Safety of COVID-19 vaccines in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS). OBJECTIVE: To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types. METHODS: Systematic review and meta-analysis of pharmacovigilance registries and observational studies. RESULTS: Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40-46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9-89.8), 12.6% (95% CI: 6.3-20.8), 6.7% (95% CI: 4.2-9.9), and 2.9% (95% CI: 1-5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12-28.2) from vaccination was 1.9% (95% CI: 1.3%-2.6%; I2 = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine (p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%-8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%-58.8%) and 0.1% (95% CI: 0%-0.2%) of vaccinations, respectively. CONCLUSION: COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.

Filaggrin and Periostin Expression Is Altered in Eosinophilic Esophagitis and Normalized With Treatment.

OBJECTIVES: Previous data have suggested that filaggrin (FLG) and periostin (POSTN) genes may be dysregulated in eosinophilic esophagitis (EoE). We aimed to further evaluate the expression patterns of FLG and POSTN proteins in esophageal tissue samples of patients with EoE, as compared to those of patients with gastroesophageal reflux disease (GERD) and normal controls. METHODS: A total of 61 prospectively collected cases, including 40 children with EoE and 21 children with GERD, and a control group of 14 sex- and age-matched healthy children were enrolled. Patients with EoE were treated with skin testing-driven elimination diet and/or corticosteroids. The immunohistochemical expression of FLG and POSTN was evaluated in esophageal biopsies obtained from patients and controls, and the results were correlated with EoE-related clinicopathological parameters. RESULTS: Positive FLG and negative POSTN staining were observed in all esophageal biopsies from normal controls. In contrast, FLG and POSTN stained negative and positive, respectively, in all pretreatment biopsies obtained from patients with EoE, whereas FLG and POSTN stained positive in 57.1% and 95.2% of GERD cases, respectively (P < 0.001). A statistically significant decrease of the proportion of cases with negative FLG and positive POSTN staining was observed from the first (pretreatment) to the second (post-treatment) biopsy in the subgroup of patients with EoE (P < 0.001 in both correlations). CONCLUSIONS: FLG and POSTN expression may be downregulated and upregulated, respectively, in the esophageal mucosa of patients with active EoE, and these changes may be restored with treatment in a significant percentage of cases.

Allergy-test-driven elimination diet is useful in children with eosinophilic esophagitis, regardless of the severity of symptoms.

BACKGROUND: A combination of PPIs and corticosteroids is the pharmacotherapy mostly used to treat eosinophilic esophagitis (EoE), while dietetic manipulations consist also an efficient option. The aim of this study was to compare the efficacy of allergy-test-driven elimination diet in children with mild symptoms of EoE to a group of children with moderate/severe symptoms. METHODS: Thirty-five children, aged 7 months to 12 yr, with EoE were enrolled in the study. They had a clinical history of GERD-like (21 children, Group A) or more severe symptoms (14 children, Group B). The diagnosis had been confirmed after two preliminary months of therapy with PPIs and an esophagogastroduodenoscopy. Soon after diagnosis, they were allergy-tested, using IgE detection (SPT and serum-specific IgE) and atopy patch tests (APTs). A 12-month tailor-made diet was prescribed according to the tests. Patients of Group B continued PPIs for two more months, while swallowed topical steroids were also prescribed to them for the first 5 months after diagnosis, followed by an 'as-needed' use of them for the rest of the study. Endoscopy was repeated at the end of the study. RESULTS: Milk and egg were the most common APT-positive allergens. Thirty-two patients were instructed to follow an elimination diet, which was completed by 15/18 of Group A and 12/14 of Group B. An improvement of symptoms was reported by 26/27 patients that completed the study. The use of swallowed corticosteroids was noticeably decreased during the as-needed period, in Group B. A remarkable reduce of eosinophils was noticed in biopsies; from 42.84 ± 18.08, they decreased to 6.41 ± 3.20, a year after. CONCLUSION: All children with EoE and mild symptoms had resolution of symptoms and normal eosinophils in the esophageal mucosa a year after an allergy-driven elimination diet. Patients with moderate/severe EoE symptoms had the same improvement, indicating that an elimination diet is an efficient complementary treatment to corticosteroids.

Giant tuberculin reaction associated with the homeopathic drug tuberculinum: a case report.

Giant reactions to the tuberculin skin test are extremely rare and have been previously reported almost exclusively in patients with lepromatous leprosy. We herein report a giant tuberculin reaction associated with the homeopathic drug Tuberculinum in a patient with no evidence of active tuberculosis or leprosy.

Significant Increase in Blood Pressure Following BNT162b2 mRNA COVID-19 Vaccination among Healthcare Workers: A Rare Event.

