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Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 60603

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Special Issue Editors

Dr. Shuen-Iu Hung

E-Mail Website1 Website2
Guest Editor

Cancer Vaccine & Immune Cell Therapy Core Lab, Department of Medical Research, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
Interests: precision medicine; pharmacogenomics; immunopharmacology; immunogenomics; cell therapy; neoantigens; allergy; hypersensitivity; immunology; clinical pharmacy; inflammation; drug safety; cellular immunology; clinical dermatology; vaccinomics; adversomics

Dr. Wen-Hung Chung

E-Mail Website
Guest Editor

Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
Interests: Parkinson's disease; dermatology; adverse drug reactions

Prof. Dr. Bruce Carleton

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Guest Editor

1. Pharmaceutical Outcomes Programme, BC Children's Hospital, Vancouver BC V5Z 4H4, Canada
2. Division Head, Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, BC V6H 3V4, Canada
Interests: pediatric medicine; asthma; the epidemiology and clinical management of adverse drug reactions

Prof. Dr. Elizabeth J. Phillips

E-Mail Website
Guest Editor

Institute of Infection, Immunology, and inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Interests: HIV; drug safety; pharmacology; personalized medicine; drug hypersensitivity; HLA; immunopathogenesis; severe H1N109 disease

Special Issue Information

Dear Colleagues,

Hypersensitivity to drugs and vaccines resulting from interactions between a pharmacologic component and the human immune system is an important clinical issue to be resolved. The manifestations of hypersensitive reactions range from milder skin reactions (e.g., urticaria, angioedema, or maculopapular exanthema) to multiple organ injury or severe systemic reactions. Some life-threatening examples include drug-induced liver injury (DILI), myocarditis, vasculitis, anaphylaxis, immune thrombotic thrombocytopenia, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). These diverse clinical manifestations not only make diagnosis and management more challenging, but also hinder public health interventions, in particular, the currently widespread vaccination against COVID-19 to control the pandemic. Hypersensitivity reactions usually involve molecular interactions between immune repertoires (e.g., antibodies, T cell receptor (TCR)) and drugs/metabolites or components of vaccines. New approaches and technologies have been emerging and applied to discover the genetic susceptibility, predisposing factors, biomarkers, and molecular mechanisms of hypersensitivity reactions to drugs, as well as vaccines. This Special Issue of Biomedicines aims to include research on the molecular aspects, immunological features, diagnostic tools, methods of prevention, and treatment strategies for hypersensitivity to drugs and vaccines. All the basic studies and translational research, including original articles or reviews of pharmacogenomics, immune repertoire, immune epitope identification, transcriptome, metagenomics, and immunopathogenesis, will be considered.

Prof. Dr. Shuen-Iu Hung
Prof. Dr. Wen-Hung Chung
Prof. Dr. Bruce Carleton
Prof. Dr. Elizabeth J. Phillips
Guest Editors

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Keywords

adverse reactions
adversomics
allergy
antibody
drug safety
hypersensitivity
immune repertoire
immunopharmacology
immunophathogenesis
pharmacogenomics
side effects
T cell
vaccinomics

Published Papers (14 papers)

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Research

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11 pages, 1379 KiB

Open AccessArticle

IL-15/IL-15Rα in SJS/TEN: Relevant Expression of IL15 and IL15RA in Affected Skin

by Teresa Bellón, Olga González-Valle, Elena Sendagorta, Victoria Lerma, Javier Martínez del Río, Celia Martínez, Guillermo Servera, Carlos González-Herrada, Lucía Cachafeiro, José A. Lorente, Rosario Cabañas, Pedro Herranz and Francisco de Abajo

Biomedicines 2022, 10(8), 1868; https://doi.org/10.3390/biomedicines10081868 - 02 Aug 2022

