key: cord-0789467-r44xve3s
authors: Vallejo-Yagüe, Enriqueta; Martinez-De la Torre, Adrian; Mohamad, Omar S.; Sabu, Shweta; Burden, Andrea M.
title: Drug Triggers and Clinic of Acute Generalized Exanthematous Pustulosis (AGEP): A Literature Case Series of 297 Patients
date: 2022-01-13
journal: J Clin Med
DOI: 10.3390/jcm11020397
sha: 88d4389c639b3cda44dbb81c909849b564c49794
doc_id: 789467
cord_uid: r44xve3s

Acute generalized exanthematous pustulosis (AGEP) is a rare skin reaction, commonly caused by drugs. Available evidence mostly relies on small studies or case reports. We collected published AGEP case reports and, subsequently, described the patient characteristics, suspect and concomitant drugs, time to onset, disease management, and clinical prognosis. This study included 297 AGEP patients (64.3% women) obtained from 250 published case reports or case series with individual patient data. AGEP affected patients of all ages, but the majority of patients (88.2%) were ≥25 years old. The most frequently reported suspect drugs were anti-infectives for systemic use (36.5%), particularly antibacterials for systemic use (31.0%), and especially beta-lactam antibacterials (18.3%) and macrolides (4.3%). Other frequent suspect drugs were antineoplastics (12.2%), and anti-inflammatory/anti-rheumatic products (5.2%) plus hydroxychloroquine (12.8%). Mean time to onset was 9.1 days (standard deviation SD 13.94). Some patients developed fever (64.3%) and systemic involvement (18.9%), and most patients (76.4%) received pharmacological treatment for AGEP. Seven patients died, although five of them were already critically ill prior to AGEP. In conclusion, antibiotics remain the most common suspected cause of AGEP. While case mortality rate may be up to 2.5%, disentangling the role of AGEP on the fatal outcome from the role of the preexisting health conditions remains challenging.

Acute generalized exanthematous pustulosis (AGEP) is a rare and severe skin reaction. While AGEP occurs most frequently as an adverse effect of pharmacological treatment or drugs, it may also result from contact with chemicals (e.g., mercury) or dyes [1, 2] , or as a response to certain organisms (e.g., cytomegalovirus, Chlamydia pneumonia, and Escherichia coli) [3] . It has been suggested that AGEP affects one to five patients per million per year, and it has been associated with up to a 5% mortality rate, often due to multi-organ failure or secondary infections [3, 4] . The key clinical feature of AGEP is the sudden presence of several miniscule, non-follicular intradermal pustules on an erythematous edematous background [5, 6] . Additionally, pyrexia and pruritic or burning sensation at the erythema may also be present [7] .

Pharmacological treatments reported as suspect agents triggering AGEP include, among others, antibiotics and other anti-infectives, cardiovascular drugs, proton pump inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and hydroxychloroquine [7] [8] [9] [10] [11] [12] [13] . In drug-driven AGEP, symptoms may appear within a few hours, a few days, or even a couple of weeks after the initial drug intervention [6] . Thus, identification of the suspect drug may be challenging. Overall, among the 297 patients, a total of 154 unique drugs were identified as suspect triggers of AGEP. The frequency of reporting of these suspect drugs is presented in Table 3 , and in more detail in the Supplementary Material S1 Table S3 . Five substances were not included in these frequency tables due to the lack of an ATC code (i.e., curcumin, neurotropin, probiotics, traditional Chinese medicine, and dai-kenchu-to herbal medicine). Among the suspect drugs, the most commonly reported were anti-infectives for systemic use (36.5%), and particularly antibacterials for systemic use (31.0%), especially beta-lactam antibacterials (18.3%) and macrolides (4.3%). Antivirals for systemic use and vaccines were identified as the suspect cause in eight (2.3%) and nine (2.6%) occasions, respectively. Antineoplastic agents and immunomodulating agents represented 14.5% of the suspected drugs, with the majority of this category including antineoplastics (12.2%). Anti-inflammatory and anti-rheumatic products represented 5.2% of the suspect drugs, and this figure increased when considering hydroxychloroquine as an anti-rheumatic treatment or conventional synthetic disease-modifying anti-rheumatic drug (csDMARD), despite its classification as an anti-malarial drug following the ATC system. Indications for hydroxychloroquine included lupus, rheumatoid arthritis, other rheumatic and immune-mediating diseases, and COVID-19. Hydroxychloroquine was reported as an AGEP trigger in 44 (12.8%) patients. Nervous system treatments represented 8.1% of the suspect drug, and other less frequently reported drugs included dermatologic treatments, cardiovascular and cardiac treatments, and drugs for the alimentary tract, respiratory system, genito-urinary system, and hormonal treatments. CARDIOVASCULAR SYSTEM 9 (2.6) 2 (1.6) 6 (2.8) Agents acting on the renin-angiotensin system Results as counts and percentage of the total number of suspect drugs in the corresponding group. The following substances, reported in one case report each, were not included due to missing ATC code: curcumin, neurotropin, probiotics, traditional Chinese medicine, and dai-kenchu-to herbal medicine. * Note that hydroxychloroquine was classified as antimalarial following the ATC system; however, it was indicated for lupus, rheumatoid arthritis, other rheumatic and immune-mediating diseases, and COVID-19.

