Search

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction (SCAR) characterized by sterile non-follicular pustules on an erythematous base that form rapidly after drug exposure. AGEP is mediated by numerous cytokines produced by drug specific T-cells that mediate neutrophilic intracorneal, subcorneal, and/or intraepidermal pustule development. Though genetic susceptibility is not fully understood, individuals with mutations in IL-36RN may be at increased risk of AGEP development. AGEP commonly presents with leukocytosis and fever in the acute pustular phase and follows a self-limited desquamative recovery phase upon removal of offending drug. Severe cases of AGEP may have multisystem organ involvement. Atypical presentations of AGEP include localized eruptions and cases with overlapping clinical and histopathological features associated with Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and generalized pustular psoriasis. Most cases of AGEP clear rapidly with systemic corticosteroids, but severe or recalcitrant cases may require other systemic therapies such as cyclosporine, and intravenous immunoglobulin.

Acute Generalised Exanthematous Pustulosis (AGEP) is a rash with multiple sterile intraepidermal or subcorneal non-follicular pustules on edematous papules, with a sudden development and rapid evolution, triggered by drugs, vaccination, insect bites, exposure to mercury, and allergens.We describe a female patient who developed extensive and abnormally prolonged AGEP following exposure to terbinafine and SARS-CoV vaccine. A detailed review of terbinafine-induced-AGEP cases was performed, with the aim of evaluating if the AGEP criteria would follow a different pattern when the disease is triggered by this drug. A PubMed search helped retrieve all terbinafine-induced AGEP case reports. AGEP-specific Sideroff criteria were analysed in terbinafine-induced cases and compared to other trigger causes.When the AGEP causative drug was terbinafine, a delay in recovery was observed, compared to the existing AGEP criteria when other causes are considered. Terbinafine frequently leads to delayed resolution AGEP probably due to the presence of the drug in the skin for several weeks after exposure, even after discontinuation, and the disease severity may be potentialised by additional factors such as concomitant viral infections or vaccination.

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. Conclusions 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.

Acute generalized exanthematous pustulosis is a rare disease. Although it is usually related to drug intake, it is occasionally associated with infections, especially in the pediatric age. It is characterized by the sudden onset of sterile non-follicular pustules on an erythematous fundus, fever, and leukocytosis, with frequent and prompt spontaneous resolution. It mainly affects adults and is uncommon in childhood. Complications have been reported in approximately 20% of cases.We report the case of a 10-year-old female patient with a 5-day history of fever and dermatosis characterized by countless non-follicular pustules, predominantly on the trunk, inguinal folds, and proximal thighs but not involving palms, soles, and mucous membranes. The patient reported an incident of upper respiratory tract infection that occurred 7 days earlier. Histopathological examination confirmed the diagnosis of acute generalized exanthematous pustulosis. Spontaneous resolution occurred within 2 weeks.This disease is one of the severe cutaneous adverse reactions that usually have a self-limited and benign course within a few weeks. We propose that a previous respiratory infection triggered the acute generalized exanthematous pustulosis in this pediatric case. Knowledge of this pathology by the medical professionals, in general, and the pediatricians, in particular, will prevent an aggressive and inappropriate approach and management.La pustulosis exantemática generalizada aguda es una enfermedad rara. Aunque usualmente se relaciona con el consumo de drogas, ocasionalmente se asocia con infecciones, sobre todo en edad pediátrica. Se caracteriza por el inicio súbito de pústulas no foliculares estériles sobre un fondo eritematoso, fiebre y leucocitosis, con frecuente y pronta resolución espontánea. Afecta principalmente a los adultos, y no es frecuente en la niñez. Se han reportado complicaciones en cerca del 20% de casos.Se presenta el caso de una paciente de 10 años con fiebre e historia de dermatosis de 5 días de evolución caracterizada por incontables pústulas no foliculares de predominio en tronco, pliegues inguinales y parte proximal de muslos, respetando palmas, plantas y mucosas. Refirió antecedente de infección respiratoria alta 7 días antes. El examen histopatológico confirmó el diagnóstico de pustulosis exantemática generalizada aguda. Presentó resolución espontánea en el transcurso de 2 semanas.Esta enfermedad es una de las reacciones adversas cutáneas severas, que tiene un curso usualmente autolimitado y benigno en pocas semanas. Proponemos que la pustulosis exantemática generalizada aguda en este caso pediátrico fue desencadenada por la infección respiratoria previa. El conocimiento de esta patología por parte del gremio médico, en general, y del pediatra, en particular, evitará un abordaje y manejo agresivo e inapropiado.

