Long-term prognosis of vaccine-induced contact allergy to aluminium: Third patch-test with additional test preparations.

BACKGROUND: A high incidence of local itching subcutaneous nodules and aluminium allergy was observed in clinical trials of a new aluminium adsorbed pertussis vaccine in Gothenburg, Sweden, in the 1990s. A total of 495 children with itching nodules were patch tested with aluminium chloride hexahydrate 2% and an empty Finn Chamber®, 377 (76%) with positive reactions. When 241 of them were re-tested some years later 186 (3 out of 4) had unexpectedly lost their patch test reactivity. AIM: To investigate the long-term prognosis of vaccine-induced contact allergy to aluminium by a third patch test about 20 years after Patch test I. METHODS: Twenty individuals with positive and 11 with negative results in Patch test II were tested a third time with the same sensitisers as in in the first two tests. Three additional aluminium preparations were also tested. RESULTS: A total 15 out of 20 persons with positive results in the second test had lost their patch test reactivity. Two of 11 with negative tests had turned positive again. The addition of the preparations gave no conclusive results. CONCLUSION: Contact allergy to aluminium caused by vaccination with aluminium-adsorbed vaccines in childhood seems to fade away with time as measured by loss of patch test reactivity.

Long-term clinical course and prognosis of vaccine-related persistent itching nodules (1997-2019): An observational study.

Background: Vaccines adsorbed to aluminium can induce long-lasting intensely itching subcutaneous nodules (granulomas) at the injection site as well as contact allergy to aluminium. In clinical trials of a new acellular pertussis vaccine performed in the 1990s (Gothenburg, Sweden) with 76 000 participants, itching nodules were reported in 745 children. A positive patch test to aluminium was verified in 77% of the tested children with itchy nodules. Aim: To describe the long-term clinical course and prognosis of vaccine-related itching nodules caused by aluminium-containing pediatric vaccines and to estimate the risk for new symptoms after future vaccination with aluminium-containing vaccines. Methods: 745 children with vaccine-related itching nodules were followed by regular interviews/questionnaires for more than 20 years. 723 of them received a booster dose of diphtheria/tetanus vaccine either with or without aluminium adjuvant during the follow-up time. Results: Most study participants (86%) reported a full recovery from their itching nodules after a median duration of 6.6 years. Only a few of the diphtheria/tetanus-booster-vaccinated children (3%) reported mild transient itching and swelling at the new injection site. Conclusion: Vaccine-induced itching granulomas caused by an aluminium-adsorbed acellular pertussis toxoid vaccine seem to disappear over time. Future vaccinations with aluminium-adsorbed vaccines can be performed with little risk for new itching nodules later in life.

Post-vaccination aluminium granulomas in children. / Aluminiumsgranulomer etter barnevaksinasjon.

BACKGROUND: Persistent itching subcutaneous granulomas related to aluminium-containing vaccines are poorly recognised in health care. They are often associated with aluminium hypersensitivity. CASE PRESENTATION: An intensely itching subcutaneous nodule appeared on the left thigh of a 17-month-old girl at the injection site for an aluminium adsorbed diphtheria-tetanus-pertussis-polio-HiB vaccine given at 3, 5 and 12 months. Ultrasound suggested a vascular malformation among other differential diagnoses. An MR investigation under general anaesthesia was planned, but the diagnosis was confirmed prior to this by a positive epicutaneous test with aluminium. INTERPRETATION: Despite a typical history of an itchy vaccination granuloma, the child underwent a thorough hospital workup to rule out malignancy. The diagnosis was delayed for two years. Vaccination granulomas have a good prognosis but can persist for many years. It is important to recognise the condition early in primary health care to avoid unnecessary anxiety and investigations.

Patch testing children with aluminium chloride hexahydrate in petrolatum: A review and a recommendation.

BACKGROUND: According to studies on adults, patch testing with aluminium chloride hexahydrate 2% pet. is insufficient to detect aluminium allergy, and a 10% preparation is recommended. Other studies suggest that a 2% preparation is sufficient for testing children. OBJECTIVES: To review three previously published Swedish studies on patch testing children with aluminium chloride hexahydrate 2% pet. PATIENTS/METHODS: Altogether, 601 children with persistent itching subcutaneous nodules (granulomas) induced by aluminium-adsorbed vaccines were patch tested with aluminium chloride hexahydrate 2% pet. and metallic aluminium in (a) a pertussis vaccine trial, (b) clinical practice, and (c) a prospective study. RESULTS: Overall, 459 children had positive reactions to the 2% pet. preparation. Another 10 reacted positively only to metallic aluminium. An extreme positive reaction (+++) was seen in 65% of children aged 1 to 2 years as compared with 22% of children aged 7 years. From 8 years onwards, extreme positive reactions were scarce. CONCLUSIONS: Aluminium chloride hexahydrate 2% pet. is sufficient to trace aluminium allergy in children. Small children are at risk of extreme reactions. We thus suggest that aluminium chloride hexahydrate 10% pet. should not be used routinely in children before the age of 7 to 8 years.