Stratifying by sex, visual assessment of the findings shows a higher frequency of hydroxychloroquine and anti-inflammatory and anti-rheumatic products as suspect drugs in women than men. Conversely, a higher frequency of analgesics may be observed in the men cohort.

A description of all drugs reported in patients developing AGEP, independently of the suspect label, is given in Table 4 , and in more detail in the Supplementary Material S1 Table S4 . Overall, antibacterials for systemic use were the most frequent drugs (25.7%), and other drugs with a high presence were blood/cardiovascular treatments (13.9%), antineoplastic agents (6.3%), anti-inflammatory and anti-rheumatic drugs (3.9%), hydroxychloroquine (6.6%), analgesics (4.5%), corticosteroids for systemic use (4.3%), and contrast media (5.7%). Results as counts and percentage of the total number of all reported drugs in the corresponding group. The following substances, reported in one case report each, were not included due to missing ATC code: acetyl choline chloride, loxoprofen, carperitide, prophylline, curcumin, neurotropin, probiotics, traditional Chinese medicine, and dai-kenchu-to herbal medicine. * Note that hydroxychloroquine was classified as antimalarial following the ATC system; however, it was indicated for lupus, rheumatoid arthritis, other rheumatic and immune-mediating diseases, and COVID-19.

This literature case series included 297 patients with drug-associated AGEP, whose information was obtained from 250 published scientific articles. AGEP affected both women (64.3%) and men (34.3%), and while patients' age covered a wide spectrum, a higher frequency was observed in patients 25 years or older (88.2%). Approximately half (50.5%) of the patients reported the use of more than one drug at the time of AGEP onset, but in 90.9% of cases, only one drug was reported as the suspect agent. Among the suspect drugs, the most frequently reported ones were antibacterials for systemic use (31.0%), particularly beta-lactam antibacterials (18.3%) and macrolides (4.3%). Other frequently reported suspect drugs were antineoplastic agents (12.2%), anti-inflammatory and antirheumatic products (5.2%), and hydroxychloroquine (12.8%). Time to onset was ≤4 days in 50% of the patients. Fever was reported in more than half of the cases (64.3%), and systemic involvement in one in every six patients (18.9%). Three-fourths of the patients received pharmacological treatment to address the AGEP reaction. Overall, seven case reports reported the death of the patient (four men, three women), six of which were seriously ill prior to AGEP. It remains unclear whether AGEP was the cause of every fatal outcome.

The patient demographics in this case series are generally comparable to other observational studies. Indeed, the higher frequency of women patients in our study is in line with the existing evidence [7, 11, 265, 266] , and there is agreement on the lower age observed among men in comparison to women patients [266] . However, we note that the overall mean age in our case series (48.6 years [SD 21.6]) was slightly lower than the 51.7-62 years mean age reported in other observational and multi-center studies [7, 8, 10, 12] , as well as the 57.3 years reported in a recent pharmacovigilance study including 2649 case reports from the World Health Organization pharmacovigilance database (WHO-VigiBase) [266] .

Aging is associated with increased frailty, higher disease burden, more medication use, and higher risk for adverse drug reactions [267] . Thus, since the majority of the study patients (67%) were older than 40, and more than the half of the study case reports included the use of two or more drugs, it remains unclear if the observed higher frequency of AGEP with increased age is due to higher frailty with aging, or due to a higher polypharmacy and its associated increased risk of interaction or additive drug effects.

