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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. [ABSTRACT FROM AUTHOR]

Acute generalized exanthematous pustulosis, an infrequent adverse drug reaction, mainly results from drugs. Clinically, acute generalized exanthematous pustulosis manifests as a high fever, with skin lesions of small monomorphic subcorneal sterile pustules on an erythematous that presents at 1-4 days after medication exposure. The incidence of acute generalized exanthematous pustulosis varies from 3/1, 000, 000 to 5/1, 000, 000, while the mortality rate is typically around 5%. We present a case of a 69-year-old female who developed a diffuse, erythematous, pustular rash over the entire body and exhibited a fever of 38.3°C after 4 days of icotinib therapy. Considering her medication history and the appearance of the lesions, she was diagnosed with acute generalized exanthematous pustulosis and received appropriate treatment. We also conducted a literature review through PubMed to compare similarities and differences between our case and those reported in the literature. [ABSTRACT FROM AUTHOR]

Abstract Background Acute generalized exanthematous pustulosis (AGEP) is a rare and severe cutaneous drug eruption. Hydroxychloroquine (HCQ) is one of the known culprit drugs with less than 60 cases reported in the literature, and may have a more severe clinical presentation compared to AGEP induced by other drugs. There are no standardized management strategies for HCQ‐induced AGEP outside of drug discontinuation. Objectives Characterize the clinical presentation of HCQ‐induced AGEP and management strategies. Methods Retrospective chart review of nine patients clinically diagnosed with HCQ‐induced AGEP using the EuroSCAR score from 2017 to 2022 at four academic medical centres in the United States. Results All patients in our series were female and the median age was 52. Four patients initially presented with fever, and eight patients had neutrophilia. Median time to rash was 15 days. Biopsies obtained in six patients showed typical characteristics of AGEP. In most patients, rash morphology consisted of generalized pinpoint pustules atop atypical targetoid lesions and annular plaques. Five patients were hospitalized for AGEP. All patients were treated with methylprednisolone and/or prednisone, and the average days treated with systemic corticosteroids was 35. Conclusions Our case series is the largest to date describing HCQ‐induced AGEP. Clinicians should be wary that HCQ‐induced AGEP may present with a longer latency period after drug initiation and with atypical targetoid and annular lesions. Early initiation of systemic corticosteroids should be considered due to the severity of this drug reaction with addition of cyclosporine in refractory cases.

Background: Severe cutaneous adverse reactions (SCARs) are associated with morbidity and mortality. Objective: The aim was to determine the different types of SCARs, their morphology, common offending drugs, interventions, and outcomes. Methods: A 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), SJS/toxic epidermal necrolysis overlap (TEN), TEN, drug reaction with eosinophilia and systemic symptoms and acute generalized exanthematous pustulosis between January 1, 2012 to June 1, 2022. Results: Fifty-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 fourth, fifth 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 1 complication. The liver was the most common extracutaneous organ affected. Mortality was 7.8%. The main cause of death was sepsis. Limitations: Results were not generalizable. There were missing data and loss to follow-up. Conclusion: Judicious use of antimicrobials and corticosteroids may be beneficial in treatment of severe cutaneous drug reactions.

Icodextrin has been widely prescribed for peritoneal dialysis (PD) patients with inadequate ultrafiltration, but icodextrin induced acute generalized exanthematous pustulosis (AGEP) has been not well recognized in clinical practice. We described a young‐aged female with IgA nephropathy and end stage kidney disease under continuous automated peritoneal dialysis. She developed skin erythema with exfoliation over the groin 7th day after initiation of icodextrin based PD dialysate. Initially, her scaling skin lesion with pinhead‐sized pustules affected the bilateral inguinal folds, and then it extended to general trunk accompanied by pruritus. She was admitted because of deterioration of skin lesion on 14th day of icodextrin exposure. She was afebrile and physical examination was notable for widespread erythematous papules with pruritus extending over her groins and trunk. Pertinent laboratory examination showed leukocytosis of 18 970 cells/μL with neutrophile count of 17 642 cells/μL (92.3%), and c‐reactive‐protein: 3.39 mg/dL. Skin biopsy revealed multifocal sub corneal abscess with papillary dermal edema, and upper‐dermal neutrophilia with perivascular accentuation, consistent with the diagnosis of AGEP. After discontinuation of PD, she underwent temporary high‐flux haemodialysis with treatment of steroid and antihistamine. Her dermatologic lesion resolved without any skin sequalae completely within 4 days, and she underwent icodextrin‐free peritoneal dialysis at 17th day. This case highlighted the fact that icodextrin‐induced AGEP should be early recognized to avoid inappropriate management. [ABSTRACT FROM AUTHOR]

