adolescent; Child; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Duodenal Diseases; Dyspepsia; Eosinophilia; Female; Humans; Intestinal Mucosa; Leukotriene Antagonists; Male; Pain; Quinolines; Sulfides; Treatment Outcome

Immune-mediated inflammation contributes to progressive pulmonary damage in cystic fibrosis (CF). Sputum cysteinyl leukotriene levels, eosinophil cationic protein (ECP), and interleukin-8 (IL-8) are significantly related to disease severity.. The aim of this study was to evaluate the anti-inflammatory and clinical effects of the cysteinyl leukotriene receptor antagonist montelukast in children with CF.. A double-blind, randomized, crossover design was used. Patients received montelukast (6 to < or = 14 years, 5 mg; > 14 years, 10 mg) or placebo as a once-daily tablet for 21 days and then, after a washout period of at least 4 weeks, crossed over to receive the alternative treatment. Blood and native nasal fluid were taken on days 1 and 21 of each treatment block, and WBC count, ECP, and IL-8 were analyzed using a chemiluminescent immunometric assay.. Sixteen CF patients (10 boys, 6 girls; age, 5 to 18 years, median 9.5 years) completed the trial. There was a significant (P < or = 0.02) reduction of serum ECP (median reduction: montelukast 7.7 microg/L vs placebo 0.15 microg/L) and eosinophils (P < or = 0.027; median reduction: montelukast 85/microL vs placebo 0/microL). There was no significant change in nasal ECP, IL-8, or serum IL-8 after a 21-day course of montelukast. Clinical symptom scores did not change significantly.. Montelukast reduces eosinophilic inflammation in CF patients. Multicenter trials providing more patients to create more data to prove the hypothesis that montelukast is an effective tool to cut down disease severity in CF patients are needed.

Topics: Acetates; Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Blood Proteins; Child; Cross-Over Studies; Cyclopropanes; Cystic Fibrosis; Double-Blind Method; Eosinophil Granule Proteins; Eosinophilia; Humans; Inflammation; Interleukin-8; Leukocyte Count; Leukotriene Antagonists; Membrane Proteins; Pilot Projects; Quinolines; Receptors, Leukotriene; Respiratory Function Tests; Ribonucleases; Sulfides; Treatment Outcome

Topics: Acetates; Anti-Allergic Agents; Arylsulfonates; Child; Cyclopropanes; Diarrhea; Diet; Enteritis; Eosinophilia; Food Hypersensitivity; Gastritis; Humans; Male; Quinolines; Sulfides; Sulfonium Compounds; Terfenadine; Treatment Outcome

The aim of our study was to analyze the montelukast effectiveness in improving oculonasal symptoms, patient-reported outcomes (PROs), and eosinophilic biomarkers in patients with nonallergic rhinitis eosinophilic syndrome (NARES).. We enrolled prospectively 80 symptomatic patients treated with 10 mg once a day of montelukast in monotherapy for 2 months. All patients were investigated before and after treatment. Nasal symptoms (nasal obstruction, rhinorrhoea, sneezing, nasal itching), ocular symptoms (redness/puffiness, watery eyes), and other PROs (olfactory dysfunction, difficulty going to sleep, nighttime awakenings, and nasal congestion on awakening) were scored by visual analogic scale. The following clinical scores were assessed: Total Nasal Symptom Score (T4NSS), Total Ocular Symptom Score (T2OSS), Total Symptom Score of Patient-Reported Outcomes (TSS-PROs), and a Composite Symptoms Score (CSS). Patients were classified as responders when a reduction of at least 50% of the CSS was observed. Before and after treatment, the eosinophilic biomarkers in nasal lavage were analyzed: nasal eosinophilia (number of eosinophils per high power field), eotaxin-1 and eotaxin-2.. After treatment, significant reductions were observed for all the symptom scores. Forty-two of 78 patients were considered responders. A significant reduction of eosinophils in nasal mucosa and of levels of eotaxin-1 and eotaxin-2 in nasal lavage were observed after treatment in responder patients. Patients with asthma had an increased probability to be responders.. NARES patients may benefit from treatment with montelukast. In particular, the presence of concomitant asthma may be predictive of a greater efficacy.. 2 Laryngoscope, 129:551-557, 2019.