Systemic involvement in AGEP patients has been described as abnormal hepatic and liver function [9, 12] , as well as acute respiratory distress [265] . Our observed percentage of AGEP patients developing fever (64.3%) was slightly higher than the previously reported frequency of 52% [10, 11] , but our estimation of the frequency of systemic involvement in AGEP patients (18.9%) lies within the previous reported range, which was 13.9% in a study of 43 cases using electronic medical records in Singapore [12] , 17.2% in a French study with 58 cases [265] , and 23.5% in study in Taiwan with 51 cases [9] .

In the literature, the AGEP case-fatality rate has been suggested to be 2-5%, which is often due to multi-organ failure or secondary infections [3, 4, 12, 13 ]. The 7 out of 297 patients in this case series whose death was reported and collected [75, 91, 104, 132, 151, 182, 221] would yield a similar case-fatality rate of 2.4%. However, disentangling the cause of death in these patients is challenging. Most of the fatal cases (five of seven) had compromised health at the time of AGEP onset (i.e., two patients had cancer [151, 221] , one was critically burned [104] , and two had respiratory infections [75, 182] ). Moreover, five out the seven patients died after AGEP was deemed resolved. Only one case report clearly stated the drug reaction as the cause of death [132] . Thus, the role of AGEP in the mortality risk of these patients is questionable. Nevertheless, we note that five out of seven patients died from multiorgan failure and/or sepsis, which suggests a common path towards the fatal outcome. Additionally, death occurred within the first four months after AGEP but for one patient, who continued treatment with the suspect drug and had what we may called 'mild chronic AGEP' for one year [221] . While the relatively short time to outcome may support the hypothesis of AGEP influencing the mortality risk, we should consider a potential publication bias. Case reports often describe the events and circumstances after the study event but within a limited timeframe. As such, deaths occurring shortly after AGEP are more likely to be included in published case reports. Consequently, we believe the suggested 2.4% case-fatality rate should be taken with caution as both over-and under-estimation is possible.

Our findings confirmed previous observational studies indicating the high frequency of antibiotics as drugs clinically associated with AGEP onset, especially beta-lactam antibacterials. Antibiotics are often the most prevalent drugs associated with AGEP onset [7] [8] [9] [10] [11] [12] [13] [14] 265, 268, 269] , accounting for 17 out of the 26 (61.4%) AGEP cases studied by Barbaud et al. [8] , 26 of the 58 (44.8%) AGEP cases studied by Hotz et al. [265] , and 14 (66.7%) out of the 21 AGEP patients studied by Choon et al. [11] . Additionally, the beta-lactam antibacterial amoxicillin was the most reported drug (21.6%) in the study of 2649 AGEP individual case safety reports (ICSRs) with at least two reported drugs in the World Health Organization (WHO) pharmacovigilance database (WHO VigiBase) [266] . In the multinational EuroSCAR case-control study, which included 97 validated AGEP cases, antibiotics, such as pristinamycin, aminopenicillins, and quinolones, were suspect drugs in 10%, 19%, and 9% of the AGEP patients, respectively. Moreover, these agents were identified as being highly associated with AGEP [7] . In our review, the most common cause of AGEP was antinfectives, including antibiotics, antimycotics, antivirals, and vaccines. Almost one-third of the AGEP reports identified antibacterials as the suspected trigger of the skin reaction, and among those, beta-lactam antibacterials were identified in more than half of the events, followed by macrolides.

Following antibacterials and other anti-infective agents, the anti-inflammatory and anti-rheumatic products including hydroxychloroquine were also frequent among the AGEP triggers. Hydroxychloroquine was identified as the suspect drug in one of every eight patients (12.8%). This result was higher than the 7% previously observed by the EuroSCAR case-control study [7] . Since our data from 22 out of the 44 patients with hydroxychloroquine as the suspect drug were obtained from 15 articles from 2019 onwards, it might suggest a potential overestimation of the frequency of this drug in comparison to other treatments, maybe due to over-reporting as a consequence of the elevated attention given to this drug during the COVID-19 pandemic [270] .

Anti-cancer drugs were also identified as a leading cause of AGEP in our case series (8.1% of cases). In a study investigating the adverse effects associated with targeted and non-targeted chemotherapy, imatinib was identified as one of the common anti-cancer drugs responsible for AGEP [271] . Our study was in line with these findings.

While the medications most frequently associated with AGEP events do not always share a common pharmacological pathway, many reflect a patient profile with an "active" immune response (e.g., infection, inflammation, or autoimmune disease), or abnormal cell regulation (cancer). This could also be observed across the patient comorbidities and/or health burdens prior to AGEP. This may suggest that the patient condition for which the treatment is provided may have an impact on the development of AGEP. However, the presence of other drugs also commonly associated with this reaction, such as those for cardiovascular disease, or treatments for neurological diseases (e.g., antiepileptics), does not necessarily support this hypothesis.

