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Therapie 2024Cutaneous adverse drug reactions (ADRs) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality....
Cutaneous adverse drug reactions (ADRs) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Maculopapular exanthema and urticaria are the most common types of cutaneous ADR. Serious cutaneous ADRs, which may cause permanent sequelae or have fatal outcome, may represent 2% of all cutaneous ADR and must be quickly identified to guide their management. These serious reactions include bullous manifestations (epidermal necrolysis i.e. Stevens-Johnson syndrome and toxic epidermal necrolysis), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Some risk factors for developing cutaneous ADRs have been identified, including immunosuppression, autoimmunity or genetic variants. All drugs can cause cutaneous ADRs, the most commonly implicated being antibiotics (especially aminopenicillins and sulfonamides), anticonvulsants, allopurinol, antineoplastic drugs, non-steroidal anti-inflammatory drugs and iodinated contrast media. Pathophysiology is related to immediate or delayed "idiosyncratic" immunologic mechanisms, i.e., usually not related to dose, and pharmacologic/toxic mechanisms, commonly dose-dependent and/or time-dependent. If an immuno-allergic mechanism is suspected, allergological explorations (including epicutaneous patch testing and/or intradermal test) are often possible to clarify drug causality, however these have a variable sensitivity according to the drug and to the ADR type. No in vivo or in vitro test can consistently confirm the drug causality. To determine the origin of a rash, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis (especially infectious etiologies) is required, completed with a literature search. Reporting to pharmacovigilance system is therefore essential both to analyze drug causality at individual level, and to contribute to knowledge of the drug at population level, especially for serious cutaneous ADRs or in cases involving newly marketed drugs.
Topics: Humans; Skin; Stevens-Johnson Syndrome; Anti-Bacterial Agents; Acute Generalized Exanthematous Pustulosis; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37980248
DOI: 10.1016/j.therap.2023.09.011 -
Current Opinion in Allergy and Clinical... Aug 2021An update of the pharmacogenetic risk factors associated with T-cell-mediated delayed hypersensitivity reactions. (Review)
Review
PURPOSE OF REVIEW
An update of the pharmacogenetic risk factors associated with T-cell-mediated delayed hypersensitivity reactions.
RECENT FINDINGS
Recent HLA associations relevant to our understanding of immunopathogenesis and clinical practice include HLA-B∗13:01 with co-trimoxazole-induced SCAR, and HLA-A∗32:01 with vancomycin-DRESS, for which an extended HLA class II haplotype is implicated in glycopeptide antibiotic cross-reactivity. Hypoactive variants of ERAP1, an enzyme-trimming peptide prior to HLA loading, are now associated with protection from abacavir-hypersensitivity in HLA-B∗57:01+ patients, and single-cell sequencing has defined the skin-restricted expansion of a single, public and drug-reactive dominant TCR across patients with HLA-B∗15:02-restricted carbamazepine-induced SJS/TEN. More recent strategies for the use of HLA and other risk factors may include risk-stratification, early diagnosis, and diagnosis in addition to screening.
SUMMARY
HLA is necessary but insufficient as a risk factor for the development of most T-cell-mediated reactions. Newly emerged genetic and ecological risk factors, combined with HLA-restricted response, align with underlying immunopathogenesis and drive towards enhanced strategies to improve positive-predictive and negative-predictive values. With large population-matched cohorts, genetic studies typically focus on populations that have been readily accessible to research studies, but it is now imperative to address similar risk in globally relevant and understudied populations.
Topics: Aminopeptidases; Drug Hypersensitivity; HLA-B Antigens; Humans; Minor Histocompatibility Antigens; Pharmacogenetics; Stevens-Johnson Syndrome; T-Lymphocytes
PubMed: 34039850
DOI: 10.1097/ACI.0000000000000754 -
American Journal of Respiratory and... Mar 2022The term "advanced sarcoidosis" is used for forms of sarcoidosis with a significant risk of loss of organ function or death. Advanced sarcoidosis often involves the lung... (Review)
Review
The term "advanced sarcoidosis" is used for forms of sarcoidosis with a significant risk of loss of organ function or death. Advanced sarcoidosis often involves the lung and is described as "advanced pulmonary sarcoidosis" (APS), which includes advanced pulmonary fibrosis, associated complications such as bronchiectasis and infections, and pulmonary hypertension. Although APS affects a small proportion of patients with sarcoidosis, it is the leading cause of poor outcomes, including death. Here we review the major patterns of APS with a focus on the current management as well as potential approaches for improved outcomes for this most serious sarcoidosis phenotype.
