Acute Generalized Exanthematous Pustulosis Research Articles

Pustular and crusted lesions in systemic lupus erythematosus: A case report

ABSTRACT Systemic lupus erythematosus (SLE) is the prototype of an autoimmune disease with various manifestations in the skin and several other organs. Subacute cutaneous lupus erythematosus may present with annular and psoriasiform lesions. There have been case reports of pustular lesions in SLE. Herein, we describe a known case of SLE, who developed pustular and crusted lesions which complicated the course of the disease. We considered Acute Generalised Exanthematous Pustulosis, Subcorneal Pustular Dermatosis, Pustular Psoriasis, Pustular Vasculitis, and Pustular Folliculitis as our initial differential diagnosis. A potassium hydroxide mount from crusted lesions showed scabies mites. With these findings, a diagnosis of SLE complicated with crusted scabies was made. She was managed with multiple systemic immunosuppressant and antiscabetic measures following which clinical improvement was seen with remission of her lesions.

54640 Validation and Optimization of EuroSCAR Criteria in Diagnosis of Acute Generalized Exanthematous Pustulosis (AGEP)

54640 Validation and Optimization of EuroSCAR Criteria in Diagnosis of Acute Generalized Exanthematous Pustulosis (AGEP)

Clinical characteristics, treatment and outcome of clindamycin induced acute generalized exanthematous pustulosis.

Acute generalized exanthematous pustulosis (AGEP) is a serious and rare adverse reaction to clindamycin. This study investigated the clinical features of clindamycin-induced AGEP and provided reference for the prevention and treatment of AGEP. Case reports, case series and clinical studies of clindamycin-induced AGEP were collected by retrieving English and Chinese database from inception until May 31, 2024. Of the 35 patients included, 25 (71.4%) were female, and the median age was 57 years (1.6-88 years). The duration of AGEP onset is 2 days (range 0.04,13) after initial administration. The main clinical morphology of AGEP is a non-follicular pustular on an erythematous base, which may be accompanied by fever (54.3%) and pruritus (40.0%). These lesions mainly involved extremities and trunk. The median elevated neutrophil count was 13.3 × 109/L (range 10.3, 31.4). Histologic features of AGEP are characterized by intracorneal, subcorneal, and/or intraepidermal pustules with papillary dermal edema containing neutrophilic, lymphocytic, andeosinophilic infiltrates. Patients gradually recovered after the withdrawal of clindamycin and supportive therapy with a median time of 9 days (range 2, 30). Clinicians should be aware of AGEP as a rare adverse effect of clindamycin. When clindamycin is prescribed, it should be stopped in time when AGEP occurs, and active systemic treatment should be given. AGEP is a self-limiting disease with a good prognosis.

Acute generalized exanthematous pustulosis: European expert consensus for diagnosis and management.

Acute generalized exanthematous pustulosis (AGEP) is a rare, usually drug-induced, acute pustular rash. Despite the lack of strong data supporting the effectiveness of topical or systemic corticosteroids in this drug reaction, they are widely used. More generally, there is no consensus on the diagnostic modalities and the management of patients with AGEP. We aimed to provide European expert recommendations for the diagnosis and management or patients with AGEP. Members of the ToxiTEN group of the European Reference Network (ERN)-skin, all dermatologists and/or allergologists with expertise in drug reactions, elaborated these recommendations based on their own experience and on a review of the literature. Recommendations were separated into the following categories: professionals involved, assessment of the diagnosis of AGEP, management of the patient and allergological work-up after the acute phase. Consensus was obtained among experts for the list of professionals involved for the diagnosis and management of AGEP, including the minimum diagnostic work-up, the setting of management, the treatments, the modalities and the timing of allergological work-up and follow-up. European experts in drug allergies propose herein consensus on the diagnosis and management of patients with AGEP. A multidisciplinary approach is warranted, including dermatologists, allergologists and pharmacovigilance services.

Antibiotic-induced severe cutaneous adverse reactions: a single-center retrospective study over ten years.