In our secondary analysis where we investigated all reported drugs at the moment of AGEP onset, independently of being considered the suspect drug or not, we confirmed the strong presence of antibacterials among the patients. Interestingly, the frequency of blood/cardiovascular treatments in the all-drugs analysis was two to four times higher than in the analysis where only the suspect drugs were included, and 21.9% of patients had pre-existing cardiac/cardiovascular disease/event. While this could indicate an underlying disease-drug interaction, whereby patients with cardiac/cardiovascular diseases are at a higher susceptibility to experience AGEP, it could also suggest the potential for currently unknown drug-drug interactions or additive effects in patients with polypharmacy. A previous study identified the potential for drug interactions to play a role in the onset of Stevens-Johnson syndrome [272] . Similarly, it has been suggested that the high frequency of cardiovascular drugs observed in a data-driven pharmacovigilance study may suggest potential off-target drug-drug interactions [266] . Conversely, an alternative hypothesis could be the consequence of cardiovascular drugs being less commonly known as AGEP triggers, and therefore being less frequently identified as the suspect drug.

This study is an extensive compilation of published case reports, and it provides a detailed overview of both the drug triggers of AGEP and the clinical characteristics of the reaction. Additionally, we provide a summary table and reference to the included articles (Supplementary Material S2 Excel File), enabling other researchers to investigate additional queries in this case series. However, we acknowledge some limitations. First, while we completed a comprehensive literature review, we may have missed case-reports indexed elsewhere or published in a language other than English. This study's focus was on extracting case reports with detailed patient information and while case-series were eligible, larger studies (e.g., by Hotz et al. [265] ) may have been missed in the search. For example, the study by Hotz. et al. [265] included 58 patients from a single center and was not identified as a case-report and therefore it was missed in our analysis. We did not include the patients described in the multi-center study by Barbaud et al. [8] due to limited information on the individual patient level (26 patients with provided sex, age, and drug(s) with a positive patch test). While the inclusion of the patients from these case-series papers would increase the overall size of the database, we do not expect it to have shifted the overall interpretation as our findings are comparable to those from Hotz et al. and Barbaud et al. Second , there are intrinsic limitations of literature case series. This study design does not allow for assessment of disease incidence or prevalence at the population level, we are heavily reliant on the accuracy of the initial case-report data, and we may be subject to some selection bias (publication bias) due to only including those cases with published reports. Thus, the external validity of the findings should be taken with caution. However, it is expected that the informative character of the study findings would aid to better understand the clinic of AGEP. Following the similarities between AGEP and ALEP, we included both as AGEP; however, we recorded information on the extent of skin involvement. This information is available in the Supplementary Material S2 Excel File. The assessment of certain information was additionally a challenge due to the lack of uniformity across study reports. To address this limitation, we established internal rules for data collection (described in the methods section) to ensure consistency along the process. We noticed that the number of all drugs may be underestimated, since there were case reports in which one would have expected more medications than the reported ones in patients with comorbidities. Similarly, while we have trusted the judgement of the authors of each corresponding case report and accepted their selected suspect drug, we acknowledge the potential misclassification of the suspect drugs. We did not collect information on the performance of the EuroSCAR score, and only less than half of the included cases reported the performance of the patch test for identification of the responsible drug. Moreover, given that the pathogenesis and pathomechanism of AGEP are not well understood, it may be that the drugs most frequently reported in the literature may have in a subsequently higher likelihood of being identified as causative agents. Hence, we acknowledge that the causative agent could have been one of the other concomitant drugs not considered as the suspect drug. Thus, to address this limitation, we provided a secondary analysis including every reported drug, independently of the suspect label. Additionally, since 50.5% of patients were treated with more than one drug, studying the impact of drug combinations with the collected data would be of interest.

This comprehensive overview of published case reports provides a large case series of drug-associated AGEP, thereby permitting further understanding of the patient characteristics and drugs associated with this rare, and potentially fatal, adverse drug reaction. Due to the difficulties of studying rare adverse drug reactions, we expect that our study strongly contributes to the current evidence on AGEP. Among the 297 studied patients (mean age of 48.8 years old; women 64.3%), more than half developed fever, and almost 20% had systemic involvement. The majority received pharmacological treatment to address the skin reaction. Antibacterial drugs were the most commonly reported drug class, both overall and as the identified suspect agent. Seven patients died, but the role of AGEP in the cause of death may be difficult to disentangle from the previous health condition of the corresponding patients, and the publication bias. Finally, we provide a comprehensive database with the 297 patients from the included published case reports, thereby providing the largest publicly available case-series. In particular, the generated dataset may be used by others to describe AGEP cases and address additional questions related to polypharmacy, drug-drug interactions, and drug-disease interactions. Nevertheless, additional observational data is required to further elucidate the case-fatality rates and longitudinal outcomes within the population.

