Adverse Reactions after Vaccination and Allergen-Specific Immunotherapy: Contact Allergy to Aluminium and Itching Nodules

The aim of the work presented in this thesis was to investigate two different types of adverse reactions, persistent itching nodules and contact allergy to aluminium, after immunization with aluminium-containing vaccines and aluminium-containing allergen extracts used for allergen-specific immunotherapy (ASIT). The first paper describes active parental reporting of adverse events (AEFIs) after a booster dose of diphtheria-tetanus vaccine (DT). A parental questionnaire elicited reports of AEFIs within seven days of vaccination. A follow-up phone call was made in all cases of positive response. Active surveillance by parental reports was shown to be a useful complement to passive surveillance of childhood immunization. The proportion of late local reactions after immunization with a fourth dose of DT vaccines containing different aluminium compounds as adjuvant was investigated in the second study, in which a prospective cluster-randomized, active surveillance study was performed in 25,232 10-year-olds. Parental reports were collected 6 months after vaccination. 3-6 children per 10,000 had a persistent itching nodule. Contact allergy to aluminium was not detected. These findings support the continued use of the vaccine presently offered in the Swedish vaccination programme. However, continued surveillance is warranted. The study described in the third paper examined retrospectively whether ASIT could induce contact allergy to aluminium, and investigated a possible association between persistent subcutaneous nodules and aluminium allergy. The study consisted of a non-clinical part based on a questionnaire, and a clinical part involving a physical examination, self-assessment of itching, and patch testing. A statistically significant association was found between contact allergy to aluminium and persistent subcutaneous nodules in children given ASIT. Contact allergy was found in eight of the participants, all given ASIT. The fourth paper presents the results of a prospective study on whether ASIT with allergen preparations containing aluminium hydroxide induces contact allergy to aluminium. The association between contact allergy to aluminium and persistent itching nodules was also studied. Three groups undergoing ASIT were patch tested with aluminium chloride hexahydrate before and during ASIT. A control group was included (untreated). At the end of the study all groups were patch tested. A high rate of contact allergy to aluminium was found. The study did not confirm or refute ASIT as a risk factor. Allergy to aluminium and itching nodules after ASIT seemed to be more common among children, and among those suffering from atopic dermatitis

Aluminum-Allergen of the Year 2022

Exposure to elemental aluminum and its salts is unavoidable. Aluminum as a metal is present in transport, construction, packaging, and electronic equipment. Aluminum salts are present in consumer products, food items and drinking water, vaccines, drugs, and antiperspirants. Aluminum in vaccines and preparations for allergen-specific immunotherapy are the major sensitization sources. The predominent clinical manifestations of aluminum allergy are pruritic subcutaneous nodules and eczematous dermatitis. Patch testing shall be performed with aluminum chloride hexahydrate (ACH) in petrolatum. The preparation with ACH 10% detects substantially more aluminum allergy than ACH 2%. A patch test with elemental aluminum, for example, an empty Finn Chamber, is only positive when there is a strong aluminum allergy. A patch test reading should be performed 1 week after the application so as not to miss 15% to 20% of aluminum allergy. Aluminum should be included in any baseline patch test series for children and investigated for a possible inclusion in baseline series for adults. Aluminum test chambers can interfere with the testing resulting in both false-negative and false-positive patch test reactions to nonaluminum contact sensitizers

Surveillance of Vaccine Safety: Comparison of parental reports with routine surveillance and a clinical trial

One way to maintain confidence in vaccination programmes is to improve monitoring of immunisation safety. We studied active parental reporting of adverse events after a booster dose of diphtheria-tetanus toxoid (DT). 7193 children received the vaccine. Questionnaires were submitted by 84.2% of the parents, who reported reactions for 9.2% of the children. Four percent of events were classified as moderate/severe by interviews. Relative risk of redness and swelling reported was 0.24 (95% CI. 0.13-0.42) compared to a clinical trial, while it was 71.0 (44-114) compared to passive surveillance. Active surveillance by parental reports is a useful complement to passive surveillance of childhood immunisations to generate hypotheses for evaluation in controlled studies. (C) 2009 Elsevier Ltd. All rights reserved