Severe cutaneous adverse reactions (SCARs) are rare but life-threatening, with antibiotics being the main cause. This retrospective study from a single center was designed to analyze the culprit drugs, clinical features and treatment outcomes of antibiotic-induced SCARs. We analyzed cases of antibiotic-induced SCARs in a tertiary hospital in China between January 2013 and January 2024, including Steven-Johnson syndrome (SJS) or Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) overlap, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Descriptive analysis of the demographic characteristics, clinical manifestations, treatment and prognosis were carried out. Among 354 cases of SCARs, 63 validated antibiotic-related cases were included. Cephalosporins (31.7%), penicillins (25.4%), and quinolones (19.0%) were the most common triggers for SCARs. Overall, liver (50.8%), lungs (31.7%), and kidneys (23.8%) were the most frequently affected organ in SCARs cases. Eight patients (28.6%) in the SJS/SJS-TEN overlap group and 8 patients (80.0%) in the TEN group received combination therapy of corticosteroids and IVIG. Patients with SCARs caused by penicillins or cephalosporins could receive alternative treatments such as lincomamides, quinolones, and tetracyclines. The mortality rate in the TEN group was the highest at 20.0%, followed by the SJS/SJS-TEN overlap group (7.1%), and no deaths were observed in the DRESS and AGEP groups. The identification of the culprit antibiotics and the application of alternative antibiotic therapies are crucial for the management of antibiotic-induced SCARs. If complicated underlying conditions and complications like advanced age, cancer and pneumonia coexist with SCARs, patients might be more at risk for mortality.

Generalised pustular psoriasis triggered by monkeypox vaccination successfully treated with spesolimab

AbstractGeneralised pustular psoriasis (GPP) is characterised by a widespread rash with pustules and fever. Clinical and the histological overlap with the delayed hypersensitivity reaction acute generalised exanthematous pustulosis may delay the diagnostics and the initiation of correct treatment. In this case‐report, we describe an Human immunodeficiency virus positive patient with GPP possible triggered by monkeypox vaccination and eventually successfully treated with spesolimab, an interleukin‐36 inhibitor.

Evolution of the spectrum of drugs associated with acute generalized exanthematous pustulosis over time: A pharmacovigilance study

Evolution of the spectrum of drugs associated with acute generalized exanthematous pustulosis over time: A pharmacovigilance study

A Swollen Red Leg: Sweet’s Syndrome

Neutrophillic dermatoses comprise a range of conditions where the hallmark is histologic infiltrate of neutrophils. Ranging from skin disorders such as acute generalised exanthematous pustulosis or subcorneal pustulosis (Sneddon Wilkinson) which affect the epidermis, the neutrophilic infiltrate can affect the dermal portion such as in Neutrophillic urticaria, Sweet’s syndrome, or eccrine neutrophilic hidradenitis, or it can affect both epidermis and dermis such as in pyoderma gangrenosum. Many times the diagnosis of a neutrophilic dermatosis poses a challenge as the main differential are infectious diseases and a high degree of suspicion needed. Generally, the diagnosis is reached with clinical and dermatopathology correlation. We present the case of an 87-year-old woman with swollen red leg in whom the diagnosis posed a challenge

Recognizing rare rashes: A case of acute generalized exanthematous pustulosis.

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.

Genetic analysis of different subtypes of aseptic pustulosis in the Chinese population.

Aseptic pustulosis involves inflammatory skin conditions with nonbacterial pustules on erythema, accompanied by neutrophil and eosinophil infiltration in the epidermis. Dysregulation of the interleukin (IL)-36 pathway leads to neutrophil aggregation and pustule formation. Variants in IL36RN, CARD14, AP1S3, MPO, SERPINA3 and BTN3A3 have been identified in generalized pustular psoriasis (GPP) in the past. Some patients with acrodermatitis continua of Hallopeau (ACH), palmoplantar pustulosis and acute generalized exanthematous pustulosis (AGEP) also exhibit mutations in IL36RN, CARD14 and AP1S3, albeit with regional and population-specific variations. This study aims to explore a shared genetic foundation among those with aseptic pustulosis. We performed Sanger sequencing on six genes in 126 patients with aseptic pustulosis. Genetic analysis identified IL36RN variants strongly associated with ACH, AGEP and subcorneal pustular dermatosis (SPD). Immunohistochemistry revealed elevated inflammatory cytokines in all subtypes. This study establishes a significant association between IL36RN variants and ACH, AGEP and SPD, emphasizing the IL-1/IL-36-chemokine-neutrophil axis as a common pathogenic mechanism. Targeting this axis holds promise for therapeutic interventions for aseptic pustulosis.

