Exanthematous Pustulosis Research Articles

Clinicopathological characteristics of cutaneous complications following COVID-19 vaccination: A case series.

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

Acute generalized exanthematous pustulosis induced by isoniazid and pyrazinamide in a child

An 8-year-old female with cervical lymph node tuberculosis, received rifampicin, isoniazid, pyrazinamide, and ethambutol. Two weeks later, she developed a fever and a generalized erythematous rash covered with pustules. Acute generalized exanthematous pustulosis diagnosis was confirmed by a skin biopsy. Antitubercular therapy was discontinued. Drug causality was found using oral provocation tests and patch tests. Cutaneous adverse drug reactions to first-line antituberculosis drugs are common. However, acute generalized exanthematous pustulosis is rare. It is a severe form of cutaneous drug reaction, primarily associated with beta-lactam antibiotics, and clinically characterized by non-follicular pustules on erythematous skin.

Association between HLA alleles and beta-lactam antibiotics-related severe cutaneous adverse reactions.

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.

Ceftriaxone induced acute generalized exanthematous pustulosis confirmed with patch test

Background: Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous drug reaction presenting with rapid-onset sterile pustules on edematous erythema. Case: A 12-year-old female patient with acute gastroenteritis was consulted with complaints of pruritic erythema and high fever developing with small pustules on the 2nd day of ceftriaxone treatment. Lab tests showed an elevated absolute neutrophil count and lymphopenia. Ceftriaxone was discontinued immediately. The fever went away within 24 hours. According to EuroSCAR, the diagnosis of AGEP was confirmed. The skin biopsy was compatible with AGEP. After 6 weeks, a patch test with ceftriaxone was performed. A strong positive reaction to ceftriaxone was detected. Three months later, amoxicillin, amoxicillin-clavulanate, clarithromycin, and trimethoprim/sulfamethoxazole patch tests were performed, all were negative, and provocation tests were also planned. Conclusion: AGEP is a severe cutaneous drug reaction. We wanted to emphasize that patch tests help identify the responsible drug and find a safe alternative.

Stevens-johnson Syndrome and Toxic Epidermal Necrolysis: An Overview of Diagnosis, Therapy Options and Prognosis of Patients.

Both Stevens-johnson syndrome (SJS) and Toxic-epidermal necrolysis (TEN) are generally medication-induced pathological conditions that mostly affect the epidermis and mucus membranes. Nearly 1 to 2 patients per 1,000,000 population are affected annually with SJS and TEN, and sometimes these maladies can cause serious life-threatening events. The reported death rates for SJS range from 1 to 5%, and 25 to 35% for TEN. The mortality risk may even be higher among elderly patients, especially in those who are affected by a significant amount of epidermal detachment. More than 50% of TEN patients who survive the illness may experience long-term lower quality of life and lesser life expectancy. The clinical and histopathological conditions of SJS and TEN are characterized by mucocutaneous discomfort, haemorrhagic erosions, erythema, and occasionally severe epidermal separation that can turn into ulcerative patches and dermal necrosis. The relative difference between SJS and TEN is the degree of ulcerative skin detachment, making them two extremes of a spectrum of severe cutaneous adverse drug-induced reactions (cADRs). In the majority of cases, serious drug-related hypercreativities are considered the main cause of SJS & TEN; however, herpes simplex virus and Mycoplasma pneumoniae infections may also produce similar type clinical conditions. The aetiology of a lesser number of cases and their underlying causative factors remain unknown. Among the drugs with a 'greater likelihood' of causing TEN & SJS are carbamazepine (CBZ), trimethoprim-sulfamethoxazole, phenytoin, aminopenicillins, allopurinol, cephalosporins, sulphonamides, antibiotics, quinolones, phenobarbital, and NSAIDs of the oxicam variety. There is also a strong genetic link between the occurrence of SJS and IEN in the Han Chinese population. Such genetic association is based on the human leukocyte antigen (HLA-B*1502) and the co-administration of carbamazepine. The diagnosis of SJS is made mostly on the gross observations of clinical symptoms, and confirmed by the histopathological examination of dermal biopsies of the patients. The differential diagnoses consist of the exclusion of Pemphigus vulgaris, bullous pemphigoid, linear IgA dermatosis, paraneoplastic pemphigus, disseminated fixed bullous drug eruption, acute generalized exanthematous pustulosis (AGEP), and staphylococcal scalded skin syndrome (SSSS). The management of SJS & TEN is rather difficult and complicated, and there is sometimes a high risk of mortality in seriously inflicted patients. Urgent medical attention is needed for early diagnosis, estimation of the SCORTEN prognosis, identification and discontinuation of the causative agent as well as highdose injectable Ig therapeutic interventions along with specialized supportive care. Historical aspects, aetiology, mechanisms, and incidences of SJS and TEN are discussed. An update on the genetic occurrence of these medication-related hypersensitive ailments as well as different therapy options and management of patients is also provided.

