Transient Eosinophilia Research Articles

Eosinophilia and Adverse Effects of Dupilumab for Respiratory Indications: A Real-World Setting

BackgroundDupilumab has been used with significant benefit in the treatment of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Phase 3 clinical trials have demonstrated transient eosinophilia and rare eosinophil-related and other adverse effects. ObjectiveTo characterize dupilumab-associated eosinophilia (absolute eosinophil count [AEC] ≥ 1.5 x 103/μL within 36 weeks of dupilumab initiation) and adverse effects associated in real-world patients with asthma and CRSwNP in the United States. MethodsRetrospective chart review of 251 patients on dupilumab for asthma and/or CRSwNP seen at a single institution. ResultsAmong the 142 patients who had AECs checked before and after treatment, 16 (11.3%) patients had post-treatment eosinophilia, including 11 (7.7%) patients who had new eosinophilia upon dupilumab initiation. Thirteen patients with post-treatment eosinophilia remained on dupilumab, 10 of whom had resolution of eosinophilia. Eosinophil-related adverse effects were rare and cases of eosinophilic granulomatous polyangiitis (EGPA) were limited to 1 patient with eosinophilia and 1 patient with normal eosinophil levels on systemic steroids. Other adverse effects included arthralgias (13/251, 5.2%), rash (8/251, 3.2%), and conjunctivitis (7/251, 2.8%). All patients with pre-treatment eosinophilia and the majority of patients with post-treatment eosinophilia received significant treatment benefit for their respiratory disease with dupilumab. ConclusionWhile dupilumab-associated eosinophilia is seen in a subset of patients, persistent eosinophilia or eosinophil-related adverse effects are rare. Furthermore, treatment benefit on dupilumab despite eosinophilia supports its continued use in both asthma and CRSwNP.

A Systematic Evaluation of Dupilumab for Bullous Pemphigoid Treatment

This paper systematically reviews the current articles regarding the use of dupilumab in the treatment of bullous pemphigoid (BP) to evaluate its safety and efficacy. PubMed, Embase, Cochrane Library, and Web of Science databases were searched for publications on dupilumab for BP from inception to 10 March, 2023. A total of 26 studies were included for systematic review. The primary outcome was clinical remission, and the secondary outcomes were recurrence and adverse events. Among 96 patients, 71.8% (n = 69/96) received systemic or topical steroids, immunosuppressants, immunomodulators, intravenous immunoglobulins, antihistamines, plasmapheresis, rituximab, and omalizumab, but none of them were successful. After dupilumab treatment, 66.7% (n = 64/96) of patients achieved complete remission, 25.0% (n = 24/96) had partial remission, 5.2% (n = 5/96) showed no remission, and no patients experienced deterioration. In addition, 1.0% (n = 1/96) and 2.0% (n = 2/96) patients stopped using dupilumab due to adverse reactions and cost, respectively. The average remission time was 4.5 months. 46.2% (n = 25/96) of the patients were followed up with a median follow-up of 8 months and only 2 patients relapsed at 8 and 7 months, respectively. Adverse event was 16.9% (n = 12/71), of which transient eosinophilia was the most common. This study indicates that the dupilumab is a promising treatment for BP with high clinical benefit associated with low recurrence rate, adverse event rate, and mortality. However, a large-scale randomized controlled trial is needed to further confirm the safety and efficacy of dupilumab in patients with BP treatment.

Dupilumab-induced eosinophilia in patients with diffuse type 2 chronic rhinosinusitis.