Trips Through the Skin: Reviewing Cutaneous Drug Reactions to Psychedelics and Hallucinogens.

Although psychedelic and hallucinogenic substances have gained popularity for therapeutic use, their dermatologic adverse effects are poorly characterized. This review characterizes the cutaneous reactions associated with psychedelic and hallucinogenic drugs. A review of PubMed and Scopus was conducted from the inception of databases to August 31, 2023. Search terms included drug names and classes (cannabis, MDMA, ecstasy, 3,4-methylenedioxymethamphetamine, psychedelics, hallucinogens, peyote, marijuana, lysergic acid diethylamide, LSD, ketamine, dimethyltryptamine, DMT, phencyclidine, PCP, dextromethorphan, psilocybin, and ayahuasca), and dermatosis terms (dermatitis, contact dermatitis, drug eruption, skin reaction, and urticaria). Studies were included if there was an association with a psychedelic or hallucinogenic and any cutaneous reaction; studies without both components were excluded. Twenty-two studies met inclusion criteria, describing reactions to cannabis (10 studies), MDMA (5 studies), ketamine (4 studies), and psilocybin (3 studies). Forty total patients were included. Among cannabis-related reactions, the most common reaction was type I hypersensitivity by topical exposure (n = 21). Three patients reported type IV hypersensitivity reactions to contact with cannabis or cannabis-derived oils, all of whom experienced vesicular contact dermatitis. Two additional patients presented with an erythema-multiforme-like reaction and acute generalized exanthematous pustulosis after systemic administration, respectively. MDMA was associated with acneiform eruptions (2 cases), an urticarial eruption, a guttate psoriasis-like reaction, a fixed drug eruption, and Stevens-Johnson syndrome (1 case). Four patients reported type I hypersensitivity reactions to ketamine. Four patients reported vesicular eruptions, cyanosis, or widespread jaundice to psilocybin. Of the cases, 8 patients had cutaneous reactions that resolved with drug cessation, 10 resolved with cessation plus treatment, and resolution in 7 cases was not reported. Zero studies were found describing other psychedelic or hallucinogenic compounds. Further research is required to characterize reactions and treatments linked to the variety of extant psychedelics and hallucinogens.

Determine and remove the drug trigger, usually antibiotics, that causes acute generalised exanthematous pustulosis

Determine and remove the drug trigger, usually antibiotics, that causes acute generalised exanthematous pustulosis

Real-World Efficacy of Spesolimab: Reports from Four Patients with Generalized Pustular Psoriasis

