Real-world experience with letermovir for cytomegalovirus-prophylaxis after allogeneic hematopoietic cell transplantation: A multi-centre observational study.

OBJECTIVES: Efficacy and safety of letermovir as prophylaxis for clinically significant cytomegalovirus infections (csCVMi) was evaluated in randomised controlled trials while most of the real-world studies are single-centre experiences. METHODS: We performed a retrospective, multi-centre case-control study at six German university hospitals to evaluate clinical experiences in patients receiving CMV prophylaxis with letermovir (n = 200) compared to controls without CMV prophylaxis (n = 200) during a 48-week follow-up period after allogeneic hematopoietic cell transplantation (aHCT). RESULTS: The incidence of csCMVi after aHCT was significantly reduced in the letermovir (34%, n = 68) compared to the control group (56%, n = 112; p < 0.001). Letermovir as CMV prophylaxis (OR 0.362) was found to be the only independent variable associated with the prevention of csCMVi. Patients receiving letermovir showed significantly better survival compared to the control group (HR = 1.735, 95% CI: 1.111-2.712; p = 0.014). Of all csCMVi, 46% (n = 31) occurred after discontinuation of letermovir prophylaxis. Severe neutropenia (<500 neutrophils/µL) on the day of the stem cell infusion was the only independent variable for an increased risk of csCMVi after the end of letermovir prophylaxis. CONCLUSIONS: Our study highlights the preventive effects of letermovir on csCMVi after aHCT. A substantial proportion of patients developed a csCMVi after discontinuation of letermovir. In particular, patients with severe neutropenia require specific attention after drug discontinuation.

Protective effect of leukotriene receptor antagonist, montelukast, against cyclophosphamide-induced placental toxicity via modulation of NLRP3/IL-1ß signaling pathway in rats.

BACKGROUNDS & AIM: Placental insufficiency is a serious complication that affects pregnancy and fetal growth. Cyclophosphamide (CYC) is considered one of the chemotherapeutic agents. Unfortunately, CYC not only affects tumor cells but also affects healthy cells causing multiple injuries including the placenta. The present study aimed to evaluate the effect of cysteinyl leukotriene receptor antagonist; montelukast (MK), on CYC-induced placental injury in rats. MATERIALS AND METHODS: Forty-eight female Wister rats were randomly divided into 8 experimental groups. Group 1: control pregnant group; Group 2: MK 5 mg-treated pregnant rats; Group 3: MK 10 mg-treated pregnant rats; Group 4: MK 20 mg-treated pregnant rats; Group 5: pregnant rats received CYC (20 mg/kg, i.p); Group 6: pregnant rats received MK 5 mg and CYC; Group 7: pregnant rats received MK 10 mg and CYC; Group 8: pregnant rats received MK 20 mg and CYC. Placental malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), placental growth factor (PlGF), and Nod-like receptor p3 (NLRP3) inflammasome were measured. Histological changes, interleukin-1ß (IL-1ß), and cleaved caspase-3 immuno-expressions were also evaluated. RESULTS: CYC showed a significant decrease in placental GSH, TAC, and PlGF with a significant increase in placental MDA, NLRP3, and immuno-expression of IL-1ß and caspase-3. MK showed significant improvement in all oxidative stress (MDA, GSH and TAC), inflammatory (NLRP3 and IL-1ß), and apoptotic (caspase-3) parameters. CONCLUSION: According to the findings, MK was proved to have a possible protective role in CYC-induced placental injury via modulation of NLRP3/IL-1ß signaling pathway with anti-oxidant, anti-inflammatory, and anti-apoptotic effects.

Impact of Primary Letermovir Prophylaxis Versus Preemptive Antiviral Therapy for Cytomegalovirus on Economic and Clinical Outcomes after Hematopoietic Cell Transplantation.

