Autoimmune/inflammatory Syndrome Induced By Adjuvants Research Articles

Multicentric reticulohistiocytosis with oral and laryngeal involvement in association with autoimmune/inflammatory syndrome induced by adjuvants (ASIA): expanding the spectrum of two uncommon entities.

Multicentric reticulohistiocytosis (MRH) is the most frequent entity in the group of reticulohistiocytoses. It is usually accompanied by a symmetrical erosive polyarthritis and is frequently associated with cancer and autoimmune disorders. Autoimmune syndrome induced by adjuvants (ASIA) is an inflammatory syndrome triggered by adjuvants such as those contained in vaccines or by silicone implants. Here we report a 71-years old female with a history of breast cancer treated with surgery and subsequent prosthesis who developed a systemic hyperinflammatory syndrome including seronegative symmetric polyarthritis, multiple skin lesions and two large nodular lesions in the oral cavity and larynx. Clinical picture was consistent with a clinical diagnosis of ASIA, with breast implant rupture and/or vaccination against SARS-CoV-2 as possible triggers. Histopathology of skin, oral and laryngeal nodules revealed cutaneous/mucous and submucosal infiltration of large epithelioid mononuclear or binucleated cells with fine granular ground glass-like cytoplasm and round to kidney-shaped nuclei with prominent nucleoli, without atypical features or relevant pleomorphism, accompanied by sparse giant cells and lymphocytes. These cells stained positive for CD68 and CD45 and negative for S100, CD1a, and markers of epithelial or neural/melanocytic differentiation, altogether consistent with a diagnosis of reticulohistiocytosis. Clinic-pathological correlation allowed the final diagnosis of MRH. To our knowledge, this is the first report of a co-occurrence of MRH with ASIA and this is relevant to broaden the spectrum of those both rare diseases.

Adjuvant-Induced Autoimmune Syndrome: A Bibliometric Analysis.

The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) encompasses various autoimmune conditions triggered by exposure to substances with adjuvant activity. Despite its potential relevance to public health, global scientific production on ASIA syndrome is significantly limited. This knowledge gap underscores the need for a comprehensive bibliometric assessment to understand global research in this field. Therefore, this article aims to conduct a bibliometric analysis to identify and evaluate research trends related to ASIA syndrome worldwide. A Scopus search identified scientific documents published between 2010 and 2022. A total of 2,133 articles meeting inclusion criteria were selected and analyzed for scientific production, authors, and institutions. Two-hundred fifty six documents were analyzed, mostly journal articles with multiple authors. The year with the highest publications was 2023, marking a notable increase since 2021. Italy and Israel had the most documents and citations, correlating with authors Yehuda Shoenfeld (Israel) and Carlo Perricone (Italy). Standout journals are "The Journal of Immunologic Research" and "Lupus." Relevant affiliations include Tel-Aviv University and the National Autonomous University of Mexico. This article identifies and analyzes scientific trends associated with ASIA syndrome. Despite increased publications, this field remains controversial and lacks full acceptance within the medical and scientific community, as evidenced by limited scientific production compared to other pathologies. These findings may motivate researchers to generate impactful publications, contributing to the global knowledge expansion on this syndrome.

Autoimmune/inflammatory syndrome induced by adjuvants in a patient after implantation of a polypropylene mesh for inguinal hernia repair (clinical case)

Aim. To report a clinical case of autoimmune/inflammatory syndrome, induced by adjuvants in patient after polypropylene mesh implantation for inguinal hernia repair.Materials and methods. Patient Z., male, 68 years old, was admitted to the hospital presenting muscle weakness and progressive dyspnoea. Interview and physical exam revealed signs of cognitive impairment and memory loss, proximal muscle weakness. Differential diagnosis was made to clarify genesis of symptoms, to rule out polymyositis, other systemic connective tissue diseases, oncologic diseases, hypothyroidism, infectious diseases.Results. Creatine kinase, thyroxine, thyreothropic hormone levels were normal. Clinical and immunological investigation revealed no data on polymyositis or any other systemic connective tissue disease. Yersiniosis, salmonellosis, malaria were ruled out. Chest CT scan, abdomen CT scan, gastroscopy, colonoscopy no data on the presence of malignant neoplasms. PSA level were normal. Electroneuromyography revealed signs of symmetrical axonal type damage to the motor portion of the ulnar nerves on both sides, and demyelinating type damage to the sensory portion. Prednisolone therapy was started at a dose of 40 mg per 24 hour (0.5 mg per kg), which lead to a significant clinical improvement. Based on the therapy response and positive diagnostic criteria (clinical manifestation after polypropylene mesh implantation, typical clinical manifestation – muscle weakness, chronic fatigue, cognitive impairment, neurological manifestations associated with demyelination) patient was diagnosed with autoimmune/inflammatory syndrome, induced by adjuvants (ASIA) after polypropylene mesh implantation for inguinal hernia repair.Conclusion. This clinical case report demonstrates possibility of a persistent course of the disease (symptoms were present for 15 years). Feature of this case is partial clinical improvement due to long-term uncontrolled dexamethasone use, which was prescribed empirically.

