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

Bergfors, Elisabet; Trollfors, Birger; Inerot, Annica

doi:10.1016/s0264-410x(03)00531-0

Cited by 135 publications

(185 citation statements)

References 23 publications

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“…Previous studies have shown that aluminum hydroxide persisted for at least 6 months after intramuscular administration [40]. The documented side effects following subcutaneous administration of aluminum hydroxide include pruritic subcutaneous nodules [41,42], delayed hypersensitivity [41] and severe granulomatous inflammation [5].…”

Section: Discussionmentioning

confidence: 99%

Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination

Zaharoff

Rogers

Hance

et al. 2007

Vaccine

305

193

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The development of safe, novel adjuvants is necessary to maximize the efficacy of new and/or available vaccines. Chitosan is a non-toxic, biocompatible, biodegradable, natural polysaccharide derived from the exoskeletons of crustaceans and insects. Chitosan's biodegradability, immunological activity and high viscosity make it an excellent candidate as a depot/adjuvant for parenteral vaccination. To this end, we explored chitosan solution as an adjuvant for subcutaneous vaccination of mice with a model protein antigen. We found that chitosan enhanced antigen-specific antibody titers over 5-fold and antigen-specific splenic CD4 + proliferation over 6-fold. Strong increases in antibody titers together with robust delayed-type hypersensitivity (DTH) responses revealed that chitosan induced both humoral and cell-mediated immune responses. When compared with traditional vaccine adjuvants, chitosan was equipotent to incomplete Freund's adjuvant (IFA) and superior to aluminum hydroxide. Mechanistic studies revealed that chitosan exhibited at least two characteristics that may allow it to function as an immune adjuvant. First, the viscous chitosan solution created an antigen depot. More specifically, less than 9% of a protein antigen, when delivered in saline, remained at the injection site after 8 hours. However, more than 60% of a protein antigen delivered in chitosan remained at the injection site for 7 days. Second, chitosan induced a transient 67% cellular expansion in draining lymph nodes. The expansion peaked between 14 and 21 days after chitosan injection and diminished as the polysaccharide was degraded. These mechanistic studies, taken together with the enhancement of a vaccine response, demonstrate that chitosan is a promising and safe platform for parenteral vaccine delivery.

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Section: Discussionmentioning

confidence: 99%

Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination

Zaharoff

Rogers

Hance

et al. 2007

Vaccine

305

193

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“…69 Contact hypersensitivity to aluminum was demonstrated in 77% of the children with itching nodules and in 8% of the symptomless siblings who had received the same vaccines, that is, not a specific test for symptoms. Subcutaneous nodules may develop and persist for months to years before they gradually disappear.…”

Section: Local Aluminum Reactionsmentioning

confidence: 99%

Vaccination and allergy: EAACI position paper, practical aspects

Nilsson

Brockow

Alm

et al. 2017

Pediatric Allergy Immunology

128

184

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Immunization is highly effective in preventing infectious diseases and therefore an indispensable public health measure. Allergic patients deserve access to the same publicly recommended immunizations as non‐allergic patients unless risks associated with vaccination outweigh the gains. Whereas the number of reported possible allergic reactions to vaccines is high, confirmed vaccine‐triggered allergic reactions are rare. Anaphylaxis following vaccination is rare, affecting <1/100 000, but can occur in any patient. Some patient groups, notably those with a previous allergic reaction to a vaccine or its components, are at heightened risk of allergic reaction and require special precautions. Allergic reactions, however, may occur in patients without known risk factors and cannot be predicted by currently available tools. Unwarranted fear and uncertainty can result in incomplete vaccination coverage for children and adults with or without allergy. In addition to concerns about an allergic reaction to the vaccine itself, there is fear that routine childhood immunization may promote the development of allergic sensitization and disease. Thus, although there is no evidence that routine childhood immunization increases the risk of allergy development, such risks need to be discussed.

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“…Occlusion may increase the potency of the topical steroid and limit scratching; hydrocolloid dressings alone have also been reported with variable effect. 15,16 Intralesional steroids and topical capsaicin have been used with varying success 18 ; side effects include atrophy and absorption. The effect of these treatments on the immune response is not clear.…”

Section: Figurementioning

confidence: 99%

“…Aluminum has been reported to be responsible for 77% to 85% of all DTH to vaccinations. 3, 15 Other reported ingredients include polysorbate, 32 thimerosal, 33,34 phenoxyethanol, 35 formaldehyde, 36 and polymyxin B 37 . Although neomycin and others are known causes of DTH, there have been no reports of vaccine DTH to date.…”

Section: Figurementioning

confidence: 99%

Case Report of Subcutaneous Nodules and Sterile Abscesses Due to Delayed Type Hypersensitivity to Aluminum-Containing Vaccines

Lauren

Belsito²,

Morel

et al. 2016

Pediatrics

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Routine childhood immunizations have resulted in great reductions in vaccine-preventable infectious diseases. Vaccine-related adverse events, albeit rare, can be of significant consequence. Although anaphylaxis, or type I hypersensitivity, is recognized as a potential reaction after vaccination, delayed type hypersensitivity or type IV reactions are less so. We present a case of persistent subcutaneous nodules and sterile abscesses in the setting of delayed type hypersensitivity to aluminum, confirmed by patch testing and recurrence on re-exposure. We review sources of aluminum in common immunizations, principles for treatment, and strategies for management of future vaccinations for this patient.

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

Cited by 135 publications

References 23 publications

Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination

Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination

Vaccination and allergy: EAACI position paper, practical aspects

Case Report of Subcutaneous Nodules and Sterile Abscesses Due to Delayed Type Hypersensitivity to Aluminum-Containing Vaccines

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