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3.
Nat Rev Dis Primers ; 10(1): 30, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664435

ABSTRACT

Severe cutaneous adverse reactions (SCARs), which include Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also known as drug-induced hypersensitivity syndrome), acute generalized exanthematous pustulosis, and generalized bullous fixed drug eruption, are life-threatening conditions. The pathogenesis of SCARs involves T cell receptors recognizing drug antigens presented by human leukocyte antigens, triggering the activation of distinct T cell subsets. These cells interact with keratinocytes and various immune cells, orchestrating cutaneous lesions and systemic manifestations. Genetic predisposition, impaired drug metabolism, viral reactivation or infections, and heterologous immunity influence SCAR development and clinical presentation. Specific genetic associations with distinct SCAR phenotypes have been identified, leading to the implementation of genetic screening before prescription in various countries to prevent SCARs. Whilst systemic corticosteroids and conventional immunomodulators have been the primary therapeutic agents, evolving strategies, including biologics and small molecules targeting tumour necrosis factor, different cytokines, or Janus kinase signalling pathways, signify a shift towards a precision management paradigm that considers individual clinical presentations.


Subject(s)
Stevens-Johnson Syndrome , Humans , Stevens-Johnson Syndrome/physiopathology , Stevens-Johnson Syndrome/diagnosis , Stevens-Johnson Syndrome/etiology , Drug Hypersensitivity Syndrome/diagnosis , Drug Hypersensitivity Syndrome/physiopathology , Drug Hypersensitivity Syndrome/etiology , Drug Eruptions/physiopathology , Drug Eruptions/diagnosis , Drug Eruptions/etiology , Acute Generalized Exanthematous Pustulosis/diagnosis , Acute Generalized Exanthematous Pustulosis/etiology , Acute Generalized Exanthematous Pustulosis/physiopathology
4.
JAAPA ; 37(5): 1-3, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38662900

ABSTRACT

ABSTRACT: Acute generalized exanthematous pustulosis (AGEP) is a rare, pustular rash that occurs most commonly after exposure to a medication (typically antibiotics or diltiazem). This case describes a patient who developed a widespread pustular eruption shortly after beginning empiric antibiotics for community-acquired pneumonia. Diagnosis of AGEP was difficult in this scenario due to the patient's pulmonary infection and atypical skin biopsy results. However, after AGEP was correctly identified, the offending agents were discontinued and the patient had subsequent resolution of her symptoms.


Subject(s)
Acute Generalized Exanthematous Pustulosis , Anti-Bacterial Agents , Humans , Acute Generalized Exanthematous Pustulosis/diagnosis , Acute Generalized Exanthematous Pustulosis/etiology , Female , Anti-Bacterial Agents/adverse effects , Community-Acquired Infections/drug therapy , Community-Acquired Infections/diagnosis , Middle Aged
5.
Australas J Dermatol ; 65(3): 243-253, 2024 May.
Article in English | MEDLINE | ID: mdl-38572842

ABSTRACT

BACKGROUND/OBJECTIVES: The immune checkpoint inhibitors (ICIs) have been increasingly associated with severe cutaneous adverse reactions (SCARs). These reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are uncommon but potentially lethal. Despite the severity of these reactions and growing association with the ICIs, their specific risk and mortality rates have been largely unexplored. METHODS: A case/non-case analysis was performed using data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine the reporting odds ratios (RORs) for ICI-associated SCARs cases under two conditions: (1) ICIs compared with all drugs in FAERS and (2) ICIs compared with a reference group of pooled anticancer drugs to control for underlying malignancy. RESULTS: A statistically significant ROR for SJS (ROR: 5.44), TEN (ROR: 5.81) and DRESS (ROR: 1.38) were identified under Condition 1. Under Condition 2, this significance was maintained for SJS (ROR: 7.31), TEN (ROR: 7.40) and DRESS (ROR: 3.90), and mild significance was identified for AGEP (ROR: 1.89). Mortality rates for the ICIs were increased compared with the anticancer medications (28.5% vs. 24.5% for SJS, 55.3% vs. 46% for TEN, 3.0% vs. 2.1% for AGEP and 7.1% vs. 6.1% for DRESS). CONCLUSIONS: Our results suggest an association between SCARs and the ICIs independent of cancer status.