Viewed by 1821

Abstract

Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening hypersensitivity reaction to medications characterized by keratinocyte apoptosis and skin detachment. IL-15 serum levels have been associated with severity and prognosis of SJS/TEN. We have measured IL-15 concentrations in serum and blister fluid (BF) from patients with SJS/TEN by ELISA and used quantitative RT-PCR to analyze the expression of IL15 and IL15RA (encoding for IL-15 Receptor-α chain) genes in peripheral blood and BF cells, including isolated monocytes, and in affected skin. A positive correlation was found between IL-15 serum levels and a percent of detached skin. BF concentrations were higher, but no correlation was found. Higher IL15 and IL15RA gene expression levels were found in skin-infiltrating blister fluid cells compared to peripheral mononuclear cells. Moreover, IL15RA transcripts were barely detected in healthy skin, being the highest expression levels found in samples from two SJS/TEN patients who did not survive. The cutaneous expression of IL-15Rα in SJS/TEN may provide an explanation to the tissue-specific immune cytotoxic response in this clinical entity, and the results suggest that the effects of IL-15 in SJS/TEN patients may be dependent on the expression of its private receptor IL-15Rα in affected skin. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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13 pages, 820 KiB

Open AccessArticle

Changes in Sensitization Patterns in the Last 25 Years in 619 Patients with Confirmed Diagnoses of Immediate Hypersensitivity Reactions to Beta-Lactams

by María del Valle Campanón Toro, Esther Moreno Rodilla, Alicia Gallardo Higueras, Elena Laffond Yges, Francisco J. Muñoz Bellido, María Teresa Gracia Bara, Cristina Martin García, Vidal Moreno Rodilla, Eva M. Macías Iglesias, Sonia Arriba Méndez, Miriam Sobrino García and Ignacio Dávila

Biomedicines 2022, 10(7), 1535; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10071535 - 28 Jun 2022

Cited by 1 | Viewed by 1296

Abstract

Beta-lactam (BL) drugs are the antibiotics most prescribed worldwide due to their broad spectrum of action. They are also the most frequently implied in hypersensitivity reactions with a known specific immunological mechanism. Since the commercialization of benzylpenicillin, allergic reactions have been described; over the years, other new BL drugs provided alternative treatments to penicillin, and amoxicillin is now the most prescribed BL in Europe. Diagnosis of BL allergy is mainly based on skin tests and drug provocation tests, defining different sensitization patterns or phenotypes. In this study, we evaluated 619 patients with a confirmed diagnosis of BL-immediate allergy during the last 25 years, using the same diagnostic procedures with minor adaptations to the successive guidelines. The initial eliciting drug was benzylpenicillin, which changed to amoxicillin with or without clavulanic acid and cephalosporins in recent years. In skin tests, we found a decrease in sensitivity to major and minor penicillin determinants and an increase in sensitivity to amoxicillin and others; this might reflect that the changes in prescription could have influenced the sensitization patterns, thus increasing the incidence of specific reactions to side-chain selective reactions. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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15 pages, 1047 KiB

Open AccessArticle

The Immunogenicity and Safety of Three Types of SARS-CoV-2 Vaccines in Adult Patients with Immune-Mediated Inflammatory Diseases: A Longitudinal Cohort Study

by Ni Tien, Yu-Chang Chang, Po-Ku Chen, Hui-Ju Lin, Shih-Hsin Chang, Joung-Liang Lan, Po-Ren Hsueh, Ching-Kun Chang and Der-Yuan Chen

Biomedicines 2022, 10(4), 911; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10040911 - 15 Apr 2022

Cited by 8 | Viewed by 5777

Abstract

Patients with immune-mediated inflammatory diseases (IMID) were seldom enrolled in the studies of SARS-CoV-2 vaccines, and real-world data regarding the immunogenicity of different types of vaccines is limited. We aimed to assess the immunogenicity and safety of three types of vaccines (AZD1222, mRNA-1273, and BNT162b2) in 253 patients with IMID and 30 healthcare workers (HCWs). Plasma levels of IgG-antibody against SARS-CoV-2 targeting the receptor-binding domain of spike protein (anti-S/RBD-IgG) were determined by chemiluminescent immunoassay 3–4 weeks after the first-dose and second-dose vaccination. The positive rate and titers of anti-S/RBD-IgG were significantly higher in mRNA-1273 or BNT162b2 than in the AZD1222 vaccine. Immunogenicity was augmented after the second dose of any vaccine type in all IMID patients, suggesting that these patients should complete the vaccination series. Anti-S/RBD-IgG titers after first-dose vaccination were significantly lower in RA patients than pSS patients, but there was no significant difference after second-dose vaccination among five groups of IMID patients. The positive rate and titers of anti-S/RBD-IgG were significantly lower in patients receiving abatacept/rituximab therapy than in those receiving other DMARDs. All three SARS-CoV-2 vaccines showed acceptable safety profiles, and the common AEs were injection site reactions. We identified SLE as a significant predictor of increased autoimmunity and would like to promote awareness of the possibility of autoimmunity following vaccination. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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13 pages, 970 KiB

