Allergy, Asthma & Clinical Immunology 2014, 10:4"Aluminium salts have been used in allergy therapy for many decades and are assumed to be safe with few established side-effects. This assumption belies their potency as adjuvants and their potential for biological reactivity both at injection sites and elsewhere in the body. There are very few data purporting to the safety of aluminium adjuvants in allergy immunotherapy and particularly so in relation to longer term health effects. There are, if only few, published reports of adverse events following allergy immunotherapy and aluminium adjuvants are the prime suspects in the majority of such incidents. Aluminium adjuvants are clearly capable of initiating unwanted side effects in recipients of immunotherapy and while there is as yet no evidence that such are commonplace it is complacent to consider aluminium salts as harmless constituents of allergy therapies. Future research should establish the safety of the use of aluminium adjuvants in sub-cutaneous allergy immunotherapy."
Contact Dermatitis. 2009 Jan;60(1):41-9"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. There was a statistically significant association between contact allergy to aluminium and persistent subcutaneous nodules in children who had had hyposensitization therapy."
For more about this study read this: Vaccinations and allergy shots causing allergies to aluminium
Dermatitis. 2005;16(3):115-120."FDA regulations limit the aluminum content of an individual dose of a vaccine to 0.85 mg of elemental aluminum.[7] The diminutive level of aluminum needed in vaccines to induce serious toxicities is evidenced by the undetectable changes in the normal plasma concentration of aluminum (5 µg/L) after intramuscular administration of an aluminum-containing vaccine.
Of individuals who undergo immunotherapy with aluminum-containing allergen extracts, 33 to 70% develop a local immediate or transient inflammatory reaction[10,11] whereas 0.5 to 6% develop nodules weeks, months, or even years after the introduction of aluminum.[12] Garcia-Patos and colleagues described 10 patients who had a persistent nodular reaction at the injection site of allergen extract preparations containing aluminum. The results of patch tests with 2% aluminum chloride in water were positive in five patients.[9] Biopsy specimens from nodules appearing 1 to 9 months after the patients were injected were associated with the histopathologic features of a histiocytic foreign-body reaction. Nodular lesions of greater than 1 year's duration, however, showed a granulomatous reaction."
World Allergy Organization Journal 2015, 8:7"Exposure occurs due to environmental, dietary and intentional exposure to aluminium, such as in vaccines where it was introduced in 1926. In spite of the fact that it is a typical Th2 adjuvant, aluminium redirects the immune response in systemic allergen immunotherapy (SIT) upon prolonged immunization. SIT in the US, and SLIT in general, are at present non-adjuvanted therapies, but in Europe aluminium is used as adjuvant in most SIT preparations. It enhances the safety of SIT by local deposition of the allergen. Undesired properties of aluminium adjuvants comprise acute and chronic inflammation at the injection site, its Th2 immune stimulatory capacity, its accumulation besides biodistribution in the body.
Further, it was reported that in rabbits i.m. injections with both aluminium hydroxide and aluminium phosphate led to increased Al levels in the blood already after 1 hour, and that after 28 days 3x more of the Al(OH)3 remained absorbed in the body, in the following tissues: kidney > spleen > liver > heart > lymph node > brain.
In SCIT with up to 54 injections during the whole course the accumulating dose may vary between 45 and 67,5 mg of aluminium
Upon injection, in the tissues all possible forms of aluminium, including ions, soluble aluminium, particulate forms, alone or bound to antigen or tissue compounds can be found. The injected AlADJ releases the biologically active form Al3+ and aluminate (Al(OH)4−) ions, which may react with water and finally lead to Al superoxide production. However, most of the injected aluminium will be phagocytized and thereby activate cells that recruit even more inflammatory cells. Due to a high binding affinity with iron, aluminium intracellularly can deplete the mitochondria from Fe and lead to the production of reactive oxygen species (ROS). Aluminium can induce DNA damage through ROS and has an apoptotic effect. This has been shown for peripheral lymphocytes, which are susceptible especially in the G0/G1 phase of the cell cycle. However, the amount of soluble Al locally after a vaccine injection may be insufficient to induce cell death. It might be considered that aluminium-containing vaccines expose children in an age when both, immune function and brain development are sensitive "
Case Report: Cutaneous-subcutaneous pseudolymphoma after specific immunotherapy with grass-rye pollen-allergen extract containing aluminium hydroxide
Post Dermatol Alergol 2011; XXVIII, 2: 134–137
"Allergen-specific immunotherapy is an important treatment procedure in IgE-mediated allergic diseases such as allergic rhinitis or insect toxin allergies. A reduction in the clinical reaction to the allergens to which the patient is known to be sensitized is intended by means of antigen-specific influence on the immune system. The allergen-specific immunotherapy can be applied by subcutaneous injections, and for selected allergens by means of sublingual application of the appropriate allergen. Occasionally, the injection of aluminium hydroxide-adsorbed sera induces a usually transient formation of granulomas. We are reporting on a rare case of cutaneous-subcutaneous pseudolymphoma in the injection area of both upper arms, probably induced by subcutaneous allergen-specific immunotherapy."