Subject(s)
Adverse Drug Reaction Reporting Systems , Immune Checkpoint Inhibitors , Stevens-Johnson Syndrome , United States Food and Drug Administration , Humans , Immune Checkpoint Inhibitors/adverse effects , Adverse Drug Reaction Reporting Systems/statistics & numerical data , United States , Stevens-Johnson Syndrome/etiology , Drug Eruptions/etiology , Female , Male , Drug Hypersensitivity Syndrome/etiology , Middle Aged , Acute Generalized Exanthematous Pustulosis/etiology , Aged
8.
Dermatol Clin ; 42(2): 317-328, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38423690

ABSTRACT

Generalized pustular rashes have various etiologies and can be challenging to diagnose and manage at first presentation. The authors provide an in-depth analysis of common pustular skin eruptions including generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis, focusing on their pathophysiology, triggers, clinical presentation, diagnostic challenges, and management strategies. The article also highlights recent advances in genetic research and biologic therapies for GPP and the future directions in personalized medicine and prevention strategies.


Subject(s)
Acute Generalized Exanthematous Pustulosis , Psoriasis , Skin Diseases, Vesiculobullous , Humans , Acute Generalized Exanthematous Pustulosis/diagnosis , Acute Generalized Exanthematous Pustulosis/etiology , Acute Generalized Exanthematous Pustulosis/therapy , Psoriasis/diagnosis , Psoriasis/therapy , Skin , Skin Diseases, Vesiculobullous/chemically induced , Skin Diseases, Vesiculobullous/diagnosis , Skin Diseases, Vesiculobullous/therapy , Acute Disease , Chronic Disease
10.
J Cutan Med Surg ; 28(1): 51-58, 2024.
Article in English | MEDLINE | ID: mdl-38189282

ABSTRACT

BACKGROUND: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) are potentially life-threatening severe cutaneous adverse reactions (SCARs). Although the classical causal agents of SCARs (antibiotics, anticonvulsants, nonsteroidal anti-inflammatory drugs, and allopurinol) are well characterized, there has been little update to this list to account for newly marketed medications. OBJECTIVE: To provide an updated and stratified list of medications with significant reporting odds ratios (RORs) of SCARs. METHODS: A case/non-case analysis using the United States FDA Adverse Event Reporting System was performed. RESULTS: As expected, the prototypical medication classes made up the majority of reported cases of SJS, TEN, AGEP, and DRESS (77%, 64%, 75%, and 72%, respectively). In addition, several infrequently or previously undescribed classes/medications implicated in SCARs were identified to have significant ROR signals, including acetylcysteine, anticoagulants, diuretics, immunotherapies, proton pump inhibitors, antivirals, and antifungals. Among these reported for SJS were acetylcysteine (ROR: 64.38) and fluconazole (ROR: 17.13). For TEN, we identified furosemide (ROR: 26.32), spironolactone (ROR: 14.45), fluconazole (ROR: 30.21), amphotericin B (39.06), and acetylcysteine (ROR: 93.12). For AGEP, we identified acyclovir (ROR: 61.72), valacyclovir (ROR: 30.76), and enoxaparin (ROR: 27.37). For DRESS, we identified vemurafenib (ROR: 17.35), acyclovir (ROR: 30.63), abacavir (ROR: 26.62), raltegravir (ROR: 23.27), and valacyclovir (ROR: 21.77) to have strong reporting odds. CONCLUSION: Our analysis provides an updated tool for physicians to reference when identifying suspected SCARs and a basis for future studies to investigate atypical medication causality.