Preemptive therapy (PET) historically has been the primary strategy to reduce early-onset cytomegalovirus (CMV) reactivation after allogeneic hematopoietic cell transplantation (HCT) but is associated with antiviral-associated toxicities and increases in healthcare resource utilization and cost. Despite its high cost, letermovir (LTV) prophylaxis has largely supplanted PET due to its effectiveness and tolerability. Direct comparisons between LTV and PET approaches on economic and clinical outcomes after allogeneic HCT remain limited. Objective: To compare total cost of care (inpatient and outpatient) between LTV prophylaxis and PET through day+180 after allogeneic HCT. Adult allogeneic CMV seropositive (R+) HCT recipients who initiated LTV <30 days after HCT between 01/01/18 and 12/31/18 were matched 1:1 to allogeneic CMV R+ HCT recipients between 01/01/15 and 12/31/17 (PET cohort). Patients were grouped into high-risk (HR) or standard-risk (SR) for CMV to compare the LTV and PET cohorts. Direct costs for each patient's index HCT admission and all subsequent inpatient and outpatient care through day+180 after HCT were determined and converted into 2021 US dollars and then to Medicare proportional dollars (MPD). A secondary analysis using 2019 average wholesale price was conducted to specifically evaluate anti-CMV medication costs. There were a total of 176 patients with 54 HR CMV pairs and 34 SR CMV pairs. No differences in survival between LTV and PET for both HR and SR CMV groups were observed. The rate of clinically significant CMV infection decreased for both HR CMV (11/54, 20.4% versus 38/54, 70.4%, P < .001) and SR CMV (1/34, 2.9% versus 12/34, 35.3%, P < .001) patients who were given LTV prophylaxis with corresponding reductions in val(ganciclovir) and foscarnet (HR CMV only) use. Among HR CMV patients, LTV prophylaxis was associated with reductions in CMV-related readmissions (3/54, 5.6% versus 18/54, 33.3%, P < .001) and outpatient visits within the first 100 days after HCT (20 versus 25, P = .002), and a decreased median total cost of care ($36,018 versus $75,525, P < .001) in MPD was observed. For SR CMV patients on LTV, a significant reduction in the median inpatient cost ($15,668 versus $27,818, P < .001) was found, but this finding was offset by a higher median outpatient cost ($26,145 versus $20,307, P = .030) that was not CMV-driven. LTV prophylaxis is highly effective in reducing clinically significant CMV reactivations for both HR and SR HCT recipients. In this study, LTV prophylaxis was associated with a decreased total cost of care for HR CMV patients through day+180. Specifically, reductions in CMV-related readmissions, exposure to CMV-directed antiviral agents, and outpatient visits in the first 100 days after HCT were observed. SR CMV patients receiving LTV prophylaxis benefited by having a reduced inpatient cost of care due to lowered room and pharmacy costs.

Neuromodulatory effects of leukotriene receptor antagonists: A comprehensive review.

Cysteinyl leukotrienes (CysLTs) are central to the pathophysiology of asthma and various inflammatory disorders. Leukotriene receptor antagonists (LTRAs) effectively treat respiratory conditions by targeting cysteinyl leukotriene receptors, CysLT1 and CysLT2 subtypes. This review explores the multifaceted effects of LTs, extending beyond bronchoconstriction. CysLT receptors are not only present in the respiratory system but are also crucial in neuronal signaling pathways. LTRAs modulate these receptors, influencing downstream signaling, calcium levels, inflammation, and oxidative stress (OS) within neurons hinting at broader implications. Recent studies identify novel molecular targets, sparking interest in repurposing LTRAs for therapeutic use. Clinical trials are investigating their potential in neuroinflammation control, particularly in Alzheimer's disease (AD) and Parkinson's diseases (PD). However, montelukast, a long-standing LTRA since 1998, raises concerns due to neuropsychiatric adverse drug reactions (ADRs). Despite widespread use, understanding montelukast's metabolism and underlying ADR mechanisms remains limited. This review comprehensively examines LTRAs' diverse biological effects, emphasizing non-bronchoconstrictive activities. It also analyses plausible mechanisms behind LTRAs' neuronal effects, offering insights into their potential as neurodegenerative disease modulators. The aim is to inform clinicians, researchers, and pharmaceutical developers about LTRAs' expanding roles, particularly in neuroinflammation control and their promising repurposing for neurodegenerative disease management.

Phenotypes of cytomegalovirus genetic variants encountered in a letermovir clinical trial illustrate the importance of genotyping validation.