The article discusses IL36RN mutations in Chinese patients with acute generalized exanthematous pustulosis (AGEP), a severe skin disease characterized by sterile pustules on an erythematous background. IL36RN mutations have been linked to AGEP development, with a specific mutation, c.115+6T>C, identified in Chinese patients. The study suggests that IL36RN mutations exacerbate IL36 signaling, leading to immune cell recruitment and pustule formation in AGEP, but not all AGEP patients carry IL36RN mutations, indicating other potential causes. Further research is needed to confirm these findings and explore other factors contributing to AGEP. [Extracted from the article]

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening skin disease characterized by relapsing and remitting flares of sterile neutrophilic pustules and systemic inflammation. The definition of GPP is inconsistent globally, with large discrepancies in clinical management. To provide clinical guidance on managing GPP, we conducted a systematic literature search for articles published within the last decade on PubMed and the Cochrane Library in October 2022 and held four consensus meetings with 12 Taiwanese dermatologists between October 2022 and July 2023. Upon review of 153 articles, we agreed to adopt the European Rare and Severe Psoriasis Expert Network GPP definition with additional clarifications on pustular flares in psoriatic plaques, circinate or annular lesions, and localized pustules. We also drafted a diagnostic algorithm to facilitate GPP diagnosis. Twenty-seven statements on GPP treatment reached consensus. We recommend using an oral retinoid or spesolimab injection for the first-line treatment in both acute (treating flares) and maintenance (preventing flares) settings in adults with GPP. For infants and juveniles with GPP, retinoids are recommended as a first-line treatment. Evidence for other conventional and investigational therapies was reviewed, and a treatment algorithm was proposed. We hope this consensus provides practical guidance for clinicians in Taiwan and helps improve outcomes for GPP patients.

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the prevalence of severe cutaneous adverse reactions to medications in hospitalized patients of two hospitals of Bogota, Colombia. MATERIALS AND METHODS: An exploratory cross-sectional observational study conducted in two hospitals in Bogota, Colombia, from 2010 to 2020 of patients diagnosed with severe cutaneous adverse reactions to medications collected by reviewing medical records. RESULTS: A total of 42 cases were found with a mean age of 40.8 years and a male predominance. The acute generalized exanthematous pustulosis was the most frequently reported reaction in 15 patients, followed by drug-induced hypersensitivity syndrome (DRESS syndrome): 11, Stevens-Johnson syndrome: 7, toxic epidermal necrolysis: 5 and generalized bullous fixed pigmented erythema: 4. The main triggering drugs were antibiotics in 19 cases and anticonvulsants in 9. Systemic corticosteroids were the main treatment received by 26 patients. Three patients died. CONCLUSIONS: Future pharmacogenetic studies are needed to determine susceptibility to different drugs in the Colombian population. [ABSTRACT FROM AUTHOR]

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction, typically characterized by the appearance of multiple pinpoint non-follicular pustules, less than 5 mm, sterile, on an erythematous-edematous base, and can be disseminated. Up to 90% of cases are associated with drug administration. It usually resolves in less than 15 days with a good prognosis. We describe the case of a 31-year-old man who experienced drug-induced AGEP with multisystem involvement. However, at the onset, he presented with purpuric lesions on the skin and oral mucosal involvement, leading to the consideration of other differential diagnoses. The clinical evolution, including pustule formation and histopathological findings, led to the diagnosis of AGEP. He received standard supportive care, including topical and systemic corticosteroids, with a favorable clinical outcome. This case highlights an atypical presentation of AGEP and the possibility of overlap with other drug adverse reactions, emphasizing the need for timely and accurate diagnosis and management. [ABSTRACT FROM AUTHOR]

Background: Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR. Methods: Prospective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites. Results: we report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%). Conclusion: In the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality. Trial registration: ANZCTR ACTRN12619000241134. Registered 19 February 2019.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous reaction. In over 90% of patients it is an adverse reaction to drugs. Delayed-type (type IV) hypersensitivity seems to play an important role in its pathophysiology. Positive patch tests have ranged from 18% to 75%, with 93 culprit drugs identified. Our case involves an 87-year-old female patient, treated for a periprosthetic joint infection with ceftriaxone and daptomycin, who developed acute generalized exanthematous pustulosis. Clinical diagnosis was confirmed by skin biopsy. Patch testing performed 5 months later confirmed sensitization to ceftriaxone. Patch testing is useful to identify the cause of AGEP when the responsible drug is unclear. [ABSTRACT FROM AUTHOR]

Key Clinical Message Crusted scabies is a severe form of scabies infestation caused by the ectoparasite Sarcoptes scabiei. Risk factors include immunosuppression, neuropathies, and psychiatric disorders. Its management poses important challenges due to its contagius nature. Here we present a case or Acute Generalized Exanthematous Pustulosis secondary to Ivermectin therapy in a patient with crusted scabies.

Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption characterized by sterile pustules on an erythematous background, which is usually associated with drugs. AGEP is described as a self-limiting disease with favorable prognosis. We reported a case of Kawasaki Disease (KD) following AGEP. A 3-year-old male, who was admitted with pustules and five days of fever at our hospital, was diagnosed with AGEP. Despite the skin lesions and fever improving drastically after prednisolone therapy, the fever recurred on hospitalization day 5. The following symptoms suggestive of KD also appeared: bulbar conjunctival hyperemia, cervical lymphadenopathy, erythema of the lips, eruption on his trunk, and erythema and edema of the hands and feet. He was diagnosed with KD and treated with intravenous immunoglobulin. He was discharged on the thirteenth day of hospitalization without cardiac complications. Drug-induced lymphocyte stimulation test revealed carbocysteine as the suspected cause of AGEP, which consequently triggered KD. Because a mucosal lesion is uncommon in AGEP, bulbar conjunctival hyperemia suggested that KD sequentially occurred after AGEP. Since AGEP is benign and self-limited in most cases, it is necessary to differentiate other diseases, including KD, when recurrent fever or rash occurs in the course of AGEP.

Key Clinical Message: Crusted scabies is a severe form of scabies infestation caused by the ectoparasite Sarcoptes scabiei. Risk factors include immunosuppression, neuropathies, and psychiatric disorders. Its management poses important challenges due to its contagius nature. Here we present a case or Acute Generalized Exanthematous Pustulosis secondary to Ivermectin therapy in a patient with crusted scabies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To report a case of keratoconjunctivitis with marginal corneal infiltrates in a patient with acute generalized exanthematous pustulosis (AGEP) secondary to trimethoprim-sulfamethoxazole. Observations: A 63-year-old female presented with a diffuse pustular skin rash and bilateral keratoconjunctivitis with marginal corneal infiltrates. Skin biopsy led to the diagnosis of AGEP secondary to trimethoprim-sulfamethoxazole use. Treatment of the ocular findings with topical corticosteroids and lubrication led to near-full resolution after two weeks. Conclusions and Importance: To the best of our knowledge, this is the first reported association between AGEP and keratoconjunctivitis with marginal corneal infiltrates. A hypersensitivity reaction to a foreign antigen is implicated in the pathogenesis of both AGEP and sterile marginal infiltrates, and we suggest that the patient's underlying hypersensitivity process associated with AGEP accounted for the ocular findings.

Generalized pustular psoriasis is an autoinflammatory skin disease characterized by the abrupt and widespread, recurrent or persistent, appearance of multiple pustules on an erythematous base that respect palms and soles. This is due to a disruption in the innate immune system, mainly in the pathways involving IL-36. Symptoms include fever and fatigue, and it generally affects women between the ages of 31 and 46. Episodes can be triggered by factors such as medications, pregnancy, infections and electrolyte imbalances. The histopathological study is characterized by the presence of spongiform pustules of Kogoj and subcorneal pustules formed by the accumulation of neutrophils. The diagnosis is based on the criteria established by the European Consensus Statement and/or the Japanese Guidelines. Acute generalized exanthematous pustulosis is the main alternate differential diagnosis to exclude, which presents as a severe skin reaction, primarily associated with medications. Treatment involves identifying triggering factors, managing potentially fatal complications, initiating systemic treatment, and establishing maintenance therapy once the disease has stabilized. Mortality is 4.2% and may vary depending on the treatment prescribed. [ABSTRACT FROM AUTHOR]