42219 Multi-institutional retrospective review of acute generalized exanthematous pustulosis (AGEP) induced by hydroxychloroquine

42219 Multi-institutional retrospective review of acute generalized exanthematous pustulosis (AGEP) induced by hydroxychloroquine

Acute localized exanthematous pustulosis of the leg: A case report

AbstractWe report a case of an unusually located site of acute localized exanthematous pustulosis in the right lower limb of a patient treated with beta‐lactams which resolved upon cessation. This case report highlights the need for vigilance as well as an index of suspicion for atypical presentations.

A Rare Dermatologic Reaction in an Adult Patient Following Coronary Angiography: Acute Generalized Exanthematous Pustulosis.

The Article Abstract is not available.

Pustular Eruption following COVID-19 Vaccination: A Narrative Case-Based Review.

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.

Immune Reactions in Major Types of Oncological Treatment.

In recent years, there has been a noticeable development in oncological treatment, including chemotherapy and biological treatment. Despite their significant effectiveness, they are not free from side effects, such as allergic and dermatological reactions. These reactions can vary in severity and outcome, including potential death. Examples, among others, are type I-IV hypersensitivity reactions of various origins and skin reactions including rashes, itching and redness, but also severe cutaneous syndromes. Due to the therapy used, these may include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis. In some cases, it is necessary to interrupt therapy, which may result in a poorer outcome and shorten the patient's survival. This paper reviews various types of research documents published since 2016. It aims to systematize the latest knowledge and highlight the need for further research into ways to avoid adverse reactions.

Acute generalized exanthematous pustulosis withsystemic involvement.

Acute generalized exanthematous pustulosis withsystemic involvement.

RARE CASE OF ACUTE LOCALIZED EXANTHEMATOUS PUSTULOSIS OVER FOREARM UNDERNEATH FIBERGLASS CAST FOR LOWER END RADIUS FRACTURE

Plaster casting is the most important tool in the practice of orthopedics. It is used to operate on fractures to treat them either permanently or afterward. Although there are disadvantages including stiffness, pressure sores, and compartment syndrome, orthopedic casting is nevertheless beneficial. Early warning indications include skin lesions like bullae and ecchymosis, as well as pain, soreness, itching, and systemic sickness that is out of proportion to the localized physical signs. The development of ALEP/AGEP is commonly within days after beginning a drug. We present a case of an uncommon orthopedic cast complication involving a previously healthy patient who developed an acute localized exanthematous pustulosis over forearm inside a fibreglass cast applied for treatment of lower end radius fracture. A less common, more localized variation of AGEP is acute localized exanthematous pustulosis, or ALEP. With the right casting procedure and routine cast reviews, all of these issues may be avoided.

Rare Skin Eruption Caused by Paracetamol: A Case of Acute Generalized Exanthematous Pustulosis

Background: This case report aims to enhance clinicians' ability to identify and effectively manage rare skin eruptions, specifically focusing on Acute Generalized Exanthematous Pustulosis (AGEP) by providing valuable insights into the context of its diagnostic challenges and clinical implications.
 Presentation of Case: We present a case of AGEP in a 16-year-old Indian boy who developed generalized pustulosis after taking Paracetamol (Acetaminophen). The patient's diagnosis was initially delayed due to the resemblance of AGEP with other skin conditions. Furthermore, the inadvertent reintroduction of Paracetamol exacerbated the condition.
 Discussion: We discuss various treatment options and emphasize the importance of prompt and accurate diagnosis of AGEP by utilizing the AGEP validation. By employing this scoring system, clinicians can enhance their diagnostic accuracy and avoid unnecessary delays in treatment initiation.
 Conclusion: The prompt identification of AGEP using the AGEP validation score is crucial for timely management. This case report highlights the potential risks associated with common drugs like Paracetamol and emphasizes the need for vigilance in prescribing medications. Clinicians should be aware of the distinctive features of AGEP and consider it as a differential diagnosis in patients presenting with pustular skin eruptions following drug intake. Improved awareness and application of diagnostic tools can aid in better patient outcomes.