Topics: Acetates; Adult; Asthma; Biomarkers; Cyclopropanes; Eosinophilia; Eye Diseases; Female; Humans; Leukotriene Antagonists; Male; Nose Diseases; Prospective Studies; Quinolines; Rhinitis; Sulfides; Syndrome

The effectiveness of budesonide (BUD), a locally active steroid, on eosinophilic gastroenteritis (EGE) is not well understood. This study is to retrospectively evaluate the efficacy of BUD in children with EGE.. Forty-four children, diagnosed with EGE, were enrolled from 2013 to 2017 in our center. According to patients' preference, all the patients were treated with dietary elimination (DE) and montelukast therapy, or combined with prednisone (PRED)/BUD. Patients' clinical manifestations, treatments, and outcomes were reviewed from the medical records. Twenty-four patients (7 PRED, 7 BUD, 10 DE) received therapy for ≥8 weeks, followed by repeat endoscopy and biopsies. Histological response was defined as <20 eos/hpf (eosinophils per high-power field).. Significant number of patients in DE+PRED (6/7, 85.7%) and DE+BUD (6/7, 85.7%) groups achieved histological response than in the DE group (3/10.30%) (p = 0.024). Mean post-treatment peak eos/hpf in the DE+PRED group was 16.57 ± 6.85 vs. 10.00 ± 5.07 in the DE+BUD group vs. 36.60 ± 24.57 in the DE group (p = 0.009). Change of eos/hpf from pre- to post-treatment was -49.86 ± 45.02 vs. -34.29 ± 23.44 in the BUD group vs. -0.3 ± 23.95 in the DE group (p = 0.011). There were no significant differences between DE+PRED and DE+BUD groups (p = 0.470, p = 0.363, respectively).. BUD is effective in the treatment of EGE and has similar effectiveness with PRED.

Topics: Acetates; Adolescent; Biopsy; Budesonide; Child; Child, Preschool; Cyclopropanes; Endoscopy; Enteritis; Eosinophilia; Eosinophils; Female; Gastritis; Humans; Infant; Male; Prednisone; Quinolines; Retrospective Studies; Sulfides; Treatment Outcome

The epidemiology of eosinophilic gastroenteritis remains unclear. We aim to determine the prevalence of eosinophilic gastroenteritis in patients with lower abdominal symptoms.. In a prospective study, colonoscopy was performed on 2,469 consecutive patients. Biopsies were taken from the terminal ileum and ascending, transverse, descending and sigmoid colon in all patients.. Sixty-four of the 2,469 patients (2.6%) had eosinophilic gastroenteritis. Only five of the 64 patients (7.8%) with eosinophilic gastroenteritis had endoscopic mucosal abnormalities during colonoscopy. Six of these 64 patients (9.4%) had severe disease at presentation, and seven of these 64 patients (10.9%) required systemic steroid treatment. An elevated absolute peripheral eosinophil count was independently associated with severe disease at presentation (4/6 [66.7%] vs 3/58 [5.2%], p=0.005; odds ratio [OR], 25.320; 95% confidence interval [CI], 2.628 to 243.910), and severe disease at the time of presentation was independently associated with the use of systemic steroid treatment (6/7 [85.7%] vs 0/57 [0%], p=0.008; OR, 18.021; 95% CI, 2.163 to 150.152).. The prevalence of eosinophilic gastroenteritis is common, and patients usually present normal-appearing mucosa on colonoscopy. Those with severe disease at presentation usually have a raised absolute peripheral eosinophil count and should be commenced on systemic steroids as an initial therapy.

Topics: Abdominal Pain; Acetates; Adolescent; Adult; Anti-Inflammatory Agents; Colon, Descending; Colon, Sigmoid; Colonoscopy; Cyclopropanes; Drug Therapy, Combination; Enteritis; Eosinophilia; Female; Gastric Mucosa; Gastritis; Humans; Ketotifen; Male; Middle Aged; Prednisolone; Prevalence; Prospective Studies; Quinolines; Republic of Korea; Sulfides; Treatment Outcome; Young Adult

The patient presented with bloody diarrhoea, and crampy abdominal pains. She was diagnosed with eosinophilic gastroenteritis (EGE) after the finding of persistently high peripheral eosinophil counts and histology of endoscopic biopsies. She responded to steroids but became dependent on it and her symptoms recurred on steroid tapering. There was little improvement with alternative treatment such as budesonides, azathioprine and montelukast. Surprisingly her symptoms improved significantly after she was treated with clarithromycin for chest infection and she was continued on clarithromycin. Her eosinophil counts fell dramatically and follow-up CT (thorax, abdomen and pelvic) scan showed the mucosal thickening had improved. She became completely free of the symptoms since she was on clarithromycin and her eosinophils counts fell within the normal range during the follow-up.

