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The Journal of Allergy and Clinical... 2019Sulfonamide antimicrobials are commonly reported as causing drug allergy and have been implicated in a variety of hypersensitivity reactions including immediate... (Review)
Review
Sulfonamide antimicrobials are commonly reported as causing drug allergy and have been implicated in a variety of hypersensitivity reactions including immediate IgE-mediated reactions, benign T-cell-mediated rashes, and severe cutaneous adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. Cross-reactivity is unlikely between sulfonamide antimicrobials and sulfonamide non-antimicrobials. In patients who develop reactions to a sulfonamide non-antimicrobial, there is no evidence to suggest that sulfonamide antimicrobials and other sulfonamide non-antimicrobials would cross-react. Although immediate skin testing can be performed in patients with histories of immediate reactions, they are infrequently positive and wane over time. Delayed skin testing including patch tests to sulfonamides is rarely positive. Drug challenges are a useful tool for patients with both immediate and delayed reactions to sulfonamides. The role of sulfamethoxazole desensitization is controversial as rates of hypersensitivity reactions are similar between desensitization and drug challenge.
Topics: Anti-Infective Agents; Chemoprevention; Cross Reactions; Desensitization, Immunologic; Drug Hypersensitivity; Drug Hypersensitivity Syndrome; HIV Infections; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Pneumonia, Pneumocystis; Radioallergosorbent Test; Skin Tests; Stevens-Johnson Syndrome; Sulfamethoxazole; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 31495421
DOI: 10.1016/j.jaip.2019.05.034 -
Immunology and Allergy Clinics of North... Aug 2023Drug hypersensitivity reactions are a diverse group of reactions mediated by the immune system after exposure to a drug. The Gell and Coombs classification divides... (Review)
Review
Drug hypersensitivity reactions are a diverse group of reactions mediated by the immune system after exposure to a drug. The Gell and Coombs classification divides immunologic DHRs into 4 major pathophysiologic categories based on immunologic mechanism. Anaphylaxis is a Type I hypersensitivity reaction that requires immediate recognition and treatment. Severe cutaneous adverse reactions (SCARs) are a group of dermatologic diseases that result from a Type IV hypersensitivity process and include drug reaction with eosinophilia and systemic symptom (DRESS) syndrome, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). Other types of reactions are slow to develop and do not always require rapid treatment. Emergency physicians should have a good understanding of these various types of drug hypersensitivity reactions and how to approach the patient regarding evaluation and treatment.
Topics: Humans; Drug Hypersensitivity; Stevens-Johnson Syndrome; Skin; Acute Generalized Exanthematous Pustulosis; Hypersensitivity, Delayed
PubMed: 37394254
DOI: 10.1016/j.iac.2022.10.005 -
Clinical Reviews in Allergy & Immunology Jun 2022Hypersensitivity reactions including IgE-mediated and delayed cell-mediated reactions to aminoglycosides, clindamycin, linezolid, and metronidazole are rare. For... (Review)
Review
Hypersensitivity reactions including IgE-mediated and delayed cell-mediated reactions to aminoglycosides, clindamycin, linezolid, and metronidazole are rare. For aminoglycosides, allergic contact dermatitis is the most frequent reaction for which patch testing can be a useful step in evaluation. For clindamycin, delayed maculopapular exanthems are the most common reactions. There are case reports of clindamycin associated with drug rash with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), acute febrile neutrophilic dermatosis, and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). For linezolid, cases of hypersensitivity were exceedingly rare and included urticaria, angioedema, anaphylaxis, delayed rashes, and DRESS. For metronidazole, only rare cases were found across a broad spectrum of reactions including allergic contact dermatitis, fixed drug eruption, angioedema, anaphylaxis, serum sickness-like reaction, SJS/TEN, AGEP, SDRIFE, and a possible case of DRESS. IgE-mediated reactions and anaphylaxis to these types of antibiotics are uncommon, and reports of skin testing concentrations and desensitization protocols are largely limited to case reports and series. Non-irritating skin testing concentrations have been reported for gentamycin, tobramycin, and clindamycin. Published desensitization protocols for intravenous and inhaled tobramycin, oral clindamycin, intravenous linezolid, and oral and intravenous metronidazole have also been reported and are reviewed.
