Maintained disease control and steroid-sparing effect of subcutaneous immunotherapy in allergic rhinitis and asthma.

BACKGROUND: Allergen immunotherapy is the only currently available treatment strategy that modifies the immune response to the causative allergen and induces clinical improvement and a steroid-sparing effect. OBJECTIVE: In this real-life study, we aimed to evaluate and compare the efficacy of subcutaneous immunotherapy (SCIT) with one allergen or multiple allergens in children and adults with asthma and/or allergic rhinitis in terms of disease control and a steroid-sparing effect. METHODS: Demographics, the initial inhaled corticosteroid (ICS) and/or intranasal corticosteroid (INS) dose, and other drugs of patients receiving SCIT for at least 12 months were recorded. Data on the final dose/use of ICS/INS and asthma and/or allergic rhinitis control were gathered. RESULTS: Of 104 patients included, 57.1% and 64.5% of patients with asthma and allergic rhinitis, respectively, were able to discontinue ICS and INS after SCIT. The median time to INS and ICS dose reduction was 6 months. SCIT with one allergen or multiple allergens effectively reduced the ICS and INS dose and led to control of asthma and allergic rhinitis, with no significant difference between the groups. When the efficacy of SCIT was compared in children and adults, there was no significant difference in terms of a steroid-sparing effect or the control of asthma and allergic rhinitis. SCIT was effective in both children and adult patients. CONCLUSIONS: In this real-life observational study, we have demonstrated a marked steroid-sparing effect while maintaining control of asthma and allergic rhinitis in children and adults treated with one allergen or multiple allergens.

Safety of Methotrexate in Chronic Urticaria Unresponsive to Omalizumab.

Omalizumab (humanized anti-immunoglobulin IgE) is currently the first choice of treatment for chronic urticaria refractory to high-dose second-generation antihistamines (sgAH). Despite its high safety profile, response to omalizumab is insufficient in one-third of patients. Some studies have suggested that methotrexate is effective in antihistamine-refractory chronic urticaria, but there are no studies on its efficacy and safety in patients unresponsive to omalizumab. This retrospective study aimed to investigate the clinical effectiveness and adverse effects of methotrexate in patients with chronic urticaria unresponsive to omalizumab + high-dose sgAH. The patients were evaluated in terms of age at disease onset, duration of the urticaria episode before methotrexate therapy, treatment before methotrexate therapy, final treatment, treatment responses, 7-day urticaria activity score (UAS7) before and after treatment, and total IgE levels. Methotrexate was administered subcutaneously at a dose of 15 mg once weekly as monotherapy or in combination with other drugs to 10 chronic urticaria patients with a history of nonresponse to omalizumab + high-dose sgAH. The mean age of the patients was 44.6±11.5 (31-65) years, and 9 (90%) of the patients were female. The mean duration of methotrexate therapy was 5.1±2.4 months (1.5-9 months). Complete response or well-controlled response was observed in 70% of the patients and partial response was observed in 1 patient (10%). Methotrexate was well tolerated by 80% of the patients. Methotrexate seems to be a useful treatment option both as monotherapy or combined therapy in patients resistant to omalizumab + sgAH.

Efficacy of drug therapies in antihistamine refractory chronic spontaneous urticaria: Real life data.

BACKGROUND: Omalizumab is a safe and effective treatment for antihistamine-refractory chronic spontaneous urticaria (CSU) but is insufficient in one-third of patients. For serious cases in which omalizumab is ineffective, cyclosporine or methotrexate may be preferred. Most drug trials in CSU have focused on omalizumab or cyclosporine monotherapy. OBJECTIVE: This retrospective study evaluated responses to monotherapy or combined therapy and real-life data on the effectiveness and safety of omalizumab in antihistamine-refractory CSU. METHODS: A total of 133 patients who received omalizumab due to antihistamine-refractory CSU were evaluated in terms of 7-day urticaria activity score, total IgE, anti-thyroid peroxidase, C-reactive protein, skin prick test with aeroallergens and disease duration. Partial or nonresponders to omalizumab monotherapy were given antihistamine, omalizumab, cyclosporine, and methotrexate as combined or monotherapy. RESULTS: Ninety-eight (73.7%) of the 133 patients were female and the mean age was 40.7 ± 14.4 years; 70.6% of the patients received omalizumab monotherapy and the others received combined or non-omalizumab monotherapy. Omalizumab monotherapy was effective in 66.9% of the patients. Of those with complete response to omalizumab monotherapy, 65.4% had early recurrence after discontinuing treatment. Treatment response was significantly better in patients who had high total IgE (p = 0.001). Patients with longer disease duration had significantly higher likelihood of early recurrence (p = 0.035). CONCLUSIONS: Omalizumab monotherapy was as effective in real life as in placebo-controlled trials. Omalizumab was well tolerated by all patients. Treatment responses were comparable in patients treated with combined therapy and those who received monotherapy.

Misleading Allergens in the Diagnosis of Latex Allergy: Profilin and Cross-Reactive Carbohydrate Determinants.