Topics: Acetates; Adult; Anti-Bacterial Agents; Azathioprine; Biopsy; Budesonide; Clarithromycin; Cyclopropanes; Endoscopy; Enteritis; Eosinophilia; Eosinophils; Female; Gastritis; Gastroenteritis; Humans; Leukocyte Count; Macrolides; Mucous Membrane; Quinolines; Sulfides

Eosinophilic peritonitis is a recognised complication of peritoneal dialysis and has an incompletely understood pathophysiology. Current treatment options, including change of dialysate, change of peritoneal dialysis modality, steroids or antihistamines, are supported only by case reports with a lack of controlled trials or evidence-based guidelines. Leukotrienes are proinflammatory arachidonic acid metabolites produced by leucocytes and are involved in eosinophil chemotaxis. Montelukast is an orally administered leukotriene receptor antagonist commonly used in managing childhood atopic illnesses and theoretically safe for use in patients with renal failure.. We describe the first reported case of recurrent, symptomatic, eosinophilic peritonitis in a 15-year-old girl successfully treated with leukotriene receptor antagonist montelukast after changes in dialysate and treatment with antihistamines failed to adequately control eosinophilic peritoneal infiltrates or symptoms.. Current scientific understanding of leukotrienes and eosinophil migration suggest that montelukast may be a well-tolerated, safe and efficacious treatment for eosinophilic peritonitis complicating peritoneal dialysis. Further cases and comparative studies are required to develop an evidence base for treatment of this condition.

Topics: Acetates; Adolescent; Cyclopropanes; Eosinophilia; Female; Humans; Leukotriene Antagonists; Peritoneal Dialysis; Peritonitis; Quinolines; Sulfides

Topics: Acetates; Aged; Anti-Bacterial Agents; Cyclopropanes; Drug Eruptions; Endocarditis, Bacterial; Eosinophilia; Humans; Immunoglobulins, Intravenous; Male; Methylprednisolone; Quinolines; Sulfides; Syndrome; Treatment Outcome; Vancomycin

The aim of this study was to further explore the possible mechanisms of montelukast on oral mice ovalbumin-induced eosinophilic gastroenteritis in a mouse model. The results indicated that montelukast could prevent levels of eotaxin-1 and interleukin-5 in intestinal mucosa homogenate when compared with model group. Interestingly, the increase of major basic protein expression in jejunal tissue also was attenuated by treated with montelukast.

Topics: Acetates; Animals; Chemokine CCL11; Cyclopropanes; Enteritis; Eosinophil Major Basic Protein; Eosinophilia; Gastritis; Gene Expression Regulation; Interleukin-5; Leukotriene Antagonists; Mice; Mice, Inbred BALB C; Ovalbumin; Quinolines; Sulfides

Gastrointestinal eosinophilic (EG) is a rare and heterogeneous condition characterized by patchy or diffuse eosinophilic infiltration of gastrointestinal tissue. Pharmacological study so far has demonstrated that montelukast, an oral leukotriene receptor antagonist, might be considered in patients with this disease. The aim of this study was to evaluate the effect of montelukast on oral ovalbumin (OVA) allergen induced EG inflammation in mice and to suggest some mechanisms underlying this effect. Twenty-four mice were divided into three experimental groups: PBS control, OVA group, and montelukast treated group. The mice were sensitized intraperitoneally and challenged intragastrically with OVA, and were treated with montelukast. Gastrointestinal symptoms were observed after challenged intragastrically with OVA. Eosinophils count in blood, serum OVA specific IgE and gastrointestinal histology were evaluated. Montelukast could significantly reduce the severity of oral allergen-induced eosinophilic inflammation, villous atrophy, and associated symptoms of weight loss associated with diarrhea. Montelukast also could ameliorate OVA-induced gastrointestinal pathological lesions, which was associated with the decrease of IgE and LTD4 levels, and this might be one of the important mechanisms of montelukast that protected gastrointestinal injury from EG. These findings indicated that montelukast therapy may be a novel therapeutic approach for EG and other eosinophil-mediated diseases.