Comparison of reactivity to a metallic disc and 2% aluminium salt in 366 children, and reproducibility over time for 241 young adults with childhood vaccine-related aluminium contact allergy.

BACKGROUND: An aluminium hydroxide-adsorbed pertussis toxoid vaccine was studied in 76 000 children in the 1990s in Gothenburg, Sweden. Long-lasting itchy subcutaneous nodules at the vaccination site were seen in 745 participants. Of 495 children with itchy nodules who were patch tested for aluminium allergy, 377 were positive. In 2007-2008, 241 of the positive children were retested. Only in one third were earlier positive results reproduced. OBJECTIVES: To further describe patch test reactions to different aluminium compounds in children with vaccine-induced aluminium allergy. PATIENTS/METHODS: Positive patch test results for metallic aluminium (empty Finn Chamber) and aluminium chloride hexahydrate 2% petrolatum (pet.) were analysed in 366 children with vaccine-induced persistent itching nodules tested in 1998-2002. Of those, 241 were tested a second time (2007-2008), and the patch test results of the two aluminium preparations were analysed. RESULTS: Patch testing with aluminium chloride hexahydrate 2% pet. is a more sensitive way to diagnose aluminium contact allergy than patch testing with metallic aluminium. A general decrease in the strength of reactions to both aluminium preparations in 241 children tested twice was observed. CONCLUSIONS: Aluminium contact allergy can be diagnosed by patch testing without using metallic aluminium.

How common are long-lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric vaccines? A prospective cohort study.

UNLABELLED: The frequency of long-lasting, intensely itching subcutaneous nodules at the injection site for aluminium (Al)-adsorbed vaccines (vaccination granulomas) was investigated in a prospective cohort study comprising 4,758 children who received either a diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (Infanrix®, Pentavac®) alone or concomitant with a pneumococcal conjugate (Prevenar). Both vaccines were adsorbed to an Al adjuvant. Altogether 38 children (0.83 %) with itching granulomas were identified, epicutaneously tested for Al sensitisation and followed yearly. Contact allergy to Al was verified in 85 %. The median duration of symptoms was 22 months in those hitherto recovered. The frequency of granulomas induced by Infanrix® was >0.66 % and by Prevenar >0.35 %. The risk for granulomas increased from 0.63 to 1.18 % when a second Al-adsorbed vaccine was added to the schedule. CONCLUSION: Long-lasting itching vaccination granulomas are poorly understood but more frequent than previously known after infant vaccination with commonly used diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b and pneumococcal conjugate vaccines. The risk increases with the number of vaccines given. Most children with itching granulomas become contact allergic to aluminium. Itching vaccination granulomas are benign but may be troublesome and should be recognised early in primary health care to avoid unnecessary investigations, anxiety and mistrust.

Unexpected loss of contact allergy to aluminium induced by vaccine.

BACKGROUND: In studies in Gothenburg, Sweden, in the 1990s of an aluminium hydroxide-adsorbed pertussis toxoid vaccine, 745 of ~76 000 vaccinated children developed long-lasting itchy subcutaneous nodules at the vaccination site. Of 495 children with itchy nodules patch tested for aluminium allergy, 376 (76%) were positive. OBJECTIVES: To study the prognosis of the vaccine-induced aluminium allergy. PATIENTS AND METHODS: Two hundred and forty-one children with demonstrated aluminium allergy in the previous study were patch tested again 5-9 years after the initial test, with the same procedure as used previously. RESULTS: Contact allergy to aluminium was no longer demonstrable in 186 of the retested 241 children (77%). A negative test result was more common in children who no longer had itching at the vaccination site; it was also related to the age of the child, the time after the first aluminium-adsorbed vaccine dose, and the strength of the reaction in the first test. CONCLUSIONS: Patch test reactivity to aluminium seems to disappear or weaken with time.

A child with a long-standing, intensely itching subcutaneous nodule on a thigh: an uncommon (?) reaction to commonly used vaccines.

A 2-year-old girl presented with an intensely itching subcutaneous nodule on the front of a thigh. The nodule persisted for 10 months until it was excised. Subsequent investigation for malignancy and systemic disease showed no pathological findings. The diagnosis, persistent itching vaccination granuloma, was revealed by hazard almost 2 years after the onset of symptoms. Persistent itching subcutaneous nodules at the injection site for aluminium containing vaccines (mostly diphtheria-tetanus-pertussis combination vaccines for primary immunisation of infants) may appear with a long delay after the vaccination (months), cause prolonged itching (years) and are often associated with contact allergy to aluminium. The condition is poorly recognised in Health Care which may lead to prolonged symptoms and unnecessary investigations.