This brief report examined the frequency and characteristics of a significant blood-pressure (BP) increase after Pfizer-BioNTech BNT162b2 vaccination among healthcare workers who were advised to measure their BP at home. A total of 797 participants (mean age 48.1 ± 10.8 years, 63% women, 39% smokers) were included in the analysis. Seven participants reported an increase in their BP (three in the range of grade 2 and four in the range of grade 3 hypertension). Only one participant had a history of treated hypertension. The BP increase was observed at the end of the first week after the first dose, lasted for 3 to 4 days, and recurred promptly after the second dose. Only one case required hospitalization, mainly due to a history of cardiovascular disease (follow-up). Individuals experiencing a BP increase compared with those not reporting issues with their BP had a higher mean age and similar distribution of sex and non-smoking status. In conclusion, a significant BP increase after Pfizer-BioNTech vaccination seems to be rare and of a benign and transient nature. Monitoring the BP before and after vaccination might be advisable only for selected individuals with a high cardiovascular risk.

Assessment of Seroconversion after SARS-CoV-2 Vaccination in Patients with Lung Cancer.

Background: SARS-CoV-2 mortality rates are significantly higher in patients with lung cancer compared with the general population. However, little is known on their immunization status after vaccination. Methods: To evaluate the humoral response (seroconversion) of patients with lung cancer following vaccination against SARS-COV-2 (Group A), we obtained antibodies against SARS-CoV-2 spike (S) protein both at baseline and at different time points after the first dose of SARS-CoV-2 vaccine (two to three weeks [T1], six weeks ± one week [T2], 12 weeks ± three weeks [T3], and 24 weeks ± three weeks [T4]). Antibodies were also acquired from a control cohort of non-lung cancer patients (Group B) as well as a third cohort containing healthy controls (Group C) at all time points and at T4, respectively, to make comparisons with Group A. Analysis of antibody response at different time points, association with clinicopathologic parameters, and comparisons with control groups were performed. Results: A total of 125 patients with lung cancer were included in the analysis (96 males [74.3%], median age of 68 years [46−91]. All study participants received two vaccine doses (BNT162b2, mRNA-1273, AZD1222). Analysis of anti-SARS-CoV-2 S antibody titers showed minimal response at T1 (0.4 [0.4−48.6] IU/mL). Antibody response peaked at T2 (527.0 [0.4−2500] IU/mL) and declined over T3 (323.0 [0.4−2500] IU/mL) and T4 (141.0 [0.4−2500] IU/mL). Active smokers had lower antibody titers at T2 (p = 0.04), T3 (p = 0.04), and T4 (p < 0.0001) compared with former or never smokers. Peak antibody titers were not associated with any other clinicopathologic characteristic. No significant differences were observed compared with Group B. However, lung cancer patients exhibited significantly decreased antibody titers compared with Group C at T4 (p < 0.0001). Conclusions: Lung cancer patients demonstrate sufficient antibody response six weeks after the first dose of vaccine against SARS-CoV-2 when vaccinated with two-dose regimens. Rapidly declining antibody titers six weeks after the first dose underline the need for a third dose three months later, in patients with lung cancer, and especially active smokers.

Hypersensitivity reactions to docetaxel: retrospective evaluation and development of a desensitization protocol.

BACKGROUND: Docetaxel (DT) is an extensively used taxane, frequently associated with hypersensitivity reactions. The aim of this study was to record the epidemiological and clinical features of hypersensitivity to DT in non-small cell lung cancer patients in order to obtain useful information concerning the management of these patients. We also developed a desensitization protocol and evaluated its clinical application. METHODS: We retrospectively reviewed records of 620 non-small cell lung cancer patients treated with DT-containing regimens in the adjuvant, first-, second- or next-line setting. Data from 102 patients who had exhibited hypersensitivity reactions were analyzed according to the Common Toxicity Criteria for Adverse Events version 3.0. Five patients were chosen for the desensitization protocol. We applied the standard protocol for parenteral desensitization to ß-lactam antibiotics, and DT treatment was carried out with a series of 10-fold dilutions in sufficient volume to administer the total dose. RESULTS: One hundred and two patients (16.5%) were recorded as having hypersensitivity to DT. Reactions were observed after approximately 2.5 ± 1.0 cycles. Only 14 patients (14/620, 2%) developed grade 3-4 hypersensitivity. Reactions were more likely in patients during second- or third-line chemotherapy, but no other correlation (age, gender, atopic status) was observed. Five patients completed a parenteral desensitization protocol and continued their treatment uneventfully. CONCLUSIONS: Hypersensitivity reactions to DT respond quickly to discontinuation along with appropriate supportive care. Premedication and increased infusion time may allow readministration. The desensitization protocol that we developed provides a reliable alternative to permanent discontinuation of DT.

