Raynaud's Phenomenon and Scleroderma Associated with Silicone Gel Breast Implants: An Example of Asia Syndrome

Abstract

Silicone-gel breast implants (SBI) have been widely used for breast augmentation. Although silicone is generally considered an inert substance, there has been much debate recently on its role in inducing chronic inflammation and systemic connective tissue diseases. The case of a young woman affected by Raynaud's Phenomenon (RP), worsening of vitiligo and of autoimmune thyroiditis following SBI is reported in this paper. Removal of SBI led to temporary RP remission; however, despite notable clinical improvement, nailfold capillary microscopy showed progressive microcirculatory abnormalities consistent with a diagnosis of early scleroderma. Follow-up of the patient led to the diagnosis of Systemic Sclerosis (SSc) with pulmonary hypertension. The development of SSc after SBI is described, a condition that falls into the recently recognized “ASIA” (Autoimmune/inflammatory Syndrome Induced by Adjuvants) syndrome. Nailfold capillary microscopy is a valuable tool in early SSc diagnosis, in monitoring disease activity and in establishing the risk of an aggressive course of connective tissue disease following silicone breast implantation. The relationship between silicone and the immune system requires further reports and investigation in order to determine the main individual risk factors predisposing to the wide spectrum of adjuvant-induced responses.

IL-36 Receptor Antagonist with Special Emphasis on IL-38

“…During the past several years many papers have described a key role for IL-36 in psoriasis which is overexpressed in the skin of human plaque psoriasis (17)(18)(19). The inhibition of IL-36 with IL-36RA in human psoriatic skin has been found to ameliorate the inflammatory reactions (20)(21)(22)(23).…”

“…Activates the MAPK and NF-kappaB pathways An important player in innate and adaptive immune response Pathophysiology of several diseases Initiation or regulation of immune responses and inflammation IL-1F5 (renamed IL-36RA) exerts receptor antagonist activities IL-l F5 inhibits NF-KB in certain cell types Mediates lesional psoriasis skin Mediates epidermis and dermis inflammation Mediates the proliferation ofkeratinocytes and in activate epithelial tissues Strongly increased in psoriatic-like mouse skin plaques IL-36a and IL-36P, but not IL-36y, directly induced TNF-a IL-36 can be induced by Th17 cytokines Directly regulates IL-8 and IL-6 Regulates the expression and enhance the function of Th 17 Interrelation with IL-22 in skin inflammation Mediate chronic kidney disease, and human rheumatoid synovial tissues Inhibits the production of IFN-y, IL-4, and IL-17 by CD4(+) T cells and splenocytes Inhibits inflammatory skin lesions Inhibits psoriasis It is a natural antagonist of IL-36R Its antagonist activity is dependent upon removal of its N-terminal methionine The mechanism ofIL-36RA antagonism is analogous to that ofIL-lRA Reduces IL-8 production induced by IL-36y Cause dose-response suppression of Candida-induced IL-22 and IL-17 It has biological effects on immune cells by engaging the IL-36R Inhibits IL-36 receptor reducing Aspergillus-induced IL-17 and IFN-y IL-36 is a family member of interIeukin-l (IL-l), is produced by many different cells, activates MAPK and NF-kB pathways, and is a common mediator-of both innate and adaptive immune responses (12-16) ( Table I). During the past several years many papers have described a key role for IL-36 in psoriasis which is overexpressed in the skin of human plaque psoriasis (17)(18)(19). The inhibition of IL-36 with IL-36RA in human psoriatic skin has been found to ameliorate the inflammatory reactions (20)(21)(22)(23).…”

Síndrome autoimune induzida por adjuvantes (ASIA): sinais e sintomas experienciados por mulheres

“…Há relatos de desenvolvimento de esclerose sistêmica em decorrência da síndrome ASIA 18 . A doença também foi referida por uma das participantes (P8) deste estudo, que, além de esclerose, apresentou o fenômeno de Raynaud e desenvolveu neoplasia intraepitelial cervical (NIC 1) por conta das próteses de silicone.…”

A Practical Guide to Managing Patients With Systemic Symptoms and Breast Implants

“… 3 The data supporting an association between breast implants and CTDs or ASIA are largely anecdotal, comprising case reports, case series, and descriptive cohort studies with small sample sizes and no or inappropriate control groups. 3-6 , 11 , 24-35 A cross-sectional population-based analysis of women identified from a large health care database found a statistically significant association of having SBIs and a greater likelihood of being diagnosed with any autoimmune/rheumatic disorder. 21 Key study limitations were that a temporal relationship could not be established between breast implant insertion and CTD diagnosis, as well as the fact that publicity regarding a potential association could cause women with implants to seek health care and make it more likely that they receive a diagnosis.…”