Introduction: Beta-lactam antibiotics are one of the most common causes of antibiotics-related severe cutaneous adverse reactions (SCARs) including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reactions with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Recent evidence demonstrated that the human leukocyte antigen (HLA) polymorphisms play important roles in the development of drug-related SCARs. This study aimed to extensively characterize the associations between HLA genetic polymorphisms and several phenotypes of SCARs related to beta-lactam antibiotics. Methods: Thirty-one Thai patients with beta-lactam antibiotics-related SCARs were enrolled in the study. A total of 183 unrelated native Thai subjects without any evidence of drug allergy were recruited as the control group. Genotyping of HLA class I and class II alleles was performed. Results: Six HLA alleles including HLA-A*01:01, HLA-B*50:01, HLA-C*06:02, HLA)DRB1*15:01, HLA-DQA1*03:01, and HLA-DQB1*03:02, were significantly associated with beta-lactam antibiotics-related SCARs. The highest risk of SCARs was observed in patients with the HLA-B*50:01 allele (OR = 12.6, 95% CI = 1.1–142.9, p = 0.042), followed by the HLA-DQB1*03:02 allele (OR = 5.8, 95% CI = 1.5–22.0, p = 0.012) and the HLA-C*06:02 allele (OR = 5.7, 95% CI = 1.6–19.9, p = 0.011). According to the phenotypes of SCARs related to beta-lactam antibiotics, the higher risk of SJS/TEN was observed in patients with HLA-A*03:02, HLA-B*46:02 (OR = 17.5, 95% CI = 1.5–201.6, p = 0.033), HLA-A*02:06, HLA-B*57:01 (OR = 9.5, 95% CI = 1.3–71.5, p = 0.028), HLA-DQB1*03:02 (OR = 7.5, 95% CI = 1.8–30.9, p = 0.008), or HLA-C*06:02 (OR = 4.9, 95% CI = 1.1–21.4, p = 0.008). While eight HLA alleles including HLA-A*02: 05, HLA-A*02:11, HLA-B*37:01, HLA-B*38:01, HLA-B*50:01, HLA-C*06:02, HLA)C*03:09, and HLA-DRB1*15:01 were associated with AGEP, the highest risk of AGEP was observed in patients with the HLA-B*50:01 allele (OR = 60.7, 95% CI = 4.8–765.00, p = 0.005). Among the four HLA alleles associated with DRESS including HLA-C*04:06, HLA-DRB1*04:05, HLA-DRB1*11:01, and HLA-DQB1*04:01, the HLA)C*04:06 allele had the highest risk of beta-lactam antibiotics-related DRESS (OR = 60.0, 95% CI = 3.0–1202.1, p = 0.043). However, these associations did not achieve statistical significance after Bonferroni’s correction. Apart from the HLA risk alleles, the HLA-A*02:07 allele appeared to be a protective factor against beta-lactam antibiotic-related SCARs (OR = 0.1, 95% CI = 0.0–0.5, p = 3.7 × 10-4, Pc = 0.012). Conclusion: This study demonstrated the candidate HLA alleles that are significantly associated with several phenotypes of beta-lactam antibiotics)related SCARs. However, whether the HLA alleles observed in this study can be used as valid genetic markers for SCARs related to beta-lactam antibiotics needs to be further explored in other ethnicities and larger cohort studies. [ABSTRACT FROM AUTHOR]

Acute generalized exanthematous pustulosis is a disease that usually presents with sudden onset and widespread rash over the body. It is a condition characterized by non-follicular, sterile pustules that develop acutely with a base of edematous erythema. Acute generalized exanthematous pustulosis is usually drug-related, and hydroxychloroquine, an antimalarial drug frequently used in rheumatology practice, is one of the rare causes of acute generalized exanthematous pustulosis. Generally, spontaneous regression is expected after drug discontinuation. A sixty-year-old female patient developed acute generalized exanthematous pustulosis while receiving hydroxychloroquine. Despite drug discontinuation and steroid treatment, the lesions were persistent. The patient was treated with methotrexate and the lesions had resolved. It is aimed to raise awareness of the rare hydroxychloroquine-acute generalized exanthematous pustulosis relationship and its treatment with methotrexate by presenting this case. [ABSTRACT FROM AUTHOR]

Meifang Wang,* Li Lin,* Leyi Wang, Linfeng Li Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linfeng Li, Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China, Tel +86-13693620186, Email zoonli@sina.comAbstract: Severe cutaneous adverse reactions (SCARs) to drugs are associated with morbidity, mortality, healthcare costs, and challenges in drug development. It is important to identify the SCAR type early by using strict diagnostic criteria because they may require different treatments, follow-ups, and short- or long-term prognoses. A 68-year-old woman admitted to our hospital presented with fever and rashes for 10 days. This case exhibited many features that suggested acute generalized exanthematous pustulosis (AGEP). However, the course of treatment and verified clinical features led to a diagnosis of AGEP and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome that was induced by carbamazepine and levofloxacin after a herpes zoster infection. AGEP combined with DRESS syndrome is a complicated and rare drug-induced dermatological eruption that follows a course similar to DRESS syndrome and more recalcitrant than the course seen with typical AGEP. The associated factors for the SCARs in our patient included age, history of allergy, viral infection, and drugs interacting with specific HLA loci. Improving our understanding of these factors can improve the treatment and prevention of SCARs in these patients.Keywords: severe cutaneous adverse reaction, SCARs, acute generalized exanthematous pustulosis, AGEP, drug reaction with eosinophilia and systematic syndrome, DRESS syndrome, overlapping feature, carbamazepine, varicella zoster virus infection

