Autoimmune/inflammatory syndrome induced by adjuvants (ASIA): A case of systemic symptoms following breast implants and vaccinations

Abstract

Introduction and importance

The Autoimmune/inflammatory Syndrome Induced by Adjuvants (ASIA) is a recently recognized entity characterized by a constellation of nonspecific symptoms that develop after exposure to adjuvants. Adjuvants can include vaccines, silicone, and other foreign substances. Here, we present the case of a 31-year-old woman who developed ASIA syndrome following breast implants and booster vaccinations, emphasizing the diagnostic challenges and treatment considerations.

Case presentation

A 31-year-old female presented with a history of progressive systemic symptoms including chronic fatigue, myalgia, arthralgia, and headaches, four months after receiving breast implants. Her clinical history was further complicated by multiple vaccinations, including influenza and SARS-CoV-2 boosters. After extensive diagnostic workup and unsuccessful medical management, she was diagnosed with ASIA syndrome. The decision was made to remove the implants, leading to rapid and complete resolution of her symptoms.

Clinical discussion

ASIA syndrome is a difficult diagnosis due to its broad symptomatology and its mimicry of other autoimmune and inflammatory conditions. Diagnostic criteria, proposed by Shoenfeld et al., include exposure to adjuvants and the appearance of typical clinical manifestations such as fatigue, myalgias, and arthralgias. In this case, the temporal association with breast implants and vaccinations made the diagnosis more evident. Surgical removal of the implants led to immediate improvement, reinforcing the diagnosis.

Conclusion

This case highlights the importance of recognizing ASIA syndrome as a potential diagnosis in patients with exposure to adjuvants and unexplained systemic symptoms. Early diagnosis and intervention, such as removal of the triggering adjuvant, are essential for patient recovery.

Evidence based medicine ranking

Level IV

Highlights

• •Rapid symptom resolution after breast implant removal in a patient with ASIA syndrome
• •Temporal link between implants, vaccines, and symptoms supports ASIA diagnosis and treatment.
• •Evidence of ASIA syndrome emphasizes the need for early detection and adjuvant removal.

1. Introduction

The Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA) has garnered increasing attention within the medical community since it was first introduced by Shoenfeld and Agmon-Levin in 2011 (1). ASIA encompasses a spectrum of autoimmune conditions triggered by exposure to adjuvants, substances known to enhance the body's immune response. Common adjuvants include aluminum hydroxide, squalene, and silica, widely used in vaccines and other medical interventions, such as silicone implants. These substances have been associated with a range of immune-mediated diseases, marking ASIA as a significant area of study in immunology (2). The incidence of ASIA has risen considerably in recent years, with over 4000 cases reported since the syndrome's initial characterization. This increase is largely attributed to heightened awareness among healthcare professionals about the syndrome. Severe cases of ASIA have primarily been linked to vaccinations, silicone implants, and mineral oil-based fillers. The ASIA syndrome registry, maintained by the Zabludowicz Center for Autoimmune Diseases, currently tracks more than 300 diverse cases, highlighting the global relevance of this condition as an emerging health concern (3).

ASIA's clinical manifestations are varied and often include myalgia, arthralgia, chronic fatigue, fever, and neurological symptoms. These symptoms are frequently observed across different conditions triggered by adjuvants, such as siliconosis and Silicone Implant Incompatibility Syndrome (SIIS). Autoimmune diseases commonly associated with ASIA include rheumatoid arthritis, scleroderma, and systemic lupus erythematosus, underscoring the syndrome's broad impact on immune function and its potential to induce significant morbidity in affected patients (4). Recent case studies, such as the one documented by Moreno Urbina et al., emphasize the potential complications related to silicone breast implants. In this particular case, a patient developed acquired hemophilia A, a rare bleeding disorder caused by autoantibodies against coagulation factor VIII, following the insertion of silicone implants. This case highlights the role that adjuvants in aesthetic procedures may play in the onset of serious autoimmune conditions, stressing the importance of vigilant monitoring and timely intervention for patients undergoing such treatments (5).