Subject(s)
Acute Generalized Exanthematous Pustulosis , Stevens-Johnson Syndrome , Humans , United States , Acetylcysteine , Cicatrix , Fluconazole , Valacyclovir , Stevens-Johnson Syndrome/etiology , Acute Generalized Exanthematous Pustulosis/etiology
12.
Curr Drug Saf ; 19(2): 218-223, 2024.
Article in English | MEDLINE | ID: mdl-37151075

ABSTRACT

INTRODUCTION: Paracetamol (Acetaminophen) is a very common OTC drug that is found in more than 200 OTC products sold as pain, cough and cold remedies. Paracetamol is commonly used as an antipyretic to reduce fever and as an alternative to Non-steroidal anti-inflammatory drugs (NSAIDs) that are contraindicated in certain patients to relieve mild-moderate pain. OBJECTIVE: This review article focuses on SJS, TEN, SJS/TEN overlap, AGEP, and DRESS syndromes associated with the use of paracetamol or paracetamol-containing products. METHODS: To find published articles relevant to paracetamol-associated SJS, TEN, AGEP, and DRESS, we searched the online databases Medline/Pubmed/PMC, Google Scholar, Science Direct, Ebsco, Scopus, Web of Science, Embase, and reference lists using keywords like Stevens-Johnson Syndrome, Acetaminophen, Paracetamol, Toxic epidermal necrolysis, Acute generalized exanthematous pustulosis, Drug reaction with eosinophilia and systemic symptoms. RESULTS: The paracetamol-associated SJS, TEN, SJS/TEN overlap, AGEP, and DRESS syndromes have been identified by a number of publications. CONCLUSION: When evaluating drug-induced hypersensitivity skin reactions, healthcare professionals, including prescribers, pharmacists, and others, should be aware of this rare risk. Patients who exhibit signs and symptoms of paracetamol-associated hypersensitivity should be referred to physicians by pharmacists for further treatment. At the first sign of a skin rash or other hypersensitivity reaction while taking paracetamol, patients should be told to stop taking it and see a doctor right away.


Subject(s)
Acute Generalized Exanthematous Pustulosis , Drug Hypersensitivity Syndrome , Stevens-Johnson Syndrome , Humans , Stevens-Johnson Syndrome/diagnosis , Drug Hypersensitivity Syndrome/diagnosis , Drug Hypersensitivity Syndrome/etiology , Acetaminophen/adverse effects , Pain
13.
J Dermatol ; 51(2): 287-293, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37334758

ABSTRACT

Cutis laxa presents as loose redundant skin folds and loss of dermal elastic tissue. Acquired cutis laxa (ACL) is characterized by later onset. It has been reported in association with various kinds of neutrophilic dermatoses, drugs, metabolic disorders, and autoimmune disorders. Acute generalized exanthematous pustulosis (AGEP) is usually classified as a severe cutaneous adverse reaction characterized by T cell-mediated neutrophilic inflammation. We previously reported a mild case of AGEP caused by gemcitabine in a 76-year-old man. Here, we report a case of ACL secondary to AGEP in this patient. He developed AGEP 8 days after gemcitabine administration. Four weeks after beginning chemotherapy, his skin had become atrophic, loose, and darkly pigmented in areas previously affected by AGEP. Histopathological examination revealed edema and perivascular lymphocytic infiltration but no neutrophilic infiltration in the upper dermis. Elastica van Gieson staining showed that the elastic fibers in all layers of the dermis were sparse and shortened. Electron microscopy showed elevated numbers of fibroblasts and altered elastic fibers with irregular surfaces. Finally, he was diagnosed with ACL secondary to AGEP. He was treated with topical corticosteroids and oral antihistamines. Skin atrophy decreased over 3 months. We summarize 36 cases (including our case) with ACL secondary to neutrophilic dermatosis. We discuss these clinical manifestations, causative neutrophilic disorders, treatments, and outcomes. The mean age of patients was 3.5 years. Five patients had an aortic lesion as systemic involvement. The most common causative neutrophilic disorders were Sweet syndrome (24 cases), followed by urticaria-like neutrophilic dermatosis (11 cases). There were no cases of AGEP except for our case. Although treatment for ACL secondary to neutrophilic dermatosis, such as dapsone, oral prednisolone, adalimumab, and plastic surgery were reported, ACL is generally refractory and irreversible. Our patient was considered reversibly cured due to the absence of continuous neutrophil-mediated elastolysis.


