ASIA syndrome and endocrine autoimmune disorders

An adjuvant is an immunological or pharmacological substance or group of substances that can be added to a given agent to enhance its effect in terms of efficacy, effectiveness and potency. Different mechanisms have been hypothesized underlying the action of the adjuvant, including boosting immune (innate and adaptive) response: this generally results in sparing the necessary amount of the agent and can potentially reduce the frequency of the needed number of therapeutic interventions. Adjuvants can be commonly found in vaccines, immunization products, mineral oils, cosmetics, silicone breast implants and other therapeutic/medical devices, being usually safe and effective. However, in a fraction of genetically susceptible and predisposed subjects, the administration of adjuvants may lead to the insurgence of serious side-effects, called “autoimmune/inflammatory syndrome by adjuvants” (ASIA) or Shoenfeld's syndrome. The present review is aimed at focusing on the “endocrine pebbles” of the mosaic of autoimmunity and of the ASIA syndrome, collecting together 54 cases of sub-acute thyroiditis, 2 cases of Hashimoto's thyroiditis, 11 cases of primary ovarian failure/primary ovarian insufficiency, 13 cases of autoimmune diabetes type 1, and 1 case of autoimmune adrenal gland insufficiency occurred after exposure to adjuvants.

Introduction

An adjuvant (from the Latin verb “adiuvare”, which has the meaning of “to help, to assist, to aid”) is an immunological or pharmacological substance or group of substances that can be added to a given agent to enhance its effect in terms of efficacy, effectiveness and potency. Different mechanisms have been hypothesized underlying the action of the adjuvant, including boosting immune (innate and adaptive) response: this generally results in sparing the necessary amount of the agent and can potentially reduce the frequency of the needed number of therapeutic interventions [1,2].

Adjuvants can be commonly found in vaccines, immunization products, mineral oils, cosmetics, silicone breast implants and other therapeutic/medical devices, being usually safe and effective [2]. However, in a fraction of genetically susceptible and predisposed subjects, the administration of adjuvants may lead to the insurgence of serious side-effects, due to the activation of autoimmune cascades and pathways, by impairing/disrupting the immunological balance of the host, fostering polyclonal activation of B lymphocytes, by molecular mimicry or other similar etiopathogenetic mechanisms [3].

In order to comprehensively collect together all these phenomena and reactions, ranging from post-vaccination side-effects, and macrophagic myofasciitis syndrome (MMF), to the so-called “functional somatic syndromes”, such as the Gulf war syndrome (GWS), siliconosis, multiple chemical sensitivity, repetition stress injury, the chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME), the complex regional pain syndrome (CRPS), the postural orthostatic tachycardia syndrome (POTS) and the sick building syndrome (SBS) [[4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]], Shoenfeld and Agmon-Levin in 2011 have coined the umbrella term of “autoimmune/inflammatory syndrome by adjuvants” (ASIA syndrome) [[17], [18], [19], ∗[20]] (Table 1, Table 2).