Open AccessArticle

Contrast Medium Hypersensitivity: A Large Italian Study with Long-Term Follow-Up

by Eleonora Nucera, Giuseppe Parrinello, Sebastiano Gangemi, Alessandro Buonomo, Arianna Aruanno, Franziska Michaela Lohmeyer, Riccardo Inchingolo and Angela Rizzi

Biomedicines 2022, 10(4), 759; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10040759 - 24 Mar 2022

Cited by 5 | Viewed by 4194

Abstract

Hypersensitivity reactions (HRs) to contrast media (CM) are a major problem. We compared differences of HRs to iodinated contrast media (ICM) versus gadolinium-based contrast media (GBCM), collecting data on prevalence, type, latency and severity. Secondly, the predisposition to perform new contrast tests, use of premedication and possible appearance of new reactions were explored in a long-term follow-up of 5 years. Clinical data, comorbidities, skin test (ST) results, re-exposure to CM procedures with any new reactions, premedication and CM used were collected. In a retrospective single-center study, 350 patients with mild to moderate HRs were enrolled. Asthma, food allergy, non-allergic drug hypersensitivity and neurologic disease were significantly more frequent in patients with HRs to GBCM compared to the high evidence of cardiovascular disease and history of cancer in patients with HRs to ICM. A marked delay in performing STs was reported by patients with negative results (66 months, p < 0.01). Iomeprol, iopamidol and gadobenic acid were the culprit CM most involved in HRs in patients with positive STs. During follow-up, 7.1% of responders reported new HRs to CM despite negative STs, premedication and infusion of alternative CM in most cases. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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Review

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13 pages, 1727 KiB

Open AccessReview

Allergic Reactions to Vaccines in Children: From Constituents to Specific Vaccines

by Ming-Han Tsai and Chih-Yung Chiu

Biomedicines 2023, 11(2), 620; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11020620 - 18 Feb 2023

Cited by 1 | Viewed by 2224

Abstract

Vaccination is an essential public health measure that helps to reduce the burden of infectious diseases in children. Although vaccines have an excellent safety record and the association of severe allergic reactions is rare, public concerns about vaccine safety can lead to incomplete vaccination coverage in children with or without allergies. Therefore, it is important to understand the mechanisms and implications of allergic reactions to vaccines and define strategies to manage them to provide the safest care for vaccine recipients. In this review, we provide an overview on the types of allergic reactions that can occur after vaccination, including those caused by various vaccine constituents. We also discuss the mechanisms underlying these allergic reactions and the recommended diagnosis and management strategies for children with a history of suspected allergic reactions to vaccines. An improved understanding of allergic reactions to vaccines can aid in the enhancement of the safety and effectiveness of vaccination. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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22 pages, 17811 KiB

Open AccessReview

A Review of Bullous Dermatologic Adverse Events Associated with Anti-Cancer Therapy

by Rose Parisi, Hemali Shah, Neil H. Shear, Michael Ziv, Alina Markova and Roni P. Dodiuk-Gad

Biomedicines 2023, 11(2), 323; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11020323 - 24 Jan 2023