Globally, research on ASIA remains concentrated in countries such as Israel and Italy, largely due to the contributions of prominent researchers like Yehuda Shoenfeld and Carlo Perricone. Despite the growing number of studies, ASIA is still underexplored compared to other autoimmune disorders, pointing to a need for further research to better understand the triggers, mechanisms, and management of this syndrome. Increasing awareness and investigation into ASIA may aid in the development of preventative strategies and improve patient outcomes. This report follows the SCARE criteria (6).

2. Clinical case presentation

A 31-year-old Caucasian woman from California presented with a progressive onset of mastalgia, chronic fatigue, arthralgia, and recurrent headaches, which began approximately four months after receiving silicone breast implants in September 2022. Her past medical history was unremarkable, except for routine vaccinations, including an influenza booster in November 2022, a third SARS-CoV-2 vaccination in December 2022, and a tetanus booster in July 2023. Following the tetanus booster, her symptoms worsened, particularly with increased fatigue and joint pain.

The patient initially attributed her symptoms to post-surgical recovery from the breast implants; however, as her condition progressively deteriorated over the subsequent months, she sought medical attention. Upon presentation, she reported systemic symptoms, including severe fatigue, irregular menstrual cycles, and chronic headaches. There was no personal or family history of autoimmune diseases.

Physical examination was notable for diffuse tenderness in the breasts and joints, particularly the wrists and knees, but no overt signs of inflammation or localized infection were identified. Initial laboratory tests, including autoimmune panels, inflammatory markers, and imaging, yielded nonspecific findings and failed to confirm an underlying autoimmune condition.

Given the temporal association between the onset of symptoms and the patient's exposure to adjuvants (silicone implants and recent vaccinations), a diagnosis of Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA) was considered. After extensive discussion, the patient was counseled regarding the potential role of the breast implants in her symptomatology, and the decision was made to proceed with explantation.

The surgical removal of the implants was performed on February 18, 2024, without intraoperative complications. During the explantation procedure, we observed a capsule surrounding the prostheses that was thickened and hardened, measuring approximately 5 mm in thickness throughout its entirety. Additionally, a thick, light yellow inflammatory fluid without odor, measuring about 10 ml, was found within each capsule. Upon removal of the implants, the patient showed remarkable improvement; in the first follow-up examination (3 to 5 days post-surgery), her clinical condition had resolved or improved by more than 50 %. Remarkably, the patient experienced rapid and near-complete resolution of her symptoms within the first week postoperatively. At her six-week follow-up, she remained asymptomatic, reporting a complete resolution of fatigue, arthralgia, and myalgia.

3. Discussion

The presented case aligns with the growing body of evidence supporting the association between adjuvants, such as silicone, and the development of autoimmune and inflammatory conditions, commonly referred to as Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA). In our patient, the onset of systemic symptoms—fatigue, arthralgia, myalgia, and headaches—four months post-implantation and following multiple vaccinations suggests a clear temporal relationship, fulfilling Shoenfeld's diagnostic criteria for ASIA. When compared to the Moreno Urbina et al. case , our case demonstrates a less severe immune-mediated complication (5). Moreno's patient developed acquired hemophilia A, characterized by autoantibodies against coagulation factor VIII, manifesting with spontaneous bruising, knee pain, and grade IV capsular contracture of the right breast. In contrast, our patient did not present hematological complications but had prominent systemic symptoms, which rapidly resolved after the removal of the silicone implants. Both cases highlight the role of silicone as a potent adjuvant capable of triggering a spectrum of immune responses, ranging from mild systemic symptoms to life-threatening coagulopathies (Table 1). In the Maldonado et al. case , the patient presented with polyarthralgia, positive ANA, anticentromere, and Sclero-70 antibodies, similar to our patient's presentation of chronic fatigue and joint pain (7). However, Maldonado's patient continued to experience Raynaud's phenomenon post-explantation, indicating a more persistent autoimmune response. This difference in outcomes suggests that while implant removal is often therapeutic, the underlying immune activation may not be entirely reversible in all cases. Similarly, Flores Padilla et al. reported a patient who developed symmetric additive polyarthritis and pulmonary manifestations after the injection of an oily substance in the buttocks (8). This case is notable for its atypical presentation, as lung involvement is rarely seen in ASIA. In our case, no respiratory symptoms were present, which may reflect the variability of organ involvement depending on the type and site of adjuvant exposure. Lastly, Barilaro et al. documented a case of calcinosis cutis, chronic kidney disease, and hypercalcemia following multiple liquid silicone injections (9). The patient developed extensive subcutaneous calcifications and severe renal damage, underscoring the potential for systemic complications beyond autoimmune activation. In contrast, our patient experienced a more localized reaction to the breast implants, primarily manifesting with systemic inflammatory symptoms that fully resolved after explantation.