Background Elevated epidermal interleukin (IL)-36 expression distinguishes psoriasis from eczematous dermatitis, but other psoriasiform dermatitides (PDs) have not been thoroughly investigated for IL-36 expression. In this study, we assess the IL-36 staining pattern (IL36-SP) in psoriasis variants and other PDs including lichen simplex chronicus (LSC), prurigo nodularis (PN), lichen planus (LP), tinea, pityriasis rubra pilaris (PRP), mycosis fungoides (MF), pemphigus foliaceus (PF), acute generalized exanthematous pustulosis (AGEP), impetigo (IMP), and syphilis (SY). Methods IL-36 immunostaining was performed on 307 cases of psoriasis and various PDs. IL36-SP in the upper epidermis was graded on a scale of 0-4. Results High IL36-SP occurred in all variants of psoriasis, as well as in AGEP, PRP, PN, tinea, IMP, and LP (P > 0.05). SY, PF, LSC, and MF showed a lower IL36-SP (P ≤ 0.05) compared with psoriasis. Conclusion All variants of psoriasis exhibit high IL36-SP. IL-36 staining can assist in differentiating MF, PF, SY, and LSC from psoriasis, particularly MF and LSC, which have consistent low IL-36 expression. AGEP, PRP, tinea, IMP, PN, and LP exhibit high IL-36 expression similar to psoriasis, indicating Th17 activation in these diseases.

Background Drug reactions with eosinophilia and systemic symptoms (DRESSs) and acute generalized exanthematous pustulosis (AGEP) are potentially severe cutaneous adverse drug reactions. Objective To describe the clinical findings and sensitization profiles of DRESS and AGEP patients who had been administered iodinated contrast media (ICM). Methods All adult patients in the dermatologist's French Investigators for Skin Adverse Reactions to Drugs (FISARD) network diagnosed with a DRESS or AGEP highly suspected to have been caused by an ICM were included retrospectively. Results Thirteen DRESS patients and 19 AGEP patients who had been administered ICM were included, and the median delay in DRESS and AGEP occurrence after ICM administration was short, 4 and 1 days, respectively. Five AGEP patients had systemic involvement. A high cosensitization rate (46%) was observed among the DRESS patients, mainly with beta-lactam antibiotics. Overall, 77% of our patients were sensitized to several ICM. Patch tests identified the suspected ICM for 21 cases (72%). The retrospective nature, the limited number of subjects, the absence of a control group of healthy individuals, and the lack of detailed information on previous exposure to sensitizing drugs are limitations of this study. Conclusions We report a large series of DRESSs and AGEPs related to ICM administration. Skin tests appear useful for diagnosis and potentially to identify alternative ICM.

Adverse drug reactions involving the skin are commonly known as drug eruptions. Severe drug eruption may cause severe cutaneous adverse drug reactions (SCARs), which are considered to be fatal and life-threatening, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). Although cases are relatively rare, approximately 2% of hospitalized patients are affected by SCARs. There is an incidence of 2 to 7 cases/million per year of SJS/TEN and 1/1000 to 1/10,000 exposures to offending agents result in DRESS. However, the mortality rate of severe drug eruptions can reach up to 50%. SCARs represent a real medical emergency, and early identification and proper management are critical to survival. The common pathogenesis of severe drug eruptions includes genetic linkage with HLA- and non-HLA-genes, drug-specific T cell-mediated cytotoxicity, T cell receptor restriction, and cytotoxicity mechanisms. A multidisciplinary approach is required for acute management. Immediate withdrawal of potentially causative drugs and specific supportive treatment is of great importance. Immunoglobulins, systemic corticosteroids, and cyclosporine A are the most frequently used treatments for SCARs; additionally, new biologics and plasma exchange are reasonable strategies to reduce mortality. Although there are many treatment methods for severe drug eruption, controversies remain regarding the timing and dosage of drug eruption. Types, dosages, and indications of new biological agents, such as tumor necrosis factor antagonists, mepolizumab, and omalizumab, are still under exploration. This review summarizes the clinical characteristics, risk factors, pathogenesis, and treatment strategies of severe drug eruption to guide clinical management.

We present a severe case of acute generalized exanthematous pustulosis (AGEP) secondary to trimethoprim-sulfamethoxazole complicated by non-infectious circulatory shock in a 16-year-old boy. Hemodynamic instability has been reported as a complication of AGEP in adults, but is rarely observed in pediatric patients. The patient we present demonstrated characteristic cutaneous findings of AGEP including isolated non-follicular, sterile pustules on a background of erythema with involvement at intertriginous areas and subsequently developed non-infectious circulatory shock. This case expands the spectrum of possible clinical presentations for AGEP in pediatric patients.

Introduction: Pharmacogenomics has great potential in reducing drug-induced severe cutaneous adverse drug reactions (SCARs). Pharmacogenomic studies have revealed an association between HLA genes and SCARs including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).Areas covered: Pharmacogenomics-guided therapy could prevent severe drug hypersensitivity reactions. The US Food and Drug Administration (FDA), Clinical Pharmacogenetics Implementation Consortium (CPIC), and Dutch Pharmacogenetics Working Group (DPWG) provided guidelines in the translation of clinically relevant and evidence-based SCARs pharmacogenomics research into clinical practice. In this review, we intended to summarize the significant HLA alleles associated with SCARs induced by different drugs in different populations. We also summarize the SCARs associated with genetic and non-genetic factors and the cost-effectiveness of screening tests.Expert opinion: The effectiveness of HLA screening on a wider scale in clinical practice requires significant resources, including state-of-the-art laboratory; multidisciplinary team approach and health care provider education and engagement; clinical decision support alert system via electronic medical record (EMR); laboratory standards and quality assurance; evidence of cost-effectiveness; and cost of pharmacogenomics tests and reimbursement.