Introduction: Generalized pustular psoriasis (GPP) is a rare, chronic, autoinflammatory skin disease characterized by widespread pustular eruptions that may be accompanied by systemic symptoms. GPP is painful, distressing, and adversely affects patient quality of life (QoL). Spesolimab is a first-in-class anti-IL-36 receptor monoclonal antibody approved for the treatment of GPP flares. Methods: We describe 4 cases from our respective clinical practices, where individuals with GPP were treated successfully with spesolimab. Results: Four patient cases of GPP were included; an 18-year-old male, a 58-year-old female; a 36-year-old male, and a 40-year-old female. One patient had a history of GPP, and had experienced 3 prior flares in the preceding year. Two patients had a history of plaque psoriasis. Events preceding the current GPP flare included hydroxychloroquine treatment (n=2), and corticosteroid treatment (n=3). All patients presented with sudden onset of worsening pustular rash (affecting lower extremities [n=1]; extremities and trunk [n=1]; whole body [n=2]). Two patients had systemic symptoms at presentation (1 case: fever, chills, malaise, fatigue; 1 case: severe weakness), and required hospitalization. Two patients received an initial mis-diagnosis of acute generalized exanthematous pustulosis (AGEP). Significant impacts on QoL were reported; all 4 patients were unable to perform normal daily activities; the 18-year-old patient was targeted at school because the skin lesions were perceived to be contagious. The 4 patients received multiple therapies prior to, and concomitantly with, spesolimab treatment, including topical agents, antibiotics, corticosteroids, retinoids, immunosuppressants, and biologics. All 4 patients received two 900 mg intravenous infusions of spesolimab with treatment intervals between 7 and 20 days. Treatment was given at an outpatient infusion center (n=3*), or using a home infusion service (n=1); *1 patient received their first infusion as an inpatient. Significant clinician-assessed improvement in pustules occurred within 1 week of the first spesolimab infusion in 3 patients; the remaining patient reported improvement 1-2 weeks after the second infusion. One of the hospitalized patients experienced 75% improvement in itching, pain, and pustules within 24 hours of the first spesolimab infusion, and was discharged the next day. Spesolimab treatment also improved QoL, with patients experiencing rapid improvements in pain, and their ability to resume their normal daily activities. Conclusions: These cases demonstrate the efficacy of spesolimab in the real-world, highlighting the ability of spesolimab treatment to rapidly improve GPP symptoms and patient QoL. Administration of spesolimab in an inpatient setting allowed for rapid patient improvement and discharge the next day. These cases also highlight the association of certain drugs as triggers for GPP flares, as well as the importance of AGEP in the differential diagnosis of GPP

Severe cutaneous adverse reactions in a tertiary care center in Jamaica

BackgroundSevere cutaneous adverse reactions (SCARs) are associated with morbidity and mortality. ObjectiveThe aim was to determine the different types of SCARs, their morphology, common offending drugs, interventions, and outcomes. MethodsA retrospective cohort study was conducted of all patients admitted to the dermatology service at the University Hospital of the West Indies with Stevens-Johnson syndrome (SJS), Stevens-Johnson syndrome/toxic epidermal necrolysis overlap (SJS/TEN), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) between January 1, 2012 to June 1, 2022. ResultsFifty-one cases (51) met the inclusion criteria for SCAR. SJS, SJS/TEN overlap and TEN together accounted for 71.2% of cases. SCARs were most frequent in the 4th, 5th and 6th decades of life and there was a female preponderance.Antibiotics (31%) and anticonvulsants (29%) were the most common causative agents for SCARs. Most patients had at least one complication. The liver was the most common extracutaneous organ affected.Mortality was 7.8%. The main cause of death was sepsis. LimitationsResults were not generalizable. There was missing data and loss to follow-up. ConclusionJudicious use of antimicrobials and corticosteroids may be beneficial in treatment of severe cutaneous drug reactions.

Abstract A003: Preliminary safety results from a phase I study of autologous transgenic T cells expressing high affinity mesothelin-specific T cell receptor (TCR) (FH-TCR TMSLN) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDA)