Emergence of drug resistance is rare after use of letermovir (LMV) as prophylaxis for post-transplant cytomegalovirus (CMV) infection. In a recent study involving renal transplant recipients, no known LMV resistance mutations were detected in those receiving LMV prophylaxis. However, uncharacterized viral amino acid substitutions were detected in LMV recipients by deep sequencing in viral subpopulations of 5%-7%, at codons previously associated with drug resistance: UL56 S229Y (n = 1), UL56 M329I (n = 9) and UL89 D344Y (n = 5). Phenotypic analysis of these mutations in a cloned laboratory CMV strain showed that S229Y conferred a 2-fold increase in LMV EC50, M329I conferred no LMV resistance, and D344Y knocked out viral viability that was restored after the nonviable clone was reverted to wild type D344. As in previous CMV antiviral trials, the detection of nonviable mutations, even in multiple study subjects, raises strong suspicion of genotyping artifacts and encourages the use of replicate testing for authentication of atypical mutation readouts. The non-viability of UL89 D344Y also confirms the biologically important locus of the D344E substitution that confers resistance to benzimidazole CMV terminase complex inhibitors, but does not feature prominently in LMV resistance.

Cysteinyl leukotriene receptor-1 as a potential target for host-directed therapy during chronic schistosomiasis in murine model.

Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature female worms that are trapped in host's tissues, resulting in chronic Th2 driven fibrogranulmatous pathology. Although the disease can be treated with a relatively inexpensive drug, praziquantel (PZQ), re-infections remain a major problem in endemic areas. There is a need for new therapeutic drugs and alternative drug treatments for schistosomiasis. The current study hypothesized that cysteinyl leukotrienes (cysLTs) could mediate fibroproliferative pathology during schistosomiasis. Cysteinyl leukotrienes (cysLTs) are potent lipid mediators that are known to be key players in inflammatory diseases, such as asthma and allergic rhinitis. The present study aimed to investigate the role of cysLTR1 during experimental acute and chronic schistosomiasis using cysLTR1-/- mice, as well as the use of cysLTR1 inhibitor (Montelukast) to assess immune responses during chronic Schistosoma mansoni infection. Mice deficient of cysLTR1 and littermate control mice were infected with either high or low dose of Schistosoma mansoni to achieve chronic or acute schistosomiasis, respectively. Hepatic granulomatous inflammation, hepatic fibrosis and IL-4 production in the liver was significantly reduced in mice lacking cysLTR1 during chronic schistosomiasis, while reduced liver pathology was observed during acute schistosomiasis. Pharmacological blockade of cysLTR1 using montelukast in combination with PZQ reduced hepatic inflammation and parasite egg burden in chronically infected mice. Combination therapy led to the expansion of Tregs in chronically infected mice. We show that the disruption of cysLTR1 is dispensable for host survival during schistosomiasis, suggesting an important role cysLTR1 may play during early immunity against schistosomiasis. Our findings revealed that the combination of montelukast and PZQ could be a potential prophylactic treatment for chronic schistosomiasis by reducing fibrogranulomatous pathology in mice. In conclusion, the present study demonstrated that cysLTR1 is a potential target for host-directed therapy to ameliorate fibrogranulomatous pathology in the liver during chronic and acute schistosomiasis in mice.

Real-World Safety and Effectiveness of Letermovir in Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation: Final Results of Post-Marketing Surveillance in Japan.

BACKGROUND AND OBJECTIVE: Cytomegalovirus (CMV) is a common opportunistic infection after allogenic hematopoietic stem cell transplantation (allo-HSCT). Letermovir, an inhibitor of CMV DNA terminase, is approved for CMV prophylaxis in allo-HSCT patients. We report the final results of post-marketing surveillance of letermovir in Japan. METHODS: The case report forms were drafted in part by the Japanese Data Center for Hematopoietic Cell Transplantation using data elements in the Transplant Registry Unified Management Program and sent to individual HSCT centers to decrease the burden of reporting. Hematopoietic stem cell transplantation patients who received letermovir between May 2018 and May 2022 were registered. Data collected included physician-assessed adverse events/adverse drug reactions and clinical effectiveness (development of CMV disease, CMV antigen status, and use of preemptive therapy). RESULTS: A total of 821 HSCT patients were included in the safety analyses. Adverse drug reactions occurred in 11.33% of patients, with serious adverse drug reactions in 3.05%. The five most common adverse drug reactions were nausea (1.58%), renal impairment (1.46%), and acute graft versus host disease, CMV test positive, and hepatic function abnormal (0.61% each). A total of 670 patients were eligible for effectiveness analyses. Among these patients, 16.57% and 28.66% required preemptive therapy through week 14 and week 48, respectively. In addition, relatively few patients developed CMV disease throughout the follow-up period (1.34% at week 14 and 3.85% at week 48). CONCLUSIONS: This final analysis of post-marketing surveillance with up to 48 weeks follow-up period in Japan provides further evidence supporting the safety profile and effectiveness of letermovir for CMV prophylaxis in patients undergoing allo-HSCT in real-world settings.