Enfermedad tiroidea posterior a vacunación contra SARS-COV-2

Introduction: Vaccines have been an essential part of the SARS-CoV-2 pandemic management and control. However, aluminum salts in vaccines, used to enhance the immune response, may be associated with autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This syndrome has been linked to other factors, such as infectious agents, silicone implants, and mineral oil inoculation. Data on autoimmune endocrine disorders and ASIA following SARS-CoV-2 vaccination is scant. Objective: to report cases of thyroid disorders following COVID-19 vaccination, in patients who attended the endocrinology clinic at Clínica Imbanaco, Cali, Colombia, in 2021. Methods: clinical, laboratory and imaging description of 8 patients who attended the endocrinology service. Results and discussion: 87.5% were females, aged 46.8 ± 10 years. Time between vaccine administration and symptoms onset was 13.8 days and the most related vaccine was the Pfizer/BioNTech vaccine followed by Sinovac-CoronaVac and AstraZeneca/AZD1222 vaccines. Subacute thyroiditis presented in 37.5%, Graves´ disease in 37.5%, silent thyroiditis in 12.5% and hypothyroidism in 12.5%. Myalgias and palpitations were the most common symptoms. Subacute thyroiditis was the most common ultrasound finding. Conclusions: our case series evidences a relationship between thyroid disease and SARS-CoV-2 vaccination. Given controversy remains, further studies will be necessary to establish causality.

One-step Glandular Reconstruction after Breast Implant Removal: Technical Refinements and Grafting of the Inferior Dermoglandular Flap.

The number of breast implant removal procedures are rising. Among the reasons why patients seek breast implant removal, the autoimmune/inflammatory syndrome induced by adjuvants (ASIA), also named breast implant illness, is increasingly common. ASIA is an entity that incorporates diverse autoimmune conditions induced by the exposure to various adjuvants, including silicone, and it is characterized by systemic symptoms reminiscent of autoimmune disorders. Implant removal has the most effective treatment for ASIA. We describe a technique for glandular cone reconstruction after complete capsulectomy and implant removal. It combines an inverted-T superomedial pedicled mastopexy with fat grafting of the breast quadrants and of the inferior dermoglandular flap in two patients affected by ASIA. Implant removal allowed symptom resolution in both patients at 10 and 12 months follow-up. Both patients were satisfied with the aesthetic outcome after implant removal in terms of breast softness, projection, and volume. Our technique is easy, reproducible, and allowed for restoration of breast contour, volume, and shape after implant removal. Although initially conceived in patients with ASIA, this technique can be used for patients seeking implant removal for any indication.

Silicone breast implants may contribute to early-onset fetal growth restriction.