Topics: Bronchiectasis; Humans; Lung; Pulmonary Fibrosis; Sarcoidosis; Sarcoidosis, Pulmonary
PubMed: 34813386
DOI: 10.1164/rccm.202106-1366CI -
The Journal of Allergy and Clinical... Jun 2021
Topics: Humans; Hypersensitivity, Delayed; Piperacillin; Piperacillin, Tazobactam Drug Combination
PubMed: 34112492
DOI: 10.1016/j.jaip.2021.03.025 -
Cutis Sep 2023Historically, US servicemembers have faced unique environmental hazards that may increase their risk for developing sarcoidosis. Cutaneous sarcoidosis is the most common... (Review)
Review
Historically, US servicemembers have faced unique environmental hazards that may increase their risk for developing sarcoidosis. Cutaneous sarcoidosis is the most common extrapulmonary manifestation of sarcoidosis and can precede systemic manifestations of the disease. In this article, we review the literature to examine the risk factors and incidence of sarcoidosis in post-9/11 veterans as well as provide recommendations for workup and management. Importantly, we also highlight that sarcoidosis is a presumptive diagnosis under the recently enacted Promise to Address Comprehensive Toxics (PACT) Act and may be service connected. Veterans with sarcoidosis should be referred to the US Department of Veterans Affairs.
Topics: Humans; Veterans; Sarcoidosis; Risk Factors; Incidence; Military Personnel
PubMed: 37903400
DOI: 10.12788/cutis.0852 -
British Journal of Hospital Medicine... Oct 2020New clinical practice guidelines for sarcoidosis provide recommendations to address uncertainties commonly confronted by clinicians, but highlight the need for good...
New clinical practice guidelines for sarcoidosis provide recommendations to address uncertainties commonly confronted by clinicians, but highlight the need for good quality clinical research for this 'neglected' inflammatory disease.
Topics: Humans; Practice Guidelines as Topic; Sarcoidosis
PubMed: 33135927
DOI: 10.12968/hmed.2020.0364 -
The Journal of Allergy and Clinical... Jul 2023
Topics: Humans; Drug Hypersensitivity; Hypersensitivity, Delayed
PubMed: 37019391
DOI: 10.1016/j.jaci.2023.03.024 -
Clinical and Experimental Dermatology Dec 2019Contrast media (CM) are an indispensable part of modern medical imaging. Adverse reactions to CM are uncommon, but frequently involve cutaneous symptoms. This two-part... (Review)
Review
Contrast media (CM) are an indispensable part of modern medical imaging. Adverse reactions to CM are uncommon, but frequently involve cutaneous symptoms. This two-part article reviews adverse events secondary to CM that are relevant to the practising dermatologist. Part 1 covers the classification of CM, immediate hypersensitivity reactions to CM and the newly described condition, gadolinium deposition disease. Given that there has only been two case reports to our knowledge of a delayed adverse reaction to gadolinium-based CM, this second part will focus on cutaneous delayed reactions caused by iodinated CM (ICM). Delayed hypersensitivity reactions to ICM commonly present as maculopapular exanthems, but more rarely, they can manifest as fixed drug eruptions, acute generalized exanthematous pustulosis, drug-related eosinophilia and systemic symptoms, Stevens-Johnson syndrome/toxic epidermal necrolysis, symmetrical drug-related intertriginous and flexural exanthema, graft-versus-host disease, vasculitis and iododerma. Delayed reactions to ICM may be underdiagnosed, as cutaneous symptoms may be attributed to oral medications, particularly if patients are on multiple drugs.
Topics: Acute Generalized Exanthematous Pustulosis; Aged; Contrast Media; Exanthema; Female; Humans; Hypersensitivity, Delayed; Iodine; Male; Middle Aged; Skin Diseases; Stevens-Johnson Syndrome
PubMed: 31162717
DOI: 10.1111/ced.13991 -
International Journal of Molecular... Jul 2023In recent years, there has been a noticeable development in oncological treatment, including chemotherapy and biological treatment. Despite their significant... (Review)
Review
In recent years, there has been a noticeable development in oncological treatment, including chemotherapy and biological treatment. Despite their significant effectiveness, they are not free from side effects, such as allergic and dermatological reactions. These reactions can vary in severity and outcome, including potential death. Examples, among others, are type I-IV hypersensitivity reactions of various origins and skin reactions including rashes, itching and redness, but also severe cutaneous syndromes. Due to the therapy used, these may include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis. In some cases, it is necessary to interrupt therapy, which may result in a poorer outcome and shorten the patient's survival. This paper reviews various types of research documents published since 2016. It aims to systematize the latest knowledge and highlight the need for further research into ways to avoid adverse reactions.
Topics: Humans; Skin; Stevens-Johnson Syndrome; Acute Generalized Exanthematous Pustulosis; Drug Hypersensitivity Syndrome; Eosinophilia
PubMed: 37511017
DOI: 10.3390/ijms241411257 -
Annals of Allergy, Asthma & Immunology... Jan 2022
Topics: Adult; Aminophenols; Benzodioxoles; Chloride Channel Agonists; Desensitization, Immunologic; Female; Humans; Hypersensitivity, Delayed; Indoles; Middle Aged; Outpatients; Pyrazoles; Pyridines; Pyrrolidines; Quinolones
PubMed: 34391901
DOI: 10.1016/j.anai.2021.08.010