Cited by 1 | Viewed by 2201

Abstract

The rapid evolution of anti-cancer therapy (including chemotherapy, targeted therapy, and immunotherapy) in recent years has led to a more favorable efficacy and safety profile for a growing cancer population, and the improvement of overall survival and reduction of morbidity for many cancers. Anti-cancer therapy improves outcomes for cancer patients; however, many classes of anti-cancer therapy have been implicated in the induction of bullous dermatologic adverse events (DAE), leading to reduced patient quality of life and in some cases discontinuation of life-prolonging or palliative therapy. Timely and effective management of adverse events is critical for reducing treatment interruptions and preserving an anti-tumor effect. Bullous DAE may be limited to the skin or have systemic involvement with greater risk of morbidity and mortality. We present the epidemiology, diagnosis, pathogenesis, and management of bullous DAE secondary to anti-cancer therapies to enable clinicians to optimize management for these patients. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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20 pages, 1690 KiB

Open AccessReview

Delayed Drug Hypersensitivity Reactions: Molecular Recognition, Genetic Susceptibility, and Immune Mediators

by Mu-Tzu Chu, Wan-Chun Chang, Shih-Cheng Pao and Shuen-Iu Hung

Biomedicines 2023, 11(1), 177; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11010177 - 10 Jan 2023

Cited by 5 | Viewed by 4628

Abstract

Drug hypersensitivity reactions are classified into immediate and delayed types, according to the onset time. In contrast to the immediate type, delayed drug hypersensitivity mainly involves T lymphocyte recognition of the drug antigens and cell activation. The clinical presentations of such hypersensitivity are various and range from mild reactions (e.g., maculopapular exanthema (MPE) and fixed drug eruption (FDE)), to drug-induced liver injury (DILI) and severe cutaneous adverse reactions (SCARs) (e.g., Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP)). The common culprits of delayed drug hypersensitivity include anti-epileptics, antibiotics, anti-gout agents, anti-viral drugs, etc. Delayed drug hypersensitivity is proposed to be initiated by different models of molecular recognition, composed of drug/metabolite antigen and endogenous peptide, HLA presentation, and T cell receptor (TCR) interaction. Increasing the genetic variants of HLA loci and drug metabolic enzymes has been identified to be responsible for delayed drug hypersensitivity. Furthermore, preferential TCR clonotypes, and the activation of cytotoxic proteins/cytokines/chemokines, are also involved in the pathogenesis of delayed drug hypersensitivity. This review provides a summary of the current understanding of the molecular recognition, genetic susceptibility, and immune mediators of delayed drug hypersensitivity. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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16 pages, 482 KiB

Open AccessReview

A Review of the Systemic Treatment of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis

by Hua-Ching Chang, Tsung-Jen Wang, Ming-Hsiu Lin and Ting-Jui Chen

Biomedicines 2022, 10(9), 2105; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10092105 - 28 Aug 2022

Cited by 8 | Viewed by 6892

Abstract

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are uncommon but life-threatening diseases mostly caused by drugs. Although various systemic immunomodulating agents have been used, their therapeutic efficacy has been inconsistent. This study aimed to provide an evidence-based review of systemic immunomodulating treatments for SJS/TEN. We reviewed 13 systematic review and meta-analysis articles published in the last 10 years. The use of systemic corticosteroids and IVIg is still controversial. An increasing number of studies have suggested the effectiveness of cyclosporine and biologic anti-TNF-α in recent years. There were also some promising results of combination treatments. Further large-scale randomized controlled trials are required to provide more definitive evidence of the effectiveness of these treatments. The pathogenesis of SJS/TEN has been elucidated in recent years and advances in the understanding of SJS/TEN may inspire the discovery of potential therapeutic targets. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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18 pages, 1327 KiB

Open AccessReview

Immune Response in Regard to Hypersensitivity Reactions after COVID-19 Vaccination

by Ming-Hsiu Hsieh and Yukie Yamaguchi

Biomedicines 2022, 10(7), 1641; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10071641 - 08 Jul 2022

Cited by 4 | Viewed by 7548

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is a member of the genus Betacoronavirus. This virus was first detected in December 2019, and the situation quickly escalated to cause a global pandemic within a few months. COVID-19 had caused more than 5.5 million deaths as of January 2022. Hence, the urgency of effective vaccination contributed to the fastest rate of vaccine development seen to date (i.e., within 1.5 years). Despite reports of good vaccine efficacy without severe systemic reactions at the clinical trial stage, hypersensitivity reactions have been reported following worldwide vaccination campaigns. We provide a brief review regarding the structure of SARS-CoV-2. We also review the most acceptable types of vaccines in terms of safety profiles, namely the BNT162b2, mRNA-1273, and AZD1222 vaccines. This review aims to facilitate an understanding of the possible immune mechanisms regarding COVID-19-vaccination-related hypersensitivity reactions, such as thrombosis and thrombocytopenia, cutaneous adverse reactions, myocarditis, and perimyocarditis. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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16 pages, 1295 KiB