Cytomegalovirus (CMV) infection is common after allogenic hematopoietic stem cell transplantation and causes both directly and indirectly a serious disease that frequently results in the death or severe outcomes for the affected patient. Letermovir is a drug that inhibits CMV replication and infection and can be administered to prevent CMV infection in at-risk patients undergoing allogenic hematopoietic stem cell transplantation. After it was approved in Japan, a post-marketing surveillance was started in order to confirm the safety profile and effectiveness of letermovir in clinical practice in Japan. The data collected included the adverse drug reactions during treatment and the effectiveness of letermovir. In this article, we describe the final results of this survey. The most common adverse drug reactions were nausea (1.58% of patients), renal impairment (1.46%), and acute graft versus host disease, CMV test positive, and hepatic function abnormal (0.61% each). There were few cases of myelosuppression, which is frequently seen in patients treated with ganciclovir/valganciclovir, and blood cells recovered steadily over time. Cytomegalovirus antigens were detected in 38.36% of patients through 48 weeks. Preemptive therapy was initiated to 28.66% of patients for up to 48 weeks. Cytomegalovirus disease was infrequent, occurring in 3.85% of patients. Overall, these findings are in alignment with the currently approved product label and provide further evidence supporting the consistent safety profile and effectiveness of letermovir for CMV prophylaxis in patients in Japan undergoing allogenic hematopoietic stem cell transplantation in clinical practice.

Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients.

BACKGROUND: Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off-label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients. METHODS: This retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post-LET initiation; secondary outcomes included hematologic changes. RESULTS: A total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R-), with LET initiated a median of 9.6 months post-transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p = .370). The median (interquartile range) white blood cell (WBC) count was 3.1 (2.1-5.6) at LET initiation which increased to 5.1 (3.9-7.2) at the end of follow-up (p <.001). For VGCV controls, WBC was 4.8 (3.4-7.2) at baseline and 5.4 (3.6-7.2) at the end of follow-up; this difference was not statistically significant (p = .395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001). CONCLUSION: LET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV.

Efficacy of montelukast for adenoid hypertrophy in paediatrics: A systematic review and meta-analysis.

INTRODUCTION: Leukotrienes play a significant role in the pathogenesis of adenoid hypertrophy (A.H.). Therefore, we aimed to analyse the role of montelukast, a leukotriene receptor antagonist, alone or in combination with mometasone, a potent local intranasal steroid, for the treatment of A.H. METHODS: Participants were children with A.H. were treated with montelukast alone or montelukast and mometasone furoate. The main outcome measures were effect of montelukast on clinical symptoms of A.H. A literature review was conducted using online search engines, Cochrane Library, PubMed, Web of Science and Scopus, for randomized clinical trials assessing children with A.H. treated with montelukast alone or montelukast and mometasone furoate. Seven randomized clinical trials (RCTs) were included with 742 children. RESULTS: Our study reveals that montelukast alone or in combination with intranasal mometasone furoate significantly improves clinical symptoms of adenoid hypertrophy such as snoring, sleeping disturbance, mouth breathing and A/N ratio. Montelukast was superior to placebo in decreasing snoring (SMD = -1.00, 95% CI [-1.52, -0.49]), sleep discomfort (SMD = -1.26, 95% CI [-1.60, -0.93]), A/N ratio (MD = -0.11, 95% CI [-0.14, -0.09]) and mouth breathing (SMD = -1.36, 95% CI [-1.70, -1.02]). No difference was detected between montelukast and mometasone versus mometasone alone in snoring (SMD = -0.21, 95%CI [-0.69, 0.27]); however, the combination group was superior to the mometasone alone in mouth breathing (SMD = -0.46, 95% CI [-0.73, -0.19]). CONCLUSIONS: The limitation of studies included a small sample size, with an overall low to medium quality. Thus, further larger, higher-quality RCTs are recommended to provide more substantial evidence.