Actas Dermosifiliogr. 2008;99:213-6"Aluminium hydroxide is used as an adjuvant in vaccines. We describe the case of a patient who presented a persistent adverse local reaction to aluminium hydroxide due to hyposensitization therapy to dust mites. Multiple painful and pruriginous subcutaneous nodules were observed in both arms, along with hypertrichosis at the injection site. Histology revealed a pseudolymphomatous B cell reaction predominantly involving cells that were CD20 positive, did not express BCL-2, and did not display the t(14;18) translocation. The cells also exhibited polyclonal rearrangement of the immunoglobulin heavy chains. X-ray spectral microanalysis revealed deposits of inorganic aluminium in the granular histiocytes among the germinal centers. The patient was diagnosed with cutaneous B-cell pseudolymphoma due to aluminium hydroxide as a result of immunotherapy."
Aluminium in allergen-specific subcutaneous immunotherapy – A German perspective
Vaccine Volume 32, Issue 33 16 July 2014, Pages 4140–4148"We are living in an “aluminium age” with increasing bioavailability of the metal for approximately 125 years, contributing significantly to the aluminium body burden of humans. Over the course of life, aluminium accumulates and is stored predominantly in the lungs, bones, liver, kidneys and brain. The toxicity of aluminium in humans is briefly summarised, highlighting links and possible causal relationships between a high aluminium body burden and a number of neurological disorders and disease states.
Aluminium salts have been used as depot-adjuvants successfully in essential prophylactic vaccinations for almost 100 years, with a convincing positive benefit-risk assessment which remains unchanged.
However, allergen-specific immunotherapy commonly consists of administering a long-course programme of subcutaneous injections using preparations of relevant allergens. Regulatory authorities currently set aluminium limits for vaccines per dose, rather than per treatment course. Unlike prophylactic vaccinations, numerous injections with higher proportions of aluminium-adjuvant per injection are applied in subcutaneous immunotherapy (SCIT) and will significantly contribute to a higher cumulative life dose of aluminium. While the human body may cope robustly with a daily aluminium overload from the environment, regulatory cumulative threshold values in immunotherapy need further addressing. Based on the current literature, predisposing an individual to an unusually high level of aluminium, such as through subcutaneous immunotherapy, has the potential to form focal accumulations in the body with the propensity to exert forms of toxicity. Particularly in relation to longer-term health effects, the safety of aluminium adjuvants in immunotherapy remains unchallenged by health authorities – evoking the need for more consideration, guidance, and transparency on what is known and not known about its safety in long-course therapy and what measures can be taken to prevent or minimise its risks. The possibility of providing an effective means of measuring aluminium accumulation in patients undergoing long-term SCIT treatment as well as reducing their aluminium body burden is discussed."
Aluminium in allergen-specific subcutaneous immunotherapy – A German perspective
Vaccine Volume 32, Issue 33 16 July 2014, Pages 4140–4148"We are living in an “aluminium age” with increasing bioavailability of the metal for approximately 125 years, contributing significantly to the aluminium body burden of humans. Over the course of life, aluminium accumulates and is stored predominantly in the lungs, bones, liver, kidneys and brain. The toxicity of aluminium in humans is briefly summarised, highlighting links and possible causal relationships between a high aluminium body burden and a number of neurological disorders and disease states.
Aluminium salts have been used as depot-adjuvants successfully in essential prophylactic vaccinations for almost 100 years, with a convincing positive benefit-risk assessment which remains unchanged.
However, allergen-specific immunotherapy commonly consists of administering a long-course programme of subcutaneous injections using preparations of relevant allergens. Regulatory authorities currently set aluminium limits for vaccines per dose, rather than per treatment course. Unlike prophylactic vaccinations, numerous injections with higher proportions of aluminium-adjuvant per injection are applied in subcutaneous immunotherapy (SCIT) and will significantly contribute to a higher cumulative life dose of aluminium. While the human body may cope robustly with a daily aluminium overload from the environment, regulatory cumulative threshold values in immunotherapy need further addressing. Based on the current literature, predisposing an individual to an unusually high level of aluminium, such as through subcutaneous immunotherapy, has the potential to form focal accumulations in the body with the propensity to exert forms of toxicity. Particularly in relation to longer-term health effects, the safety of aluminium adjuvants in immunotherapy remains unchallenged by health authorities – evoking the need for more consideration, guidance, and transparency on what is known and not known about its safety in long-course therapy and what measures can be taken to prevent or minimise its risks. The possibility of providing an effective means of measuring aluminium accumulation in patients undergoing long-term SCIT treatment as well as reducing their aluminium body burden is discussed."
