Aluminium in allergen-specific subcutaneous immunotherapy – A German perspective

AbstractWe 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