Su Wang, Juan Bai, Jianjun Qiao Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of ChinaCorrespondence: Jianjun Qiao; Juan Bai, Email qiaojianjun@zju.edu.cn; 1515033@zju.edu.cnAbstract: Acute generalized exanthematous pustulosis (AGEP), an uncommon severe cutaneous adverse reaction, is believed to be a T cell-mediated hypersensitivity reaction, of which the most common cause is medication. However, infections have also been reported to be associated with AGEP. Here, we present a case of AGEP possibly related with Staphylococcus pettenkoferi.Keywords: acute generalized exanthematous pustulosis, Staphylococcus pettenkoferi

Abstract Duloxetine is a serotonin and norepinephrine reuptake inhibitor. Some rare duloxetine‐induced hypersensitivity skin reactions have been reported. We report a case of acute generalized exanthematous pustulosis potentially induced by duloxetine. Skin pustules appeared 8 days after the introduction of duloxetine. Treatment with topical clobetasol propionate led to gradual remission of the lesions. As there are no cases of duloxetine‐induced acute generalized exanthematous pustulosis(AGEP) in the literature, we did a research in the World Health Organization (WHO) pharmacovigilance database (21 March 2022) and found three cases of duloxetine‐induced AGEP. The French causality assessment score for our case of duloxetine‐induced AGEP was 15 (C2S3). The Naranjo score was 7, indicating a possible correlation between AGEP and the use of duloxetine. This was consistent with the WHO causality score. We inform clinicians of the possibility of AGEP following therapy with duloxetine.

Acute generalized exanthematous pustulosis is an infrequent but severe pattern of cutaneous adverse reaction. It is characterized by the sudden appearance of sterile pustules on edematous-erythematous skin, which is mostly caused by the consumption of medications. However, it may also be associated with viral infections, toxins, or food allergens, although this is rare. We reported a case of AGEP in a 33-year-old male shortly after a spider bite, a rare cause of AGEP. It was improved by oral corticosteroid treatment after seven days.

Introduction: Beta-lactam antibiotics are one of the most common causes of antibiotics-related severe cutaneous adverse reactions (SCARs) including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reactions with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Recent evidence demonstrated that the human leukocyte antigen (HLA) polymorphisms play important roles in the development of drug-related SCARs. This study aimed to extensively characterize the associations between HLA genetic polymorphisms and several phenotypes of SCARs related to beta-lactam antibiotics.Methods: Thirty-one Thai patients with beta-lactam antibiotics-related SCARs were enrolled in the study. A total of 183 unrelated native Thai subjects without any evidence of drug allergy were recruited as the control group. Genotyping of HLA class I and class II alleles was performed.Results: Six HLA alleles including HLA-A*01:01, HLA-B*50:01, HLA-C*06:02, HLA-DRB1*15:01, HLA-DQA1*03:01, and HLA-DQB1*03:02, were significantly associated with beta-lactam antibiotics-related SCARs. The highest risk of SCARs was observed in patients with the HLA-B*50:01 allele (OR = 12.6, 95% CI = 1.1–142.9, p = 0.042), followed by the HLA-DQB1*03:02 allele (OR = 5.8, 95% CI = 1.5–22.0, p = 0.012) and the HLA-C*06:02 allele (OR = 5.7, 95% CI = 1.6–19.9, p = 0.011). According to the phenotypes of SCARs related to beta-lactam antibiotics, the higher risk of SJS/TEN was observed in patients with HLA-A*03:02, HLA-B*46:02 (OR = 17.5, 95% CI = 1.5–201.6, p = 0.033), HLA-A*02:06, HLA-B*57:01 (OR = 9.5, 95% CI = 1.3–71.5, p = 0.028), HLA-DQB1*03:02 (OR = 7.5, 95% CI = 1.8–30.9, p = 0.008), or HLA-C*06:02 (OR = 4.9, 95% CI = 1.1–21.4, p = 0.008). While eight HLA alleles including HLA-A*02:05, HLA-A*02:11, HLA-B*37:01, HLA-B*38:01, HLA-B*50:01, HLA-C*06:02, HLA-C*03:09, and HLA-DRB1*15:01 were associated with AGEP, the highest risk of AGEP was observed in patients with the HLA-B*50:01 allele (OR = 60.7, 95% CI = 4.8–765.00, p = 0.005). Among the four HLA alleles associated with DRESS including HLA-C*04:06, HLA-DRB1*04:05, HLA-DRB1*11:01, and HLA-DQB1*04:01, the HLA-C*04:06 allele had the highest risk of beta-lactam antibiotics-related DRESS (OR = 60.0, 95% CI = 3.0–1202.1, p = 0.043). However, these associations did not achieve statistical significance after Bonferroni’s correction. Apart from the HLA risk alleles, the HLA-A*02:07 allele appeared to be a protective factor against beta-lactam antibiotic-related SCARs (OR = 0.1, 95% CI = 0.0–0.5, p = 3.7 × 10−4, Pc = 0.012).Conclusion: This study demonstrated the candidate HLA alleles that are significantly associated with several phenotypes of beta-lactam antibiotics-related SCARs. However, whether the HLA alleles observed in this study can be used as valid genetic markers for SCARs related to beta-lactam antibiotics needs to be further explored in other ethnicities and larger cohort studies.

