Angioedema due to C1 inhibitor deficiency (AE-C1-INH) is a rare disease characterized by recurrent and unpredictable attacks of angioedema. Multiple trigger factors, including trauma, emotional stress, infectious diseases, and drugs, could elicit angioedema attacks. The aim of this study was to collect data on the safety and tolerability of COVID-19 vaccines in a population of patients affected by AE-C1-INH. Adult patients with AE-C1-INH, followed by Reference Centers belonging to the Italian Network for Hereditary and Acquired Angioedema (ITACA), were enrolled in this study. Patients received nucleoside-modified mRNA vaccines and vaccines with adenovirus vectors. Data on acute attacks developed in the 72 h following COVID-19 vaccinations were collected. The frequency of attacks in the 6 months after the COVID-19 vaccination was compared with the rate of attacks registered in the 6 months before the first vaccination. Between December 2020 and June 2022, 208 patients (118 females) with AE-C1-INH received COVID-19 vaccines. A total of 529 doses of the COVID-19 vaccine were administered, and the majority of patients received mRNA vaccines. Forty-eight attacks of angioedema (9%) occurred within 72 h following COVID-19 vaccinations. About half of the attacks were abdominal. Attacks were successfully treated with on-demand therapy. No hospitalizations were registered. There was no increase in the monthly attack rate following the vaccination. The most common adverse reactions were pain at the site of injection and fever. Our results show that adult patients with angioedema due to C1 inhibitor deficiency can be safely vaccinated against SARS-CoV-2 in a controlled medical setting and should always have available on-demand therapies.
Nickel allergy is the most common contact allergy. Some nickel-sensitive patients present systemic (cutaneous and/or digestive) symptoms related to the ingestion of high nickel-content foods, which significantly improve after a specific low nickel-content diet. The etiopathogenetic role of nickel in the genesis of systemic disorders is, furthermore, demonstrated by the relapse of previous contact lesions, appearance of widespread eczema and generalized urticaria-like lesions after oral nickel challenge test. The aim of this study is to investigate the safety and efficacy of a specific oral hyposensitization to nickel in patients with both local contact disorders and systemic symptoms after the ingestion of nickel-containing foods. Inclusion criteria for the recruitment of these patients were (other than a positive patch test) a benefit higher than 80% from a low nickel-content diet and a positive oral challenge with nickel. Based on the previous experiences, our group adopted a therapeutic protocol by using increasing oral doses of nickel sulfate associated to an elimination diet. Results have been excellent: this treatment has been effective in inducing clinical tolerance to nickel-containing foods, with a low incidence of side effects (gastric pyrosis, itching erythema).
The prevalence of latex allergy has rapidly increased. Clinical manifestations range from contact urticaria-angioedema and rhinoconjunctivitis to more severe bronchial asthma and anaphylactic shock. The only effective therapy is desensitization. We studied 24 patients allergic to latex: 12 of them underwent a rush (4-day) sublingual desensitization to latex, performed by putting increasing doses of latex extract under the patients' tongues for 3 min every 20 min, followed by a maintenance therapy. The other 12 patients were considered controls. The sublingual rush desensitization protocol was successfully completed in all patients with no side effects. After 3 mo, all patients underwent an allergological evaluation, which showed a significant improvement of symptoms scores after challenges in the treated group as compared with the controls. All the desensitized patients can now wear latex gloves and undergo medical procedures without any symptoms.
In the literature there are several reports dealing with the possibility of a desensitising treatment in food allergy, but there are very few studies about the immunological mechanisms of oral desensitisation. We studied the immunological modifications in four children who underwent oral desensitisation with cow milk. Four children with cow milk allergy underwent oral desensitisation according to a standardized protocol. Total IgE, eosinophilic cationic protein in serum, and specific IgE and IgG4 to α-lactalbumin, to β-lactoglobulin and to casein were determined at the beginning of the treatment and after 6, 12 and 18 months in the 4 children treated. All the 4 treated patients successfully completed the treatment. Specific IgE to casein showed a significant reduction (p<0.01), while specific IgG4 to α-lactalbumin (p<0.02), to β-lactoglobulin (p<0.01) and to casein (p<0.01) showed a significant increase. Total IgE, eosinophilic cationic protein, and specific IgE to α-lactalbumin and to β-lactoglobulin did not show any significant modification. Control patients did not show any immunological modification and still had a positive double-blind, placebo-controlled food challenge. These results make us think that oral desensitisation in food allergy happens with the same mechanisms of traditional desensitising treatments for respiratory and insect sting allergies.