Abstract Background: We previously demonstrated murine CD8+ T cells engineered to express a high affinity MSLN-specific TCR exhibit efficacy in the KPC mouse model, particularly with serial infusions, and thus developed a human TCR for expression in autologous T cells for targeting MSLN, which is overexpressed by 80% of PDAs. In this first-in-human phase I trial, we are determining safety, preliminary efficacy, as well as persistence, activation, localization, and functional capacity of autologous FH-TCR-TMSLN (T) cells in refractory, MSLN+ mPDA. Methods: Eligible pts have ECOG PS 0-1, ≥1 prior therapy for mPDA, life expectancy ≥12 weeks, MSLN 2+ expression in ≥30% tumor cells by IHC, HLA-A*2:01, no HLA-B*13:02. Pts undergo leukapheresis, and 3-4 weeks later receive the first T cell infusion. Three T-cell infusions, if sufficient T cells can be manufactured, are being administered every 21 days (d) at 3 dose level cohorts: 1 × 109, 3.3 × 109 and 1 × 1010 T cells, with a 3+3 design. Dose limiting toxicities (DLTs) are assessed during the 21d after each T cell dose. Only pts who receive ≥75% of the assigned T cell dose are DLT evaluable, but all pts are evaluable for safety. Lymphodepleting chemotherapy (LDC) with fludarabine/cyclophosphamide is administered prior to the last T cell infusion (cohorts 1-2) or prior to the first T cell infusion (cohort 3). Primary endpoints are safety and DLTs. Secondary endpoints are response rate, progression-free and overall survival. Exploratory endpoints include TCR-TMSLN cells in tumor biopsies and blood as biomarkers. Results: Between Dec 2021 to July 2023, 7 pts were enrolled, and 6 pts treated (n=3 at dose at level 1, n=3 at dose level 2), 4 women, median age 60 years (range 51-70), median 3 prior systemic therapies. All pts underwent research-related tumor biopsies at baseline, and 2-3 weeks post first T cell infusion, and 2 pts had biopsies after the last T-cell infusion. Treatment exposure was median 3 (range 1-3) T cell infusions. No DLTs occurred among 6 pts treated at dose levels 1 × 109 and 3.3 × 109 T cells. Treatment related adverse events (TRAE) thought at least possibly related to T cells infusions were fever [n=2 grade (gr) 1, n=1 gr 2], and gr 2 chills, cytokine release syndrome (CRS), dizziness, fatigue, hypertension, hypotension, nausea, acute generalized exanthematous pustulosis (AGEP) rash, and sinus tachycardia (n=1 each). TRAE due to LDC were transient leukopenia (n=2 gr 4, n=1 gr 3, n=2 gr 2), neutropenia (n=4 gr 4, n=1 gr 2), lymphopenia (n=3 gr 4), dysgeusia (n=2 gr 2), anemia (n=1 gr 3) and fatigue (n=1 gr 2). One patient had a serious adverse event with gr 2 CRS and gr 2 AGEP, which resolved. Due to anticipated difficulty attaining sufficient T cells doses for three high dose infusions, we amended the protocol to allow treatment with at least one T cell infusion, with the first dose preceded by LDC at the 1 × 1010 T cells dose level. Conclusions: FH-TCR-TMSLN cells are well tolerated with no on-target toxicity, and the study is open to accrual (NCT04809766). Citation Format: Elena G. Chiorean, Aude Chapuis, Andrew Coveler, Cecilia Yeung, Ted Gooley, David B. Zhen, Gentry King, Stacey Cohen, Lindsay Hannan, Rachael Safyan, Anthony Germani, Susan Ra, Jennifer Casserd, Tom Schmitt, Philip Greenberg. Preliminary safety results from a phase I study of autologous transgenic T cells expressing high affinity mesothelin-specific T cell receptor (TCR) (FH-TCR TMSLN) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDA) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A003.

Acute generalized exanthematous pustulosis secondary to spider bites: Clinico-dermoscopic findings and review of literature

Acute generalized exanthematous pustulosis (AGEP) or toxic pustuloderma is a febrile adverse cutaneous reaction, characterized by small non-follicular sterile pustules. AGEP can occur in any age group and is found to be more common in women. A large proportion (>90%) of cases are triggered by medications, particularly macrolides and aminopenicillins. The occurrence of AGEP following spider bite has been rarely documented in the literature.We report two cases who presented to us with AGEP following spider bite along with dermoscopic findings and also present a brief review of literature on the same.