Open AccessReview

Immediate Hypersensitivity Reactions Induced by COVID-19 Vaccines: Current Trends, Potential Mechanisms and Prevention Strategies

by Shuen-Iu Hung, Ivan Arni C. Preclaro, Wen-Hung Chung and Chuang-Wei Wang

Biomedicines 2022, 10(6), 1260; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10061260 - 28 May 2022

Cited by 7 | Viewed by 8035

Abstract

As the world deals with the COVID-19 pandemic, vaccination remains vital to successfully end this crisis. However, COVID-19-vaccine-induced immediate hypersensitivity reactions presenting with potentially life-threatening systemic anaphylactic reactions are one of the reasons for vaccine hesitancy. Recent studies have suggested that different mechanisms, including IgE-mediated and non-IgE-mediated mast cell activation, may be involved in immediate hypersensitivity. The main culprits triggering hypersensitivity reactions have been suggested to be the excipients of vaccines, including polyethylene glycol and polysorbate 80. Patients with a history of allergic reactions to drugs, foods, or other vaccines may have an increased risk of hypersensitivity reactions to COVID-19 vaccines. Various strategies have been suggested to prevent hypersensitivity reactions, including performing skin tests or in vitro tests before vaccination, administering different vaccines for the primary and following boosters, changing the fractionated doses, or pretreating the anti-IgE antibody. This review discusses the current trends, potential mechanisms, and prevention strategies for COVID-19-vaccine-induced immediate hypersensitivity reactions. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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12 pages, 604 KiB

Open AccessReview

Thrombotic Complications after COVID-19 Vaccination: Diagnosis and Treatment Options

by Katharina Guetl, Reinhard Bernd Raggam and Thomas Gary

Biomedicines 2022, 10(6), 1246; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10061246 - 26 May 2022

Cited by 6 | Viewed by 2213

Abstract

Coronavirus disease 2019 (COVID-19) vaccines were developed a few months after the emergence of the pandemic. The first cases of vaccine-induced thrombotic complications after the use of adenoviral vector vaccines ChAdOx1 nCoV-19 by AstraZeneca, and Ad26.COV2.S by Johnson & Johnson/Janssen, were announced shortly after the initiation of a global vaccination program. In these cases, the occurrence of thrombotic events at unusual sites—predominantly located in the venous vascular system—in association with concomitant thrombocytopenia were observed. Since this new entity termed vaccine-induced thrombotic thrombocytopenia (VITT) shows similar pathophysiologic mechanisms as heparin-induced thrombocytopenia (HIT), including the presence of antibodies against heparin/platelet factor 4 (PF4), standard routine treatment for thrombotic events—arterial or venous—are not appropriate and may also cause severe harm in affected patients. Thrombotic complications were also rarely documented after vaccination with mRNA vaccines, but a typical VITT phenomenon has, to date, not been established for these vaccines. The aim of this review is to give a concise and feasible overview of diagnostic and therapeutic strategies in COVID-19 vaccine-induced thrombotic complications. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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14 pages, 1106 KiB

Open AccessReview

Hypersensitivity Reactions to Iodinated Contrast Media

by Tsu-Man Chiu and Sung-Yu Chu

Biomedicines 2022, 10(5), 1036; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051036 - 30 Apr 2022

