| 期刊全称 | Advances in Diagnosis and Management of Cutaneous Adverse Drug Reactions | | 期刊简称 | Current and Future T | | 影响因子2023 | Neil H. Shear,Roni P. Dodiuk-Gad | | 视频video | | | 发行地址 | Clear clinical scenarios help guide the reader to understand the science and treatment of cutaneous drug reactions.Special chapters on the pharmacology, immunology and genetics of cutaneous drug erupt | | 图书封面 |  | | 影响因子 | This resource guides prescribers, pharmacists, and regulators with an update on the recent expansion of basic and clinical knowledge that forms a framework for understanding cutaneous reactions. This understanding will lead, in turn, to better outcomes and decisions in treatment and management, both in the clinic and in the life cycle of drug development..The skin is a common target for adverse drug events and even mild rashes can be part of life-threatening syndromes. Patients and practitioners often face important decisions about therapy after a drug eruption, including treatment, cross-reactivity with future pharmaceuticals, genetic considerations and dealing with long-term sequelae after a reaction. An international team of experts and leaders in the field share their story and insights into the scientific details and relevant clinical context.. | | Pindex | Book 2019 |
| 1 |
Front Matter |
|
|
Abstract
|
| 2 |
|
|
|
Abstract
|
| 3 |
Introduction: Classification, Terminology, Epidemiology, and Etiology of Cutaneous Adverse Drug Reac |
Maja Mockenhaupt |
|
Abstract
Whenever a cutaneous adverse drug reactions (cADR) is suspected, it is important to establish the dermatological diagnosis, since reaction patterns may differ in causality, time latency between the beginning of drug use and reaction onset, and prognosis. Few epidemiologic studies have been performed on frequent non-life-threatening cADR, such as maculopapular exanthema, fixed drug eruption, and urticaria. For rare but life-threatening severe cutaneous adverse reactions, e.g., Stevens-Johnson syndrome/toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms, several epidemiologic studies have been or are currently performed. They allow for estimation of incidence rates, demographic data, and drug risks.
|
| 4 |
|
|
|
Abstract
|
| 5 |
Immunology of Cutaneous Adverse Drug Reactions |
Chuang-Wei Wang,Shuen-Iu Hung |
|
Abstract
Cutaneous adverse drug reactions (cADR) range from mild skin rash to life-threatening severe cutaneous adverse reactions (SCAR), which constitute a major clinical problem worldwide. Cutaneous adverse drug reactions show different clinical presentations, and most of them involve T cell-mediated immune response specific against drug/metabolite antigens, leading to the various phenotypes of cADR. This chapter focuses on the immune pathogenesis and reviews the cutting edge research on the molecular interaction of the human leukocyte antigens (HLA)/drug/T cell receptors (TCR), mechanism of T cell activation, and the downstream immune signaling of cytotoxic proteins as well as dysregulated cytokines/chemokines in cADR. Understanding the molecular interaction and regulation gives us new insights into the immune pathomechanism, the biomarkers for early diagnosis, and disease prevention as well as the development of therapeutic targets for the treatments of cADR.
|
| 6 |
Pharmacogenomics and Cutaneous Adverse Drug Reactions |
Ren-You Pan,Chun-Bing Chen,Wen-Hung Chung |
|
Abstract
Cutaneous adverse drug reactions (cADRs) are unpredictable and may range from mild maculopapular exanthema (MPE) to life-threatening severe cutaneous adverse drug reactions (SCARs), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Increasing pharmacogenomic studies showed specific . alleles are strongly associated with cADRs. The pathogenic checkpoints of cADRs include genetic polymorphisms affecting the immune synapse of HLA/drugs/T cell receptor interactions, specific . loci, T cell-mediated responses, and drug metabolism. Recently, pharmacogenomic screening for specific . alleles or high-risk genes prior to drug prescriptions to prevent cADRs has been widely implemented in clinical practice.
|
| 7 |
Viral Reactivation in Cutaneous Adverse Drug Reactions |
Tetsuo Shiohara,Yoko Kano,Yoshiko Mizukawa,Yumi Aoyama |
|
Abstract
Viral infections are likely to act as an inducible trigger of cutaneous adverse drug reactions (cADRs) in an HLA-associated manner. The most likely candidate involved in the development of cADRs is the family .. Although reactivation of herpesviruses observed in cADRs is generally regarded as the result, but not the cause, of general immune dysregulation in cADRs, we also discuss the alternative possibility that the reactivation may be a causal factor in the pathogenesis. If so, the implications could open up new areas for potential therapeutic intervention in cADRs.