BACKGROUND & AIMS Severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are high-mortality adverse drug reactions. The risk factors and prognosis of drug-induced liver injury (DILI) concomitant with SCAR warrant clarification. We aimed to evaluate the characteristics and outcomes of DILI with SCAR. METHODS We analysed the database of a 10-year multi-centre prospective study in Taiwan from 2011 to 2020. RESULTS A total of 1415 patients with DILI were enrolled, including 81 cases combined with SJS/TEN, 74 with DRESS, 3 with AGEP and 1257 with pure DILI. Approximated 11.2% of patients had SCAR, of which allopurinol was the leading incriminated drug, followed by sulphonamides and carbamazepine. The SJS/TEN group had the highest mortality (34.6%). Jaundice, acute kidney injury and SJS/TEN were independent risk factors of mortality (odds ratio: 29.54, 4.43 and 4.86, respectively, P

Introduction: Acute Generalized Exanthematous Pustulosis (AGEP) is a cutaneous reaction that may appear after using certain medications, such as cephalexin. This disease is characterized by non-follicular sterile pustules, erythematous, urticaria, fever over , and leukocytosis. Cephalexin belongs to the family of β-lactam antibiotics, which are widely used to treat infections. However, cephalexin skin sensitivities have been reported rarely. Herein, in this case, we aimed to report a patient presented with AGEP due to cephalexin usage. Case Presentation: A 12-year-old boy presented with warm skin lesions that gradually appeared on the limbs, trunk, face, and neck after using cephalexin powder on his left leg injury. Because of his symptoms, acetaminophen, fexofenadine hydrochloride, loxoprofen sodium, and ointment, including difluprednate and hydrocortisone, were prescribed. Over time, the patient’s fever subsided, and 8 days later, the symptoms of AGEP, including urticaria, erythematous, and pustules in the neck and trunk, disappeared. Conclusions: Cephalexin is one of the antibiotics that doctors and patients consider when there is a possibility of infection. AGEP is a rare but severe reaction that can manifest as skin rashes in any age and sex following the use of cephalexin, so the patient should be careful when using this antibiotic.

Background Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse drug reaction. Although acutely patients have significant morbidity and occasional systemic involvement, the clinical course is generally self-limited. To date, there has been no consensus on treatment. Objective The aim of our current study was to evaluate the clinical features, drug association, treatment, and outcomes in a cohort of patients treated in an academic medical center. Methods A retrospective review of electronic medical records over a period of 10 years from 2009 to 2018 in a single tertiary academic medical center in Singapore was performed. Forty-three medical records with probable/definite diagnosis of AGEP were identified and analyzed for statistical significance. Results Drug association was identified in 93% of cases. The most frequent drug class was antibiotics, including penicillins, cephalosporins, and vancomycin. Systemic involvement was reported in 13.9% of patients. All cases of AGEP resolved with cessation of the offending drug. There was no mortality attributed to AGEP. Treatment with systemic steroid was associated with a decreased length of hospital stay (P = .035) in patients with AGEP. Conclusion AGEP was a self-limiting adverse drug reaction that was commonly caused by antibiotics. Although there was no difference in mortality, there was a significant reduction in the length of hospitalization with systemic corticosteroid treatment compared with that of topical corticosteroid treatment of AGEP.

Acute localized exanthematous pustulosis (ALEP), a localized variant of acute generalized exanthematous pustulosis, is characterized by pin-sized, non-follicular, sterile pustules that typically appear on the face, neck, and chest.The purpose of this report is to describe a case of ALEP in an 11-year-old girl because of cefixime and the etiological factors and clinical presentation of ALEP in pediatric group.We described a case of ALEP in an 11-year-old girl because of cefixime; a systematic review of the literature was performed to identify the etiological factors and clinical presentation of ALEP in children.We identified eight pediatric cases with ALEP. The causative agent was an herbal product in six cases, and pustular eruption was located on the face. In two cases, responsible agents were drugs (lamotrigine and amoxicillin-clavulanic acid). The eruptions were localized on the penis and extremities, respectively.ALEP is very rare in the pediatric age group, and topical/systemic drugs or herbal products may be involved in the etiology.