Topics: Acetates; Animals; Body Weight; Cyclopropanes; Enteritis; Eosinophilia; Eosinophils; Female; Gastric Mucosa; Gastritis; Gastroenteritis; Immunoglobulin E; Inflammation; Jejunum; Leukotriene D4; Mice; Mice, Inbred BALB C; Ovalbumin; Quinolines; Stomach; Sulfides

Previously described treatments used for eosinophilic diseases of the gastrointestinal tract have included dietary restrictions primarily of cow milk protein, anti-inflammatory therapy utilizing suplatast, budesonide and corticosteroids, cromolyn sodium, anti-histamines and oral inhalable steroids. We describe a 12-year-old girl with diarrhea and malabsorption, who was later diagnosed to have eosinophilic gastroenteritis, was unresponsive to standard therapies, but exhibited marked improvement with use of montelukast.

Topics: Acetates; Child; Cyclopropanes; Diagnosis, Differential; Diarrhea; Endoscopy, Gastrointestinal; Enteritis; Eosinophilia; Female; Gastritis; Humans; Leukotriene Antagonists; Malabsorption Syndromes; Quinolines; Sulfides; Treatment Outcome

Hypereosinophilic syndrome (HES) is defined by significant eosinophilia (>1,500 eos/μl), which often leads to end-organ damage/dysfunction. It is unclear if the presence of significant peripheral eosinophilia (>1,500 eos/μl) indicates a more aggressive form of eosinophilic gastrointestinal disorder (EGID).. A database query of the Mayo Clinic Rochester electronic records (1995-2008) was performed using several search terms for eosinophilic gastrointestinal disease, and 161 records were reviewed. Patients under 18 years age, those without Mayo-reviewed pathology specimens, those with eosinophilic esophagitis only, and/or those with evidence of secondary etiologies for GI eosinophilia were excluded. A total of 39 were found to have primary EGID. We compared individuals with biopsy-proven primary EGID based on whether they had significant peripheral eosinophilia (≥1,500 eos/μl) (group A) or not (group B).. Group A tended to have more atopy (A: 12/15; B: 11/24; p = 0.03) and more extensive segmental involvement of the GI tract (p = 0.001). None with available studies had evidence of cardiac (A: 7/15; B: 6/24) or bone marrow (A: 10/15; B: 6/24) involvement. The two thromboembolic events in group A after diagnosis did not translate to significantly greater risk (HR = infinity, p = 0.13; group A vs. B). Doses of initial (A: 40 mg/day; B: 55 mg/day; p = 0.17) and maintenance prednisone (A; 8.75 mg/day; B: 7.5 mg/day; p > 0.90) were similar. Group A was significantly more likely to need maintenance prednisone (77 vs. 8%, p = 0.001), with a median treatment duration of 52 weeks. Recurrence of symptoms (and peripheral eosinophilia) during prednisone taper was common in both groups. Prednisone-sparing agents (hydroxyurea, imatinib mesylate, interferon (IFN)-α2b, anti-interleukin (IL-5) monoclonal antibody) were more commonly used in group A (73 vs. 8%; p < 0.0001).. EGID with peripheral eosinophilia ≥1,500/μl is associated with atopy, greater GI segmental involvement, and uncertain risk of thrombosis. The common use of long-term steroids and variable responsiveness to nonsteroidal agents, particularly in group A, underscores the need for targeted therapies.

Topics: Acetates; Adolescent; Adult; Aged; Antibodies, Monoclonal; Antineoplastic Agents; Biomarkers; Cyclopropanes; Enteritis; Eosinophilia; Female; Gastritis; Gastrointestinal Tract; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Retrospective Studies; Sulfides; Young Adult

Eosinophilic Gastroenteritis (EG) is a rare condition, caused by eosinophilic inflammatory infiltrates in the gastrointestinal tract. It is usually treated successfully with systemic glucocorticoids. Because of frequent relapses, however, there is need for alternatives. We describe a 38-year old man with steroid-dependent EG, who was successfully treated with montelukast, a leukotriene receptor antagonist. It inhibits leukotriene D4, an important cytokine in the inflammatory cascade. Although montelukast could not replace steroid therapy, it acted as a steroid sparing agent in our patient. Review of the literature shows that montelukast is efficient in the treatment of EG in a part of the patients. The low cost, the low number of side effects and its efficiency make it an interesting alternative in relapsing or steroid dependent EG. There is need for multicentric studies regarding the treatment of EG.