Table 1.

Main characteristics of reported cases of ASIA syndrome in different countries.

Author and year	Triggering event	Country	Clinical findings
André D, 2022 (7)	Exposure to silicone used in mammoplasty.	Madeira Island, Portugal	Two distinct histological patterns are described in ASIA patients, resulting from silicone exposure. Additionally, there is a noted risk for the development of undifferentiated connective tissue disease, with a close association to autoimmune conditions.
Moreno S, 2023 (5)	Silicone breast implants	México	The patient developed acquired hemophilia type A, documented by the presence of autoantibodies against factor VIII. She also exhibited systemic symptoms such as spontaneous bruising, intermittent knee pain, myalgias, and grade IV capsular contracture in the right breast. Following diagnosis, implant removal was performed, leading to symptom control.
Flores Padilla G, 2014 (8)	Injection of oily material in the buttocks.	México	The patient developed symmetric additive polyarthritis, upper and lower airway involvement, and foreign body granulomas. The diagnosis was adjuvant-induced autoimmune/inflammatory syndrome (ASIA) with atypical pulmonary and joint manifestations.
Maldonado G, 2021 (9)	Silicone breast implants	Ecuador.	The patient presented with polyarthralgia, positive antinuclear antibodies (ANA), anticentromere antibodies, and moderate positivity for Sclero-70 antibodies. These findings were consistent with ASIA syndrome related to silicone incompatibility. The patient continued to experience Raynaud's phenomenon despite the removal of the breast implants.
Barilaro G, 2016 (10)	Multiple liquid silicone injections.	Italy	The patient developed ASIA syndrome, calcinosis cutis, hypercalcemia, and chronic kidney disease following liquid silicone injections. Symptoms included fever, fatigue, nausea, vomiting, arthralgia, and extensive subcutaneous calcifications. The patient also presented ulcers at the injection sites, and renal biopsy revealed severe sclerosis and glomerular damage.

4. Conclusions

Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA) is a clinically significant but often underrecognized condition. This case emphasizes the need for healthcare professionals to maintain a high index of suspicion in patients with exposure to adjuvants, such as silicone implants, who present with unexplained systemic symptoms. Early identification and prompt intervention, including the removal of the triggering adjuvant, are crucial for preventing long-term complications and achieving favorable outcomes. Our case contributes to the growing evidence linking breast implants and vaccinations to ASIA and underscores the importance of further research to elucidate the underlying mechanisms and optimize management strategies for affected patients.

Author contribution

FARG - Diagnosis and follow-up and Surgical approach plan.

CESR- Surgical assistant.

TSQL- Article redaction.

Consent

Informed consent was obtained from the patient involved in this clinical case. All efforts were made to ensure confidentiality and compliance with ethical guidelines.

Ethical approval

The present study is a presentation of a clinical case. We point out that, in our institution, it is not necessary to be submitted to or approved by an ethics committee.

Guarantor

Quitzia Libertad Torres Salazar

Funding

This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

The authors declare that there are no conflicts of interest regarding the publication of this article.