Sixty-four children with persistent itching nodules and contact allergy to aluminium after vaccination with aluminium-adsorbed vaccines-prognosis and outcome after booster vaccination.

UNLABELLED: Persistent itching subcutaneous nodules and aluminium (Al) allergy have been described after vaccination with Al-adsorbed vaccines but are considered rare. Little is known about the prognosis. Sixty-four children with itching nodules following vaccination with diphtheria-tetanus-pertussis (DTP) vaccines currently used in Sweden (Infanrix® and Pentavac®) were spontaneously reported to the authors from 1999 and followed for up to 12 years. The median duration of itching was 5 years in the 44 children who were free or almost free from symptoms at the latest follow-up. Typical findings were a long interval between vaccination and onset of symptoms (months or years) and intensified itching during intercurrent infections. Contact allergy to aluminium was demonstrated in 60/63 children (95 %). Neither the incidence nor differences between the two vaccines can be estimated from this study, but vaccine-induced itching nodules are probably more common than hitherto realised. The median interval between onset of symptoms and diagnosis was 8 months in a region where nurses were educated to recognise the condition compared to 2 years in other regions. Booster vaccination with DTP-polio was postponed or declined by 15/40 families in fear for new problems. Out of 25 children who received a booster dose, only two had new itching nodules. CONCLUSION: Intensely itching subcutaneous nodules (vaccination granulomas) and contact allergy to aluminium may occur after primary vaccination with the two most commonly used DTP vaccines in Europe. The condition is probably underreported. Symptoms may last for at least 4-5 years but eventually seem to subside.

Could gastrointestinal disorders differ in two close but divergent social environments?

BACKGROUND: Many public health problems in modern society affect the gastrointestinal area. Knowledge of the disease occurrence in populations is better understood if viewed in a psychosocial context including indicators of the social environment where people spend their lives. The general aim of this study was to estimate the occurrence in the population and between sexes of common gastrointestinal conditions in two neighborhood cities representing two different social environments defined as a "white-collar" and a "blue-collar" city. METHODS: We conducted a retrospective register study using data of diagnosed gastrointestinal disorders (cumulative incidence rates) derived from an administrative health care register based on medical records assigned by the physicians at hospitals and primary care. RESULTS: Functional gastrointestinal diseases and peptic ulcers were more frequent in the white-collar city, while diagnoses in the gallbladder area were significantly more frequent in the blue-collar city. Functional dyspepsia, irritable bowel syndrome, and unspecified functional bowel diseases, and celiac disease, were more frequent among women while esophageal reflux, peptic ulcers, gastric and rectal cancers were more frequent among men regardless of social environment. CONCLUSIONS: Knowledge of the occurrence of gastrointestinal problems in populations is better understood if viewed in a context were the social environment is included. Indicators of the social environment should therefore also be considered in future studies of the occurrence of gastrointestinal problems.

Diphtheria, tetanus and pertussis antibodies in 10-year-old children before and after a booster dose of three toxoids: implications for the timing of a booster dose.

UNLABELLED: In an open study, 502 10-year-old children, who had received primary vaccination against diphtheria and tetanus in infancy and had varying histories of pertussis disease and vaccination, were vaccinated with diphtheria-tetanus vaccine (DT) alone or with the addition of 20 microg or 40 microg of pertussis toxoid. Diphtheria toxin neutralising antibodies, pertussis toxin IgG and tetanus toxoid IgG antibodies were measured before and 1 month after the booster. All toxoids were highly immunogenic. In pertussis toxoid recipients, median levels of pertussis toxin IgG increased to 16.5 U/ml (DTaP20) and to 36 U/ml (DTaP40) in children with non-detectable (<1 U/ml) antibodies before vaccination and to >400 U/ml in children (both DTaP20 and DTaP40) with detectable antibodies before vaccination. A total of 60 children (12%) with non-detectable (<0.01 IU/ml) diphtheria antibodies and 36 children (7%) with non-detectable (<0.01 IU/ml) tetanus antibodies before the booster had lower median antibody concentrations post-vaccination than children with detectable antibodies before the booster (diphtheria: 5.12 vs. 20.48 IU/ml; tetanus: 4.0 vs. 10.0 IU/ml). There were no differences in diphtheria and tetanus antibodies after vaccination between children who did and did not receive pertussis toxoid. CONCLUSION: 10-year-old children with non-detectable diphtheria and tetanus antibodies before the booster had lower post-vaccination antibodies than those with detectable antibodies before the booster indicating a poor immunological memory. Addition of pertussis toxoid to diphtheria-tetanus vaccine did not affect the antibody responses to diphtheria and tetanus toxoids when the three toxoids were combined as a booster. Even though immunity to diphtheria and tetanus was only estimated by surrogate markers (serum antitoxin antibodies) the results indicate that a lower age for the booster dose of diphtheria-tetanus vaccine or diphtheria-tetanus acellular pertussis vaccine should be considered.