Clinical Characteristics, Treatment, and Prognosis of Amoxicillin-Induced AGEP/ALEP

Background. Amoxicillin was associated with acute generalized exanthematous pustulosis (AGEP), and the clinical characteristics were not clear. The purpose of this study was to explore the clinical characteristics of amoxicillin-induced AGEP and to provide a basis for prevention and treatment. Methods. Case reports and case series of amoxicillin-induced AGEP were collected for retrospective analysis by searching the Chinese and English databases from inception to January 31, 2023. Results. A total of 46 patients were included with a median age of 40 years (range 1.4, 87). The onset time of AGEP ranged from 6 hours to 28 days, with a median of 2.5 days. Fever occurred in 32 patients (69.6%), and pruritus occurred in 13 patients (28.3%). Ten patients (21.7%) had mucous membrane involvement and systemic involvement, respectively. Twenty-two patients had elevated neutrophils, with a median of 12850/mm3 (range 7880, 29140). Skin biopsy mainly showed subcorneal pustules (22 cases, 47.8%), spongy pustules (14 cases, 30.4%), and inflammatory cell infiltration (26 cases, 56.5%). Skin lesions disappeared in a median of 10 days (range 2, 42) after discontinuation of amoxicillin and administration of topical steroids (26 cases, 56.5%) as well as systemic corticosteroids (13 cases, 28.3%). Conclusions. AGEP is a rare complication of amoxicillin and is self-limiting. Clinicians should correctly identify AGEP and should avoid represcribing amoxicillin. Clinicians should correctly identify AGEP and avoid represcribing amoxicillin, which can prevent unnecessary treatment measures.

Acute generalized exanthematous pustulosis caused by sulfasalazine

In the landscape of cutaneous adverse drug reactions (cADRs), acute generalized exanthematous pustulosis (AGEP) remains a pertinent dermatological manifestation. This research delineates a clinical presentation consistent with AGEP precipitated by the administration of sulfasalazine in a 68-year-old female. Drawing from the EuroSCAR study’s diagnostic parameters, the patient exhibited salient features such as facial erythema and a pervasive papular rash, concomitant with specific hematological perturbations, including leukocytosis and elevated hepatic enzymes. Utilizing the EuroSCAR AGEP validation score, a definitive diagnosis was ascertained, obviating the need for histological confirmation. Subsequent therapeutic interventions facilitated symptomatic resolution, leading to the patient’s discharge with a categorical advisory against future sulfasalazine exposure. This elucidation accentuates the causative potential of sulfasalazine in AGEP manifestation and underscores the imperativeness of vigilant diagnosis and timely intervention. Key words: sulfasalazine, AGEP, Drug hypersensitivity, Drug eruptions

Severe cutaneous adverse drug reactions: incidence, clinical characteristics, treatment, and outcome in pediatric patients.

Severe cutaneous adverse drug reactions (SCARs) can cause significant morbidity and mortality. Clinical data regarding such conditions is still limited in the pediatric population. To investigate the incidence, clinical characteristics, treatment, and outcome of SCARs in Thai pediatric patients. This retrospective study enrolled 52 patients aged less than 18 years who were diagnosed with acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or SJS/TEN overlap during January 2005 to August 2021 at Siriraj Hospital. SCARs were slightly more prevalent in females than in males (51.9% vs. 48.1%). Median age at diagnosis was 97 months, and median length of hospital stay was 11 days. DRESS, SJS, TEN, AGEP, and SJS/TEN overlap was found in 44.2%, 36.5%, 9.6%, 5.8%, and 3.8%, respectively. The most common etiologies were antimicrobial agents (40.3%) and anticonvulsants (35.5%). Target lesions, vesicobullous lesions, purpura, positive Nikolsky's sign, and skin tenderness were significant in blistering SCARs. Hematologic (84.6%) and hepatic (65.5%) manifestations were common. Treatment varied according to the clinical features of each condition. Systemic corticosteroids showed some benefit in SJS/TEN. One patient diagnosed with TEN died for an overall SCARs mortality rate of 1.9%. The unique characteristics of SCARs described herein can lead to timely and accurate diagnosis and proper management.

Medication Associations With Severe Cutaneous Adverse Reactions: A Case/Non-Case Analysis Using the FDA Adverse Event Reporting System.

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. To provide an updated and stratified list of medications with significant reporting odds ratios (RORs) of SCARs. A case/non-case analysis using the United States FDA Adverse Event Reporting System was performed. 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. 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.