Topics: Aminoglycosides; Anaphylaxis; Angioedema; Anti-Bacterial Agents; Clindamycin; Dermatitis, Allergic Contact; Drug Eruptions; Drug Hypersensitivity; Eosinophilia; Humans; Hypersensitivity, Delayed; Immunoglobulin E; Linezolid; Metronidazole; Tobramycin
PubMed: 34910281
DOI: 10.1007/s12016-021-08878-x -
Clinical Reviews in Allergy & Immunology Jun 2022Beta-lactam antibiotics are the most commonly reported drug allergy in adults and children. More than 95% of those with reported allergy labels to beta lactams are not... (Review)
Review
Beta-lactam antibiotics are the most commonly reported drug allergy in adults and children. More than 95% of those with reported allergy labels to beta lactams are not confirmed when subjected to allergy testing. Beta lactam antibiotics are associated with a wide spectrum of immediate and delayed drug hypersensitivity reactions. The latency period to symptoms and clinical presentation aids in the causality assessment. Risk stratification based on diagnosis and timing then allows for appropriate management and evaluation. Skin prick testing, intradermal testing and oral challenge are well established for evaluation of immediate reactions. Delayed intradermal testing, patch testing and oral challenge can also be considered for evaluation of mild to moderate delayed reactions. Cross-reactivity between beta-lactams appears to be driven most commonly by a shared R1 side-chain. Standardized algorithms, protocols and pathways are needed for widespread implementation of a pragmatic and effective approach to patients reporting beta lactam allergy.
Topics: Adult; Anti-Bacterial Agents; Child; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Skin Tests; beta-Lactams
PubMed: 34767158
DOI: 10.1007/s12016-021-08903-z -
Allergy and Asthma Proceedings Nov 2019As the primary defense against pathogens, the immune system uses numerous strategies to ensure optimal protection for the host. When immune responses go awry, however,... (Review)
Review
As the primary defense against pathogens, the immune system uses numerous strategies to ensure optimal protection for the host. When immune responses go awry, however, they can cause great damage. "Hypersensitivity" is a broad term used to describe an excessive and/or pathogenic immune response to either foreign or self antigens. Gell and Coombs were the first to categorize hypersensitivity reactions into 4 types according to pathophysiology, but more recent insights into the mechanisms of these disorders have since modified the original classification system. This review describes the immune mechanisms involved in each of the modern Gell-Coombs categories.
Topics: Antigen-Antibody Reactions; Drug Hypersensitivity; Humans; Hypersensitivity; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Immunity, Cellular
PubMed: 31690397
DOI: 10.2500/aap.2019.40.4274 -
Current Problems in Dermatology 2015Tattoos cause a broad range of clinical problems. Mild complaints, especially sensitivity to sun, are very common and seen in 1/5 of cases. Medical complications are... (Review)
Review
Tattoos cause a broad range of clinical problems. Mild complaints, especially sensitivity to sun, are very common and seen in 1/5 of cases. Medical complications are dominated by allergy to tattoo pigment haptens or haptens generated in the skin, especially in red tattoos but also in blue and green tattoos. Symptoms are major and can be compared to cumbersome pruritic skin diseases. Tattoo allergies and local reactions show distinct clinical manifestations, with plaque-like, excessive hyperkeratotic, ulcero-necrotic, lymphopathic, neuro-sensory, and scar patterns. Reactions in black tattoos are papulo-nodular and non-allergic and associated with the agglomeration of nanoparticulate carbon black. Tattoo complications include effects on general health conditions and complications in the psycho-social sphere. Tattoo infections with bacteria, especially staphylococci, which may be resistant to multiple antibiotics, may be prominent and may progress into life-threatening sepsis. Contaminated tattoo ink is an open-window risk vector that can lead to epidemic tattoo infections across national borders due to contaminated bulk production. Hepatitis B and C and human immunodeficiency virus (HIV) transferred by tattooing remain a significant risk needing active prevention. It is noteworthy that cancer arising in tattoos, in regional lymph nodes, and in other organs due to tattoo pigments and ingredients has not been detected or noted as a significant clinical problem hitherto, despite millions of people being tattooed for decennia. Clinical observation and epidemiology disagree with register data, which indicate an increased risk of cancer due to chemical carcinogens present in some inks. Registers rely on chronic dosaging of cell lines and animals. However, tattooing in humans is essentially a single-dose exposure, which might explain the observed discrepancy.