Acute generalized exanthematous pustulosis (AGEP) is a rare skin eruption characterized by widespread erythematous lesions covered with numerous pustules. Leukocytoclastic vasculitis is now considered an uncommon but possible histopathological feature within the clinical and pathological spectrum of AGEP. Our report describes a rare case of AGEP overlapping with cutaneous small vessel vasculitis, a condition that has only been reported once in the literature. [ABSTRACT FROM AUTHOR]

From the beginning of public vaccinations until the relaxation of COVID-19 measures, many case reports, case series and case–control studies have been published indicating cutaneous side effects of COVID-19 vaccination. Post-vaccination pustular eruption was reported as well, with a challenging differential diagnosis between pustular psoriasis, AGEP (acute generalized exanthematous pustulosis) and neutrophil pustular eruptions. We report a case of 56-year-old woman presented with acute generalized pustular flare up culminated 5 days after the second dose of BNT162b2(Pfizer) vaccination. She was diagnosed with pustular psoriasis flare and due to the regulating role of IL-1 in pustular psoriasis and in the cytokine storm observed in cases of COVID-19 postvaccination inflammation; we decided to treat the patient with an IL-1 antagonist, subcutaneous anakinra (100 mg daily) along with acitretin. One week later, after anakinra withdrawal, she presented a pustular psoriasis flare and a 7-day anakinra re-administration led to a satisfactory improvement in the skin lesions. We also reviewed the medical literature and found 28 case reports with pustular eruption after the COVID-19 vaccination. We compared the patients reported, regarding sex, age, number of doses, post-vaccination period and vaccine brand, and compared those results with our patient. Finally, as indicated by our case and other cases with similarly treated pustular eruptions. targeted therapy to this cytokine imbalance such as anakinra (IL-1) antagonist can improve the clinical course of the patient. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Hydroxychloroquine (HCQ) has been reported to cause pustular drug eruptions such as acute generalized exanthematous pustulosis (AGEP) and putular psoriasis (PP). Clinical differentitation of these entities is often difficult. This case emphasizes characteritics of AGEP and PP as well as the need for clinicans to proactively follow‐up these patients to monitor for the more aggressive outcome of PP. [ABSTRACT FROM AUTHOR]

BACKGROUND: Drug reactions are frequent, resulting a wide spectrum of manifestations in different organs and systems. One of the most frequent reactions is found at the tegumentary level, which could vary from localized to generalized. Acute generalized exanthematous pustulosis, Stevens-Johnson’s syndrome and toxic epidermal necrolysis are part of the adverse reactions that present a generalized dermatosis. Acute generalized exanthematous pustulosis is a rare and poorly understood adverse reaction. CLINICAL CASE: A 35-year-old female patient, with a history of self-medication, who manifested generalized dermatosis, with no affection of palms, soles and mucous membranes, characterized by multiple 1-2 mm pinpoint pustules with an erythematous base that tended to converge; the biopsy report described a rare variety of toxicoderma. CONCLUSIONS: Reports of acute generalized exanthematous pustulosis are scarce, mostly associated with drugs. Differential diagnoses can lead us to the erroneous administration of other drugs, which could worsen the reaction. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We report a challenging AGEP case following COVID‐19 infection and a history of remdesivir use. Our study highlights the importance of considering history of COVID‐19 and remdesivir as possible causative factors when visiting new‐onset AGEP patients. [ABSTRACT FROM AUTHOR]