|
| 8 |
Using Technology to Learn About Immunology of Cutaneous Adverse Drug Reactions |
Ryan J. Schutte,David A. Ostrov |
|
Abstract
Analysis of genes associated with cADRs revealed strong associations with specific HLA alleles. Since HLA molecules function in presentation of antigens to T cells, these data suggested immunological mechanisms in which drugs trigger cADRs by stimulation of pathogenic T cells through HLA-restricted T-cell recognition events. Application of biochemical, biophysical, and structure-based molecular docking technologies has the potential to gain new insight into mechanisms of drug hypersensitivity. Abacavir hypersensitivity syndrome was strongly associated with HLA-B*57:01 and provides an example of how technology can provide evidence for mechanisms that promote immunologically mediated adverse events.
|
| 9 |
|
|
|
Abstract
|
| 10 |
Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (Epithelial Necrolysis) |
Jean-Claude Roujeau |
|
Abstract
Incidence of epithelial necrolysis (EN) is approximately two cases/million inhabitants/year. Adult women are overrepresented, and in childhood the sex ratio is more equal. The diagnosis of EN is often clinically apparent on examination of the skin and mucous membranes. Skin pathology helps differentiation from other blistering diseases. A prognosis score (SCORTEN) estimates the risk of death and the emergency of transfer to specialized wards (intensive care unit (ICU), Burn Units). A few “high-risk” medications cause close to 50% of cases (allopurinol, sulfamethoxazole, lamotrigine, carbamazepine, phenytoin, phenobarbital, .). Immediate withdrawal of suspect drug(s) and symptomatic therapeutic measures gives similar outcomes to those used in extensive burns. Cyclosporine A and etanercept likely decrease mortality.
|
| 11 |
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) |
Sylvia H. Kardaun |
|
Abstract
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a delayed, potentially life-threatening, hypersensitivity reaction characterized by a widespread, long-lasting skin eruption, fever, lymphadenopathy, hematological abnormalities, and organ involvement. Time to onset and course are relatively long; relapses may occur. Clinical and biological variability make DRESS a challenging diagnosis. Pathogenesis is not exactly known, but probably reflects a complex interplay of drug and viral-related factors in which genetics and abnormal metabolic pathways of drugs play an important role. Although associated with many drugs, DRESS is mainly observed after a limited number of “high risk” drugs. Early recognition, prompt withdrawal of the culprit, and treatment with corticosteroids are the mainstay of management.
|
| 12 |
Acute Generalized Exanthematous Pustulosis |
Sima Halevy |
|
Abstract
Acute generalized exanthematous pustulosis (AGEP) is a rare, severe, pustular reaction pattern, attributed mainly to drugs. Other triggers such as infections, spider bite, and contact sensitivity have been implicated. AGEP is characterized by typical morphology, unique histology, and a rapid clinical course. The AGEP validation score (EuroSCAR group criteria) is a useful tool for establishing the diagnosis. The immune pathogenesis involves drug-specific T-cells, neutrophils, and the release of cytokines/chemokines (i.e., IL-8/CXCL8). In view of the remarkable clinical and histological similarity between AGEP and pustular psoriasis, the genetic basis of AGEP should be further evaluated.
|
| 13 |
Urticarial Reactions to Drugs |
Daniel F. Carr |
|
Abstract
Urticarial reactions are characterised by recurrent pruritic edematous lesions (wheals). They are broadly categorised into three subtypes: acute urticaria with reactions lasting <6 weeks; chronic urticaria which is characterised by continuous or persistent symptoms for >6 weeks; and contact urticaria, an immediate reaction to topical application of an agent which resolves within 2 h. Urticarial reactions can occur to a wide range of drugs but are most commonly with penicillins and NSAIDs. The pathogenic mechanism of urticarial reactions can be divided into immunological (Type I, IgE-mediated or Type III complement activation) and non-immunological (degranulation of mast cells).
|
| 14 |
Dermatologic Adverse Events from Cancer Treatments |
Jennifer Wu,Alina Markova,Mario E. Lacouture |
|
Abstract
The incidences of adverse events to cancer treatments have increased as new treatments are being developed. Dermatologic adverse events (dAEs) strongly impact patients’ quality of life (QoL). Severe dAEs can result in dose reduction or discontinuation, which may compromise clinical outcomes and even lead to life-threatening conditions. Prevention, early diagnosis, and proper management of dAEs are crucial for optimizing anticancer response and maintaining QoL. This chapter addresses dAEs induced by cytotoxic and targeted therapies, radiotherapy, stem cell transplantation, immunotherapies, and CAR-T cell therapy. Proposed underling mechanisms and recommended treatment approaches for these dAEs are presented.