Supplementary Materials: The following are available online at https://www.mdpi.com/article/ 10.3390/jcm11020397/s1, Supplementary Material S1 Figure S1 : Time to onset (days) histogram, Supplementary Material S1 Table S1 : Patient baseline comorbidities, Supplementary Material S1 Table S2 : Treatment for the Acute Generalized Exanthematous Pustulosis (AGEP) reaction, Supplementary Material S1 Table S3 : Suspect drugs. Information from 297 patients, who can contribute with more than one drug each, Supplementary Material S1 Table S4 : All reported drugs, independently of being or not suspect. Information from 297 patients, who can contribute with more than one drug each, Supplementary Material S2 Excel File. 

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Acute Generalized Exanthematous Pustulosis Induced by Topical Lindane

Acute Generalized Exanthematous Pustulosis in a Child with Fasciitis

COVID-19 Vaccine-Induced Acute Generalized Exanthematous Pustulosis

Acute Generalized Exanthematous Pustulosis Caused by Morphine, Confirmed by Positive Patch Test and Lymphocyte Transformation Test

Acute Generalized Exanthematous Pustulosis Induced by Etanercept: Another Dermatologic Adverse Effect

Cetirizine Induced Acute Generalized Exanthematous Pustulosis Confirmed by Patch Testing

Acute Generalized Exanthematous Pustulosis Caused by Diltiazem

Acute Generalized Exanthematous Pustulosis Caused by Radiocontrast Media

Acute Localized Exanthematous Pustulosis Induced by Docetaxel

Acute Generalised Exanthematous Pustulosis and Other Severe Drug Eruptions from over the Counter Medications: A Case Report and Review of the Literature

Photoinduced Acute Exanthematous Pustulosis Caused by Ciprofloxacin and Sunlight Exposure

Acute Generalized Exanthematous Pustulosis Caused by Erlotinib in a Patient with Lung Cancer

Acute Localized Exanthematous Pustulosis Due to Metronidazole

A Rapidly Progressive and Fatal Case of Atypical Acute Generalized Exanthematous Pustulosis

Acute Generalized Exanthematous Pustulosis Secondary to Acyclovir Confirmed by Positive Patch Testing

Hydroxyzine-Induced Acute Generalized Exanthematous Pustulosis: An Uncommon Side Effect of a Common Drug

Acute Generalized Exanthematous Pustulosis Induced by Pseudoephedrine in a Combination Tablet with Fexofenadine

Piperacillin/Tazobactam as Cause of Acute Generalized Exanthematous Pustulosis

An Unusual Photodistributed Acute Generalized Exanthematous Pustulosis Induced by Terbinafine

Lapatinib-Induced Acute Generalized Exanthematous Pustulosis

Lornoxicam-Induced Acute Generalized Exanthematous Pustulosis

Localized Toxic Pustuloderma Associated with Nimesulide Therapy Confirmed by Patch Testing

Acute Generalized Exanthematous Pustulosis with Severe Organ Dysfunction

Acute Generalized Exanthematous Pustulosis in Children and Adolescents in Singapore: A Ten-Year Retrospective Review

Acute Patchy Exanthematous Pustulosis Caused by Sulfamethoxazole-Trimethoprim

Acute Generalized Exanthematous Pustulosis

Acute Generalized Exanthematous Pustulosis Induced by a Digestive Enzyme Drug, Festal ®

Acute Generalized Exanthematous Pustulosis in a Six-Year-Old Boy

Acute Generalized Exanthematous Pustulosis Caused by Daptomycin

Acute Generalized Exanthematous Pustulosis Secondary to Levetiracetam and Valproic Acid Use

Acute Generalized Exanthematous Pustulosis with Airway Mucosa Involvement: A Case Report

Importance of Allergological Evaluation and Skin Testing for Severe Cutaneous Adverse Reactions: A Case Report

Sorafenib-Induced Acute Localized Exanthematous Pustulosis in a Patient with Hepatocellular Carcinoma