Topics: Cicatrix; Color; Coloring Agents; Humans; Hypersensitivity, Delayed; Photosensitivity Disorders; Skin Diseases, Bacterial; Tattooing; Urticaria; Virus Diseases
PubMed: 25833625
DOI: 10.1159/000369645 -
Annals of the Rheumatic Diseases Mar 2022Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1...
OBJECTIVES
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1 (IL-1) or IL-6 in a small group of patients with Still's disease with atypical lung disease. We sought to characterise features of patients with Still's disease with DRESS compared with drug-tolerant Still's controls. We analysed human leucocyte antigen (HLA) alleles for association to inhibitor-related DHR, including in a small Kawasaki disease (KD) cohort.
METHODS
In a case/control study, we collected a multicentre series of patients with Still's disease with features of inhibitor-related DRESS (n=66) and drug-tolerant Still's controls (n=65). We retrospectively analysed clinical data from all Still's subjects and typed 94/131 for HLA. European Still's-DRESS cases were ancestry matched to International Childhood Arthritis Genetics Consortium paediatric Still's cases (n=550) and compared for HLA allele frequencies. HLA association also was analysed using Still's-DRESS cases (n=64) compared with drug-tolerant Still's controls (n=30). KD subjects (n=19) were similarly studied.
RESULTS
Still's-DRESS features included eosinophilia (89%), AST-ALT elevation (75%) and non-evanescent rash (95%; 88% involving face). Macrophage activation syndrome during treatment was frequent in Still's-DRESS (64%) versus drug-tolerant Still's (3%; p=1.2×10). We found striking enrichment for HLA-DRB1*15 haplotypes in Still's-DRESS cases versus INCHARGE Still's controls (p=7.5×10) and versus self-identified, ancestry-matched Still's controls (p=6.3×10). In the KD cohort, DRB1*15:01 was present only in those with suspected anakinra reactions.
CONCLUSIONS
DRESS-type reactions occur among patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes. Consideration of preprescription HLA typing and vigilance for serious reactions to these drugs are warranted.
Topics: Adult; Alleles; Antirheumatic Agents; Case-Control Studies; Drug Hypersensitivity Syndrome; Drug Tolerance; Female; HLA-DRB1 Chains; Haplotypes; Humans; Hypersensitivity, Delayed; Interleukin-1; Interleukin-6; Male; Mucocutaneous Lymph Node Syndrome; Retrospective Studies; Still's Disease, Adult-Onset
PubMed: 34789453
DOI: 10.1136/annrheumdis-2021-220578 -
Clinical Reviews in Allergy & Immunology Feb 2018Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered a delayed-type hypersensitivity reaction to drugs. They represent true medical... (Review)
Review
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered a delayed-type hypersensitivity reaction to drugs. They represent true medical emergencies and an early recognition and appropriate management is decisive for the survival. SJS/TEN manifest with an "influenza-like" prodromal phase (malaise, fever), followed by painful cutaneous and mucous membrane (ocular, oral, and genital) lesions, and other systemic symptoms. The difference between SJS, SJS/TEN overlap, and TEN is defined by the degree of skin detachment: SJS is defined as skin involvement of < 10%, TEN is defined as skin involvement of > 30%, and SJS/TEN overlap as 10-30% skin involvement. The diagnosis of different degrees of epidermal necrolysis is based on the clinical assessment in conjunction with the corresponding histopathology. The mortality rates for SJS and TEN have decreased in the last decades. Today, the severity-of-illness score for toxic epidermal necrolysis (SCORTEN) is available for SJS/TEN severity assessment. Drugs with a high risk of causing SJS/TEN are anti-infective sulfonamides, anti-epileptic drugs, non-steroidal anti-inflammatory drugs of the oxicam type, allopurinol, nevirapine, and chlormezanone. Besides conventional drugs, herbal remedies and new biologicals should be considered as causative agents. The increased risk of hypersensitivity reactions to certain drugs may