Topics: Acetates; Adult; Cyclopropanes; Eosinophilia; Gastroenteritis; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides

The de novo development of myocarditis during left ventricular assist device support for dilated cardiomyopathy has not been previously described. We report a case of severe eosinophilic myocarditis associated with the use of leukotriene-receptor antagonist montelukast that developed during left ventricular assist device support accompanied by intra-device thrombus formation that was hemodynamically tolerated and subsequently discovered in the explanted heart. There may be no visible change in cardiac function as assessed by echocardiography, but the diagnosis should be entertained with the development of peripheral eosinophilia.

Topics: Acetates; Cardiomyopathy, Dilated; Cyclopropanes; Eosinophilia; Female; Heart Transplantation; Heart-Assist Devices; Humans; Leukotriene Antagonists; Middle Aged; Myocarditis; Quinolines; Sulfides; Thrombosis

Eosinophilic esophagitis in adults (EE) is a disease of unknown cause, characterized by symptoms such as reflux and dysphagia that traditionally do not respond to antacid treatment. It affects mostly young men with a strong personal or familial history of atopy asthma and allergies. We report three male patients aged 10, 14 and 15 years, all with symptoms of dysphagia, two of them with chest pain caused by spasm of the esophagus, with heterogeneous endoscopic findings which included from leucoplakia to stenosis that needed endoscopic dilatation. All of them had abnormal findings in immunity studies (prick test or IgE levels). They received treatment based on diet measures, acid suppression and leukotriene inhibitors, with satisfactory clinical, endoscopic and histological response. EE should be suspected in children and adults with esophageal symptoms and personal or family history of allergy and asthma.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetates; Adolescent; Child; Cyclopropanes; Eosinophilia; Esophagitis; Esophagoscopy; Humans; Lansoprazole; Male; Omeprazole; Quinolines; Sulfides

A 47 year old woman who had a history of asthma for 15 years referred to our hospital because of infiltrates on her chest radiograph that not responded to antibiotic treatment. We found that she had eosinophilia in peripheral blood (38%) and bronchoalveolar lavage (54%), nasal polyposis, and transient pulmonary infiltrates, and in the base of these findings we diagnosed as Churg-Strauss Syndrome (CSS). She has been using montelukast for 2 years. By examining her previous medical records, we observed that while eosinophil rates in peripheral blood were normal before montelukast usage, after this therapy eosinophil rates were greater 10 percent. Therefore, we thought that CSS was to be associated with montelukast usage. After just montelukast therapy was discontinued, clinical and radiographic parameters and the eosinophil counts (20%) improved. We present this case of CSS associated with montelukast in whom spontaneous remission was observed without using corticosteroids and cytotoxic agents.

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Churg-Strauss Syndrome; Cyclopropanes; Eosinophilia; Eosinophils; Female; Humans; Middle Aged; Quinolines; Sulfides

A 75-year-old woman with a history of asthma, rhinitis and nasal polyps was admitted due to petechial lesions on the lower left leg and weakness of the right foot. Six weeks prior to admission, she had started treatment with montelukast 10 mg daily. Based on the asthma, eosinophilia, mononeuritis of the right leg and a skin biopsy showing small vessel vasculitis with eosinophilic granulocytes, the patient was diagnosed with Churg-Strauss syndrome (CSS). After consulting with the pulmonologist, montelukast therapy was discontinued and replaced with a combined preparation of a parasympatholytic and a P2-sympathomimetic. The patient was also given prednisone 60 mg daily, which resulted in prompt clinical improvement and resolution of the eosinophilia. Development of CSS has been associated with the use of montelukast and should be considered in patients with asthma who develop new symptoms, such as neuritis, vasculitis of the skin or pulmonary infiltrates with an increase in eosinophilia during montelukast therapy. In these patients, treatment with montelukast should be discontinued, although whether a causal relationship exists between montelukast and CSS continues to be debated in the literature.