Deadly drug rashes: Early recognition and multidisciplinary care.

Potentially deadly drug rashes include Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, and drug-induced vasculitis. Differentiating them can be a challenge. Factors to consider include timing of rash to drug exposure, rash distribution and clinical appearance, and the presence of systemic features such as mucosal involvement, organ failure, or eosinophilia. Various scoring systems aid in the diagnosis, but skin biopsy is the gold standard. Prompt identification and withdrawal of the suspected offending agent are the crucial first steps in management.

Acute Localized Exanthematous Pustulosis Induced by a Spider Bite.

Acute Localized Exanthematous Pustulosis Induced by a Spider Bite.

Cutaneous Loxoscelism On 5 Moroccan Cases

Introduction: Loxoscelism is an under-diagnosed condition due to lack of awareness among practitioners. It is a serious form of araneism that can be strictly cutaneous with variable clinical aspects that can be deadly. Materials and methods: Five cases were collected over a period of 3 years presenting with envenomation by a supposed spider bite highly suggestive of cutaneous loxoscelism. Results: We collected five cases of post-spider bite envenomation with an average age of 45 years, predominantly female, of rural origin. The bite occurred in the summer in all cases. The average time to consultation was 2 days. Four patients had felt and located the spider nearby. Two patients had an erysipéloïde placard centred by a necrotic ulceration, while one had post-bite erythema multiforme, one had acute exanthematous pustulosis and one had acute urticaria. Biological tests were normal in all cases. Antihistamines and dermocorticoids were prescribed. Discussion: This type of envenomation is common in the summer months and in rural areas, with a clear female predominance. It is generally induced by the venom of spiders of the sicariidae family and of the Loxosceles genus. The diagnosis is based on a combination of epidemiological, clinical and biological evidence. Conclusion: Envenomation by spider bites has been little reported in Morocco until now. This rare cause of necrosis, skin rash deserves to be known by practitioners for an adequate management.

Key factors predicting the in-hospital mortality of patients with severe cutaneous adverse reactions in Thailand.

At present, no predictive models are available to determine the probability of in-hospital mortality rates (HMRs) in all phenotypes of severe cutaneous adverse reactions (SCARs). Our study explored whether simple clinical and laboratory assessments could help predict the HMRs in any phenotypes of SCAR patients. Factors influencing HMRs in 195 adults diagnosed with different SCAR phenotypes were identified, and their optimal cut-offs were determined by Youden's index. Predictive equations for HMRs for all SCAR patients and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) patients were determined using the exact logistic regression models. Acute generalized exanthematous pustulosis (AGEP) patients were significantly older, with a short time from drug exposure to reaction, and higher neutrophil count compared to SJS/TEN and drug reaction with eosinophilia and systemic symptoms (DRESS, p < 0.001). Peripheral blood eosinophilia, atypical lymphocytosis and elevated liver transaminase enzymes were significantly higher in DRESS. SJS/TEN phenotype, age ≥ 71.5 years, neutrophil-to-lymphocyte ratio ≥ 4.08 (high NLR) and systemic infection were factors predicting in-hospital mortality in all SCAR subjects. The ALLSCAR model developed from these factors demonstrated high-diagnostic accuracy for predicting HMRs in all SCAR phenotypes (area under the receiver-operator curve (AUC) = 0.95). The risk of in-hospital death was significantly increased in SCAR patients with high NLR after adjusting for systemic infection. The model derived from high NLR, systemic infection and age yielded higher accuracy than SCORTEN (AUC = 0.77) for predicting the HMRs in SJS/TEN patients (AUC = 0.97). Being older, having systemic infection, having a high NLR and SJS/TEN phenotype increases ALLSCAR scores, which in turn increases the risk of in-hospital mortality. These basic clinical and laboratory parameters can easily be obtained in any hospital setting. Despite its simple approach, further validation of the model is warranted.