There are many studies showing that silicone breast implants may affect lactation, but few analyzed whether these implants affect placentation. We observed that many mothers with growth-restricted pregnancies had inflammatory conditions, such as silicone breast implants or giardiasis. This single-center cohort study assessed the prevalence of inflammatory conditions in normotensive growth-restricted singleton pregnancies. Next, we stratified the patients according to the presence or absence of silicone breast implants, to determine whether these implants influence fetal growth restriction onset or severity. Twelve (32%) of the 38 participants underwent cosmetic breast augmentation 4-18years before pregnancy. Half of the patients with and 38% without silicone breast implants had giardiasis. Half of the mothers with and 35% without silicone breast implants had autoantibodies. Silicone breast implants were associated with a 70% increased risk of fetal growth restriction before 32weeks' gestation (95% confidence interval [CI], 1.2-2.5). Fetal growth restriction was diagnosed significantly earlier in mothers with than in those without silicone breast implants, respectively at 27 (95% CI, 25-30) and 30weeks' gestation (95% CI, 29-32). Silicone breast implants also tripled the risk of fetuses being below the third percentile, but the difference was not significant. Our results suggest that the association of inflammatory conditions, such as silicone breast implants, giardiasis, and autoantibodies may contribute to placental insufficiency. Silicone breast implants older than four years increased the risk of early-onset fetal growth restriction. Studies with large samples are needed to validate our findings and define whether silicone-related fetal growth restriction should be included in autoimmune/inflammatory syndrome induced by adjuvants (ASIA) criteria. Key Points • Fetal growth restriction (FGR), responsible for 30% of stillbirths, is the most common cause of prematurity and intrapartum asphyxia. • In this study, including 38 mothers with normotensive FGR, all participants had 2-4 inflammatory conditions, such as giardiasis, sinusitis, candidiasis, dysbiosis, extreme fear or autoantibodies. • Silicone breast implants were associated with a 70% increased risk of fetal growth restriction before 32 weeks' gestation. • FGR was diagnosed at 27 weeks' gestation (95% CI, 25-30) in mothers with and at 30 weeks' gestation (95% CI, 29-32) in mothers without silicone breast implants.

Transient Perivascular Inflammation of the Carotid Artery (TIPIC) Syndrome after Breast Implant Surgery (P2-5.003)

<h3>Objective:</h3> Describe a rare case of TIPIC syndrome in a patient with breast implants. <h3>Background:</h3> TIPIC syndrome is a rare cause of neck pain caused by inflammation of unknown etiology. Silicone from the breast implant shell may may leak in the systemic circulation and trigger silicone implant incompatibility syndrome (SIIS) a form of autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Several autoimmune conditions including vasculitis at distance from the implant were described. The association between breast implantation and TIPIC syndrome was not reported yet. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> 38-year-old woman with a history of asthma, HIV, and depression complained of refractory left-sided neck pain for ten days. Pain started gradually, was sharp, radiating to the left face, and was aggravated by motion and swallowing. Three weeks before onset, she had transient respiratory infection. She denied preceding neck trauma or other neurological symptoms. Acetaminophen, oxycodone, morphine and ketorolac provided moderate, short-lived relief. She had sex reassignment surgery including breast implants. Her home medications were spironolactone, estradiol, aripiprazole, emtricitabine and tenofovir disoproxil fumarate. She drinks alcohol occasionally. Clinical examination revealed left neck tenderness but no bruit, warmth, or swelling. Neurological examination was normal. CT showed eccentric hypoattenuation surrounding the left distal common carotid artery and a soft intimal plaque. MRI showed enhancement surrounding the left as well as the right common carotid artery without luminal narrowing, suggestive of TIPIC. Neck pain resolved after a short course of oral prednisone. ESR and CRP were normal. Repeated MRI after 6 months showed resolution of the perivascular inflammation. <h3>Conclusions:</h3> This is the first TIPIC case reported after breast implantation, suggesting an autoimmune response. Reactivity against the left carotid plaque is an alternative cause, but it does not explain the inflammation around the right carotid artery where is no plaque. TIPIC syndrome should be differentiated from other causes of vasculitis and dissection. <b>Disclosure:</b> Dr. Peringassery Sateesh has nothing to disclose. Dr. Marchidann has stock in Eli Lilly. Dr. Marchidann has stock in Pfizer. Dr. Marchidann has stock in Merck. Dr. Marchidann has stock in Illumina. Dr. Marchidann has stock in Aeterna Zentaris. Dr. Marchidann has stock in Abbot. Dr. Marchidann has received publishing royalties from a publication relating to health care. Dr. Marchidann has received publishing royalties from a publication relating to health care.

Sarcoidosis and Autoimmune Inflammatory Syndrome Induced by Adjuvants.