Topics: Acetates; Aged; Anti-Asthmatic Agents; Asthma; Churg-Strauss Syndrome; Cyclopropanes; Eosinophilia; Female; Humans; Quinolines; Sulfides

An otherwise healthy 20-year-old man was admitted to our hospital with obstruction of the oesophagus by a bolus after eating a chicken meal. These symptoms continued over the past 12 years and required multiple interventions at different hospitals. There was no history of any other previous illness and both the physical examination and routine laboratory tests were unremarkable.. Esophagogastroduodenoscopy (EGD) revealed segmental circular trachea-like constrictions of the esophagus and two stenoses at 35 cm and 40 cm. Histopathology of several biopsies favored the diagnosis of eosinophilic esophagitis.. After initial balloon dilatation and dilatation with a Savary bougie the patient was put on systemic steroids and montelukast (a leukotriene receptor antagonist). The symptoms subsequently disappeared.. Eosinophilic esophagitis, a unique form of esophageal inflammatory disease, consists of dense eosinophilic infiltration of the epithelium and is associated with various macroscopic findings, such as the rare but striking circular trachea-like constrictions, nodules, plaques and other forms of constriction of the esophagus. Several lines of evidence favor an allergic cause. The leading symptom is recurrent dysphagia after solid foods, sometimes accompanied by heart-burn. Medical treatment consists of topical or systemic administration of steroids and/or montelukast. A history of chronic dysphagia after eating solid food, combined with endoscopic findings atypical for reflux disease is highly suspicious of eosinophilic esophagitis in the differential diagnosis of gastroesophageal reflux disease in adults.

Topics: Acetates; Adult; Biopsy; Catheterization; Cyclopropanes; Deglutition Disorders; Diagnosis, Differential; Dilatation; Drug Therapy, Combination; Endoscopy, Digestive System; Eosinophilia; Esophageal Stenosis; Esophagitis; Esophagus; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Prednisolone; Quinolines; Sulfides

We report a rare case of eosinophilic cystitis in a 6-year-old boy who presented with irritative voiding symptoms, peripheral eosinophilia, and a bladder mass initially visualized on ultrasonography. Cystoscopy and transurethral biopsy confirmed the diagnosis. Complete resolution of his symptoms occurred within 1 week of corticosteroid use and the x-ray findings improved within 6 weeks. At 6 months of follow-up, the patient continued to require a leukotriene receptor antagonist (montelukast sodium) despite several attempts to discontinue its use. We propose that eosinophilic cystitis in children who present with peripheral eosinophilia will often require long-term treatment.

Topics: Acetates; Child; Cyclopropanes; Cystitis; Eosinophilia; Humans; Leukotriene Antagonists; Male; Quinolines; Remission Induction; Sulfides; Time Factors

Topics: Acetates; Adolescent; Cyclopropanes; Eosinophilia; Gastroenteritis; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Prednisolone; Quinolines; Recurrence; Sulfides

Topics: Acetates; Adult; Androstadienes; Anti-Inflammatory Agents; Biopsy; Cyclopropanes; Diagnosis, Differential; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Eosinophilia; Esophagitis; Fluticasone; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides

Eosinophilic gastrointestinal disorders are an emerging disease entity characterized by eosinophilic infiltration of the intestinal wall. Oral steroids can be still considered as first line treatment. Unfortunately relapses are quite common. Usually long term low-dose prednisone or immunosuppressive therapy is required, which is especially problematic in young patients. Thus a reliable steroid sparing agent with low side effects suitable for long term use is needed. There are strong hints to a similar pathophysiology of eosinophilic gastrointestinal disorders to that of asthma. Indeed leukotriene D4 plays an important role in the recruitment of eosinophils into the intestinal tissue causing damage. This patho-mechanism provides the rationale for the treatment with a leukotriene D4 receptor antagonist. Recently there have been first reports about successful short term use of Montelukast in eosinophilic gastrointestinal disorders.. We report the case of a 17 year old girl with a long history of severe abdominal complaints leading to several hospitalizations in the past. Mimicking the picture of an intestinal tuberculosis she received an anti mycobacterial treatment without any success. Marked eosinophilia in blood, ascites and tissue samples of the intestinal tract finally lead to the diagnosis eosinophilic gastroenteritis. Tapering off prednisone caused another severe episode of abdominal pain. At that point leukotriene antagonist Montelukast was started at a dose of 10 mg once daily. Steroids could be tapered off completely within six weeks. The patient has been free of symptoms for over two years by now. Routine examinations, blood tests and endoscopy have rendered regular results. So far no side effects were noted.. Here report about successful long term remission of eosinophilic gastroenteritis under Montelukast. Further randomized control trials are required to asses the full benefits of Montelukast therapy in the whole spectrum of eosinophilic gastrointestinal disorders.