Severe cutaneous adverse reactions (SCARs) are potentially lethal adverse drug reactions that involve the skin, mucous membranes, and internal organs, resulting in disability. SCARs include drug-induced epidermal necrolysis, which is Steven Johnson syndrome (SJS)/ Steven Johnson syndrome and toxic epidermal necrolysis overlap (SJS-TEN overlap)/ toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP), generalised bullous fixed drug eruption (GBFDE), and acute erythroderma. Awareness of local epidemiology of SCARs plays an important role in prescribing practices by healthcare provider. Recognition of SCARs enables the offending drug to be withdrawn immediately, which is the definitive treatment of SCARs.This is a retrospective study reviewing SCAR cases reported to the Malaysian Adverse Drug Reactions Advisory Committee (MADRAC) registry at the Department of Dermatology, Hospital Melaka, for 5 years and 3 months from December 2014 to February 2020.A total of 41 SCARs cases were identified over the study duration. The incidence rate was 0.18%. All 41 cases require hospitalisations, with four cases (9.8%) managed in ICU and one mortality (2.4%) due to SJS-related complication. One patient had two episodes of SCARs. There were 22 male patients and 18 female patients. The majority were Malays (33, 80.5%), followed by Chinese (7, 17.1%) and Indonesian (1, 2.4%). There was no Indian patient with SCARs in this study. The mean age of patients was 47.2±17 years. Drug-induced epidermal necrolysis was the commonest type of SCARs (63.4%), and out of this, SJS accounted for the majority of cases (48.8%). Antibiotic was the main group of offending medication in this SCAR study (29.3%). The top five individual causative drugs of SCARs in sequence include allopurinol, phenytoin, carbamazepine, co-amoxiclav, and cephalexin. Allopurinol was the commonest culprit drug for drug-induced epidermal necrolysis and DRESS, phenytoin for acute erythroderma, and co-amoxiclav for AGEP.SJS was the most common manifestation and Allopurinol was the commonest culprit drug for SCAR cases in our cohort.

Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous adverse drug reaction characterized by rapid occurrence of dozens to thousands pinhead-sized, non-follicular, sterile pustular eruptions. AGEP is infrequent with an incidence of one to five millions per year. There are only two previous reports of paracetamol induced AGEP in literature. The clinical course of AGEP is characterised by spontaneous resolution on drug withdrawal. Resolution is marked by a characteristic desquamation. Diagnosis of AGEP depends on morphology of skin lesions, presence of fever, laboratory and histopathological findings. Factors that favours the diagnosis of AGEP include onset of pustules within few hours or in few days after the causative agent is administered. The most frequent causative drugs are Aminopenicillins, ampicillin, amoxixillin, sulphonamides, pristinamycin, quinolones, hydroxychloroquine, terbinafin diltiazem. In some cases it is induced by bacterial, viral or parasitic infections. In our case, a 50 year male patient developed multiple pus filled lesions, burning sensations all over the body caused by administering paracetamol drug where, the lesions desiccated immediately after cessation of offending drug in two daysleaving exfoliations .Upon diagnosis the white blood cell count was increased indicating lymphocytosis. He was administered with antihistamines, emollients and corticosteroids during his course of stay in hospital. Pustular rashes were reduced and patient recovered with treatment. Paracetamol is one of the most widely used safer drug worldwide, herein draws special attention that no drug is completely safe hence proper medication history interview would be recommended to overcome the drugs causing adverse drug reactions, that can be possibly dangerous and life threatening.

Acute Generalized Exanthematous Pustulosis is a rare drug-induced skin disorder that can present at any age. It is typically noted by swelling and erythema, with numerous facial and/or anogenital nonfollicular pustules that quickly disseminate. Staphylococcal scalded skin syndrome presents with erythema and swelling that similarly favor the head and intertriginous sites with subsequent bullae formation. We present a case of a four-year-old female who presented with SSSS complicated by the development of AGEP and discuss the course of her condition and treatment.

Background: Patch tests are used to diagnose nonimmediate T-cell‐mediated drug hypersensitivity reactions. The aim of this study was to evaluate the results of patch tests performed with suspect drugs in children. Methods: Patients < 18 years of age who had a drug patch test at the pediatric allergy outpatient clinic of our hospital between January 2014 and January 2020 were included in the study. Age, sex, culprit drug(s), reaction characteristics, and patch test results were recorded from the patients' files. Results: A total of 105 drug patch tests were performed on 71 patients during the study period. The patients' median age was 7 years (interquartile range, 4‐11 years), and 57.7% (n = 41) were boys. Twenty-three patients (32.3%) had severe cutaneous adverse reaction (Stevens-Johnson syndrome in 11, drug reaction with eosinophilia and systemic symptoms in 9, and acute generalized exanthematous pustulosis in 3 patients), 45 (63.3%) had maculopapular rashes, and 3 (4.2%) had fixed drug eruption. A total of 20 patch test results (28%) were positive: 18 of 44 patch tests (40.9%) with antiepileptic drugs and 2 of 48 patch tests (4.1%) with antibiotics. Positive results were obtained in 23% of the patch tests (6/26) in 20 patients with severe cutaneous adverse reactions and in 17.7% of the patch tests (14/79) in 51 patients with mild cutaneous reactions. No adverse reactions occurred during or after the patch tests. Conclusion: In our study, patch test positivity was more common with antiepileptic drugs and in patients with severe cutaneous drug reaction.