Alcohol intake among women and its relationship to diabetes incidence and all-cause mortality: the 32-year follow-up of a population study of women in Gothenburg, Sweden.

OBJECTIVE: The purpose of the study was to explore the predictive value of women's alcohol habits in relation to incidence of diabetes and all-cause mortality. Special attention was paid to potential confounding factors such as age, heredity, education, socioeconomic group, physical inactivity, smoking, blood pressure, serum lipids, and, in particular, obesity. RESEARCH DESIGN AND METHODS: A longitudinal population study consisting of a representative sample of 1,462 women aged 38-60 started in Göteborg, Sweden, in 1968-1969 monitoring for diabetes and mortality over 32 years. RESULTS: Alcohol intake, expressed as intake of wine, hard liquor, or total grams of alcohol, was significantly negatively associated to 32-year diabetes incidence independent of age. However, the apparently protective effect of the alcohol variables was attenuated when BMI was included as a covariate. The inverse relationship between wine intake and diabetes did not remain after adjustment for physical activity or socioeconomic group. Beer and wine intake were significantly negatively associated to mortality. Increase of alcohol intake between the examination in 1968-1969 and 1980-1981 was significantly inversely related to the mortality between 1980-1981 and 2000-2001 and independent of all covariates. No relationship was observed between an increase in alcohol intake and diabetes incidence. However, after adjustment for age, family history, and basal alcohol consumption altogether, a significant inverse relationship was observed between increase of alcohol and diabetes incidence. CONCLUSIONS: The initially significant inverse associations observed between alcohol and diabetes as well as mortality were dependent on a number of confounding factors, of which BMI seems to be the most important.

Nineteen cases of persistent pruritic nodules and contact allergy to aluminium after injection of commonly used aluminium-adsorbed vaccines.

Rare cases of persistent pruritic nodules, sometimes associated with aluminium (Al) allergy, have been reported after the use of several Al adsorbed vaccines. During vaccine trials in the 1990s a high incidence of pruritic nodules (645 cases/76,000 recipients), in 77% associated with Al allergy, was observed after the administration of diphtheria-tetanus / acellular pertussis (DT/aP) vaccines from a single producer. In the present report 19 children with pruritic nodules after vaccination with Al hydroxide-adsorbed DTaP/polio+Hib (Infanrix, Pentavac) are described. The children had intensely itching nodules at the injection site, often aggravated during upper respiratory tract infections, and local skin alterations. So far, the symptoms have persisted for up to 7 years. The median time between vaccination and onset of symptoms was 1 month. 16 children were epicutaneously tested for Al, all with positive reactions indicating delayed hypersensitivity to Al. The condition is not commonly known but is important to recognise, as the child and the family may suffer considerably. Future vaccinations with Al-adsorbed vaccines may cause aggravation of the symptoms and the Al allergy. Al-containing skin products, such as antiperspirants, may cause contact dermatitis. Nodules may be mistaken for tumours. Even though the incidence of itching nodules and Al allergy after administration of Infanrix, Pentavac and other Al-adsorbed vaccines is probably low, research to replace Al adjuvants seems appropriate. We conclude that intensely itching subcutaneous nodules, lasting for many years, and hypersensitivity to aluminium may occur after DTaP/polio+Hib vaccination of infants.

Unexpectedly high incidence of persistent itching nodules and delayed hypersensitivity to aluminium in children after the use of adsorbed vaccines from a single manufacturer.

During trials of aluminium adsorbed diphtheria-tetanus/acellular pertussis vaccines from a single producer, persistent itching nodules at the vaccination site were observed in an unexpectedly high frequency. The afflicted children were followed in a longitudinal observational study, and the presence of aluminium sensitization was investigated in the children with itching nodules and their symptomless siblings by patch tests. Itching nodules were found in 645 children out of about 76,000 vaccinees (0.8%) after both subcutaneous (s.c.) and intramuscular (i.m.) injection. The itching was intense and long-lasting. So far, 75% still have symptoms after a median duration of 4 years. Contact hypersensitivity to aluminium was demonstrated in 77% of the children with itching nodules and in 8% of the symptomless siblings who had received the same vaccines (P<0.001). Children with persistent itching nodules and/or aluminium sensitization should be warned about aluminium containing products (e.g. vaccines and antiperspirants). The reason for the high incidence of itching nodules after SSI vaccines is unknown and should be further investigated.