Dupilumab, a monoclonal anti-IL-4Rα antibody, is approved for several type 2 mediated inflammatory diseases like asthma, atopic dermatitis, and diffuse type 2 chronic rhinosinusitis (CRS). Clinical studies had reported a transient increase in blood eosinophils during dupilumab therapy. This study aimed to assess the impact of elevated blood eosinophils on clinical outcome and to investigate the cause of high blood eosinophil levels under dupilumab therapy. Patients suffering from diffuse type 2 CRS treated with dupilumab were examined on days 0, 28, 90, and 180 after therapy start. Sino-Nasal-Outcome-Test Score (SNOT-22), Total Nasal Polyp Score (TNPS), and blood samples were collected. Cytokine measurements and proteomics analysis were conducted. Flow cytometry analysis measured receptor expression on eosinophils. Sixty-eighty patients were included. Baseline eosinophilia ≥0.3G/L was observed in 63.2% of patients, and in 30.9% of patients, eosinophils increased by ≥0.5G/L under dupilumab. Subjects with eosinophilia ≥0.3G/L at baseline had the best SNOT-22 mean change compared to no eosinophilia. Eosinophil elevation during dupilumab therapy had no impact on clinical scores. The eosinophil adhesion molecule VCAM-1 decreased significantly during therapy in all patients. The chemokine receptor CXCR4 was significantly down- and IL-4 upregulated in subjects with eosinophil increase. Our findings suggest that increased eosinophils in type 2 CRS are associated with a good clinical response to dupilumab. Patients with elevated IL-4 at baseline developed dupilumab-induced transient eosinophilia. We identified the downregulation of VCAM-1 and surface markers CD49d and CXCR4 on eosinophils as possible explanations of dupilumab-induced eosinophilia.

Eosinophilic granulomatosis with polyangiitis developed after dupilumab administration in patients with eosinophilic chronic rhinosinusitis and asthma: a case report

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is a form of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis characterized by eosinophil-rich granulomatous inflammation and small-to-medium vessel vasculitis associated with asthma, rhinosinusitis, and eosinophilia. EGPA is often difficult to distinguish from severe asthma and eosinophilic chronic rhinosinusitis (ECRS) in cases when there are no findings that suggest vasculitis. Dupilumab, an anti-IL-4Rα monoclonal antibody, is expected to be effective in eosinophilic airway inflammatory diseases, such as refractory asthma and chronic rhinosinusitis (CRS). Although transient eosinophilia and eosinophilic pneumoniae have been reported in patients with refractory asthma and CRS associated with dupilumab, few studies have examined the development of EGPA.Case presentationWe report a case of a 61-year-old woman treated with dupilumab for refractory ECRS and eosinophilic otitis media (EOM) complicated by severe asthma. Although she had a previous history of eosinophilic pneumoniae and myeloperoxidase (MPO) ANCA positivity, there were no apparent findings of vasculitis before the initiation of dupilumab. After the second administration of dupilumab, several adverse events developed, including worsening of ECRS, EOM and asthma, and neuropathy. A blood test showed an eosoinophilia and re-elevation of MPO-ANCA levels after the administration of dupilumab. Therefore, dupilumab was discontinued owing to the development of EGPA, and prednisolone and azathioprine administration was initiated for a remission induction therapy.ConclusionTo the best of our knowledge, this is the first case report that suggests that dupilumab may directly trigger the manifestation of vasculitis in patients who were previously MPO-ANCA-positive. Although the precise mechanism of how dupilumab could trigger the development of EGPA requires further elucidation, measuring MPO-ANCA in patients with multiple eosinophilic disorders before the initiation of dupilumab might be helpful when considering the possibility of a latent EGPA. When administering dupilumab to patients with a previous history of MPO-ANCA positivity, clinicians must carefully monitor and collaborate with other specialists in the pertinent fields of study for appropriate usage.