Lin Deng,1 Beilei He,2 Kamran Ali,1,3 Zhangyu Bu1 1Department of Dermatology Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of the Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Dermatology, International Education College of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of ChinaCorrespondence: Zhangyu Bu, Department of Dermatology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, No. 261, Huansha Road, Hangzhou, People’s Republic of China, Tel +8657156006617, Email buzyhz@163.comAbstract: Acute generalized exanthematous pustulosis (AGEP) is generally caused by drugs and is characterized by the rapid development of numerous non-follicular sterile pustules on an erythematous base, fever, and neutrophilia. We report an association between terbinafine, with AGEP, and adalimumab treatment. A 24-year-old teenage female patient with a history of onychomycosis was treated with terbinafine. On the second day of the first dose, multiple edematous and erythematous lesions appear with pinhead pustules. Neutrophilia was observed in the blood report. The clinical history, lesions, and laboratory evaluations were consistent with AGEP. We discontinued the terbinafine therapy, and the systemic corticosteroid was initiated; however, the patient’s condition worsened. Adalimumab subcutaneously was initiated, and the symptoms cleared up in weeks. The European Study of Severe Cutaneous Adverse Reactions (EuroSCAR) scoring system and Naranjo’s algorithm scale were used to check the possibility of a drug-induced adverse reaction. The Association of AGEP with the terbinafine drug is not rare. However, there are no reports or literature of drug-related rash or exanthematous eruptions unresponsive to corticosteroids and treated with adalimumab.Keywords: acute generalized exanthematous pustulosis, AGEP, adalimumab, terbinafine, drug-induced adverse reaction, Naranjo’s algorithm scale, EuroSCAR

Introduction Acute generalized exanthematous pustulosis is a type of severe cutaneous drug adverse reaction. While apalutamide is known for its high incidence of cutaneous adverse events, it remains unknown whether acute generalized exanthematous pustulosis can develop during apalutamide treatment. Case presentation A 72‐year‐old man with metastatic castration‐sensitive prostate cancer developed small erythema on the face and trunk after 41 days of apalutamide treatment. Three days later, apalutamide was discontinued. However, 9 days after the discontinuation of apalutamide, the patient had a high fever with hemodynamic instability and showed diffuse erythema throughout the body with numerous small pustules. Skin biopsy revealed subcorneal and intraepidermal pustules admixed with many eosinophils, which led to the diagnosis of acute generalized exanthematous pustulosis. The skin rash improved in 14 days with systemic corticosteroid administration. Conclusion We present the first case of a skin rash with clinical features of acute generalized exanthematous pustulosis during apalutamide treatment.

Background: Acute generalized exanthematous pustulosis (AGEP) is a potentially severe adverse cutaneous drug reaction, which typically occurs within 24–48 h after the intake of the culprit drug. Summary: AGEP is characterized by numerous sterile subcorneal pustules on erythematous skin and in less than a third of cases it can be associated with organ manifestations possibly leading to life-threatening symptoms (e.g., cholestasis, nephritis, and lung and bone marrow involvement). In contrast to generalized pustular psoriasis, it can involve mucosal regions and typically resolves rapidly if the culprit drug is removed, and adequate therapy with topical or systemic steroids administered. Diagnosis based on patient history, clinical signs, and characteristic cutaneous histology is rarely challenging. Identification of the culprit drug may be aided by patch testing or lymphocyte transformation tests that are of limited value. Key Messages: Recent experimental data reviewed herein are supportive of an early role of drug-induced innate immune activation and innate cytokines such as interleukin (IL)-1, IL-36, and IL-17 in the pathogenesis of AGEP. This explains the rapid onset and neutrophilic character of the cutaneous inflammation, but also provides new avenues for in vitro tests aimed at better identifying the culprit drug. [ABSTRACT FROM AUTHOR]

Key Clinical Message Hydroxychloroquine (HCQ) has been reported to cause pustular drug eruptions such as acute generalized exanthematous pustulosis (AGEP) and putular psoriasis (PP). Clinical differentitation of these entities is often difficult. This case emphasizes characteritics of AGEP and PP as well as the need for clinicans to proactively follow‐up these patients to monitor for the more aggressive outcome of PP.

Key Clinical Message We report a challenging AGEP case following COVID‐19 infection and a history of remdesivir use. Our study highlights the importance of considering history of COVID‐19 and remdesivir as possible causative factors when visiting new‐onset AGEP patients.

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction triggered in most cases by drugs. It is characterized by abrupt onset and rapid evolution of fields of sterile pustules on an erythematous background. The role of genetic predisposition in this reactive disorder is being explored. We report the simultaneous occurrence of AGEP in two siblings after being exposed to the same drug. [ABSTRACT FROM AUTHOR]