Food allergy-related paediatric constipation: the usefulness of atopy patch test.

The aims of this study were to evaluate the implication of food allergy as a cause of paediatric constipation and to determine the diet period needed to tolerate the constipation-causing foods. Fifty-four children aged 6 months to 14 years (median, 42 months) suffering from chronic constipation (without anatomic abnormalities, cοeliac disease or hypothyroidism), unresponsive to a 3-month laxative therapy, were prospectively evaluated. All participants were evaluated for allergy to cow's milk, egg, wheat, rice, corn, potato, chicken, beef and soy, using skin tests (SPT), serum specific IgE and atopy patch test (APT). A withdrawal of the APT-positive foods was instructed. Thirty-two children had positive APT; 15 were positive to one; six, to two and 11, to three or more food allergens, wheat and egg being the commonest. After withdrawing the APT-positive foods for an 8-week period, constipation had improved in 28/32 children, but a relapse of constipation was noticed after an oral food challenge, so they continued the elimination diet. Tolerance to food allergens was achieved in only 6/28 after 6 months, compared to 25/28 after 12 months and to all after a 2-year-long elimination. Food allergy seems to be a significant etiologic factor for chronic constipation not responding to treatment, in infants and young children. APT was found to be useful in evaluating non-IgE allergy-mediated constipation, and there was no correlation of APT with IgE detection. Tolerance was adequately achieved after 12 months of strict food allergen elimination.

Efficacy of a Quail Eggs-Based Dietary Supplement for Allergic Rhinitis: Results of a Single-Arm Trial.

Previous data suggested the potential treatment effect of a proprietary quail eggs-based blend on allergic rhinitis (AR) symptoms, induced by allergen challenge. We herein aimed to investigate the efficacy and safety of a similar dietary supplement, comprising the bioactive ingredients of quail eggs and the zinc mineral, in the setting of active AR. Adult patients (n = 77), aged 18- 60 years, with mild, intermittent AR were enrolled in this single-arm, open-label trial. Patients' responses were assessed based on peak nasal inspiratory flow (PNIF) measurements at two visits (Day 1/Visit 1 and Day 7/Visit 2) and self-rating of AR-associated symptoms on a Visual Analog Scale (VAS) throughout the entire 7-day study period. PNIF values at 15, 30, 60, 90 and 120 min (Visit 1) following administration of an oral dose of the study product were the primary efficacy endpoint. PNIF values (Visit 1) gradually increased from baseline (pre-treatment), with statistical significance first reached 30 min later (p = 0.002). VAS scores (Visit 1) for all AR symptoms gradually decreased with statistical significance first reached at 15 min (rhinorrhea, p = 0.042; itchy nose, p = 0.001; sneezing p < 0.001), 30 min (nasal congestion, p < 0.001; itchy eyes, p = 0.003) or 60 min (watery eyes, p = 0.04). PNIF improvement and decline of VAS scores were significantly more apparent at Visit one vs. Visit 2. Treatment-emergent adverse events were limited to cough and muscle strain (one patient each). Our results support the efficacy, rapid mode of action and tolerability of the investigated product for symptomatic treatment of mild intermittent AR.

Administration of cisplatin in three patients with carboplatin hypersensitivity: is skin testing useful?

Carboplatin is a chemotherapeutic agent approved in the first-line setting of numerous malignancies. Hypersensitivity to carboplatin has been reported in up to 44% of patients receiving this antineoplastic agent, usually occurring after several courses of treatment. The aim of this study was to determine the usefulness of skin tests in ruling out cross-reaction to cisplatin to continue platinum-based chemotherapy in patients who are responsive to these agents. Prick tests and intradermal tests with a series of dilutions of carboplatin and cisplatin were performed on three patients who had exhibited medium and severe hypersensitivity reactions to carboplatin. Prick tests were negative in both the antineoplastic agents. Intradermal tests with carboplatin were positive in all three patients and negative with cisplatin. In all patients, the administration of cisplatin instead of carboplatin was well tolerated without the need of premedication. In conclusion, intradermal skin tests can be a useful tool for detecting a potential cross-reaction between platinum salts. It allows safe administration of a different platinum agent in patients who seem to benefit from platinum-based therapy. Discontinuation of chemotherapy, desensitization protocols and steroid premedication can be avoided.

Hypersensitivity reactions to oxaliplatin: a retrospective study and the development of a desensitization protocol.