CLINICAL CHARACTERISTICS, ETIOLOGIES, AND OUTCOMES OF SEVERE EOSINOPHILIA IN PEDIATRIC PATIENTS

<h3>Introduction</h3> There is limited data in pediatric patients with severe eosinophilia defined as absolute eosinophil count (AEC) >5000 cells/µL. The goal of this study is to examine patient characteristics and outcomes of severe eosinophilia in pediatrics. <h3>Methods</h3> A retrospective chart review was conducted for patients (≤18 years old) with severe eosinophilia at a tertiary pediatric hospital from August 2010 to August 2020. Demographics, AEC at presentation and peak, resolution time, medications, underlying diagnoses, and treatment during eosinophilia were evaluated. <h3>Results</h3> Of 139,000 CBCs reviewed, 45 patients had severe eosinophilia and 56% were male and 67% were Caucasian. Severe eosinophilia was most commonly found during infancy (33%). The median presentation AEC was 6.08 K/µL (range 5.02-28) and median peak AEC was 6.68 K/µL (5.02-42). The median resolution time was 43 days (interquartile range 11.5-141.5). Nearly all but 2 patients had secondary eosinophilia from other conditions including neoplasm (n=10), prematurity with infection (n=7), atopic dermatitis (n=5), parasitic infection (n=3), asthma (n=2), primary immunodeficiency (n=2), ulcerative colitis (n=1), systemic juvenile idiopathic arthritis (n=1). 28 patients were exposed to antibiotic or antiepileptic drug within 3 months of eosinophilia, but none thought to be primarily associated with eosinophilia. None had drug reaction with eosinophilia and systemic symptoms. Majority of patients had resolution of severe eosinophilia: 2 with hypereosinophilic syndrome received steroids, 29 treated for underlying condition, 4 with transient eosinophilia, and 10 with unknown outcome. <h3>Conclusion</h3> Severe eosinophilia was most common in infancy. Majority of patients had secondary eosinophilia with resolution after treatment of underlying disease.

Use of Dupilumab in Glucocorticoid-Dependent Asthma

Of the patients with asthma, 20% to 25% progress to severe symptoms, resulting in poor quality of life and increased episodes of exacerbation. There is a broad range of drugs used for asthma; the most used medications for severe asthma are inhaled glucocorticoids with or without long-acting β-agonists. Systemic glucocorticoids and other treatments as add-on therapies are also given as needed. Chronic glucocorticoid use is associated with numerous adverse effects, including diabetes mellitus, osteoporosis, anxiety, depression, and cataracts. The occurrence of these side effects has been reduced because of the emergence of new biological therapies. One such treatment is dupilumab, which helps in the reduction of type 2 inflammation involved in the pathophysiology of asthma. We conducted a literature review to assess the efficacy, adverse effects, and pharmacological benefits of dupilumab in glucocorticoid-dependent asthma. In most randomized controlled trials, dupilumab has shown significant efficacy and safety profile in patients with severe asthma with corticosteroid dependence. Associated adverse effects such as injection site reaction and transient eosinophilia have been reported. Our review of the literature indicates that dupilumab has proven to improve lung function, reduce the rate of asthma exacerbations, and reduce the use of corticosteroids.

Elevation of peripheral blood eosinophils during dupilumab treatment for atopic dermatitis is associated with baseline comorbidities and development of facial redness dermatitis and ocular surface disease

Introduction Transient eosinophilia is not uncommon in patients with moderate-to-severe atopic dermatitis (AD) treated with dupilumab. Methods A retrospective, single center, observational study was conducted to assess the difference in terms of absolute eosinophil count (AEC) change at 4 months and at 12 months, relative to the baseline, in predefined subgroups of patients affected by moderate-to-severe AD treated with dupilumab. Results Complete data for 373, 289 and 210 patients were available at the baseline, 4 months and 12 months, respectively. Patients with a history of conjunctivitis (n = 152) had greater increases in AEC at 4 months as compared with those (n = 137) who did not (+16%vs0%,p = 0.01). Patients with food allergies (n = 46) showed similar increases (+39%vs + 5%, p = 0.01). Patients experiencing facial redness dermatitis on dupilumab (n = 46) had greater increases in AEC at 4 months than those (n = 243) who did not (+40%vs + 5%, p = 0.03). Patients that had dupilumab-induced ocular surface disease (n = 44) had greater increases in AEC at 4 months than those (n = 245) who did not (+43%vs + 5%, p = 0.01). Conclusions Atopic comorbidities are associated with a paradoxical increase in AEC at 4 months in AD patients treated with dupilumab. Patients experiencing dupilumab-related ocular surface disease or facial redness dermatitis also have remarkable increases in AEC at 4 months.

