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Autoimmune/inflammatory syndrome induced by adjuvants—ASIA—related to biomaterials: analysis of 45 cases and comprehensive review of the literature

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Abstract

Systemic autoimmune or granulomatous disorders related to biomaterials of human use have rarely been described. The aim of this study was to report cases of autoimmune/inflammatory syndrome induced by adjuvants (ASIA) related to biomaterial injections and prostheses, mainly silicone, hyaluronic acid, acrylamides and methacrylate compounds in a Spanish patient cohort. This study is a retrospective analysis of clinical, laboratory, histopathological and follow-up data of 45 cases of patients suffering from late-onset, non-infectious inflammatory/autoimmune disorders related to bioimplants. Late onset was defined as 3 months or more post injection. Data were obtained through a further non-systematic but comprehensive review of the literature. Forty-five cases of late-onset adverse reactions related to biomaterial injections or prostheses were reviewed. All cases had systemic complaints that could be categorised as ASIA. In all but four patients, inflammatory features at the implantation site preceded distant or systemic manifestations. Abnormal blood tests were common. Localised inflammatory nodules and panniculitis in 40/45 (88.88%) evolved into a variety of disorders, viz., primary biliary cirrhosis, Sjögren’s syndrome, sarcoidosis, human adjuvant disease, vasculitis, inflammatory bowel syndrome and inflammatory polyradiculopathy. Five (11.11%) cases presented primarily with systemic autoimmune disorders. Biomaterials and prostheses can provoke late-onset systemic autoimmune disorders fulfilling ASIA criteria, or present primarily local/regional inflammatory reactions that may eventually evolve into systemic autoimmune and/or granulomatous disorders which fall under ASIA.

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Abbreviations

ANXA11:

Annexin-A11

ACE:

Angiotensin-converting enzyme

aFL:

Antiphospholipid antibodies

AMA:

Antimitochondrial antibodies

ANA:

Antinuclear antibodies

ANCA:

Antineutrophil cytoplasmic antibodies

ASIA:

Autoimmune/inflammatory syndrome induced by adjuvants

ASD:

Autoimmune systemic diseases

CD:

Cluster differentiation

CRP:

C-reactive protein

EBV:

Epstein-Barr virus

HA:

Hyaluronic acid

HAD:

Human adjuvant disease

HLA:

Human leukocyte antigen

IL:

Interleukin

IFN-γ:

Interferon-gamma

MHC:

Major histocompatibility complex

NASHA:

Non-animal stabilised hyaluronic acid

PBMC:

Peripheral blood mononuclear cells

PHA:

Phytohaemagglutinin

PLLA:

Poly-l-lactic acid

SMG:

Silicone medical grade

SS:

Sjögren’s syndrome

SPEP:

Serum protein electrophoresis

SSc:

Systemic sclerosis

TLR:

Toll-like receptors

TNF-α:

Tumour necrosis factor-alpha

UCTD:

Undifferentiated connective tissue disease

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Authors and Affiliations

  1. Systemic Autoimmune Diseases Unit, Department of Internal Medicine-1, Vall d’Hebron University Hospital, Passeig Vall d’Hebron 119-129, 08035, Barcelona, Spain

    Jaume Alijotas-Reig

  2. Department of Medicine, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain

    Jaume Alijotas-Reig

  3. Department of Internal Medicine, Althaia Network Health, Manresa, Barcelona, Spain

    Enrique Esteve-Valverde & Natalia Gil-Aliberas

  4. Europe Medical Centre, Barcelona, Spain

    Victor Garcia-Gimenez

  5. Spanish Society of Cosmetic Medicine & Surgery, Barcelona, Spain

    Victor Garcia-Gimenez

Authors
  1. Jaume Alijotas-Reig
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  2. Enrique Esteve-Valverde
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  3. Natalia Gil-Aliberas
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  4. Victor Garcia-Gimenez
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Contributions

All authors have made substantial contributions to all or some of the following: conception and design of the study, acquisition of data, analysis and interpretation of data (JAR, EEV, NGA, VGG), drafting of the article (JAR), critical revision for important intellectual content (JAR, EEV, NGA) and final approval of the version to be submitted (JAR, EEV, NGA, VGG).

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Correspondence to Jaume Alijotas-Reig.

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The authors declare that they have no conflict of interest.

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Take-home messages

1. In a predisposed host, biomaterials, prostheses and heavy metals may induce delayed immune-mediated adverse reactions, including ASIA.

2. Biomaterials, prostheses and metals act more as adjuvants than as direct T cell activators.

3. All the previously mentioned compounds may first present clinically as ASIA, as an inflammatory, undifferentiated syndrome, or evolve into fully blown ASIA later.

4. Long-term immunomodulating therapy is required. Explantation does not ensure cure.

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Alijotas-Reig, J., Esteve-Valverde, E., Gil-Aliberas, N. et al. Autoimmune/inflammatory syndrome induced by adjuvants—ASIA—related to biomaterials: analysis of 45 cases and comprehensive review of the literature. Immunol Res 66, 120–140 (2018). https://doi.org/10.1007/s12026-017-8980-5

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