Topics: Acetates; Adolescent; Cyclopropanes; Eosinophilia; Female; Gastroenteritis; Humans; Leukotriene Antagonists; Quinolines; Remission Induction; Sulfides

Topics: Acetates; Child; Cyclopropanes; Deglutition Disorders; Diet; Eosinophilia; Esophagitis; Esophagus; Follow-Up Studies; Humans; Leukotriene Antagonists; Quinolines; Steroids; Sulfides; Treatment Outcome

Topics: Acetates; Airway Obstruction; Asthma; Bronchial Hyperreactivity; Cyclopropanes; Eosinophilia; Humans; Leukotriene Antagonists; Quinolines; Respiratory Hypersensitivity; Sulfides; Treatment Outcome

The leukotriene modifiers are a novel generation of therapeutic agents in the treatment of allergic asthma. However, the mechanisms by which the cysteinyl (cys) leukotrienes (LTs) participate in allergen-induced airway eosinophilia and airway hyperresponsiveness (AHR) are still unclear. In the present study, we have investigated the role of cys-LTs in ovalbumin (OVA)-induced airway responses in a murine model of asthma. Montelukast (3 or 10 mg/kg), a selective cys-LT1 receptor antagonist, reduced airway eosinophilia and AHR after OVA challenge. The levels of interleukin (IL)-5 and eotaxin in the bronchoalveolar lavage fluid (BALF) from montelukast-treated (3 mg/kg) mice were unaffected, although a decrease in IL-5 was observed with a dose of 10 mg/kg. LTD4 (50 ng) instilled intranasally to immunized mice augmented macrophages in the BALF, but in conjunction with OVA challenge it caused BALF eosinophilia and neutrophilia when given before challenge and BALF neutrophilia but not eosinophilia when given 2 h after challenge. However, there were no increases of IL-5 or eotaxin in BALF following LTD4 treatment. Repeated instillations of LTD4 to immunized mice, mimicking allergen challenge, did not induce AHR but in conjunction with OVA challenge LTD4 enhanced AHR. These results indicate that allergen-induced eosinophilia and AHR are in part mediated by the cys-LT1 receptor, and that, although LTD4 alone has no effect on airway eosinophilia, in conjunction with antigenic stimulation it potentiates the degree of airway inflammation and AHR.

Topics: Acetates; Allergens; Animals; Bronchi; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Chemokine CCL11; Chemokines, CC; Cyclopropanes; Eosinophilia; Interleukin-5; Leukotrienes; Male; Mice; Mice, Inbred BALB C; Quinolines; Sulfides

Eosinophilic oesophagitis is a rarely diagnosed condition involving eosinophil infiltration of the oesophageal mucosa and creating significant symptoms of dysphagia. Failure to diagnose this disorder relates to reluctance to biopsy an apparently normal oesophagus. This is essential for histological diagnosis. To date, treatment success has been achieved only with corticosteroids. We describe here the use of an eosinophil stabilising agent Montelukast for the symptomatic relief of these patients.. Twelve patients have been identified with this condition in our unit since 1995, after thorough investigation of their dysphagia. We commenced eight of these patients on the leukotriene receptor antagonist Montelukast to symptomatically improve their swallowing while avoiding the use of long term corticosteroids.. Many of these patients had been previously misdiagnosed, and therefore inappropriately and unsuccessfully treated for an extensive period prior to referral to our unit. All patients were unresponsive to acid suppression therapy alone but showed improvement in their swallowing on Montelukast. Six of eight reported complete subjective improvement, five patients remaining completely asymptomatic on a maintenance regimen.. Eosinophilic oesophagitis is a disease that is often misdiagnosed due to lack of awareness and reluctance of clinicians to biopsy an apparently normal oesophagus in dysphagic patients, and therefore obtain a histological diagnosis. Investigation of these patients adds further evidence to this condition being a separate pathological state from gastro-oesophageal reflux and eosinophilic enteritis. Montelukast has been found to be of significant help in the symptomatic control of these patients while avoiding long term corticosteroids use.