Onset of eosinophilic esophagitis during a clinical trial program of oral immunotherapy for peanut allergy

Onset of eosinophilic esophagitis during a clinical trial program of oral immunotherapy for peanut allergy

Clozapine-associated eosinophilia with multiple systemic involvement - case report and review of literature

IntroductionDue to its mood-stabilizing properties, clozapine is known for reducing symptom severity in manic episodes of treatment-resistant bipolar disorder as well as in treatment-resistant schizophrenia. However, its use may be hindered by potential adverse effects, including hematologic ones, such as non-dose-dependent eosinophilia. The mechanism of the underlying process probably involves a type-I hypersensitivity reaction, which can manifest as either transient asymptomatic eosinophilia or as eosinophilia with multiorgan dysfunction.ObjectivesWe present the case of a patient diagnosed with manic episode of schizoaffective disorder who developed eosinophilia, with severe systemic manifestations, in response to clozapine therapy. A review of literature will be conducted in order to provide further insight into the phenomenon.MethodsCase report and literature review.ResultsThe incidence of eosinophilia reported in literature ranges between 0.2% and 62%, with its appearance about three weeks after clozapine initiation. Although clozapine is an antipsychotic that normally requires frequent monitoring due to the potential side effect of agranulocytosis, we would like to place emphasis on the possible risk of eosinophilia, in connection with potential fatal complications. As described in this report, eosinophilia could long remain unrecognized due to subsequent multiorgan involvement, including lymphadenopathy, leukocytosis, lymphopenia, anemia, liver enzyme elevations, as well as pleural effusion, all of which were described in our patient.ConclusionsClozapine-associated eosinophilia may be used as an early marker of possible clozapine-induced systemic complications and it may warrant prompt discontinuation of the causing drug, as suggested by the literature.

Dupilumab‐associated hypereosinophilia in patients treated for moderate‐to‐severe atopic dermatitis

Trials assessing dupilumab in atopic dermatitis (AD) showed transient eosinophilia in less than 2% of patients (1). The frequency of hypereosinophilia (HE), defined as eosinophil blood count (EBC) ≥1500/mm3 (2), was higher (15.8%) in our previous real-life cohort of AD patients treated with dupilumab (3). Since symptomatic HE was reported in asthma trials, we aimed to assess the clinical impact of HE in AD patients receiving dupilumab.

Eosinophils in Eosinophilic Esophagitis: The Road to Fibrostenosis is Paved With Good Intentions.

Eosinophilic esophagitis (EoE) is an antigen-driven disease associated with epithelial barrier dysfunction and chronic type 2 inflammation. Eosinophils are the defining feature of EoE histopathology but relatively little is known about their role in disease onset and progression. Classically defined as destructive, end-stage effector cells, eosinophils (a resident leukocyte in most of the GI tract) are increasingly understood to play roles in local immunity, tissue homeostasis, remodeling, and repair. Indeed, asymptomatic esophageal eosinophilia is observed in IgE-mediated food allergy. Interestingly, EoE is a potential complication of oral immunotherapy (OIT) for food allergy. However, we recently found that patients with peanut allergy may have asymptomatic esophageal eosinophilia at baseline and that peanut OIT induces transient esophageal eosinophilia in most subjects. This is seemingly at odds with multiple studies which have shown that EoE disease severity correlates with tissue eosinophilia. Herein, we review the potential role of eosinophils in EoE at different stages of disease pathogenesis. Based on current literature we suggest the following: (1) eosinophils are recruited to the esophagus as a homeostatic response to epithelial barrier disruption; (2) eosinophils mediate barrier-protective activities including local antibody production, mucus production and epithelial turnover; and (3) when type 2 inflammation persists, eosinophils promote fibrosis.