Severe Cutaneous Adverse Drug Reactions at a Tertiary Care Center in Saudi Arabia.

Severe cutaneous adverse drug reactions (SCARs), although rare, are known to be associated with significant morbidity and mortality. SCARs include drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and acute generalized exanthematous pustulosis (AGEP). Studies on SCARs are limited in Saudi Arabia. This study aims to characterize SCARs at a tertiary care center in Saudi Arabia. A cross-sectional study was conducted at King Abdulaziz Medical City, Riyadh, Saudi Arabia. All inpatient and emergency department consultations to dermatology were electronically reviewed during the period from January 2016 to December 2020. All patients who developed an adverse cutaneous drug reaction were enrolled. Detailed analysis was performed only for SCARs. The culprit medication was determined based on the latency period, history of previous intake of the medication, and drug notoriety. There were 3050 hospital consultations to dermatology during the study period. Cutaneous adverse drug reactions constituted 253 (8.3%) cases. A total of 41 patients with SCARs were identified, accounting for 16.2% of all cutaneous drug reactions. Antibiotics and anticonvulsants were the most common causative drug groups accounting for 28 (68.3%) and 9 (22%) cases, respectively. DRESS was the most common SCAR. The latency period was the longest for DRESS and shortest for AGEP. Vancomycin was responsible for approximately a third of DRESS cases. Piperacillin/tazobactam was the most common cause for SJS/TEN and AGEP. The majority of drugs causing AGEP were antibiotics. The mortality rate was the highest in SJS/TEN (5/11 (45.5%)), followed by DRESS (1/23 (4.4%)) and AGEP (1/7 (14.3%)). SCARs are rare in Saudis. DRESS appears to be the most common SCAR in our region. Vancomycin is responsible for most cases of DRESS. SJS/TEN had the highest mortality rate. More studies are required to further characterize SCARs in Saudi Arabia and Arabian Gulf countries. More importantly, thorough studies of HLA associations and lymphocyte transformation tests among Arabs with SCARs are likely to further improve patient care in the Arabian Gulf region.

Acute Generalized Exanthematous Pustulosis: Clinical Features, Differential Diagnosis, and Management.

Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, and drug-induced etiologies. Diagnosis of AGEP depends on both clinical and histologic criteria, as cases of overlap with other disease processes have been reported. Management includes removal of the offending drug or treatment of the underlying cause, if necessary, and supportive care, as AGEP is a self-limited disease. This review aims to provide an overview and update on the epidemiology, pathogenesis, reported precipitating factors, differentials, diagnosis, and management of AGEP.

Current understanding of genetic associations with delayed hypersensitivity reactions induced by antibiotics and anti-osteoporotic drugs.

Drug-induced delayed hypersensitivity reactions (DHRs) is still a clinical and healthcare burden in every country. Increasing reports of DHRs have caught our attention to explore the genetic relationship, especially life-threatening severe cutaneous adverse drug reactions (SCARs), including acute generalized exanthematous pustulosis (AGEP), drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). In recent years, many studies have investigated the immune mechanism and genetic markers of DHRs. Besides, several studies have stated the associations between antibiotics-as well as anti-osteoporotic drugs (AOD)-induced SCARs and specific human leukocyte antigens (HLA) alleles. Strong associations between drugs and HLA alleles such as co-trimoxazole-induced DRESS and HLA-B*13:01 (Odds ratio (OR) = 45), dapsone-DRESS and HLA-B*13:01 (OR = 122.1), vancomycin-DRESS and HLA-A*32:01 (OR = 403), clindamycin-DHRs and HLA-B*15:27 (OR = 55.6), and strontium ranelate (SR)-SJS/TEN and HLA-A*33:03 (OR = 25.97) are listed. We summarized the immune mechanism of SCARs, update the latest knowledge of pharmacogenomics of antibiotics- and AOD-induced SCARs, and indicate the potential clinical use of these genetic markers for SCARs prevention in this mini review article.