|
| 15 |
Cutaneous Adverse Drug Reactions in Pediatric Population |
Ilan Fridental,Yaron Finkelstein |
|
Abstract
Cutaneous adverse drug reactions (CADR) are the most common drug reactions in the pediatric population. Several aspects of CADR and other rashes are more unique to children and impact the diagnosis and management of CADRs in this population. Such factors include different age groups, each with unique features, concurrent viral/bacterial illnesses which could be associated with an exanthem and age-specific pharmacokinetics. The proportional dominance of offending drug classes is different than in adults—anti-infectives make the majority, followed by antipyretics and antiepileptics. In this chapter, unique CADR features in the pediatric population are discussed, and a morphologic approach, based on simple and complex/severe eruptions, is suggested.
|
| 16 |
Cutaneous Drug Reactions in the Elderly |
James W. S. Young |
|
Abstract
Cutaneous adverse drug reactions (CADRs) often have unanticipated and far-reaching consequences for the elderly patient, which may persist long after the initial event. The reasons for this are related to the presence of polypharmacy, multimorbidity, frailty, and geriatric syndromes in the elderly. Involvement of a geriatrician may be beneficial in the identification of previously unidentified geriatric issues and minimization of treatment-related adverse outcomes.
|
| 17 |
Cutaneous Adverse Drug Reactions in Human Immunodeficiency Virus Infection |
Rannakoe J. Lehloenya,Jonny Peter |
|
Abstract
CADR is more common in HIV-infected persons, although the incidence is declining because of the new safer drugs and early initiation of antiretroviral therapy. The presentation and clinical course does not seem to differ from that in the general population. Antiretrovirals, antituberculosis drugs, and drugs for treating opportunistic infections are most commonly implicated. HIV-associated CADR poses major diagnostic and management challenges because of polypharmacy, overlapping drug toxicities, drug interactions, overlap of CADR with other diseases, and limited alternative drugs. We discuss pragmatic management strategies of HIV-associated CADR focusing on resource-limited settings, where HIV infection and associated CADR are most common.
|
| 18 |
Cutaneous Adverse Drug Reactions from Antituberculosis Treatment |
Jonny Peter,Rannakoe J. Lehloenya |
|
Abstract
Effective treatment for drug-sensitive TB remains a long, multidrug endeavor. Therapeutic complexity is increased by HIV coinfection (>60% of incident TB cases are co-infected in HIV/TB endemic settings) and the growing burden of multi- and extremely drug-resistant TB (MDR- and XDR-TB). CADRs are common adverse reactions in both drug-sensitive and resistant anti-TB regimens, and the majorities are delayed T-cell-mediated reactions. Individual anti-TB drugs cause different CADR phenotypes of varying severity, while SCAR phenotypes such as DRESS, SJS/TEN, and LDE have been associated with many chemically different anti-TB drugs. The key management challenges include (1) multiple possible offending drugs, with a lack of accurate diagnostic testing, (2) high TB-related mortality with prolonged treatment interruptions, and (3) not unnecessarily excluding effective non-culprit anti-TB drugs in CADR patients. We discuss the spectrum of anti-TB drug-associated CADRs and offending drugs, as well as the pragmatic utility of drug provocation testing to identify culprit drugs and minimize treatment interruptions.
|
| 19 |
|
|
|
Abstract
|
| 20 |
Practical Approach to Diagnosis and Management of Cutaneous Adverse Drug Reactions |
Cristina Olteanu,Neil H. Shear,Roni P. Dodiuk-Gad |
|
Abstract
Drug eruptions have a wide spectrum of clinical manifestations, are caused by various drugs, and result from varied pathophysiological mechanisms. Hence, their diagnosis and management is challenging. Drug eruptions can range from a mild, simple eruption involving only the skin to severe complex eruptions with systemic involvement, such as toxic epidermal necrolysis. Systemic involvement should be explored even in a mild cutaneous eruption due to a drug since the severity of skin manifestation does not necessarily mirror the severity of the systemic involvement. This chapter aims to provide a practical approach to a patient with a suspected drug eruption.
|
|
|
发表于 2025-3-21 20:02:08