Eosinophilic fasciitis in common variable immunodeficiency with hypereosinophilia

Eosinophilic fasciitis or Shulman disease is a rare disorder that presents with scleroderma-like changes of connective tissues accompanied by elevated erythrocyte sedimentation rate, hypergammaglobulinemia, and transient peripheral eosinophilia. 1 Mazori D.R. Femia A.N. Vleugels R.A. Eosinophilic fasciitis: an updated review on diagnosis and treatment. Curr Rheumatol Rep. 2017; 19: 74 Crossref PubMed Scopus (34) Google Scholar To date, there have been 2 cases of common variable immunodeficiency (CVID) associated with eosinophilic fasciitis reported in Europe. Here, we report the first case of CVID associated with eosinophilic fasciitis in the setting of hypereosinophilia in the United States.

The role of eosinophils in immunotherapy

The purpose of this review is to provide a brief discussion on the differential diagnosis for peripheral eosinophilia. We will then focus on targeted immunotherapies for atopic disease, their effects on absolute peripheral eosinophil counts, and use of peripheral eosinophils as a predictor of treatment response. In atopic disease, lower absolute peripheral eosinophil counts are typically associated with improved outcomes. Much of the current evidence on eosinophils as a biomarker comes from post-hoc analyses in therapeutic immunotherapy. While changes in eosinophilia were not the primary outcome of interest in many studies, some patterns did emerge. Cytolytic mAbs AK002 and benralizumab completely reduce peripheral and tissue eosinophil numbers. Dupilumab may have paradoxical transient eosinophilia despite observed clinical efficacy. Atopic inflammation is complex largely due to the various cytokines which affect eosinophils activation, proliferation, differentiation, and survival. This demonstrates the challenges of using peripheral eosinophilia alone as a biomarker for atopic disease activity. More attention should spotlight how different immunotherapy modalities affect eosinophil-driven responses.

The Role of Eosinophils in Immunotherapy.

The purpose of this review is to provide a brief discussion on the differential diagnosis for peripheral eosinophilia. We will then focus on targeted immunotherapies for atopic disease, their effects on absolute peripheral eosinophil counts, and use of peripheral eosinophils as a predictor of treatment response. In atopic disease, lower absolute peripheral eosinophil counts are typically associated with improved outcomes. Much of the current evidence on eosinophils as a biomarker comes from post hoc analyses in therapeutic immunotherapy. While changes in eosinophilia were not the primary outcome of interest in many studies, some patterns did emerge. Cytolytic monoclonal antibodies AK002 and benralizumab completely reduce peripheral and tissue eosinophil numbers. Dupilumab may have paradoxical transient eosinophilia despite observed clinical efficacy. Atopic inflammation is complex largely due to the various cytokines which affect eosinophil activation, proliferation, differentiation, and survival. This demonstrates the challenges of using peripheral eosinophilia alone as a biomarker for atopic disease activity. More attention should spotlight how different immunotherapy modalities affect eosinophil-driven responses.

DUPILUMAB REDUCES SEVERE EXACERBATIONS IN PATIENTS WITH ORAL CORTICOSTEROID-DEPENDENT SEVERE ASTHMA WITH AND WITHOUT EARLY IMPROVEMENTS IN LUNG FUNCTION

DUPILUMAB REDUCES SEVERE EXACERBATIONS IN PATIENTS WITH ORAL CORTICOSTEROID-DEPENDENT SEVERE ASTHMA WITH AND WITHOUT EARLY IMPROVEMENTS IN LUNG FUNCTION

Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma

BackgroundDupilumab is a fully human anti–interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. Its effectiveness in reducing oral glucocorticoid use in patients with severe asthma while maintaining asthma control is unknown.MethodsWe randomly assigned 210 patients with oral glucocorticoid–treated asthma to receive add-on dupilumab (at a dose of 300 mg) or placebo every 2 weeks for 24 weeks. After a glucocorticoid dose-adjustment period before randomization, glucocorticoid doses were adjusted in a downward trend from week 4 to week 20 and then maintained at a stable dose for 4 weeks. The primary end point was the percentage reduction in the glucocorticoid dose at week 24. Key secondary end points were the proportion of patients at week 24 with a reduction of at least 50% in the glucocorticoid dose and the proportion of patients with a reduction to a glucocorticoid dose of less than 5 mg per day. Severe exacerbation rates and the forced expiratory volume in 1 second (FEV1) before bronchodilator use were also assessed.ResultsThe percentage change in the glucocorticoid dose was −70.1% in the dupilumab group, as compared with −41.9% in the placebo group (P<0.001); 80% versus 50% of the patients had a dose reduction of at least 50%, 69% versus 33% had a dose reduction to less than 5 mg per day, and 48% versus 25% completely discontinued oral glucocorticoid use. Despite reductions in the glucocorticoid dose, in the overall population, dupilumab treatment resulted in a severe exacerbation rate that was 59% (95% confidence interval [CI], 37 to 74) lower than that in the placebo group and resulted in an FEV1 that was 0.22 liters (95% CI, 0.09 to 0.34) higher. Injection-site reactions were more common with dupilumab than with placebo (9% vs. 4%). Transient blood eosinophilia was observed in more patients in the dupilumab group than in the placebo group (14% vs. 1%).ConclusionsIn patients with glucocorticoid-dependent severe asthma, dupilumab treatment reduced oral glucocorticoid use while decreasing the rate of severe exacerbations and increasing the FEV1. Transient eosinophilia was observed in approximately 1 in 7 dupilumab-treated patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA VENTURE ClinicalTrials.gov number, NCT02528214.)

Clozapine versus other antipsychotics during the first 18 weeks of treatment: A retrospective study on risk factor increase of blood dyscrasias

Blood dyscrasias excluding agranulocytosis received limited attention in antipsychotic-treated patients during the first 18 weeks of therapy, although severe clinical conditions have been reported in a few cases. We extracted data records of 285 Caucasian patients after 18 weeks of antipsychotic treatments to investigate risk factors of blood dyscrasias. We observed a higher risk to develop both transient and persistent anemia, neutrophilia and eosinophilia in clozapine-treated patients, whereas in those treated with other atypical antipsychotics when compared to a reference group under typical antipsychotics, emerged an increased risk for transient neutrophilia and eosinophilia. Male patients revealed a higher risk of persistent eosinophilia, neutrophilia, and leukocytosis. Concomitant treatments with mood stabilizers or benzodiazepines proved to be risk factors for transient anemia, antidepressants for transient eosinophilia. Severe complications emerged in 3 cases of agranulocytosis. Cross-tabulation analysis showed a higher probability of a poor response in clozapine-treated patients with persistent anemia and a positive with persistent neutrophilia and eosinophilia. Our data evidenced that emerging blood dyscrasias were not associated with critical adverse effects, and only agranulocytosis required a treatment interruption. Other atypical antipsychotics might represent a viable alternative to potentially harmful clozapine and typical antipsychotics at the onset of life-threatening haematological alterations.

Immune responses and parasitological observations induced during probiotic treatment with medicinal Trichuris suis ova in a healthy volunteer

Ingestion of eggs (ova) of the porcine nematode parasite Trichuris suis (TSO) may reduce the severity of autoimmune disorders, however the development of TSO treatment as a useful therapy for autoimmune diseases is hampered by a lack of knowledge on the development of the parasite and the nature of the local immune responses in humans. Here, we used colonoscopy to investigate the development of T. suis and related mucosal and systemic immune responses during TSO treatment in an intestinally healthy male volunteer. TSO treatment induced T. suis-specific serum antibodies, a transient blood eosinophilia, and increases in IFNγ+ and IL4+ cells within the circulating CD4+ T-cell population. Increased expression of genes encoding cytokines (IL4, IL10, IL17 and TGF-β), and transcription factors (FOXP3, GATA3 and RORC) were apparent in the ascending and transverse colon (the predilection site of the worms), whereas only limited changes in gene expression were observed proximally (ileum) and distally (descending colon) to the infected tissue. We further show that T. suis is able to colonise the human colon, with a number of worms developing to a similar size and morphology observed in the natural pig host, and a small number of unembryonated eggs were passed in the faeces, indicating patent infection. Notably, the volunteer experienced a substantial improvement in psoriasis during the course of TSO treatment. Thus, TSO treatment induced a mixed Th1/Th2/T regulatory response at the local site of infection, which was also reflected to some extent in the peripheral circulation. These results, together with the first definitive observations that T. suis can mature to adult size and reproduce in humans, shed new light on the interaction between the human immune system and probiotic helminth treatment, which should facilitate further development of this novel therapeutic option.