The First Pediatric Case of Acute Generalized Exanthematous Pustulosis Caused by Hydroxychloroquine

Acute Generalized Exanthematous Pustulosis Induced by Erlotinib (Tarceva) with Superimposed Staphylococcus Aureus Skin Infection in a Pancreatic Cancer Patient: A Case Report

Acute Generalized Exanthematous Pustulosis Induced by Terbinafine

A Case of Severe Cutaneous Adverse Reaction Following Administration of the Janssen Ad26.COV2.S COVID-19 Vaccine

Acute Generalized Exanthematous Pustulosis Induced by Iomeprol with Cross-Reactivity to Other Iodinated Contrast Agents and Mild Reactions after Rechallenge with Iopromide and Oral Corticosteroid Premedication

Etoricoxib-Induced Acute Generalized Exanthematous Pustulosis

Acute Generalized Exanthematous Pustulosis Induced by Paroxetine in an Adolescent Girl

Acute Generalized Exanthematous Pustulosis Induced by Cetuximab

Acute Generalized Exanthematous Pustulosis Caused by Fexofenadine

Acute Generalized Exanthematous Pustulosis Caused by the Combination of Pembrolizumab Plus Chemotherapy in a Patient With Squamous-Cell Carcinoma

Acute Generalized Exanthematous Pustulosis Induced by Hydroxychloroquine Successfully Treated with Etretinate

Influenza Vaccine-Induced Acute Generalized Exanthematous Pustulosis during Pregnancy

Vancomycin-Induced Acute Generalized Exanthematous Pustulosis (AGEP) Masquerading Septic Shock-an Unusual Presentation of a Rare Disease

Acute Generalized Exanthematous Pustulosis in Close Temporal Association with MRNA-1273 Vaccine

Acute Generalized Exanthematous Pustulosis Caused by Iopamidol with Recurrence on Rechallenge with Iopromide. JAAD Case Rep

Tosufloxacin-Induced Acute Generalized Exanthematous Pustulosis Confirmed by a Drug-Induced Lymphocyte Stimulation Test. JAAD Case Rep

The Necessity of Patch Testing in Determining the Causative Drug of AGEP

A Case of Prolonged Generalized Exanthematous Pustulosis Caused by Hydroxychloroquine-Literature Review

Acute Generalized Exanthematous Pustulosis Secondary to Oral Nystatin

Acute Generalized Exanthematous Pustulosis Simulating Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Associated with the Use of Vismodegib

Cutaneous Vasculitis Overlap with Acute Generalised Exanthematous Pustulosis (AGEP)

Acute Generalized Exanthematous Pustulosis Triggered by Acetaminophen in an IL36RN Variant Heterozygote

Acute Generalized Exanthematous Pustulosis Due to Etodolac in a Patient with an Iliopsoas Muscle Abscess

Photoinduced Acute Exanthematous Pustulosis Caused by Dicloxacillin and Exposure to Sunlight

A Severe Presentation of Acute Generalized Exanthematous Pustulosis with Non-Infectious Circulatory Shock in an Adolescent

Nystatin-Induced Acute Generalized Exanthematous Pustulosis

Prolonged Acute Generalized Exanthematous Pustulosis and Atypical Target-like Lesions Induced by Hydroxychloroquine

A Case of Acute Generalized Exanthematous Pustulosis Caused by Lincomycin

Localized Acute Generalized Exanthematous Pustulosis with Amoxicillin and Clavulanic Acid

Acute Generalized Exanthematous Pustulosis Associated with Tigecycline

Acute Generalized Exanthematous Pustulosis Induced by Iodixanol (Visipaque): A Serious Reaction to a Commonly Used Drug

Acute Generalized Exanthematous Pustulosis Associated with Ipilimumab and Nivolumab

Acute Generalized Exanthematous Pustulosis-like, Folliculitic Drug Reaction Pattern Caused by Celecoxib

Severe Drug-Induced Kidney Injury in Acute Generalized Exanthematous Pustulosis

Acute Generalized Exanthematous Pustulosis Induced by Hydroxychloroquine: Three Cases and a Review of the Literature

A Case of Hydroxychloroquine Induced Acute Generalized Exanthematous Pustulosis Confirmed by Accidental Oral Provocation

Acute Generalized Exanthematous Pustulosis (AGEP) Secondary to Olanzapine

Acute Generalized Exanthematous Pustulosis as a Delayed Dermatotoxic Reaction to IV-Administered Nonionic Contrast Media

