Basophil Activation Test with Different Polyethylene Glycols in Patients with Suspected PEG Hypersensitivity Reactions.

Allergic reactions to COVID-19 vaccine components are rare but should be considered. Polyethylene glycol (PEG) is responsible for anaphylaxis in mRNA vaccines. Skin tests have been used in the allergological work-up programs for COVID-19 vaccine evaluation. However, the reproducibility of the skin prick test is time-dependent and the reactivity declines over time. Therefore, we combined the administration of the skin tests with the basophil activation test (BAT) using PEG2000, PEG4000 and DMG-PEG2000, where the BAT was considered positive when the percentage of activated basophils was higher than 6%, 5% and 6.5%, for PEG 4000, PEG2000 and DMG-PEG2000, respectively. To this end, among the subjects that underwent allergy counseling at the Allergy Unit of our Institution during the 2020/2021 vaccination campaign, 13 patients had a suggested medical history of PEG/drug hypersensitivity and were enrolled together with 10 healthy donors. Among the enrolled patients 2 out of 13 tested patients were positive to the skin test. The BAT was negative in terms of the percentages of activated basophils in all analyzed samples, but the stimulation index (SI) was higher than 2.5 in 4 out of 13 patients. These data evidenced that, when the SI is higher than 2.5, even in the absence of positivity to BAT, the BAT to PEG may be a useful tool to be coupled to skin tests to evidence even low-grade reactions.

Vernal Keratoconjunctivitis: A Case of Anti-IgE Treatment with Short-Lasting Remission.

Vernal keratoconjunctivitis (VKC) is a persistent, severe allergic eye disease, mainly occurring in children, that can lead to severe ocular complications including visual loss. The underlying etiology and pathophysiology of VKC remain unclear. Common therapies include topical antihistamines and mast cell stabilizers that are effective in mild-to-moderate forms of VKC but are often ineffective in severe forms that require topical or systemic corticosteroids. Dependence on steroids is common with potential adverse effects both local, as increased intraocular pressure, glaucoma, infection and cataract, as well as systemic ones, as reduction in child growth velocity. Alternative therapies are immunosuppressive drugs, like cyclosporine A and tacrolimus, that usually are effective but may also cause adverse effects. A promising therapeutic option is omalizumab, a recombinant anti-IgE humanized monoclonal antibody, currently used as add-on therapy for moderate to severe uncontrolled allergic asthma and chronic spontaneous urticaria. Here, we report the short-time duration of effective relief of symptoms after the prolonged use of omalizumab in a patient affected by refractory VKC. However, in our case any apparent beneficial effect was short lasting, and we propose that the duration of the disease and the concomitant long-term use of steroids leads to iatrogenic damage; thus, the disease becomes refractory to anti-IgE treatment.

Omalizumab in chronic spontaneous urticaria: steroid sparing effect.

Omalizumab has been recognized to be effective in the treatment of chronic spontaneous urticaria (CSU). The Italian Medicines Agency authorizes two omalizumab courses, only for patients with CSU unresponsive to antihistamines, and this schedule may limit omalizumab use. Unfortunately, in the majority of CSU, the schedule is unsatisfactory because symptoms usually recur shortly after discontinuation of treatment. A case of a patient needing more than two treatment courses with omalizumab is reported, in order to discuss the rationale for its long-term use. Patient had needed systemic steroids almost continuously for 4 years. Two severe glucocorticoid-associated adverse events (GAEs) occurred during long-term treatment. Omalizumab 300 mg monthly was started with immediate disappearance of the urticarial lesions. Beneficial effects waned shortly after discontinuation of treatment, and further steroid use was needed. A second omalizumab course showed the same clinical pattern, with prompt response and recurrence of symptoms after suspension. Therefore, we decided to repeat the 6 months omalizumab treatment as soon as symptoms recurred, to avoid further emergency steroid treatments and GAEs. This experience suggests that long-term use of omalizumab could be useful. Evidences show that omalizumab is effective and safe for re-treatment and long-term use of responding patients after recurrence.

Fluticasone/formoterol association favors long-lasting decrease in bronchial reactivity to methacholine and weekly PEF variability.

Inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) association offers a better asthma control than a higher steroid dose with short-acting beta-agonists as needed. In this study, we evaluated the effect of the association on bronchial hyperreactivity (BHR) and peak expiratory flow (PEF) variability, as such parameters are positively correlated with increased asthma morbidity and exacerbations. Thirty-six adult patients with mild persistent asthma were enrolled. After a 7-day run-in, they were randomly assigned to three therapy regimens for 6 weeks: Group 1, fluticasone 125 µg + formoterol 5 µg in the same device; Group 2, fluticasone 125 µg + formoterol 12 µg as needed; Group 3, fluticasone 250 µg + formoterol 12 µg as needed. We evaluated changes induced in weekly PEF variability (measured during the entire study and 4 weeks of follow-up) and pre- and post-study PD20 methacholine (MCH). Weekly PEF variability decreased in all groups during treatment with the greatest reduction in Group 1, followed by Group 3, and finally Group 2. During the follow-up, no significant changes were detected in Group 1, whereas a trend towards an increased variability was found in Groups 2 and 3. Post-treatment PD20 MCH was significantly higher versus the pre-treatment. The increase observed in Group 1 was significantly higher compared to Groups 2 and 3 and that observed in Group 3 in respect to Group 2. The study proves that both BHR and PEF variability are influenced by ICS. This effect was greater with fluticasone/formoterol association compared to fluticasone alone with formoterol as needed even at higher steroid dose.

Treatment of chronic idiopathic urticaria and positive autologous serum skin test with cyclosporine: clinical and immunological evaluation.

This study evaluates the effectiveness and safety of cyclosporine (CsA) in the treatment of patients with chronic idiopathic urticaria with a positive autologous serum skin test (ASST), who fail to respond to conventional therapy, and requiring long-term oral steroid treatment. In a double-blind study, 40 adults were assigned randomly to receive CsA (5 mg/kg per day for 8 weeks and then 4 mg/kg per day for 8 weeks) or cetirizine (10 mg/day) and then they were followed up for 9 months. After 2 weeks, the study was opened because 16 patients (40%) had daily severe relapses requiring systemic steroids treatment. All of these patients had been receiving antihistamines and, therefore, all patients also were assigned to the CsA treatment regimen (5 mg/kg per day for 8 weeks and then 4 mg/kg per day for 8 weeks). The ASST and clinical severity score were evaluated before and after treatment. All of the 40 patients completed the 16-week CsA course without dropping out because of relevant side effects. In three patients, CsA was reduced by 0.5 mg/kg per day after the 1st month of treatment for a mild and reversible increase in serum creatinine. During CsA treatment, 20 patients had relapses resolving spontaneously (8 patients) or with antihistamines (12 patients). During the 9-month follow-up period, 22 patients had relapses resolving spontaneously (10 patients) or with antihistamines (12 patients). Only two patients failed to complete the study because of severe symptoms occurring after 4 and 7 days of follow-up and requiring long-term steroid treatment. After 9 months of follow-up, 16 patients were still in full remission. The clinical severity score of chronic idiopathic urticaria dropped significantly by the end of the 4th month of treatment (p = 0.002) as well as by the completion of follow-up (p = 0.007). The ASST was negative in 13 patients and positive in 3 of 16 patients, with total remission of symptoms. Significant score reduction also was observed in patients experiencing relapses that resolved spontaneously (p = 0.005) or with antihistamines (p = 0.03). These results show the long-term efficacy and tolerability of CsA in patients with severe chronic idiopathic urticaria, unresponsive to conventional treatments.

Common variable immunodeficiency and eosinophilic fasciitis.

The association of eosinophilic fasciitis and immunological defects is rare, especially hypogammaglobulinemia. We report a case of eosinophilic fasciitis occurring in a female, 53 years old, with common variable immunodeficiency. The diagnosis of common variable immunodeficiency was established by chance observation of persistently low levels of all immunoglobulin classes unrelated to protein loss or immunosuppressive treatment, one year after the appearance of eosinophilic fasciitis, which is usually characterized by hypergammaglobulinemia. Our description may prompt the investigation of an increased rate of simultaneous occurrence of eosinophilic fasciitis and common variable immunodeficiency.