Background Hydroxychloroquine (HCQ)-induced acute generalized exanthematous pustulosis (AGEP) is poorly described in the literature. The aim of our study was to characterize the clinical, laboratory, allergological, and genetic features of HCQ-induced AGEP. Methods We conducted a retrospective study of patients with HCQ-induced AGEP diagnosed between 2011 and 2019. We performed molecular analysis to identify variations in the IL36RN gene. We also reviewed similar cases reported between 1991 and March 2020. Results Seven female patients were included. The mean age was 47 years old, and the average time from HCQ start to onset of symptoms was 40 days. All patients received topical steroids with a full resolution of the rash within an average of 39 days after HCQ withdrawal. Patch tests were performed for three patients with positive results in one case. Genetic analyses were performed for three patients, and no mutation in the IL36RN gene was identified. Conclusion The latent period and the duration for resolution of HCQ-induced AGEP may be longer than with other drugs due to the metabolic characteristics of HCQ. Mutations in the IL36RN gene were not identified in our patients.

Differentiating cutaneous diseases that mimic each other clinically and histopathologically can at times be a challenging task for the dermatopathologist. At the same time, differentiation of entities with overlapping features may be crucial for patient management. Although not seen in normal skin, plasmacytoid dendritic cells usually infiltrate the skin in several infectious, inflammatory/autoimmune and neoplastic entities. Plasmacytoid dendritic cells can be identified in tissue using specific markers such as CD123 and/or blood-derived dendritic cell antigen-2. Plasmacytoid dendritic cells are the most potent producers of type I interferons and their activity may therefore be assessed indirectly in tissue using human myxovirus resistance protein A, a surrogate marker for type I interferon production. In recent years, accumulating evidence has established the utility of evaluating for specific plasmacytoid dendritic cell-related parameters (plasmacytoid dendritic cell content, distribution and clustering and/ or human myxovirus resistance protein A expression) as a diagnostic tool in differentiating cutaneous diseases with overlapping features such as the alopecias, lupus and its mimics, and neoplastic entities. In this review, we provide an update on the current evidence on this topic and on the contexts where this can be a useful adjunct to reach the histopathological diagnosis.

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading throughout the world. The study describes 12 patients with SARS-CoV-2 pneumonia, who developed an acute erythematous rash with nonfollicular pinhead-sized pustules, without mucosal involvement. The clinical differential diagnosis was viral rash, acute generalized exanthematous pustulosis (AGEP), or multiform erythema. computed tomography with a diagnosis of interstitial pneumonia and a respiratory tract sample positive for SARS-CoV-2 in a reverse transcriptase polymerase chain reaction assay. Patients had signs of respiratory distress and were treated with hydroxychloroquine, darunavir, ritonavir, heparin, ceftriaxone, and azithromycin. Punch biopsies showed subcorneal pustules typical of AGEP. Dermal microvascular injury and thrombosis as described in skin damage by SARS-CoV-2 infection was not observed. The direct immunofluorescence for IgG, IgA, IgM, and C3 was negative in 8 patients investigated. A polymerase chain reaction for RNA SARS-CoV-2 performed on frozen skin was negative in 5 of 6 patients. Most of our patients were treated with systemic corticosteroids. After some days (4-10), the diffuse erythema and pustules had improved. AGEP is classified as a severe cutaneous adverse reaction, provoked by drugs and acute infections. Characteristically, removal of the offending agent leads to spontaneous resolution typically in less than 15 days. The recognition of AGEP is important, in order to avoid confusion with a systemic infection and consequently to avoid incorrect treatment. Cutaneous adverse reactions to drugs are common and are major health problems worldwide causing considerable costs for health care systems. We suggest that in the patients with AGEP during SARS-CoV-2 pneumonia, viral infection is a risk factor for developing drug reaction.

Drug eruptions are among the most common diseases of the skin. The majority of cases are benign and self-limited, however particular variants are very severe and potentially life threatening. A precise and rapid diagnosis is essential but can be difficult in some instances as drug eruptions may lack specific histological criteria. Furthermore, pitfalls in the diagnosis are frequent and heightened awareness to the possible mimicry of other skin diseases is required. This article focuses on three particularly dangerous forms of cutaneous adverse reactions, namely acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome and toxic epidermal necrolysis. As histological assessment alone may be insufficient to establish the diagnosis, special attention is also paid to clinical features and differential diagnosis.