Currently, sarcoidosis remains one of the diseases with unknown etiology, which significantly complicates its diagnosis and treatment. Various causes of sarcoidosis have been studied for many years. Both organic and inorganic trigger factors, provoking the development of granulomatous inflammation are considered. However, the most promising and evidence-based hypothesis is the development of sarcoidosis as an autoimmune disease, provoked by various adjuvants in genetic predisposed individuals. This concept fits into the structure of the autoimmune/inflammatory syndrome, induced by adjuvants (ASIA) that was proposed in 2011 by Professor Shoenfeld Y. In this paper, the authors reveal the presence of major and minor ASIA criteria for sarcoidosis, propose a new concept of the course of sarcoidosis within the framework of ASIA, and point out the difficulties in creating a model of the disease and the selection of therapy. It is obvious that the data obtained not only bring us closer to understanding the nature of sarcoidosis, but also potentiate new studies confirming this hypothesis by obtaining a model of the disease.

Takayasu arteritis associated with autoimmune/inflammatory syndrome induced by adjuvants: a case-based review.

Takayasu's arteritis (TA) is a chronic granulomatous vasculitis that predominantly affects the aorta and its major branches. Despite advancements in the understanding of the pathogenic pathways of vascular inflammation, the etiology and predisposing factors of TA remain to be fully understood. In susceptible individuals, exposure to adjuvants may trigger, unlock or unmask an autoimmune disorder, presenting as non-specific constitutional symptoms or a fully developed autoimmune syndrome such as vasculitis. Here, we hypothesize that TA could be triggered by siliconosis, a subtype of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). ASIA, also known as Shoenfeld syndrome, encompasses a wide range of autoimmune and immune-mediated diseases resulting from dysregulation of the immune response after exposure to agents with adjuvant activity. This case report describes the development of large artery vasculitis, TA, in an individual one year following the placement of silicone breast implants. The patient initially presented with non-specific symptoms, and multiple imaging methods were employed, including ultrasound diagnostics, CT angiography, and 18-fluorodeoxyglucose positron emission tomography/CT. These techniques revealed vasculitic alterations in the carotid arteries and thoracic aorta. Initial treatment with glucocorticosteroids proved ineffective, prompting the addition of steroid-sparing immunosuppressive agents. Due to the distinct clinical symptoms, disease progression, implant-associated fibrosis, and resistance to therapy, the potential involvement of implants in the development of large-vessel vasculitis was considered, and a potential association with ASIA was postulated. Although there is limited evidence to support a direct link between adjuvants and the pathogenesis of TA, similarities in cellular immunity between the two conditions exist. The diagnosis of this complex and potentially debilitating condition requires a comprehensive clinical examination, laboratory evaluation, and instrumental assessment. This will aid in identifying potential contributing factors and ensuring successful treatment.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) with postural orthostatic tachycardia syndrome after silicone breast implantation: Case report.

This study illustrates two patients who developed autoimmune/inflammatory syndrome induced by adjuvants (ASIA) with postural orthostatic tachycardia syndrome (POTS) after silicone breast implant (SBI) and improved after SBI extraction.

Vaccines and Autoimmunity-From Side Effects to ASIA Syndrome.

Since vaccines are in fact manufactured chemical compounds such as drugs, the appearance of side effects following their use is not surprising. Similarly, as the main goal of vaccines is to stimulate the immune system bringing out the production of protective antibodies, autoimmune-related side effects as a consequence of increased immune activity do not seem irrational. Fortunately, the rate of such side effects is low; however, the importance of reporting adverse events following vaccinations, understanding the mechanisms behind their appearance, making early diagnosis, and appropriate treatment cannot be overemphasized. In fact, autoimmune-related side effects of vaccines, particularly those based on adjuvants, were reported long before the introduction of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Nevertheless, ASIA gathered and united the side effects of vaccines under one title, a step which helped organize the research and call for better immune stimulators than adjuvants. New technologies and methods of making vaccines were clearly noticed during the pandemic of COVID-19 after the introduction of mRNA-based vaccines. In our current paper, we introduce the notion of side effects to vaccines, particularly those of autoimmune nature, the mechanisms of ASIA, and the main vaccines linked with the syndrome including the recent COVID-19 vaccines. The transition from side effects to ASIA is the main idea behind our work.