Cannabidiol-Induced Acute Generalized Exanthematous Pustulosis

A Case of Vancomycin-Induced Acute Generalized Exanthematous Pustulosis Confirmed by Patch Testing

Acute Generalized Exanthematous Pustulosis

Acute Generalized Exanthematous Pustulosis: The First Pediatric Case Caused by a Contrast Agent

Probable Fenofibrate-Induced Acute Generalized Exanthematous Pustulosis

Acute Generalized Exanthematous Pustulosis Induced by Sorafenib

Widespread Pustular Eruption Following Probiotic Use

Recurrent Localized Pustular Eruption Induced by Amoxicillin

Cutaneous Eruption in COVID-19-Infected Patients in Thailand: An Observational Descriptive Study

Acute Localized Exanthematous Pustulosis Caused by Cefoperazone and Sodium Sulbactam

Two Cases of Amoxycillin-Induced Follicular Acute Localised Exanthematous Pustulosis

Acute Generalized Exanthematous Pustulosis Due to Dextromethorphan

Acute Localized Exanthematous Pustulosis (ALEP) Caused by Ibuprofen A Case Report

Hydrochlorothizide-Induced Acute Generalised Exanthematous Pustulosis Presenting with Bilateral Periorbital Impetigo

Fever, and a Fiery Red Rash: A Case of AGEP Secondary to Diltiazem

Acute Generalized Exanthematous Pustulosis Overlapping with Toxic Epidermal Necrolysis Successfully Treated with Etanercept

Acute Generalized Exanthematous Pustulosis with Erythema Multiforme-like Lesions Induced by Hydroxychloroquine in a Woman with Coronavirus Disease 2019 (COVID-19)

Acute Generalized Exanthematous Pustulosis with Multisystem Manifestations: Pinpoint Pustules and Purulent Lakes

Acute Generalized Exanthematous Pustulosis Due to Terbinafine

Acute Localised Exanthematous Pustulosis: Case Report, Review of the Literature and Proposed Diagnostic Criteria

Fluconazole-Induced Acute Generalized Exanthematous Pustulosis

Acute Generalized Exanthematous Pustulosis Due to Ceftriaxone: Report of a Pediatric Case with Recurrence after Positive Patch Test

A Plethora of Pustules: Acute Generalized Exanthematous Pustulosis

Hydroxychloroquine-induced Acute Generalized Exanthematous Pustulosis: An Adverse Reaction to Keep in Mind during COVID-19 Pandemic

Acute Generalized Exanthematous Pustulosis Induced by Docetaxel and Recurrent With Letrozole: A Case Report

Dabigatran-Associated Acute Generalized Exanthematous Pustulosis (AGEP) in a Psoriatic Patient Undergoing Ixekizumab and Its Pathogenetic Mechanism

Imatinib-Induced Acute Generalized Exanthematous Pustulosis (AGEP) in Two Patients with Chronic Myeloid Leukemia

Acute Generalized Exanthematous Pustulosis (AGEP) Secondary to Imatinib in a Patient with Chronic Myeloid Leukaemia

Infliximab-Induced Acne and Acute Localized Exanthematous Pustulosis: Case Report

Triad of Acute Generalized Exanthematous Pustulosis, Delirium, and Lactic Acidosis Due to Azithromycin. JAAD Case Rep

Gefitinib-Induced Acute Generalized Exanthematous Pustulosis in Two Patients with Advanced Non-Small-Cell Lung Cancer

A Case of Celecoxib Induced Acute Generalized Exanthematous Pustulosis

Acute Generalized Exanthematous Pustulosis Caused by Praziquantel

Rare Case of Phenytoin Induced Acute Generalized Exanthematous Pustulosis with Cerebellar Syndrome

Recurrent Pustular Eruption Following Amoxycillin Administration

Acute Localized Exanthematous Pustulosis on the Face

Carbamazepine-Induced Acute Generalized Exanthematous Pustulosis: A Case Report

DRESS and AGEP Reactions to Iodinated Contrast Media: A French Case Series

FISARD (French Investigators for Skin Adverse Reaction to Drugs). Cutaneous Adverse Drug Reactions with Antimalarials and Allergological Skin Tests

Images in Emergency Medicine: Acute Generalized Exanthematous Pustulosis

Severe Adverse Drug Reaction in SARS-CoV-2 Infection: AGEP Induced by Ceftriaxone and Confirmed by Patch Test

A Case of Acute Generalized Exanthematous Pustulosis after Injection of an Erythropoiesis-Stimulating Agent