Background Acute generalized exanthematous pustulosis (AGEP) is a rare, severe, cutaneous adverse reaction. Although most commonly caused by drugs, it can also be triggered by infections, especially in children. Methods This is a retrospective study involving children and adolescents aged 16 years or younger, diagnosed with AGEP between January 2010 and March 2020 in our tertiary pediatric hospital. Information pertaining to the patient's demographics, clinical presentation and progress, biochemical, microbiological, and histopathological investigations, treatment, and outcomes was analyzed. Results Eight patients were diagnosed with AGEP with mean age 8.2 years (range: 1.7-16.0 years). None of the patients had a personal or family history of psoriasis. Almost all patients had fever (n = 7, 87.5%). Although all 8 patients had intercurrent illness, 5 cases were attributed to infection, while the other 3 were likely precipitated by drugs. Abnormal hematological and biochemical parameters included a raised absolute neutrophil count (mean: 11.5 × 109 /L, range: 5.0-30.9 × 109 /L), C-reactive protein (mean: 52.5 mg/L, range: 5.0-143.7 mg/L), and erythrocyte sedimentation rate (mean: 38.6 mm/h, range: 6-64 mm/h). All patients developed post-pustular desquamation and subsequently recovered. The mean duration from onset to cessation of acute pustulation was 5.6 days (range: 3.0-10.0 days). One patient developed a recurrent episode of AGEP. Conclusion AGEP is rare and may be more commonly caused by infections in children. The condition is self-limiting with overall good outcomes in this age-group. In cases with concomitant infection and drug use, formal allergy testing should be arranged after resolution of the infection to confirm the underlying etiology.

Preamble: Skin and soft tissue infections (SSTI) are an important cause of sepsis. Acute skin failure may result from many dermatological conditions. In this study we tried to highlight the role of skin failure as a component of multiple organ dysfunctions. Materials and Methods: All adult patients (>18 years) diagnosed clinically as sepsis due to skin and soft tissue infections were included. Risk assessment was done using various parameters. Identification of pathogens and their antibiotic sensitivity pattern was performed by blood and skin swab cultures. Results: A total of 55 patients (31 male and 24 female) were included in the study. The common causes of SSTI were surgical site infections, cellulites, necrotisingfasciitis, traumatic open wounds, Toxic epidermal necrolysis, acute generalized exanthematous pustulosis, burns, bed-sores, unknown wounds and others. The major risk factors identified were the percentage of skin involvement, depth of wounds, presence of unhealthy granulation tissue and co morbidities like diabetes and immunodeficiency. MRSA and ESBL producing gram negative bacteria were important causative microbes for SSTI induced sepsis. Conclusion: SSTI is one of the important causes of sepsis. Early recognition and management of risk factors can prevent adverse outcome. Knowing microbiological etiology and drug sensitivity pattern is important is connection with SSTI related sepsis. Septic shock was identified as most important organ failure on admission leading to death in patients having SSTI related sepsis. Keywords: Skin and Soft tissue infections (SSTI), Multiple organ dysfunction syndrome, Risk factors, SCORTEN.

A woman was admitted for sepsis secondary to cellulitis. After clinical improvement of sepsis, non-follicular small pustules were observed on the trunk, limbs and face while vesicles/bullae and skin exfoliation were noted on upper extremities. Larger systemic manifestations included fever, hypertension and tachycardia. Laboratory results revealed neutrophilic leukocytosis, eosinophilia, mild transaminitis and acute renal failure. Despite treatment for potential sepsis and discontinuation of offending agents, her condition worsened leading to haemodynamic instability and renal failure requiring vasopressor support, intubation and continuous veno-venous haemodialysis. Skin biopsy revealed a diagnosis of acute generalised exanthematous pustulosis (AGEP), a rare condition usually caused by antibiotic treatment. The suspected offending drug was clindamycin, with possible combined effects by metronidazole and/or vancomycin. Improvement of skin manifestations were seen within 48 hours of starting systemic steroids. Here, we present an uncharacteristic case of AGEP clinically presenting with atypical skin lesions, severe systemic involvement mimicking septic shock, which culminated in multisystem organ failure.

Favipiravir is an antiviral agent used in the treatment of COVID-19 infection, and related cutaneous adverse events are rare 1 . Acute generalized exanthematous pustulosis (AGEP) has been reported in COVID-19 patients, mostly associated with hydroxychloroquine (HCQ). There are few AGEP cases in COVID-19 patients reported due to β-lactam antibiotics 2,3 in the literature. Herein, we report the first case of favipiravir-induced AGEP with histologic findings.

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction characterized by the development of numerous sterile and non-follicular pustules on an erythematous base with no or minimal mucous membrane involvement associated with fever and leucocytosis. Cefixime is a cephalosporin-type beta-lactam antibiotic commonly used for the management of several infections. The Cefixime-induced AGEP cases are known to be rare. Here, we present the case report of a 26-year old female who developed Cefixime-induced AGEP with mucosal membrane involvement. To the best of our knowledge, this is the first case to report the mucosal membrane involvement in Cefixime-induced AGEP. We are presenting this case report to draw the attention on the existence and plethora of symptoms of Cefixime-induced AGEP hoping that the clinicians will reckon these in their differential diagnosis and implement the appropriate management strategies for this rare adverse event in their clinical practice.