The effect of explantation on systemic disease symptoms and quality of life in patients with breast implant illness: a prospective cohort study

Silicone breast implants (SBIs) have been subject to scientific scrutiny since the 1960’s because of their potential link with systemic disease symptoms. Breast implant illness (BII) is a cluster of over 56 (systemic) symptoms attributed by patients to their SBIs. BII remains an unofficial medical diagnosis, although its symptoms include but are not limited to the clinical manifestations of autoimmune/inflammatory syndrome induced by adjuvants (ASIA). The aim of this study was to prospectively analyse the effect of explantation on clinical manifestations of ASIA/BII symptoms, as well as to compare (breast-surgery specific) QoL in patients pre- and postoperatively while recording relevant perioperative/patient data. A prospective cohort study was conducted on 140 patients consulting a single surgeon for explantation of SBIs at a single clinic from 2019 to 2021 via their general practitioner, a medical specialist or self-referral. Of all patients, medical (implant) history, lifestyle factors and biometric data were obtained. Patients filled out a novel ASIA/BII symptom-survey termed the ASIA-scale, three domains of the SF-36 and the augmentation module of the BREAST-Q before and four months after the operation. A total of 109 patients completed both the pre- and postoperative survey with a mean follow-up duration of 205 days. There was a significant decrease in all individual symptom scores as well as ASIA-scale summary scores after explantation (p < .001). All SF-36 subdomains showed significant improvement postoperatively (p < .001). The BREAST-Q subdomain ‘satisfaction with breasts’ improved significantly after explantation (p = .036). No statistically significant association was found between any clinical parameters (such as age, capsulectomy, rupture etc.) and the recovery of symptom scores. This is the largest prospective cohort study on SBI explantation to date showing significant improvement of the most common systemic complaints in SBI patients as well as improvement of satisfaction with breasts and overall quality of life.

Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA) Following SARS-CoV2 Vaccination

A 67-year-old man presented with joint swelling, muscular weakness, pain and anemia after the second dose of BNT162b2 (Pfizer-Biontech) mRNA COVID-19 vaccination. The signs and symptoms in the case met criteria for post-vaccination polymyalgia rheumatica (PMR) and Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA) demonstrating the close association between these two conditions. The patient underwent a broad workup to rule out other causes and improved with corticosteroid therapy. Vaccine-associated autoimmune syndromes likely have heterogenous presentations and require a high index of suspicion to expedite recognition and treatment.

PSAT347 New Onset of Graves’ Disease after COVID-19 Vaccination

Abstract Introduction Adjuvants are substances that are commonly found in vaccines. They can enhance the efficacy and potency of a vaccine via an immunological response. However, in some susceptible individuals, these adjuvants can lead to a serious autoimmune response known as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This can lead to the onset of autoimmune disorders following vaccination. There are many case reports of the onset of autoimmune disorders following COVID-19 vaccination. However, new onset of Graves’ disease within one day after COVID-19 vaccination, is of rare occurrence. Clinical Case We present the case of a 33-year-old Caucasian male who presented to his primary care physician with chief complaints of fever ranging between 99.2F to 101.3F, palpitations and hand tremors which started one day after he received his first dose of COVID-19 vaccine. Initial laboratory evaluation included a negative throat swab for Group A Streptococcus, a negative nasal swab for Influenza A &amp; Influenza B and a negative nasopharyngeal swab for SARS-COV-2 RNA. On physical examination, he was afebrile, pulse rate 101/min, blood pressure 125/74 mm Hg and oxygen saturation 98%. Due to persistence of tachycardia, an EKG was done which showed a normal sinus rhythm with no other abnormalities. Further laboratory testing was remarkable for a suppressed TSH 0.005 (0.300-4.00 uUI/ml), elevated FT4 2.36 (0.80-1.80 ng/dl) and an elevated TSH receptor Antibody (TRAb) 8.67 (0.00-1.75 IU/L), which confirmed the diagnosis of Graves’ disease. Subsequently, patient established care at our endocrinology clinic. Labs were repeated which showed persistence of hyperthyroidism with TSH &amp;lt;0.005, high normal FT4 1.56 and an elevated FT3 5.36 (2.00-4.40 pg/ml). Thyroid ultrasound was remarkable for mild thyromegaly with increased vascularity and no discrete nodules. Patient was initiated on Methimazole 10 mg daily and propranolol 10 mg twice daily. During the first follow-up visit, the dose of Methimazole was reduced to 5 mg daily based on improved labs. However, it had to be increased back to 10 mg daily due to subsequent worsening of labs. Since then, patient has been maintained on a stable dose of Methimazole 10 mg once daily and the beta-blocker has been discontinued. It has been almost 1 year since the diagnosis and the Graves’ disease specific Thyroid Stimulating Immunoglobulin (TSI) antibody is still elevated at 1.31 (0.00-0.55 IU/L). Conclusion Graves’ disease should be considered high in the differential diagnosis in a patient presenting with fever and tachycardia following COVID-19 vaccination. Our unique case supports the current literature available on the various autoimmune conditions caused by the autoimmune/inflammatory syndrome induced by adjuvants, also known as ASIA. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

