ASIA syndrome: Adverse reaction or autoimmunity? (2024)

Abstract

Keywords: ASIA Syndrome, Silicone, Adjuvants, Shoenfeld

Introduction

The adjuvant-induced autoimmune / autoinflammatory syndrome (ASIA) is an entity, recognisedin 2011 by Shoenfeld, which encompasses autoimmune phenomena that are induced after exposureto adjuvants, that is, substances that enhance an immune response, whether innate andadaptive. This hyperactivation phenomenon of the immune system can culminate in autoimmunereactions or a chronic inflammatory state. The conditions used to define this syndrome are:siliconosis, Gulf War syndrome (GWS), macrophage myofasciitis syndrome (SMM) andpost-vaccination phenomena.^1–5

The ASIA diagnoses are often late and with considerable controversy. The grosshistopathological examination of focal lesions and the tissue surrounding the foreignimplanted elements, often provide direct information. Typically, there is fibroblast andcollagen deposition, infiltration of macrophages, lymphocytes, and foreign body giant cellswith apparent granulomas. There may be lymphoid hyperplasia.⁴

This syndrome has the following manifestations: myalgia, arthralgia, chronic asthenia andxerostomia, as well as neurological symptoms, which include cognitive disorders and memoryloss. The clinic of this entity varies between men and women, particularly depending on theadjuvants to which they were exposed. Like autoimmune conditions, this entity has anepigenetic component, which often evolves into a condition of undifferentiated connectivetissue disease.

Patients considered to have ASIA have at least 2 major criteria (exposure to externalstimulus that precedes the clinic; typical manifestations; improvement of symptoms with theremoval of the provocative agent; suggestive biopsy of the organs involved) or 1 major and 2minor criteria (self- antibodies or antibodies against adjuvant; other clinicalmanifestations; HLA-DRB1 or HLA-DQB1 haplotypes; evolution to autoimmune disease).^1–3

Since the recognition of this entity, more than 4000 cases have been notified and reported.However, it remains challenging to establish a temporo-causal relationship betweensymptomatology and suspected symptoms, given the scarcity of reported cases.¹

Case series of a cluster of cases

CASE 1: A 42-year-old Caucasian woman with a personal history of fibromyalgia, hepatitis C,hepatitis B, who had been abstinent for 15 years from drug addictive habits, who had hadbilateral breast silicone implants for 9 years (Figure1). Oriented to Internal Medicine, due toasthenia, non-selective anorexia, fever and weight loss of about 20 kg in 12 months.Objectively, it denoted axillary and inguinal adenopathies. Analytically unchanged.Pathological anatomy of excision of axillary adenopathy revealed a pattern of follicularimmunoreactivity. The patient started corticosteroid therapy, with regression ofadenomegalies.

CASE 2: Caucasian woman, 53 years old, with a history of mastectomy (2001) due to neoplasiaand then by mammoplasty with silicone (2003), anterior uveitis (2007). In 2008, a patientreported weight loss, extreme asthenia and a cervical nodule. Analytically unchanged.Computed tomography: multiple non-necrotizing cervical lymphadenopathies and micro-nodulesin the lung. PETscan suggested metastatic lymphadenopathies (Figure2). Fine needle aspiration revealednon-necrotizing granulomatous and caseous lymphadenitis. Antituberculostatics were startedempirically (interrupted 5 months after poor response). Bronchoalveolar lavage, respiratoryfunction tests and cultural exam did not show any changes. There was regression ofadenopathy with corticosteroids.

Discussion

Silicone, once considered an inert material, like other adjuvants, is capable to enhanceantigen-specific immune response that can spread into lymph nodes, lungs, liver, and othertissues. Later inducing immunoreactivity phenomena manifested with an extensive complexpattern of symptoms, leading to the definition of “siliconosis”, also known as “adjuvantdisease”, in the early 90 s. There is some debate as whether silicon-based reaction is anacquired or cross-reactive entity, or even a direct immune reaction stimulated afternon-specific polyclonal activation. However, silicone has proven to be immunogenic fordelayed-type hypersensitivity reactions.^4,5

ASIA by silicone does not meet all diagnostic criteria for a connective tissue disease, butit* relationship is unequivocal given that 0.8% of exposed individuals are at risk ofmanifesting a diffuse connective tissue disease (DCTD).³

Balk et al. have demonstrated a possible association between siliconeimplants and a variety of DCTD such as dermatomyositis, polymyositis, scleroderma. Authorsalso report a possible association between autoimmune symptoms with silicone breastimplantation and Human Leukocyte Antigen (HLA) genotype positive for HLA-DR5 and HLA-DQ2.⁵

Thus, the link between silicone and autoimmunity involves a broader spectrum of autoimmunemanifestations. In 2016 more than 200 cases of ASIA were reported after exposure to siliconeimplants, despite modifications in the silicone implants’ constituents in the last century.⁵

Since there are no screening methods or diagnostic/laboratory markers for ASIA, this entitycontinues to represent an exclusion diagnosis. These cases aim to alert the medicalcommunity to the existence of this entity, to encourage the notification of situationsresulting from the exposure of adjuvants, as well as to emphasize the need to createprospective controlled studies that confirm the development of autoimmune processes withother adjuvants to be identified. In view of the findings described in the respectiveclinical cases, the authors highlight the need to investigate the presence of a suggestivehistological pattern in excisional biopsies of satellite adenomegalies, identify individualswith HLA genotype predisposition, as well as the existence of a hormonal component that canjustify the prevalence of this syndrome in feminine gender.

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