Topics: Acetates; Adult; Age of Onset; Biopsy; Cyclopropanes; Deglutition Disorders; Eosinophilia; Esophagitis; Esophagoscopy; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Sulfides; Treatment Outcome

Eosinophilic gastroenteritis (EG) is an uncommon entity of which the pathogenesis is unclear. As no controlled treatment trials exist, treatment of EG remains largely empiric. Limited results have been achieved with oral cromolyn, ketotifen, and other antihistamines. Oral corticosteroids are effective, but long-term use is complicated by side effects including growth retardation, diabetes, and osteoporosis.. We sought to determine whether treatment with montelukast would improve symptoms and decrease both peripheral blood and tissue eosinophilia (TE) in a patients with steroid-dependent EG for 20 years complicated by esophageal stricture.. In an unblinded, n = 1 trial, we treated the patient for 5 months with montelukast (20 to 30 mg daily) while his baseline dose of prednisone (10 mg daily) was continued. Complete blood counts and symptoms were monitored weekly. Esophageal biopsies were obtained before and after 5 months of therapy with montelukast. After the posttreatment biopsy was obtained, montelukast was discontinued. Outcome measures included patient symptoms and peripheral and tissue eosinophil counts.. During treatment with montelukast, the mean peripheral blood eosinophil count fell from 5,064 cells/microL (average 28 determinations over 20 years; range 1,408 to 12,500 cells/microL) to 1,195 cells/microL (average 14 determinations over 16 weeks; range 556 to 2,193 cells/microL), a 76% reduction. The corresponding TE as calculated from esophageal biopsies was 31 eosinophils/high power field before and 70 eosinophils/high power field after treatment. The patient noted no appreciable improvement in esophageal symptoms.. Montelukast dramatically reduced peripheral blood eosinophilia, but did not affect TE or symptoms in this patient with severe, long-standing EG complicated by esophageal stricture.

Topics: Acetates; Adult; Cyclopropanes; Eosinophilia; Eosinophils; Esophageal Stenosis; Gastroenteritis; Humans; Leukocyte Count; Leukotriene Antagonists; Male; Quinolines; Sulfides; Treatment Outcome

Topics: Acetates; Adolescent; Child; Child, Preschool; Cyclopropanes; Eosinophilia; Female; Gastroenteritis; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides; Treatment Outcome

Topics: Acetates; Cyclopropanes; Eosinophilia; Esophagitis; Humans; Leukotriene Antagonists; Quinolines; Sulfides

Topics: Acetates; Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Churg-Strauss Syndrome; Cyclopropanes; Dose-Response Relationship, Drug; Eosinophilia; Fluticasone; Humans; Nebulizers and Vaporizers; Prednisolone; Quinolines; Sulfides

Patients with eosinophilic gastroenteritis generally respond well to corticosteroids but relapses are common. Patients with relapsing disease are usually placed on long-term low-dose prednisone or immunosuppressive therapy. Here we reported on a patient with severe steroid-dependent eosinophilic gastroenteritis who was able to successfully taper off steroids and maintain remission after starting montelukast, a leukotriene receptor antagonist. To our knowledge, this is the first use of montelukast as a steroid sparing agent for eosinophilic gastroenteritis.

Topics: Acetates; Adult; Cyclopropanes; Eosinophilia; Gastroenteritis; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Prednisone; Quinolines; Recurrence; Sulfides

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Autoimmune Diseases; Chromones; Churg-Strauss Syndrome; Cyclopropanes; Drug Hypersensitivity; Eosinophilia; Humans; Indoles; Leukotriene Antagonists; Leukotrienes; Lupus Erythematosus, Systemic; Phenylcarbamates; Quinolines; Sulfides; Sulfonamides; Th2 Cells; Tosyl Compounds

Topics: Acetates; Adolescent; Cyclopropanes; Eosinophilia; Female; Gastroenteritis; Humans; Leukotriene Antagonists; Quinolines; Sulfides