RF35 | PSAT298 Subacute Thyroiditis Following SARS-CoV-2 mRNA Vaccine

Abstract Background In 2011, Shoenfeld and Agmon-Levin described a distinct clinical entity called the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Adjuvants are primarily used in vaccines for directing the adaptive immune response. However, adjuvants sometimes trigger undesirable autoimmune effects, especially in genetically predisposed individuals such as those with DRB1 allele mutations. The mRNA vaccine may exert "self-adjuvant" properties through activation of tumor necrosis factor, interferon-alpha and other cytokines secreted by immune cells or cross reactivity of mRNA targeting CoV-2 spike protein with thyroid tissue antigens. With the recent widespread use of SARS-CoV-2 mRNA vaccine, cases of vaccine associated thyroid disorders are becoming more apparent. Case Summary A 45-year-old male with well controlled hypertension and type 2 diabetes mellitus was evaluated for abnormal thyroid function tests with a TSH of 0.078 uIU/mL and Free T4 of 2.17 ng/dl. He reported a history of Hashimoto's chronic thyroiditis. He received the second dose of mRNA COVID-19 vaccine one month prior to presentation. He denied any change in the size of his thyroid gland. He also reported no local neck symptoms, dysphagia, odynophagia or change in voice. A nuclear thyroid uptake and scan showed mildly asymmetric thyroid lobes with markedly decreased 24-hour uptake of 0.7%. Based on his clinical presentation, labs and nuclear imaging he was diagnosed with painless thyroiditis. His thyroid function normalized to a TSH of 0.96uIU/ml and Free T4 of 1.29 ng/dl within 2 months without any intervention. There is a strong possibility that the SARS-CoV-2 vaccine accentuated his underlying Hashimoto's chronic thyroiditis enough to cause this transient episode of painless thyroiditis, particularly considering the close interval between the vaccine and onset of his thyroid abnormalities. Conclusion Autoimmune thyroid abnormalities induced by vaccines have been historically associated with protein vaccines for protection from HPV, HBV, seasonal influenza, etc. The spectrum of these disorders can potentially manifest as a transient side effect or even years later with non-specific findings. The SARS-CoV-2 mRNA vaccine may incite similar immunogenicity though yet unestablished, and physicians should be mindful of this phenomenon. Due to limited data, more rigorous studies are needed to fully understand the underlying pathogenesis of thyroiditis following SARS-CoV-2 vaccine in future. As there have been minimal cases of thyroiditis reported, SARS-CoV-2 vaccine should still be strongly recommended. References Bragazzi NL, Hejly A, Watad A, Adawi M, Amital H, Shoenfeld Y. ASIA syndrome and endocrine autoimmune disorders. Best Pract Res Clin Endocrinol Metab. 2020 Jan;34(1): 101412. doi: 10.1016/j.beem.2020.101412. Epub 2020 Mar 11. PMID: 32265102. Watad A, David P, Brown S, Shoenfeld Y. Autoimmune/Inflammatory Syndrome Induced by Adjuvants and Thyroid Autoimmunity. Front Endocrinol (Lausanne). 2017 Jan 24;7: 150. doi: 10.3389/fendo.2016.00150. PMID: 28167927; PMCID: PMC5256113. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.

PSAT319 A 34-year-old Male with Subacute Thyroiditis Following COVID-19 Vaccination: A Case Report