Some haematological parameters of albino mice experimentally inoculated with Trypanosoma brucei brucei after administration of Halofantrine hydrochloride, chloroquine and diaminazine aceturate

Trypanosomosis has been a menace. When animals become infected with trypanosomosis, their physiology is altered leading to haematological aberrations. The comparative effects of Halofantrine chloride (Halfan), chloroquine and diaminazine aceturate (DA) were experimentally investigated in the treatment of Trypanosoma brucei brucei infected albino mice. This is to know whether Halfan and chloroquine can provide alternatives to diaminazine aceturate. White albino mice experimentally infected with T. brucei brucei which were separately treated 7 days post infection with Halfan at 100 mg/kg body weight as a single dose orally, chloroquine phosphate at 0.12 mg/kg body weight, administered intraperitoneally (IP) and DA given IP at 3.5 mg/kg body weight and the last group served as the untreated control. There was a slight depression of the packed cell volume (PCV) after infection of all the groups. However, following treatment, there was significant rise (P < 0.05) in the PCV values for animals in groups 1, 2, 3 but not for the control group, in which there was progressive reduction. Following infection with T. brucei brucei, this led to lymphocytosis in all the experimental groups but after treatment with Halfan, chloroquine and DA, there was gradual lymphocytopenia. There was neutropenia from day 0 to day 7 when they were subjected to different chemotherapeutic treatment; there was variable neutrophilia but never to pre-infection level till the termination of the experiment. Although, there was transient eosinophilia which subsided to normalcy just before treatment but stabilized after treatment except in group 3 (DA treated). There was significant decrease (P < 0.05) in monocyte count in Halfan treated group and untreated control throughout the experimental period; this changed by day 30 when the study was voluntarily terminated. In groups 2 and 3, there was fluctuation over time but, the overall trend was that of an increase of monocytes throughout the experimental period. There is a possibility that parenteral formulation of Halfan may, if explored, provide maximal blood levels that can be used therapeutically alone or in combination with diaminazine aceturate, instead of oral formulations used in this study.

Eosinophilia associated with clozapine – A case report

ObjectivesClozapine is an atypical anti-psychotic used in the treatment of schizophrenia and other psychotic disorders. It is associated with several side effects, namely, hematologic disorders, the more common being agranulocytosis. Some cases of eosinophilia have been described. This work describes a case of transient eosinophilia caused by clozapine.MethodsDescription of a clinical case.ResultsA 22-year-old female patient, with a treatment resistant psychotic disorder initiated clozapine in a slow titration to 300 mg. Ten days after initiating clozapine, the patient presented with eosinophilia (started with 6.6 × 108/L and peaked at 10.0 × 108/L). Two weeks later, the patient presented with a skin rash in the arms and legs. The case was discussed with internal medicine service and other causes of eosinophilia were excluded. Since the eosinophilia was mild, the rash was not severe and the patient did not present any other symptoms or signs, it was not considered necessary to stop clozapine. During the next three months, with close monitoring, the eosinophilia and the skin rash slowly resolved.ConclusionsThis is a case of a patient who presented mild eosinophilia and skin rash, associated to clozapine, with spontaneous resolution. We draw attention to the need of close monitorization and exclusion of other causes of eosiniphilia and rash. Furthermore, other hematologic disorders should be considered besides agranulocytosis, namely eosinophilia, when prescribing clozapine.Disclosure of interestThe authors have not supplied their declaration of competing interest.