Table 11 Adjuvant-induced rheumatic diseases

ASIA syndrome - Siliconosis

Silicone (breast implant)

HLA-DRB1;

and

HLA-DQB1

Weakness, myalgia, or myositis, arthritis or arthralgia, chronic fatigue, malaise, or sleep disturbances, neurological manifestations related to demyelination, cognitive deficits, fever, dry mouth, or other sicca syndrome–like symptoms

Positivity for autoantibodies or antibodies targeting the suspected adjuvant; High-resolution histocompatibility HLA-DR and HLA-DQ

Removal of the adjuvant leads to a full or at least partial recovery

ASIA syndrome - Post-vaccination/ MMF

Aluminum

HLA-DRB1;

and

HLA-DQB1

Systemic: weakness, myalgia, or myositis, arthritis or arthralgia, chronic fatigue, malaise, or sleep disturbances, neurological manifestations related to demyelination, cognitive deficits, fever, dry mouth, or other sicca syndrome–like symptoms; Local: active lesion at the site of inoculation

Positivity for autoantibodies or antibodies targeting the suspected adjuvant; CK elevated levels. High-resolution histocompatibility HLA-DR and HLA-DQ; Muscle biopsy with PAS-positive, MHC-1-positive macrophages; Aluminum hydroxide engulfed by macrophages in EM

Avoid repeated exposure to triggering adjuvants

ASIA syndrome - Gulf War syndrome

Sarin gas?

Pesticides?

Vaccine?

HLA-DRB1;

and

HLA-DQB1

Fatigue, joint pain, headaches, rashes or skin problems, insomnia

Presence of antibodies to the adjuvant squalene correlated (lack of standardization); High-resolution histocompatibility HLA-DR and HLA-DQ

Removal of the adjuvant leads to a full or at least partial recovery

Eosinophilia-myalgia syndrome

L-tryptophan

----*

Severe muscle pain, cough or dyspnea, fever, rash, arthralgia, thickened skin, myocarditis, neuropathy

Peripheral blood eosinophilia; Histopathology with perimyositis with inflammatory cells predominantly mononuclear cells and eosinophils

Removal of the adjuvant leads to a full or at least partial recovery

Toxic oil syndrome

Aniline rapeseed oil

----*

Diffuse interstitial or alveolar interstitial infiltrates, pulmonary hypertension, incapacitating myalgia, cardiomyopathy, and skin rash

Peripheral blood eosinophilia; Imaging tests: diffuse interstitial or alveolar interstitial infiltrates, with or without pleural effusion

Removal of the adjuvant leads to a full or at least partial recovery

Nephrogenic systemic fibrosis

Gadolinium

----*

Severe skin thickening after gadolinium exposure with joint contracture

Skin biopsy: Fibrosis of the dermis with extension to the subcutaneous fat pads; Notably absent inflammatory infiltrate

Preventing gadolinium exposure in chronic kidney patients

Metallosis

Cobalt and chromium

----*

Vision and hearing impairment, fatigue, peripheral neuropathy, weight loss, cardiotoxicity, skin rash and hypothyroidism

Co and Cr increased blood levels; Increased thyrotropin. Imaging tests with joint metallosis

Removal of the Co and Cr prosthesis; Chelation therapy

Vinyl chloride monomer related diseases

VCM

----*

Acro-osteolysis, thickened skin, vascular alterations (Raynaud’s phenomenon), liver cirrhosis, hepatocellular carcinoma, arthralgia, and myalgia

Increased urinary TDGA levels

The removal of the adjuvant leads to a full or at least partial recovery

PPD induced arthritis

PPD

----*

Symmetrical polyarthritis after PPD exposure; Allergic contact dermatitis and/or angioedema

Increased IM during disease flares, positive patch test for PPD

The removal of the adjuvant leads to a full or at least partial recovery