Abstract Background Few cases of subacute thyroiditis (SAT) have been reported after exposure to SARS-CoV-2 vaccines, which may stimulate immunogenic cross-reactivity in genetically susceptible individuals. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) should be considered as post-vaccination phenomenon, which may cause an underrecognized cause of autoimmune endocrine disease. Clinical Case A 34-year-old, Filipino male, presented with neck pain and throat discomfort, which started 5 days after his first dose of COVID-19 vaccine (Pfizer Bio-NTech mRNA vaccine). He reported sore throat, palpitations, easy fatigability, weight loss, diarrhea and mood changes. He had no recent history of any viral or respiratory illness. Premorbid, he was clinically and biochemically euthyroid. He had maternal history of thyroid carcinoma. Initial examination showed enlarged left thyroid nodule, tender on palpation. Laboratory work-up showed elevated C-reactive protein (8.16 mg/dL, n: 0.50 mg/dL), suppressed TSH (&amp;lt;0.005 uIU/mL, n: 0.27-4.20 uIU/mL) and elevated FT4 (89.15 pmol/L, n: 12-22 pmol/L), consistent with thyrotoxic phase of SAT. Thyroid peroxidase antibody, TSH receptor antibody and thyroglobulin were within reference range, while the thyroglobulin antibody was elevated (33.73, n: 4.11). SARS-CoV-2 RT-PCR was negative. Thyroid ultrasonography showed enlarged left thyroid lobe, with diffuse parenchymal disease and increased thyroid vascularity. Thyroid scintigraphy with 99mTc-pertechnetate demonstrated no tracer accumulation in thyroid beds and low thyroid uptake, consistent with thyroiditis. He was initially treated with nonsteroidal anti-inflammatory drug (Celecoxib) to relieve the neck discomfort and beta-blocker (Propranolol) to control his palpitations. Celecoxib was shifted to prednisone after 1 week due to further increase in FT4 (&amp;gt;100 pmol/L, n: 12-22 pmol/L), and persistence of neck pain. Prednisone was eventually tapered to discontinue when symptoms improved. Repeat thyroid function test after 4 weeks demonstrated results transitioning to the hypothyroid phase of SAT, elevated TSH (3.910 uIU/mL) and low-normal FT4 (15.71 pmol/mL). Levothyroxine was initiated at 25 g daily. After 4 weeks, repeat TSH was 3.75 uIU/mL. His levothyroxine dose was maintained and he remained well. Second dose of Pfizer Bio-NTech vaccine was administered when his thyroid status was stable, and he had no adverse effects thereafter. Conclusion Thyroid dysfunction occurring after COVID-19 vaccination is probably an underreported adverse effect. To our knowledge, no case of thyroid dysfunction after COVID-19 vaccination had been reported yet in the Philippines. SAT should be considered in patients presenting with neck pain, fever and thyroid dysfunction. Awareness of potential thyroid dysfunction after administration of COVID-19 vaccine, in the context of safety monitoring, is important. References (1) Saygılı ES, Karakilic E. Subacute thyroiditis after inactive SARS-CoV-2 vaccine. BMJ Case Rep 2021;14: e244711. doi: 10.1136/bcr-2021-244711 Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Two Cases of Autoimmune Thyroid Disorders after COVID Vaccination in Dialysis Patients

SARS-CoV-2 infection and vaccination have been associated with autoimmune thyroid dysfunctions. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and molecular mimicry have been referred to as potential causes. Such a case has not been reported in immunocompromised end-stage renal disease (ESRD) patients. Herein we present two dialysis patients with no previous history of thyroid disease who developed immune mediated thyroid disorders after BNT162b mRNA vaccine against SARS-CoV-2. The first patient is a 29-year-old man on hemodialysis diagnosed with Grave’s disease four months post-vaccination and the second one is a 67-year-old female on peritoneal dialysis who developed Hashimoto’s thyroiditis two months post-vaccination. Grave’s disease is uncommon in dialysis patients, whereas Hashimoto’s thyroiditis has a higher incidence in this population. Time proximity in both cases suggests potential causality. To our knowledge, this is the first report of de novo immune-mediated thyroid disorders in dialysis patients following vaccination against SARS-CoV-2.

The predictive potential of autoimmune-inflammatory syndrome induced by adjuvants (ASIA) criteria to assess the risk of adverse events and efficacy of immune checkpoint inhibitor therapy.