Clinical Implications•In Italian patients with hereditary angioedema, life expectancy is the same as that of the general population, and laryngeal edema is not the main cause of death. •In Italian patients with hereditary angioedema, life expectancy is the same as that of the general population, and laryngeal edema is not the main cause of death. C1-inhibitor (C1-INH) deficiency due to mutation in the SERPING1 gene is the most common cause of hereditary angioedema (HAE).1Cicardi M. Zuraw B.L. Angioedema due to bradykinin dysregulation.J Allergy Clin Immunol Pract. 2018; 6: 1132-1141Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar C1-INH-HAE occurs worldwide; its prevalence in Italy has been calculated to be 1:64,000.2Zanichelli A. Arcoleo F. Barca M.P. Borrelli P. Bova M. Cancian M. et al.A nationwide survey of hereditary angioedema due to C1 inhibitor deficiency in Italy.Orphanet J Rare Dis. 2015; 10: 11Crossref PubMed Scopus (85) Google Scholar It is characterized by self-limiting edema of the extremities, face, genitals, and gastrointestinal and upper airway mucosae, in absence of urticaria. Attacks that involve the upper airways place patients at risk of asphyxiation.3Bork K. Siedlecki K. Bosch S. Schopf R.E. Kreuz W. Asphyxiation by laryngeal edema in patients with hereditary angioedema.Mayo Clin Proc. 2000; 75: 349-354Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar The mortality related to C1-INH-HAE depends on the presence of correct diagnosis and availability of on-demand treatment. In a previous earlier retrospective observation in Italian families,4Agostoni A. Cicardi M. Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients.Med (Baltimore). 1992; 71: 206-215Crossref PubMed Scopus (557) Google Scholar it has been recorded that more than 50% of subjects could have died of laryngeal edema. A survey in Germany confirms that a correct diagnosis drastically reduced the disability of laryngeal edema. Nevertheless, even in diagnosed patients, asphyxiation remained a common cause of death.5Bork K. Hardt J. Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency.J Allergy Clin Immunol. 2012; 130: 692-697Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar There are no studies assessing life expectancy and cause of death in patients with C1-INH-HAE. An Italian database showed that male patients older than 70 years were represented in a reduced proportion compared with the general population; however, this survey did not consider the causes of death.2Zanichelli A. Arcoleo F. Barca M.P. Borrelli P. Bova M. Cancian M. et al.A nationwide survey of hereditary angioedema due to C1 inhibitor deficiency in Italy.Orphanet J Rare Dis. 2015; 10: 11Crossref PubMed Scopus (85) Google Scholar Here, we analyzed patients followed at Italian centers for C1-INH-HAE to compare their life expectancy and causes of death with those of Italian residents. We included a cohort of patients diagnosed from 1973 data collected by the ITAlian network for C1-INH-HAE in the HAE Global Registry (ClinicalTrials.gov NCT03828279). The Local Ethic Committee gave approval to the study. Diagnosis was based on personal and/or family history of angioedema and functional and/or antigenic plasma levels of C1-INH less than or equal to 50% of normal.6Cicardi M. Aberer W. Banerji A. Bas M. Bernstein J.A. Bork K. et al.Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group.Allergy. 2014; 69: 602-616Crossref PubMed Scopus (453) Google Scholar Data regarding the causes of death were extracted from medical records rather than death certificates and integrated by telephone interviews to relatives and analyzed for life expectancy. All collected data were compared with data of the Italian Institute of Statistics on Italian residents. Descriptive statistical analysis was performed and reported as mean, median, SD, range, and distribution percentage. Mortality rate compares actual versus expected number of deaths in a population observed for a specific interval of time (observed person per year [OPY]). To assess this parameter, the study population was clustered in time intervals of 5 years. Statistical significance of differences between actual and expected deaths was calculated as standardized mortality rate (SMR) expressed as percentage and CIs. Until March 2018, the study population consisted of 1113 patients; 90 died during the observation. Mean age at death considering the entire period of observation was 69.6 years in females and 64.3 in males; median age at diagnosis was 28.1 years (0-88), and median age at death was 73.5 years for females and 72.8 for males (Figure 1). The mean age at death, grouped by sex in the period 2011 to 2017, was 78.2 years for females versus 72.6 for males in the study population and 82.9 versus 77.4 in Italian residents. OPY progressively grew: 39 in the period 1970 to 1975, 4519 in the period 2011 to 2015, and 20530 for the entire period. Sixty-nine percent of OPY were from 2000 onward and 72% of deaths (65 of 90) occurred in the same period. On calculating age-specific mortality of Italian residents in comparable years, we found that the expected number of deaths in the study population was 54.4 in females and 39.8 in males. Observed numbers were 43 in females (SMR = 79%) and 47 in males (SMR = 118%). Differences between expected and observed numbers did not reach statistical significance for either sex (females: CI 55%