Severe cutaneous adverse reactions (SCARs) [Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic syndrome (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed eruption (GBFE)] are severe drug reactions that often require hospitalization and could be fatal. BRAF and MEK inhibitors (BRAF/MEKi) are a standard of care in patients with BRAF-mutated metastatic melanomas. These agents are administered until disease progression or unacceptable toxicity occurs. This review has focus on BRAF/MEKi-induced SCARs. A systematic search of the following terms: 'vemurafenib', 'cobimetinib', 'dabrafenib', 'trametinib', 'encorafenib', 'binimetinib', 'Acute Generalized Exanthematous Pustulosis', 'Stevens Johnson syndrome', 'Toxic Epidermal Necrolysis', 'Generalized Bullous Fixed Eruption' 'Drug Hypersensitivity Syndrome', and 'DRESS' in simple combination (every drug with each disease) and all in combination, was performed on MEDLINE, EMBASE, Web of Knowledge and The Cochrane Library repositories, with no restriction on language, for original studies. One hundred sixty-eight original articles were found, 26 (retrospective series, case reports and conference abstracts) were selected, and 21 were included in the qualitative synthesis. A total of 31 SCAR cases (23 DRESS and 8 SJS/TEN - 1 SJS and 7 TEN -) were identified. Vemurafenib was the culprit drug in all but one case, which was dabrafenib-induced. Mean time to SCAR onset from drug intake was 15.5 and 11.4 days, for SJS/TEN and DRESS, respectively. For the DRESS cases, hepatic involvement occurred in 96% and renal alterations in 87% of patients. Overall, BRAF/MEKi-induced SCARs are rare. Among them, vemurafenib is the drug that requires more close monitoring for SCARs. Prior immunotherapy can favour SCARs. Vemurafenib DRESS is likely to occur within the first fifteen days of treatment accompanied by hepatic and renal involvement. Following vemurafenib-induced SCAR resolution, switching to dabrafenib seems to be a safe alternative for these patients' treatment.

Background Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction characterized by sterile pustules on erythematous skin associated with fever and leukocytosis. The annual incidence of AGEP is estimated to be 1-5 cases per million. Cases of AGEP with oral mucosa involvement have been reported. However, reports of AGEP involving airway mucosa are limited. Case summary We report a 42-year-old woman with serious AGEP involving the airway mucosa. The patient initially developed fever and a small rash on her forehead and face. Over the next 2 d, she developed a diffuse, pustular rash over her trunk and legs. In addition, she complained of a cough with white foam-like sputum, chest tightness and dyspnea. Four days later, due to dyspnea, her mental status started to gradually deteriorate. She became more and more drowsy. Biopsies of the skin and airway mucosa suggested the diagnosis of AGEP. According to the European study of severe cutaneous adverse reactions group's scoring system, the patient scored +6 indicating a probable diagnosis of AGEP. She received intravenous methylprednisolone 120 mg/12 h for 3 d, and was eventually discharged in good condition. This patient had already experienced respiratory failure and airway mucosa involvement on admission; however, the clinicians had an insufficient understanding of AGEP. Glucocorticoid was administered for more than 10 d following onset of the disease, and her overall prognosis was satisfactory. Conclusion This case represents a rare clinical feature of AGEP and an important finding for clinicians.

Background Hydroxychloroquine is associated with myriad adverse dermatologic effects, most of which are poorly characterized by the literature, with unknown frequencies and risk factors. Objective To conduct a systematic review of the adverse dermatologic effects and predisposing factors of hydroxychloroquine toxicity. Results The review included 94 articles comprising 689 dermatologic adverse effects. A total of 21 unique dermatologic reactions were reported, most commonly drug eruption or rash (358 cases), cutaneous hyperpigmentation (116), pruritus (62), acute generalized exanthematous pustulosis (27), Stevens-Johnson syndrome or toxic epidermal necrolysis (26), hair loss (12), and stomatitis (11). Almost all underlying conditions were rheumatologic or autoimmune in nature, composed primarily of lupus erythematous (72% of all cases) and rheumatoid arthritis (14%). The range of reported mean cumulative dosages was wide, with some adverse reactions found after as little as 3 g or as much as 2500 g. Limitations Dermatologic adverse events and primary diagnoses related to the use of hydroxychloroquine may be under-reported as only case reports and clinical trials that reported at least 1 dermatologic adverse effect were included. Conclusion Although hydroxychloroquine is generally well tolerated, dermatologic adverse effects involving the skin, hair, or nails are a frequent and significant complication. Most of these reactions occurred after treatment of autoimmune conditions, often manifesting on the skin after a wide range of cumulative dosages.