At the moment, there are no approved predictive markers of immune adverse events (irAES) induced by immune checkpoint inhibitors (ICIs) and the treatment efficacy. The early stages of irAES have some similarities with adjuvant-induced autoimmune/pro-inflammatory syndrome (ASIA). This study aims to assess the predictive possibility of using the "ASIA questionnaire" in patients on immune checkpoint inhibitor therapy in comparison with determination of PD-L1 expression to predict the risk of irAES development and therapy efficacy. We examined patients (n = 91) being treated for solid tumors. The signs of ASIA were found in 74% (66/91), while ASIA syndrome was diagnosed in 54% of cases (49/91). No statistically significant difference in the frequency of ICI-dependent complication development regarding the presence of previous ASIA clinical manifestations, hereditary factors, sex, different trigger factors was found. Index based on combination of PD-L1 determination and ASIA index was created. With reference &gt; 2.5 units, the disease control rate (DCR) could be predicted with sensitivity 100.0% and specificity 70.00%, p = 0.007. The study did not reveal the diagnostic value of ASIA questionnaire to assess the risk of adverse events; however, in early stages, the development of ASIA symptoms diagnosed with the questionnaire in complex with PD-L1 expression allowed to predict a treatment efficacy.

Autoimmune and inflammatory thyroid diseases following vaccination with SARS-CoV-2 vaccines: from etiopathogenesis to clinical management.

Since the Covid-19 pandemic emerged in 2019, several adenoviral-vectored, mRNA-based and inactivated whole-virus vaccines have been developed. A massive vaccination campaign has been undertaken around the world, and an increasing number of SARS-CoV-2 vaccine-induced thyroid diseases have been described in the literature. Subacute thyroiditis has been reported in 52 patients, mean age 45.5 ± 1.8 years, mainly in women (n = 39). Graves’ disease is more frequent in women (n = 22) than in men (n = 10), mean age 46.2 ± 2.6 years, reported as new onset, recurrent or exacerbation of well-controlled hyperthyroidism. The mean time to symptoms onset is 9.0 ± 0.8 days in subacute thyroiditis, and 15.1 ± 2.6 days in Graves’ patients. Rare patients (n = 6) present silent or painless autoimmune thyroiditis. Thyroid function and autoimmune tests, inflammatory markers, thyroid echography with colour flow Doppler, radio-activity uptake on thyroid scan, medical treatment and follow-up are described and compared in patients with SARS-CoV-2 vaccine-induced thyroid diseases. The underlying pathogenic mechanisms of vaccine-induced thyroid diseases, molecular mimicry (various SARS-CoV-2 proteins sharing a genetic homology with a large heptapeptide human protein) or autoimmune/inflammatory syndrome induced by adjuvants (ASIA) are discussed in the context of predisposition or genetic susceptibility. The benefits of SARS-CoV-2 vaccination far outweigh the potential vaccine-induced adverse effects, but clinicians should be aware of possible autoimmune and inflammatory thyroid diseases, and can advise patients to seek medical assistance when experiencing anterior neck pain, fever or palpitations following SARS-CoV-2 vaccines. Further studies are warranted to investigate the etiopathogenesis and to clarify the factors which predispose patients to SARS-CoV-2 vaccine-induced thyroid diseases.

Disease presentation and surgical treatment of patients with foreign-body granulomas and ASIA syndrome: case series.

BackgroundThe result of illicit polymer injection is chronic inflammation with foreign-body granuloma (FBG) formation. Treatment can be divided into medical and surgical. Some patients develop severe complications with need surgical treatment. This study aims to describe patients who underwent surgical removal of the FBGs and autoimmune/inflammatory syndrome induced by adjuvants (ASIA); additionally, we evaluated the quality of life after surgery.MethodsIn this retrospective single-center study, the authors examined data of patients who underwent surgical removal of FBG caused by illicit polymer injection for cosmetic purposes and confirmed ASIA from 2015 to 2020 by three different surgical approaches. Descriptive summary statistics were reported on patient demographics, presenting symptoms and clinical examination features, treatment strategies, histopathology reports and quality of life.ResultsThe cohort included 11 female patients with FBGs and ASIA. The most affected anatomical zones were the combination of gluteal region, thighs and legs (40%); and thighs with legs (20%). Main presentation was: skin hyperpigmentation (90.9%), skin induration (63.6%), chronic fatigue (63.6%), and ulcers (36.4%). Surgical modalities consisted of: ultrasonic-assisted liposuction in four patients (36.4%); open en bloc excision and primary closure in four patients (36.4%); and open en bloc excision and microsurgical reconstruction in three patients (27.2%). The postoperative quality of life visual analog scale score was 83.9.ConclusionsASIA treatment represents a challenge for the plastic surgeon. Adequate surgical treatment emphasizing, when possible, the total or near-total resection of the FBG must be performed to improve ASIA evolution.