Eosinophilic granulomatosis with polyangiitis and its association with montelukast: a case-based review.

The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is well established. More recently, cases of immune-related adverse events ranging from inflammatory polyarthritis to necrotizing myositis in patients taking checkpoint inhibitors have been reported. However, data linking drugs to systemic vasculitis are scarce and at times debatable. Propylthiouracil, hydralazine, and minocycline have been associated with rare cases of ANCA-associated syndromes, including life-threatening pulmonary-renal syndromes and systemic polyarteritis nodosa-like diseases. Eosinophilic granulomatosis with polyangiitis (EGPA) has been reported in patients taking leukotriene inhibitors. Since the link between the use of leukotriene inhibitors and occurrence of EGPA remains highly controversial, we performed a literature review for cases of EGPA in patients taking montelukast without prior history of oral corticosteroid use. We found 24 cases, along with our own two cases described, making 26 cases in total. The mean age was 43 and a majority (18/26) were female. In majority of cases EGPA-like disease never relapsed after they were taken off leukotriene inhibitors suggesting a clear causal relationship between the use of these drugs and occurrence of eosinophil-rich systemic EGPA.

Evaluating Acetate as a Renoprotective Agent After Kidney Ischemia in a Porcine Model.

Objective: Renoprotection from reperfusion injury appears to be conferred by HIF-2a activation, which can be stimulated by exogenous acetate administration. The study objective was to assess whether administration of acetate in a porcine model can mitigate kidney injury related to ischemia-reperfusion after renal hilar occlusion. Methods: A porcine single-kidney model was created by performing a laparoscopic nephrectomy followed by animal recovery. After 2 days, the animals underwent laparoscopic hilar dissection. Block randomization was used to assign pigs into one of four experimental groups. One treatment block of pigs received 150 mEq of sodium acetate intravenously during 90 minutes of en bloc occlusion of the renal hilum (herein noted as "cross-clamping"). Another block received 0.75 g/kg of oral sodium acetate for 3 days prior to cross-clamping. A third block received no acetate and underwent hilar dissection without cross-clamping (negative control). The final block received no acetate and underwent cross-clamping (positive control). Serum creatinine was used to estimate renal function post-nephrectomy. Results: A total of 16 animals (4 pigs in each group) completed the study protocol. Median pig weight was 34.6 kg. One pig receiving IV acetate was excluded from the final analysis because of unrecoverable renal failure after cross-clamping. There was a significantly lower mean serum creatinine for the IV acetate group compared with the positive control group 72 hours after cross-clamping (p = 0.012). The same effect was not observed for the pigs receiving oral acetate. By day 7, renal function had recovered without significant difference in all groups. Conclusions: We observed that the administration of intravenous acetate conferred a significant renoprotective benefit in our single kidney ischemia-reperfusion porcine model 72 hours after hilar occlusion. This work is hypothesis-generating, and further work in human subjects undergoing renal hilar occlusion during partial nephrectomy is warranted.

Montelukast Influence on Lung in Experimental Diabetes.

Background and Objectives: The influence of montelukast (MK), an antagonist of cysLT1 leukotriene receptors, on lung lesions caused by experimental diabetes was studied. Materials and Methods: The study was conducted on four groups of six adult male Wistar rats. Diabetes was produced by administration of streptozotocin 65 mg/kg ip. in a single dose. Before the administration of streptozotocin, after 72 h, and after 8 weeks, the serum values of glucose, SOD, MDA, and total antioxidant capacity (TAS) were determined. After 8 weeks, the animals were anesthetized and sacrificed, and the lungs were harvested and examined by optical microscopy. Pulmonary fibrosis, the extent of lung lesions, and the lung wet-weight/dry-weight ratio were evaluated. Results: The obtained results showed that MK significantly reduced pulmonary fibrosis (3.34 ± 0.41 in the STZ group vs. 1.73 ± 0.24 in the STZ+MK group p < 0.01) and lung lesion scores and also decreased the lung wet-weight/dry-weight (W/D) ratio. SOD and TAS values increased significantly when MK was administered to animals with diabetes (77.2 ± 11 U/mL in the STZ group vs. 95.7 ± 13.3 U/mL in the STZ+MK group, p < 0.05, and 25.52 ± 2.09 Trolox units in the STZ group vs. 33.29 ± 1.64 Trolox units in the STZ+MK group, respectively, p < 0.01), and MDA values decreased. MK administered alone did not significantly alter any of these parameters in normal animals. Conclusions: The obtained data showed that by blocking the action of peptide leukotrienes on cysLT1 receptors, montelukast significantly reduced the lung lesions caused by diabetes. The involvement of these leukotrienes in the pathogenesis of fibrosis and other lung diabetic lesions was also demonstrated.