Background: Pustular Psoriasis (PP) and Acute Generalized Exanthematous Pustulosis (AGEP) clinically resemble each other. There are many patients with generalized pustular presentations like hydroxychloroquine-induced pustular reaction who do not completely fall within PP or AGEP categories and needed to be more evaluated. So we examined a large series of these reactions to hydroxychloroquine (HCQ) and reviewed the literature in this regard.Materials and Methods: Records of 20 patients admitted to Razi Hospital, Tehran, Iran with acute onset of generalized pustular eruption following hydroxychloroquine therapy were retrieved, and their demographic and clinical features were reviewed. In the meantime, all related articles in PubMed and Google scholar databases were studied as well.Results: All 20 patients were female with an Mean±SD age of 48.35±13.76 years. The Mean±SD between the first dose and skin eruption was 3.62±1.42 weeks. HCQ was prescribed for them, mainly for rheumatologic conditions and joint problems other than psoriasis. Treatment was planned according to the first clinical judgment, pathological findings, and clinical behavior of the disease. Eleven patients were treated as PP and 9 as AGEP. Conclusion: No evident history of psoriasis, drug-related eruption, as well as rapid and complete response to steroids in some patients, favor AGEP diagnosis. However, the long interval of symptoms appearance, prolonged disease course, relapses despite discontinuation of the responsible drug, and no appropriate response to the steroid, favor PP. So, it could be a new entity.

Acute Generalized Exanthemataous Pustulosis (AGEP) is a rare acute pustular eruption that is mostly induced by drugs. Aside from cutaneous eruptions, systemic symptoms such as leukocytosis, neutrophilia, and internal organ involvement such as liver, kidney, respiratory system, and bone marrow, may occur, although uncommon. Liver involvement usually results in a two- or three-fold increase of liver enzymes and rarely exceeds that. Pyrazinamide is the first-line anti-tuberculosis drug that is potentially hepatotoxic, but rarely shows dermatologic manifestations. We report a rare case of AGEP with drug induced liver injury due to pyrazinamide in a young patient with tuberculosis.

Background: Mycoplasma pneumoniae pneumonia is sometimes associated with skin or mucous membrane eruptions. Available reviews do not address the association of Chlamydophila pneumoniae pneumonia with skin eruptions. We therefore conducted a systematic review of the literature addressing this issue. The National Library of Medicine, Excerpta Medica, and Web of Science databases were employed. Summary: In two reports, skin lesions and especially urticaria were more common (p < 0.05) in atypical pneumonia caused by C. pneumoniae as compared with M. pneumoniae. We found 47 patients (n = 16; ≥18 years, n = 31) affected by a C. pneumoniae atypical pneumonia, which was associated with erythema nodosum, erythema multiforme minus, erythema multiforme majus, isolated mucositis, or cutaneous vasculitis. We also found the case of a boy with C. pneumoniae pneumonia and acute generalized exanthematous pustulosis. We did not find any case of C. pneumoniae respiratory infection associated with either Gianotti-Crosti syndrome, pityriasis lichenoides et varioliformis acuta Mucha-Habermann, or varicella-like skin eruptions.

Immune checkpoint inhibitors (ICPi) have emerged as a new frontier of cancer therapy. Although monoclonal antibodies to cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) have revolutionized oncologic management, these agents may result in a spectrum of immune-related adverse events (irAE) of which dermatologic toxicities are among the most frequent. Prompt recognition and management of irAE is essential for dermatologists caring for the expanding population of cancer patients exposed to these drugs. Cutaneous toxicities range from mild cases to severe and life-threatening presentations that may cause significant morbidity and mortality. This review provides an overview of severe cutaneous adverse reactions (SCARs) that may develop during ICPi therapy, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). In addition, immunobullous disorders, erythroderma, neutrophilic dermatoses, and cutaneous eruptions associated with systemic manifestations are discussed.

The literature on positive patch-test results in acute generalized exanthematous pustulosis (AGEP) is reviewed. Ninety-three drugs were identified that have together caused 259 positive patch tests in 248 patients with AGEP. The drug classes causing the highest number of reactions are beta-lactam antibiotics (25.9%), other antibiotics (20.8%), iodinated contrast media (7.3%), and corticosteroids (5.4%), together accounting for nearly 60% of all reactions. The highest number of reactions to individual drugs was to amoxicillin (n = 36), followed by pristinamycin (n = 25), diltiazem (n = 14), amoxicillin-clavulanic acid (n = 13), clindamycin (n = 11), and iomeprol (n = 8); 59 of the 93 drugs each caused a single case only. The "Top-10" drugs together caused over 50% of all reactions. The sensitivity of patch testing (percentage of positive reactions) in patients with AGEP is largely unknown, but may generally be ~50%, which also applies to pristinamycin. Patch testing in AGEP appears to be safe, although mild recurrence of AGEP skin symptoms or other rashes may occur occasionally. Clinical aspects of AGEP, including epidemiology, etiology and pathophysiology, clinical features, histology, treatment, and prognosis are briefly presented, as are diagnosing the disease and identifying the culprit drugs with patch tests, intradermal tests, in vitro tests, and challenge tests.