Contact allergy in atopic individuals in relation to allergen-specific immunotherapy

Background: Type I sensitizations and atopic dermatitis (AD) often appear in the same patient. Beneficial effects of allergen-specific immunotherapy (ASIT) in patients with bothADand type I allergies have been reported. The predisposing role of AD to the development of type IV sensitization is discussed. Whether ASIT for type I allergy also influences type IV allergies is unknown. Objectives: To compare the number of contact allergies between patients with and without AD, before and after one year’s treatment with ASIT. Materials and Methods: A controlled, single-blind multicentre study of children/adults with allergic asthma and/or rhinoconjunctivitis, treated or untreated with ASIT, was performed. The history of AD was collected using questionnaires. The number of contact allergies was assessed by patch testing with a baseline series. Results: 205 individuals completed the study; 133 treated with ASIT (exposed) and 72 before starting ASIT (unexposed). For participants with AD, significantly more contact allergies were found in the groups of all children (p = 0.002), all exposed children (p<0.001), and all exposed study persons (p = 0.013). Independent of AD, significantly more contact allergies were noted in the groups of all unexposed adults (p = 0.004) and all unexposed study persons (p = 0.004). Conclusions: The higher number of contact allergies in patients with AD indicates that AD may be a risk factor for type IV sensitization in those with allergic asthma and/or rhinoconjunctivitis. The lower number of contact allergies in patients exposed to ASIT suggests an immunomodulatory effect on type IV sensitization

Young individuals with atopic disease and asthma or rhinoconjunctivitis may have clinically relevant contact allergies.

Children and adolescents with atopic disease who have allergic asthma and/or rhinitis with and without atopic dermatitis may have hidden, clinically relevant contact allergies

Pertussis-Specific Memory B-Cell and Humoral IgG Responses in Adolescents after a Fifth Consecutive Dose of Acellular Pertussis Vaccine

In order to impede the increase in pertussis incidence in the adolescent group, a school-leaving booster dose administered at the age of 14 to 16 years will be introduced in Sweden in 2016. Preceding this introduction, an open-label, randomized, multicenter, clinical trial without a control group and with blinded analysis was performed, investigating both safety and immunogenicity. Reported here are the memory B-cell and serological responses detected in a smaller cohort (n = 34) of the 230 subjects recruited to the study. All subjects had received primary vaccination consisting of three doses of diphtheria-tetanus-5-component pertussis (DTaP5) vaccine, at 3, 5, and 12 months of age, and a tetanus-low-dose diphtheria-5-component pertussis (Tdap5) vaccine booster at 5.5 years. In this study, the subjects were randomly assigned and received either a Tdap1 or Tdap5 booster. Of the 230 participants, 34 subjects had samples available for evaluation of IgG-producing memory B-cell responses. Both vaccine groups had significant increases in pertussis toxin-specific serum IgG levels, but only the 1-component group showed significant increases in pertussis toxin-specific memory B cells. The 5-component group had significant increases in filamentous hemagglutinin- and pertactin-specific memory B-cell and serum IgG levels; these were not seen in the 1-component group, as expected. In conclusion, this study shows that a 5th consecutive dose of an acellular pertussis vaccine induces B-cell responses in vaccinated adolescents.Funding Agencies|Statens Serum Institute; Sanofi Pasteur MSD (Sweden)</p

Highest Vaccine Uptake after School-Based Delivery - A County-Level Evaluation of the Implementation Strategies for HPV Catch-Up Vaccination in Sweden