Background/purpose: Taiwan Drug-Injury Relief System (TDRS) has been implemented since 1999. More than 60% of the approved applications were associated with severe cutaneous adverse reactions (SCARs). Studies assessing SCARs using real-world evidence are very limited. TDRS offers abundant case information as a source of real-world evidence to investigate the characteristics of SCARs in Taiwan. The purpose of this study is to understand the trends and characteristics of SCARs in Taiwan. Methods: Applications from Drug-Injury Relief Database (TDRD) from 1999 to 2016 were retrospectively analyzed. Results: A declining trend in SCARs application was noticed after 2012, and 952 applications of SCARs were identified. The most common subtypes of SCARs were SJS/TEN (n = 455/206), DRESS (n = 228), GBFDE (n = 34) and AGEP (n = 18). The most common culprit drugs were allopurinol, carbamazepine, phenytoin, diclofenac and lamotrigine for SJS/TEN; allopurinol, phenytoin, co-trimoxazole, carbamazepine and phenobarbital for DRESS; mefenamic acid for GBFDE; non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibacterials for AGEP. The proportions of mortality cases were 28.9% for SJS/TEN; 36% for DRESS; 11.8% for GBFDE and 5.6% for AGEP. The mean latent period of SJS/TEN, DRESS, GBFDE and AGEP were 21.8 days, 29.2 days, 3.3 days and 6.7 days, respectively. Conclusion: The approved drug-injury relief applications associated with SCARs were mainly SJS, TEN and DRESS. The most common culprit drugs were antiepileptics, antibacterials, antigout agents, and NSAIDs. The latent periods showed some distinct features for different types of SCARs. In light of the high mortality rate, public awareness and vigilance of SCARs are crucial for the patient safety.

Abstract Herein, we report a case of a 73‐year‐old female patient diagnosed with cT4N0M1a lung adenocarcinoma with KRAS G12C mutation, PDL1

IntroductionAcute generalized exanthematous pustulosis (AGEP) is a rare condition characterized by superficial pustules following drug ingestion or infection. Currently, there is no clear link between rheumatism and AGEP. It has been described that hydroxychloroquine (HCQ) is a rare cause of acute generalized epidermal necrolysis (AGEP). Presently, there are limited studies on HCQ-induced AGEP. We aimed to explore the clinical features and associated gene expression of AGEP induced after HCQ treatment exposure in rheumatology patients.MethodsWe assessed patients with HCQ-induced AGEP diagnosed at the Second Affiliated Hospital of Guizhou University of Chinese Medicine between January 1, 2017, and May 1, 2022. We also reviewed similar cases reported in specific databases.ResultsThe study included five females (mean age, 40.2 years), and the mean time from initiation of HCQ treatment to symptom onset was 12.2 d. All patients received steroids and allergy medications after HCQ discontinuation, and the rash completely resolved within an average of 25.2 d. We performed whole exome sequencing and Sanger validation in our patient sample. CARD14 gene mutations were detected in three patients. Additionally, seven mutation sites were detected.DiscussionHCQ-induced AGEP may have a longer latency period and regression time than AGEP induced by other drugs. Our patients all experienced CARD14 gene mutations. AGEP often resolves with topical therapy and drug discontinuation, although some cases require systemic steroid therapy. In the future, patients with rheumatism should pay attention to the effectiveness of HCQ during treatment and be aware of the associated skin toxicity.

What is Known and Objective: Acute generalized exanthematous pustulosis (AGEP) is a serious and rare adverse reaction of cephalosporins. We aimed to describe the clinical features of cephalosporin‐induced AGEP and provide a reference for rational clinical use of cephalosporins. Methods: We systematically searched Chinese and English databases for cephalosporin‐induced TGEP‐related case reports, retrospective studies, clinical studies, and review articles published before May 2022. Results and Discussion: A total of 43 patients from 35 articles were eligible, of which 28 (65.1%) were female, with a median age of 69 years. A total of 11 cephalosporins were suspected, the most commonly involved were ceftriaxone (41.9%), cephalexin (16.3%), and cefepime (9.3%). AEGP erupted primarily within 14 days after administration, manifested as nonfollicular pustules on an erythematous base, distributed favourably to the extremities (44.2%), trunk (23.3%), face (23.3%), and could involve the oral mucosa (11.6%). During AGEP resolution, the affected area had desquamation (39.5%). The acute phase of the disease may be accompanied by fever (>38.0°C) and elevated neutrophil count (>7500/mm3). Histology of AGEP showed subcorneal pustules (56.3%), intraepidermal cavernous pustules (37.5%), with papillary dermal edema (37.5%), containing neutrophils and eosinophilic infiltration (71.9%). After drug discontinuation, the median time to resolution of AGEP symptoms was 10 days (range 2, 90). What is New and Conclusion: Cephalosporin‐induced AGEP is rare and should be properly diagnosed. This serious cutaneous adverse reaction is self‐limiting and has a favourable prognosis, usually resolves with drug interruption, and may require additional interventions, such as topical steroids. [ABSTRACT FROM AUTHOR]

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