BACKGROUND: It has been suggested that latex-specific IgE analysis may lead to false-positive results, especially in patients with pollen allergy. In the present study, the reasons underlying clinically irrelevant latex-specific IgE positivity were investigated. METHODS: Thirty patients with latex allergy (group 1), 89 patients sensitised to aeroallergens (group 2a), and 98 healthy individuals without allergy (group 2b) were enrolled. Participants from all 3 groups were subjected to skin prick tests with aeroallergens including latex, latex-specific IgE analysis (ImmunoCAP), and nasal provocation test with latex. All cases demonstrating positive latex-specific IgE also underwent specific IgE tests (ImmunoCAP) with latex profilin, birch pollen profilin, peach lipid transfer protein, and pineapple bromelain as cross-reactive carbohydrate determinants. RESULTS: Comparison of the atopic and healthy control groups showed that the rate of positive latex-specific IgE was significantly higher in group 2a. Latex profilin-, birch pollen profilin-, and bromelain-specific IgE were remarkably higher in group 2a. CONCLUSION: False positivity to latex-specific IgE in ImmunoCAP analysis may be observed in approximately 19% of patients with pollen allergy. Profilins and bromelain are the main contributors to clinically irrelevant positive latex-specific IgE.

Desensitization effect of preseasonal seven-injection allergoid immunotherapy with olive pollen on basophil activation: the efficacy of olive pollen-specific preseasonal allergoid immunotherapy on basophils.

BACKGROUND: It has previously been demonstrated that subcutaneous immunotherapy with allergoids positively affects clinical and immunological parameters even after 7 preseasonal injections. However, its effect on basophil activation remains unclear. We investigated the effect of preseasonal allergoid immunotherapy on basophils and concomitantly assessed its clinical and immunological efficacy in olive pollen-monosensitized patients. METHODS: This study enrolled 437 consecutive patients with respiratory allergy and positive skin prick tests (SPTs); 212 (48.5%) patients were sensitized to olive pollen, and 33 (7.5%) patients were sensitized to olive pollen only. Of these patients, 23 received preseasonal immunotherapy with an olive pollen allergoid. The olive pollen-specific basophil activation, the titrated nasal provocation test, the nasal symptom score, and olive pollen-specific IgE, IgG1 and IgG4 levels were evaluated before immunotherapy and 8 months after the end of immunotherapy in the follow-up visit. RESULTS: In comparison to baseline evaluation, 7 preseasonal injections of an allergoid resulted in a significant decrease in the percentage of basophils expressing CD63 (29 vs. 7%, respectively, p < 0.0001) and a significant increase in the titrated nasal provocative dose (1/10 vs. 1/1, respectively, p < 0.01). SPT induration diameters caused by an olive pollen extract decreased (12 mm at baseline vs. 5.5 mm at follow-up, p < 0.005), as did nasal symptom score (7 at baseline vs. 3 at follow-up, p < 0.01). Olive pollen-specific IgE (17.5 vs. 50 kU/l, p < 0.012), IgG1 (0.16 vs. 2.9 µg/ml, p < 0.0001) and IgG4 (0.07 vs. 1.92 µg/ml, p < 0.0001) levels significantly increased. CONCLUSIONS: Immunotherapy with 7 preseasonal injections of an olive pollen allergoid decreases olive pollen-specific basophil activation over 8 months, an effect observed in vitro and in vivo.

Diagnostic value of specific IgE analysis in latex allergy.

BACKGROUND: The precision of the methods used to diagnose latex allergy is of great importance due to false-positive results. Neither the skin prick test (SPT) nor the latex-specific IgE assay has 100% diagnostic accuracy. We analysed the diagnostic value of latex-specific IgE by the first-ever concomitant use of the SPT and nasal provocation test (NPT). METHODS: Twenty-seven latex-sensitive patients (group 1), 46 aeroallergen-sensitive patients (group 2a) and 33 healthy subjects (group 2b) participated in the study. All groups underwent an SPT with latex and aeroallergens and an NPT with latex. Latex-specific IgE and total IgE levels were measured by the ImmunoCAP assay. RESULTS: Latex-specific IgE was positive in 92.6, 30.4 and 9.1% of groups 1, 2a and 2b, respectively. The 11 aeroallergen-sensitive patients in group 1 and all of the patients in group 2a were predominantly sensitised to pollens (grass, weed and tree) and reacted to a lesser degree to house dust mite, moulds and animal dander. Combined pollinosis was remarkably more prevalent in patients with positive latex-specific IgE in group 2a than in those with negative latex-specific IgE (p = 0.001). The NPT was positive in 84.6% of group 1 and negative in all control subjects. The sensitivity, specificity, negative predictive value and positive predictive value of the latex-specific IgE assay were 90.9, 72.2, 96.3 and 50%, respectively. CONCLUSION: The high rate of false-positive results for latex-specific IgE by ImmunoCAP should be taken into account when making a diagnosis of latex allergy in patients with pollinosis, especially in those sensitised to more than one pollen species.