Background The Swedish school-based vaccination programme offers HPV vaccine to girls born &gt;= 1999 in 5-6th grade. In 2012, all counties introduced free-of-charge catch-up vaccination campaigns targeting girls born 1993-1998. Varying vaccine uptake in the catch-up group by December 2012 suggested that some implementation strategies were more successful than others. In order to inform future vaccination campaigns, we assessed the impact of different implementation strategies on the county-level catch-up vaccine uptake. Methods We conducted an ecological study including all Swedish counties (n = 21), asking regional health offices about the information channels they used and where vaccination of the catch-up target group took place in their counties. The uptake of &gt;= 1 dose by 30 September 2014 was estimated using data from the voluntary national vaccination register. We investigated associations between counties' catch-up vaccine uptake, information channels and vaccination settings by calculating incidence rate ratios (IRR) and 95% confidence intervals (CI), using negative binomial regression models. Results County level catch-up vaccine uptake varied between 49-84%. All counties offered vaccination through primary health care settings. Apart from this eight (34%) also offered the vaccine in some of their schools, four (19%) in all their schools, and two (10%) in other health care centres. The information channels most frequently used were: information at the national on-line health care consulting web-page (100%), letter/invitations (90%), and advertisement (81%). Counties offering vaccination to girls in all schools and counties offering vaccination in some of their schools, reached higher vaccine uptake compared to counties not offering vaccination in any of their schools (all schools adjusted IRR: 1.3, 95% CI: 1.1-1.5, some schools adjusted IRR: 1.2, 95% CI: 1.1-1.3). Conclusion Counties offering HPV vaccination to catch-up groups in schools reached the highest vaccine uptake. No information channel explained differences in county-level vaccine uptake. Our findings suggest that catch-up vaccination outside the national vaccination program can reach a high uptake at the population level if it is implemented primarily with an organized delivery (e.g. in schools)

Does Allergen-specific Immunotherapy Induce Contact Allergy to Aluminium?

Persistent, itching nodules have been reported to appear at the injection site after allergen-specific immuno-therapy with aluminium-precipitated antigen extract, occasionally in conjunction with contact allergy to aluminium. This study aimed to quantify the development of contact allergy to aluminium during allergen-specific immunotherapy. A randomized, controlled, single-blind multicentre study of children and adults entering allergen-specific immunotherapy was performed using questionnaires and patch-testing. A total of 205 individuals completed the study. In the 3 study groups all subjects tested negative to aluminium before allergen-specific immunotherapy and 4 tested positive after therapy. In the control group 4 participants tested positive to aluminium. Six out of 8 who tested positive also had atopic dermatitis. Positive test results were found in 5/78 children and 3/127 adults. Allergen-specific immunotherapy was not shown to be a risk factor for contact allergy to aluminium. Among those who did develop aluminium allergy, children and those with atopic dermatitis were more highly represented

There is an association between contact allergy to aluminium and persistent subcutaneous nodules in children undergoing hyposensitization therapy.

BACKGROUND: The development of persistent itchy nodules at the injection site following hyposensitization therapy with aluminium-precipitated antigen extract has been described in several reports. Occasionally, contact allergy to aluminium has been reported in individuals with such nodules. OBJECTIVES: To investigate if hyposensitization therapy can induce contact allergy to aluminium and examine if there is any association between persistent subcutaneous nodules and aluminium allergy. PATIENTS/METHODS: Sixty-one children with allergic asthma and/or allergic rhinitis participated in the study of whom 37 had had hyposensitization therapy. The study consisted of a non-clinical part based on a questionnaire and a clinical part with a physical examination, self-assessment of itching, and patch testing. To secure an unbiased evaluation of possible reactions, the investigators were blinded. RESULTS: Contact allergy to aluminium was found in eight participants, all in the exposed group (8/37 versus 0/24, P = 0.02). Examination showed nodules on the upper arms in 13 participants, all in the group exposed to hyposensitization therapy. Nodules were over-represented in patients with contact allergy to aluminium. CONCLUSIONS: There was a statistically significant association between contact allergy to aluminium and persistent subcutaneous nodules in children who had had hyposensitization therapy