Subject(s)
Acute Generalized Exanthematous Pustulosis , Cutis Laxa , Dermatitis , Sweet Syndrome , Male , Humans , Child, Preschool , Aged , Acute Generalized Exanthematous Pustulosis/diagnosis , Acute Generalized Exanthematous Pustulosis/etiology , Acute Generalized Exanthematous Pustulosis/pathology , Gemcitabine , Skin/pathology , Sweet Syndrome/pathology , Dermatitis/pathology
15.
J Dermatol ; 51(1): 110-114, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37732499

ABSTRACT

Apalutamide is an antiandrogen used to treat prostate cancer. Although it sometimes induces mild cutaneous adverse events and occasionally severe ones, clinical differences between severe and mild cases remain unclear. To assess the risks in patients experiencing apalutamide-related cutaneous adverse events (ARCAEs), we aimed to characterize severe and mild ARCAEs in terms of onset time and lymphocyte transformation test (LTT) for apalutamide. We reviewed 41 ARCAE cases: 24 from our institute and 17 from the literature, comprising (i) eight severe cases including six with toxic epidermal necrolysis, one with acute generalized exanthematous pustulosis, and one with drug reaction with eosinophilia and systemic symptoms, and (ii) 33 mild cases. Patients with evere cases developed ARCAEs significantly earlier than patients with mild cases (5.2 vs 9.6 weeks). No severe cases appeared ≥8 weeks after initiation of apalutamide. LTTs showed positive results in two of seven mild cases (28.6%) and four of four severe cases (100.0%). In conclusion, we found that severe ARCAEs are characterized by earlier onset and LTT positivity. Dermatologists and urologists should pay special attention to patients who develop ARCAEs <8 weeks after initiating apalutamide and/or show positive LTT results.


Subject(s)
Acute Generalized Exanthematous Pustulosis , Prostatic Neoplasms , Stevens-Johnson Syndrome , Male , Humans , Stevens-Johnson Syndrome/etiology , Stevens-Johnson Syndrome/diagnosis , Skin , Acute Generalized Exanthematous Pustulosis/diagnosis , Prostatic Neoplasms/drug therapy
16.
J Cosmet Dermatol ; 23(3): 725-730, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37899662

ABSTRACT

INTRODUCTION: Several vaccine-related cutaneous adverse events occurred following the widespread use of vaccines to prevent coronavirus disease 2019 (COVID-19). This case series reports 25 patients with de novo or accentuated dermatologic conditions after receiving the Sinopharm, Sputnik V, AstraZeneca, or BIV1-CovIran vaccine in Iran. METHODS AND RESULTS: Twenty-five eligible patients with a mean age of 46.80 years were investigated. The cutaneous adverse events included pityriasis rosea, zoster, viral exanthema, urticaria, bullous pemphigoid, pemphigus vulgaris, and acute generalized exanthematous pustulosis. The manifestations appeared 14.45 ± 6.98 and 20.79 ± 22.18 days following injection of the first and second doses of COVID-19 vaccines, respectively. All patients experienced new cases of cutaneous disease other than two who developed flare-ups of lichen planus and psoriasis. CONCLUSION: Several cutaneous reactions, ranging from allergic events to skin diseases, have been reported following the injection of COVID-19 vaccines. Focal injection-site reactions are the most common cutaneous adverse events; however, de-novo skin diseases and a flare-up of preexisting cutaneous disorders have also been described. Although many cases of COVID-19 vaccine-related cutaneous diseases have been published, our zoster/lichen planus and AGEP cases after vaccination are interesting. A more detailed understanding of cutaneous adverse events following COVID-19 vaccination will facilitate better diagnosis and management.


Subject(s)
Acute Generalized Exanthematous Pustulosis , COVID-19 Vaccines , COVID-19 , Herpes Zoster , Lichen Planus , Humans , Middle Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Vaccination/adverse effects
18.
Therapie ; 79(2): 239-270, 2024.
Article in English | MEDLINE | ID: mdl-37980248

ABSTRACT

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.


Subject(s)
Acute Generalized Exanthematous Pustulosis , Stevens-Johnson Syndrome , Humans , Skin , Stevens-Johnson Syndrome/epidemiology , Stevens-Johnson Syndrome/etiology , Stevens-Johnson Syndrome/diagnosis , Anti-Bacterial Agents/adverse effects , Acute Generalized Exanthematous Pustulosis/diagnosis , Acute Generalized Exanthematous Pustulosis/epidemiology , Acute Generalized Exanthematous Pustulosis/etiology , Anti-Inflammatory Agents, Non-Steroidal/adverse effects
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