Cited by 9 | Viewed by 4881

Abstract

At present, iodinated contrast media (ICM) are mostly non-ionic, have low osmolality, and are safe. Even if adverse drug reactions (ADRs) occur, most are chemo-toxic symptoms and require only observation or H1 antihistamines. However, rare, unpredictable, and even life-threatening hypersensitivity can still occur. The aim of this review is to summarize the issues that all relevant staff need to know about and be able to respond to. The most significant risk factor for ICM hypersensitivity is a history of ICM hypersensitivity. For high-risk populations, we must cautiously weigh the advantages and disadvantages of premedication and be aware that breakthrough reactions may still occur. The best policy for patients with a history of severe ICM hypersensitivity is to avoid the same ICM. If ICM are inevitable, skin tests, in vitro tests, and drug provocation tests may help to find a feasible alternative that is safer. The severity of the hypersensitivity is correlated with the positivity rate of these tests, so there is no need for further investigations for patients with only mild reactions. We should also keep in mind that even excipients in ICM may induce hypersensitivity. Detailed, standardized documentation is essential for correct diagnosis and the prevention of future occurrence. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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22 pages, 730 KiB

Open AccessReview

Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS)/Drug-Induced Hypersensitivity Syndrome (DiHS)—Readdressing the DReSS

by Hannah Stirton, Neil H. Shear and Roni P. Dodiuk-Gad

Biomedicines 2022, 10(5), 999; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10050999 - 26 Apr 2022

Cited by 22 | Viewed by 4215

Abstract

Drug reaction with eosinophilia and systemic symptoms (DReSS), also known as drug-induced hypersensitivity syndrome (DiHS), is a severe, systemic, T cell mediated drug reaction with combinations of cutaneous, hematologic, and internal organ involvement. Pathogenesis of DReSS is multi-factorial, involving drug-exposure, genetic predisposition through specific human leukocyte antigen (HLA) alleles and metabolism defects, viral reactivation, and immune dysregulation. Clinical features of this condition are delayed, stepwise, and heterogenous, making this syndrome challenging to recognize and diagnose. Two sets of validated diagnostic criteria exist that can be employed to diagnose DReSS/DiHS. Methods to improve early recognition of DReSS and predict disease severity has been a recent area of research focus. In vitro and in vivo tests can be employed to confirm the diagnosis and help identify culprit drugs. The mainstay treatment of DReSS is prompt withdrawal of the culprit drug, supportive treatment, and immunosuppression depending on the severity of disease. We present a comprehensive review on the most recent research and literature on DReSS, with emphasis on pathogenesis, clinical features, diagnosis, confirmatory testing modalities, and treatment. Additionally, this summary aims to highlight the differing viewpoints on this severe disease and broaden our perspective on the condition known as DReSS. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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22 pages, 5777 KiB

Open AccessReview

Immunogenicity, Effectiveness, and Safety of COVID-19 Vaccines in Rheumatic Patients: An Updated Systematic Review and Meta-Analysis

by Kuo-Tung Tang, Bo-Chueh Hsu and Der-Yuan Chen

Biomedicines 2022, 10(4), 834; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10040834 - 01 Apr 2022

Cited by 16 | Viewed by 3132

Abstract

Background: Vaccination is one of the most important measures worldwide to halt the spread of the corona virus disease 2019 (COVID-19). However, the efficacy and safety of these vaccines in rheumatic patients are not well explored. Therefore, we conducted a systematic review and meta-analysis. Methods: We performed a literature search of the PubMed and EMBASE databases on 17 November 2021. Forty-seven studies relevant to the immunogenicity, efficacy/effectiveness, and safety of COVID-19 vaccines were selected. Results: Our results demonstrated that COVID-19 vaccination is effective in protecting rheumatic patients from severe illness caused by the virus. Both the humoral and cellular immunogenicity of vaccines were impaired in rheumatic patients, which were greatly enhanced after the second vaccine dose. Receiving anti-CD20 therapy was associated with impaired humoral immunogenicity. Adverse events due to COVID-19 vaccines in rheumatic patients were similar to those in healthy controls, except for an increased incidence of arthralgia. The incidence of disease flares after COVID-19 vaccination was low. Conclusion: Our systematic review indicated the importance of full vaccination in rheumatic patients. Withholding anti-CD20 therapy was found to be potentially beneficial for the immunogenicity. Furthermore, the vaccines were found to be safe in general. Despite significant heterogeneity between studies, we recommend that rheumatic patients receive these vaccines amidst the global pandemic. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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