Advances in pharmacotherapies for cytomegalovirus infection: what is the current state of play?

INTRODUCTION: Cytomegalovirus (CMV) remains a serious opportunistic infection in hematopoietic cell transplant (HCT) and solid-organ transplant (SOT) recipients. Traditional anti-CMV drugs are limited by toxicities and the development of resistance. Letermovir and maribavir are newly approved antivirals for the prevention and treatment of CMV. AREAS COVERED: Prior reviews have discussed use of letermovir for prevention of CMV after HCT and maribavir for resistant or refractory (R/R) CMV post HCT or SOT. Subsequent data have expanded their use including letermovir for primary CMV prophylaxis in high-risk renal transplant recipients and new recommendations for extending prophylaxis through day + 200 in certain HCT patients. Data on the use of maribavir for first asymptomatic CMV infection post-HCT has also been published. This review compares the pharmacology of anti-CMV agents and discusses the updated literature of these new drugs in the prevention and treatment of CMV. EXPERT OPINION: Letermovir and maribavir are much needed tools that spare toxicities of ganciclovir, foscarnet, and cidofovir. High cost is a challenge preventing their integration into clinical practice in resource-limited countries. Transplant centers need to exercise restraint in overuse to avoid resistance, particularly in the setting of high viral loads.

Clinical Characteristics, Investigations and Treatment in Children with Chronic Urticaria: An Observational Study.

Background and Objectives: The guidelines for chronic urticaria in children contain recommendations that are often based on adult studies. The diagnostic pathway has not been standardized and the effectiveness of anti-H1, omalizumab, montelukast, and systemic glucocorticoids is rarely reported in the pediatric population. There is a wide variation in the rate of remission of chronic urticaria between studies. The aim of this study is to enhance our understanding of pediatric chronic urticaria. Materials and Methods: This study enrolled 37 children with chronic urticaria aged from 0 to 18 years. Demographic parameters, medical history, clinical features, laboratory data and treatment information were collected. Children were treated with the recommended dosage of second-generation H1-antihistamines, which was increased by up to twofold. Omalizumab was added for refractory anti-H1 patients. A three-day course with systemic glucocorticoids was administered for severe exacerbations. Montelukast was administered to some children. Results: Wheals without angioedema were common. Chronic urticaria was spontaneous in 32 children (86.48%), inducible in 2 (5.41%), induced by a parasite in 1 and vasculitic in 2. Treatment of the potential causes of chronic urticaria was of no benefit, except for eradication of Dientamoeba fragilis. Chronic urticaria was resolved within three years in 45.9% of cases. Allergic diseases were present in nine children (24.32%) and autoimmune diseases were present in three (8.11%). All children were treated with anti-H1 at the licensed dose or at a higher dose. A partial or complete response to anti-H1 was observed in 29 (78.38%) patients. Montelukast showed no benefit. All children treated with omalizumab responded. Systemic glucocorticoids were successfully used to treat exacerbations. Conclusions: Our findings indicate that laboratory tests should not be routinely performed in children with chronic urticaria without clinical suspicion. However, comorbidities such as thyroid autoimmune disease and coeliac disease are suggested to be monitored over the chronic urticaria course. These clinical conditions could be diagnosed from the diagnostic framework of chronic urticaria. Increasing the dosage of anti-H1 and omalizumab was effective in children resistant to standard treatment but we still need further studies to generate a standard patient-centered treatment.