Acute Generalized Exanthematous Pustulosis with Multiple Organ Failure

Life-Threatening Atypical Case of Acute Generalized Exanthematous Pustulosis

An Uncommon Side Effect of Bupropion: A Case of Acute Generalized Exanthematous Pustulosis

Acute Generalized Exanthematous Pustulosis Caused by an Intravenous Radiocontrast Medium

Severe Acute Generalized Exanthematous Pustulosis (AGEP) Induced by Miconazole Oral Gel with Overlapping Features of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Acute Generalized Exanthematous Pustulosis with Photodistribution Pattern Induced by Sertraline

DeRmpath&Clinic: Acute Generalised Exanthematous Pustulosis

A Case of Cefditoren-Induced Acute Generalized Exanthematous Pustulosis during COVID-19 Pandemics. Severe Cutaneous Adverse Reactions Are an Issue

Acute Generalized Exanthematous Pustulosis in a Postpartum Woman

Cell-Mediated Acute Localized Exanthematous Pustulosis Caused by Finasteride

Prolonged Course of Acute Generalized Exanthematous Pustulosis with Liver Involvement Due to Sensitization to Amoxicillin and Paracetamol

Acute Localized Exanthematous Pustulosis Caused by a Herbal Medicine, Dai-Kenchu-To

Acute Generalized Exanthematous Pustulosis (AGEP) Caused by Telavancin

Paediatric Acute Generalized Exanthematous Pustulosis Induced by Paracetamol with High Serum Levels of Interleukin-8 and -22: A Case Report

Acute Generalized Exanthematous Pustulosis Caused by an Iodinated Contrast Radiocontrast Medium for Computed Tomography Arthrography of the Knee

Acute Localized Exanthematous Pustulosis: A Cutaneous Drug Reaction in a Dental Setting

Oral Lesions of Acute Generalized Exanthematous Pustulosis

Acute Localized Exanthematous Pustulosis (ALEP): Review of Literature with Report of Case Caused by Amoxicillin-Clavulanic Acid

Diltiazem-Induced Acute Generalised Exanthematous Pustulosis

Acute Generalized Exanthematous Pustulosis Induced by Generic Hydroxychloroquine

A Case of Acute Generalized Exanthematous Pustulosis Possibly Induced by Ritodrine

Acute Generalized Exanthematous Pustulosis Possibly Induced by Acarbose

Curcumin-Induced Acute Generalized Exanthematous Pustulosis

Oxford-AstraZeneca COVID-19 Vaccine-Induced Acute Localized Exanthematous Pustulosis

Successful Treatment of Hydroxychloroquine-Induced Recalcitrant Acute Generalized Exanthematous Pustulosis with Cyclosporine: Case Report and Literature Review

A Case of Eperisone Hydrochloride-Induced Acute Generalized Exanthematous Pustulosis

Acute Generalized Exanthematous Pustulosis Associated with Helicobacter Pylori Eradication Therapy with Elevated Serum Procalcitonin

Ibuprofen-Induced Acute Generalized Exanthematous Pustulosis

A Case of Paracetamol-Induced Acute Generalized Exanthematous Pustulosis in a Pregnant Woman Localized in the Neck Region

First Case Report of Acute Generalized Exanthematous Pustulosis (AGEP) Caused by Mifepristone

Acute Generalized Exanthematous Pustulosis

A Case of Ceftriaxone-Induced Acute Generalized Exanthematous Pustulosis/Generalized Pustular Psoriasis Overlap

Systemic Involvement of Acute Generalized Exanthematous Pustulosis: A Retrospective Study on 58 Patients

A Network Analysis of Drug Combinations Associated with Acute Generalized Exanthematous Pustulosis (AGEP)

A Systematic Review of the Prevalence and Risk Factors for Adverse Drug Reactions in the Elderly in the Acute Care Setting

Acute Generalized Exanthematous Pustulosis: Analysis of Cases Managed in a Tertiary Hospital in Singapore

Acute Generalized Exanthematous Pustulosis: Analysis of 63 Cases

Use of Repurposed and Adjuvant Drugs in Hospital Patients with COVID-19: Multinational Network Cohort Study

Adverse Reactions to Targeted and Non-Targeted Chemotherapeutic Drugs with Emphasis on Hypersensitivity Responses and the Invasive Metastatic Switch

Correlation between Drug-Drug Interaction-Induced Stevens-Johnson Syndrome and Related Deaths in Taiwan