be linked to specific HLA antigens. Our understanding of the pathogenesis of SJS/TEN has improved: drug-specific T cell-mediated cytotoxicity, genetic linkage with HLA- and non-HLA-genes, TCR restriction, and cytotoxicity mechanisms were clarified. However, many factors contributing to epidermal necrolysis still have to be identified, especially in virus-induced and autoimmune forms of epidermal necrolysis not related to drugs. In SJS/TEN, the most common complications are ocular, cutaneous, or renal. Nasopharyngeal, esophageal, and genital mucosal involvement with blisters, erosions as well as secondary development of strictures also play a role. However, in the acute phase, septicemia is a leading cause of morbidity and fatality. Pulmonary and hepatic involvement is frequent. The acute management of SJS/TEN requires a multidisciplinary approach. Immediate withdrawal of potentially causative drugs is mandatory. Prompt referral to an appropriate medical center for specific supportive treatment is of utmost importance. The most frequently used treatments for SJS/TEN are systemic corticosteroids, immunoglobulins, and cyclosporine A.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Cyclosporine; Humans; Hypersensitivity, Delayed; Immunoglobulins, Intravenous; Skin; Stevens-Johnson Syndrome; Sulfonamides
PubMed: 29188475
DOI: 10.1007/s12016-017-8654-z -
Journal of the American Academy of... May 2024Drug-induced hypersensitivity syndrome, also known as drug reaction with eosinophilia and systemic symptoms, is a severe cutaneous adverse reaction characterized by an... (Review)
Review
Drug-induced hypersensitivity syndrome, also known as drug reaction with eosinophilia and systemic symptoms, is a severe cutaneous adverse reaction characterized by an exanthem, fever, and hematologic and visceral organ involvement. The differential diagnosis includes other cutaneous adverse reactions, infections, inflammatory and autoimmune diseases, and neoplastic disorders. Three sets of diagnostic criteria have been proposed; however, consensus is lacking. The cornerstone of management is immediate discontinuation of the suspected drug culprit. Systemic corticosteroids remain first-line therapy, but the literature on steroid-sparing agents is expanding. Longitudinal evaluation for sequelae is recommended. Adjunctive tests for risk stratification and drug culprit identification remain under investigation. Part II of this continuing medical education activity begins by exploring the differential diagnosis and diagnosis of drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms and concludes with an evidence-based overview of evaluation and treatment.
Topics: Humans; Drug Hypersensitivity Syndrome; Eosinophilia; Skin; Adrenal Cortex Hormones; Fever
PubMed: 37516356
DOI: 10.1016/j.jaad.2023.02.073 -
Journal of the American Academy of... May 2024Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe cutaneous adverse reaction (SCAR)... (Review)
Review
Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part I. Epidemiology, pathogenesis, clinicopathological features, and prognosis.
Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe cutaneous adverse reaction (SCAR) characterized by an exanthem, fever, and hematologic and visceral organ involvement. Anticonvulsants, antibiotics, and allopurinol are the most common triggers. The pathogenesis involves a complex interplay between drugs, viruses, and the immune system primarily mediated by T-cells. DiHS/DRESS typically presents with a morbilliform eruption 2-6 weeks after drug exposure, and is associated with significant morbidity, mortality, and risk of relapse. Long-term sequelae primarily relate to organ dysfunction and autoimmune diseases. Part I of this continuing medical education activity on DiHS/DRESS provides an update on epidemiology, novel insights into pathogenesis, and a description of clinicopathological features and prognosis.
Topics: Humans; Drug Hypersensitivity Syndrome; Eosinophilia; Anticonvulsants; Skin; Prognosis
PubMed: 37516359
DOI: 10.1016/j.jaad.2023.02.072