Autoimmune/auto-inflammatory syndrome induced by adjuvant (ASIA) in patients refusing breast implant explantation: two case reports and a review of the literature

Figures & data

Figure 1. Autoimmune/auto-inflammatory syndrome induced by adjuvant (ASIA) in women with breast silicone implants – suggested screening and therapeutic approach (criteria according to Schoenfeld and Agmon-Levin, 2011 [1]). AID – autoimmune disturbances; ANA – anti-nuclear antibodies; RF- rheumatoid factor; ASO- antistreptolysin-O titer; ACL – anticardiolipin antibodies; MRI –magnetic resonance imaging; + yes; − no.

Table 1. Laboratory characteristics of the investigated patients before and after treatment.

	ESR mm/h (<25)	WBC 10^9/L (3.5–10.5)	Ly 10^9/L (1.0–4.0)	Hgb g/L (120–160)	C-RP mg/L (<5.0)	ANA (<1:160)
Patient 1/before treatment/	36	4.40	0.63	116	14.33	>1:3200
Patient 1/1 year after treatment/	16	5.16	0.90	137	4.7	1:320
Patient 2/before treatment/	110	9.4	2.2	98	73.9	1:1280
Patient 2/1 year after treatment/	15	6.4	2.8	124	2.6	1:320

ESR, sedimentation rate of erythrocytes; WBC, white blood cells; Ly, lymphocytes; Hgb,haemoglobin; C-RP, C-reactive protein, ANA, anti-nuclear antibodies.

Table 2. Case reports* of the autoimmune/auto-inflammatory syndrome induced by adjuvant (ASIA) in women with breast implantation.

Age	Breast implants – exposure /implant changes/	Clinical complaints/ diseases	Therapy	Brest implant removal	Outcome	Reference
32	3 months	Overlapping connective tissue disease	Oral CS therapy; Azathioprine Leflunomide	IR	Moderate improvement	Here (case 1)
31	3 months	Fever, arthralgia, anemia, hair loss with positive anti-nuclear antibodies;	Pulse CS therapy; Oral CS therapy; Hydroxychloroquine;	No	Improvement	Here (case 2)
73	18 years /implant rupture/	Autoimmune hemolytic anemia	Oral CS therapy;	Yes	Improvement	Loftis et al., 2022 [27]
37	20 years	Raynaud’s phenomenon; Systemic lupus erythematosus with cutaneous, musculoskeletal, hematological, neurological, and renal involvement; Anti-phospholipid syndrome;	Pulse CS therapy; Oral CS therapy; Tacrolimus; Hydroxychloroquine;	No	Fatal thrombosis after therapy self-discontinuation	Mir et al., 2022 [28]
44	20 years /implant rupture/	Sjögren’s Syndrome; Sensory ganglionopathy;	Oral CS therapy; Hydroxychloroquine; Methotrexate;	Yes	Improvement	Van Assche et al., 2022 [29]
45	5 years /implant rupture/	Systemic sclerosis; Anti-neutrophil cytoplasmic antibody anti-myeloperoxidase vasculitis with renopulmonary syndrome;	Pulse CS therapy; Oral CS therapy; Methotrexate; Rituximab; Cyclophosphamide; Plasmapheresis.	No	Improvement, but still on haemodialysis	Carrera Muñoz et al., 2021 [30]
38	8 years /implant deformation/	Raynaud’ s phenomenon; Late onset nemaline myopathy with positive anti-nuclear antibodies;	Oral CS therapy; Methotrexate;	IR	Improvement	De Stefano et al., 2021 [31]
48	11 years /implant deformation/	Raynaud’ s phenomenon; Scleroderma-like syndrome	No	Yes	Progression	Wroński et al., 2019 [32]
48	2 years	Chronic fatigue syndrome, myalgia, muscle weakness, arthralgia, and arthritis;	Oral CS therapy; Symptomatic treatment	No	Improvement	Fenoglio et al., 2019 [33]
40	15 years /implant rupture/	Chronic fatigue syndrome, muscle weakness, arthralgia, and arthritis; Fever; Membranous nephropathy;	Pulse CS therapy; Oral CS therapy; Rituximab; Cyclophosphamide;	Yes	Improvement	Fenoglio et al., 2019 [33]
23	3 years	Lupus-like manifestation with localized cutaneous impairment	Hydroxychloroquine;	No	Improvement	Nunes et al., 2019 [34]
55	10 years /implant rupture/	Sjögren’s syndrome; Hepatic silicone infltration	N.R.	N.R.	N.R.	Posso-Osorio et al., 2018 [35]
55	15 years /breast infection/	Raynaud’s phenomenon; Scleroderma with positive antibodies	Cyclophosphamide; Methotrexate; Intravenous antimicrobial therapy	Yes	Without improvement	Pavlov-Dolijanovic et al., 2017 [13]
25	1 year	Adult-onset Still’s disease;	Oral CS therapy; Methotrexate;	Yes	Improvement	Wehr et al., 2017 [36]
24	3 years	Adult onset Still’s disease	Pulse CS therapy; Oral CS therapy;	No	Without improvement	Dagan et al., 2016 [25]
64	30 years /implant rupture/	Fibromyalgia-like diffuse musculoskeletal pain; fatigue; cognitive impairment;	N.R.	Yes	Without improvement	Nesher et al., 2015 [37]
25	3 years /implant rupture/	Underlying juvenile idiopathic arthritis Transient lupus-like syndrome; Still’s disease;	Pulse CS therapy; Oral CS therapy; Azathioprine	Yes	Improvement	Jara et al., 2012 [38]
56	3 years	Eosinophilic fasciitis; Morphea;	Oral CS therapy;	Yes	Minor improvement	Kivity et al., 2012 [39]

CS, corticosteroids; IR, implant replacement; N.R., non reported.

*Case reports were selected through PUBMED search with key words: breast implant, siliconosis, ASIA. Only case reports with sufficient clinical data in English published after the definition of ASIA in 2011 were included (13, 25, 27-39). Case series are described separately in the text.

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Data availability

Data are available upon reasonable request.