BACKGROUND: We recorded the epidemiologic and clinical features of hypersensitivity reactions (HSRs) to oxaliplatin in colorectal cancer (CRC) patients in order to provide information on the management of these patients. We also developed a desensitization protocol and evaluated its clinical application. For these reasons, we analyzed retrospectively the records of 215 CRC patients treated with oxaliplatin-containing regimens either as an adjuvant, first-line, second-line, or more. PATIENTS AND METHODS: Data from 52 patients with HSRs were analyzed according to the Common Toxicity Criteria for Adverse Events (CTCAE), v3.0. Three patients were chosen for the desensitization protocol. After determining the starting point for desensitization, we applied the standard protocol for parenteral desensitization to b-lactam antibiotics. Oxaliplatin treatment was then carried out with serial 10-fold dilutions in sufficient volume to administer the total dose. A total of 52 patients (24.2%) were recorded as having an allergic reaction to oxaliplatin. RESULTS: Hypersensitivity reactions were recorded after a mean of 6.5 (SD +/- 4.5) cycles. Only 4 patients (4 of 215; 1.8%) developed CTCAE grade 3/4 HSRs. Hypersensitivity reactions were seen more likely in patients receiving second-line or more of chemotherapy compared with chemotherapy-naive patients. No other correlations were seen (the presence of atopic disease, positive skin prick test). The 3 patients, having completed the parenteral desensitization protocol, completed their treatment uneventfully as well. CONCLUSION: Hypersensitivity reactions from oxaliplatin respond quickly to the discontinuation of the drug and appropriate support. Premedication and an increased infusion time could allow for readministration. The desensitization protocol we developed can provide a reliable alternative to permanent discontinuation of oxaliplatin.

Hypersensitivity reactions to antineoplastic agents: an overview.

Hypersensitivity reactions to antineoplastic agents are defined as unexpected reactions with signs and symptoms inconsistent with known toxicity of antineoplastic drugs. These reactions are uncommon and usually associated with certain antineoplastic categories, such as taxanes, platinum-containing compounds, epipodofyllotoxins, asparaginase, procarbazine and, more rarely, with doxorubicin and 6-mercaptopurine. The mechanisms that are responsible for hypersensitivity reactions are unclear and vary between agents. Symptoms of these reactions range from mild skin rashes to more severe reactions, such as arthralgia, respiratory arrest or even death in some cases. Once hypersensitivity reactions are observed, basic principles that allow their management and possible continuance and completion of the regimen should be followed.

Treatment response to omalizumab in patients with refractory chronic spontaneous urticaria.

BACKGROUND: Previous clinical trials have demonstrated the efficacy and safety of the anti-IgE monoclonal antibody omalizumab in chronic spontaneous urticaria (CSU) not responding to antihistamine treatment. The primary aim of our study was to describe the response patterns of patients with refractory CSU treated with omalizumab in a real-world clinical setting. METHODS: A retrospective analysis of medical records of 20 patients with refractory CSU was performed. Demographic, clinical, and laboratory features were retrieved and analyzed in correlation with treatment data. RESULTS: Mean age of our patient population was 54.5 years, while the majority were females (15/20 cases, 75%). Mean disease duration prior to omalizumab administration was 21.8 months. All patients had a history of chronic urticaria, refractory to high antihistamine and corticosteroid treatment, and responded favorably to omalizumab after administration of 1-5 doses of omalizumab; complete response was observed in 17/20 patients (85%) and well-controlled disease in the remaining 3/20 patients (15%). In a subset of cases (6/20, 30%), best response to omalizumab was achieved after interval administration of a 9-day course of methylprednisolone (total dose of 188 mg). Late response to omalizumab (after three-month treatment) was significantly correlated (P = 0.026) with shorter disease duration before initiation of omalizumab. CONCLUSION: In the present series, omalizumab, either alone or in combination with a short-term course of corticosteroids, was highly effective in resolution of refractory CSU. Furthermore, disease duration prior to omalizumab had a significant effect on timing of response.

Acute Generalized Exanthematous Pustulosis Induced by Amoxicillin/Clavulanic Acid: Report of a Case Presenting With Generalized Lymphadenopathy.

Drug-induced acute generalized exanthematous pustulosis is a rare pustular skin reaction, most commonly triggered by antibiotics. Although its diagnosis is based primarily on the presence of specific clinical and histopathologic features, additional in vivo (patch testing) or in vitro testing may be required, especially in atypical cases, to more accurately determine the causative agent. The authors report a histologically confirmed case of acute generalized exanthematous pustulosis that was induced by amoxicillin/clavulanic acid, as documented by subsequent patch testing, and presented with generalized painful lymphadenopathy, mimicking an acute infectious process. This is a very rare and diagnostically challenging clinical presentation of acute generalized exanthematous pustulosis, which has been reported, to the best of our knowledge, only once previously.