Acute Generalized Exanthematous Pustulosis Research Articles

Genotyping HLA alleles to predict the development of Severe cutaneous adverse drug reactions (SCARs): state-of-the-art

ABSTRACT 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.

Drug-induced liver injury associated with severe cutaneous adverse drug reactions: A nationwide study in Taiwan.

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. We analysed the database of a 10-year multi-centre prospective study in Taiwan from 2011 to 2020. 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<.003). Chronic kidney disease with high-dose allopurinol also contributed to high mortality (78.9%) in cases of allopurinol-induced DILI with SCAR. The HLA-B*5801 was associated with a high risk and mortality of allopurinol-induced DILI with SCAR. Likewise, the HLA-B*1502 was closely related to carbamazepine-induced DILI with SCAR. DILI patients combined with SCAR are common and have a high mortality in Taiwan. Allopurinol is the leading incriminated drug. Jaundice, acute kidney injury and SJS/TEN are risk factors of mortality. HLA-B*5801, chronic kidney disease and high drug dosage also contribute to high mortality in allopurinol-induced DILI with SCAR.

Acute Generalized Exanthematous Pustulosis Due to Cephalexin: A Case Report and Literature Review

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.

Acute generalized exanthematous pustulosis in a postpartum woman.

The distribution of pustular erythema, characteristic clinical course, and pathological findings can help diagnose acute generalized exanthematous pustulosis. Clinical management should include discontinuation of the suspected drug, hydrocortisone administration, and careful follow‐up examination.

Histopathologic interpersonal overview of generalized pustular cutaneous reaction to Hydroxychloroquine (HCQ): New challenging clinical manifestation

Background: Pathologic examination of Acute Generalized Exanthematous Pustulosis (AGEP) and Pustular Psoriasis (PP) are similar. We encountered many patients with PP or AGEP who cannot be distinguished clinically, pathologically and based on disease course from each so we designed a comprehensive interpersonal histopathologic overview of these patients' samples. Method: Histopathological data of 16 patients over 3.5 years were analyzed. Four pathologists separately reviewed specimens based on eighteen criteria (9 Epidermal and 9 Dermal). Severity score for each criterion was considered as to be (0 to 3+). We compared the final pathologic diagnosis with primary one. Results: Neutrophilic and lymphocytic infiltration in dermis were seen in all cases of AGEP while intraepithelial pustules. Subcorneal and intraepithelial pustules, spongiosis, neutrophilic exocytosis, neutrophilic and lymphocytic infiltration in dermis were observed in all cases of PP. The most severe neutrophilic inflammation; acanthosis and neutrophilic or lymphocytic infiltration were seen in PP. The authors of this study have been reported generalized pustular clinical presentations of patients have been taken HCQ, and in the recent pandemic it is also one of the concerns that many studies have been focused (....). Conclusion: When primary histopathologic report is AGEP/PP overlap, clinical judgment is the best way to manage and it is more probable that the final diagnosis being PP. When only AGEP or PP is histopathologic diagnostic report, it is usually enough to make final diagnosis and appropriate management. Key words: hydroxychloroquine, HCQ, generalized pustular cutaneous eruption, Pustular Psoriasis (PP), Acute Generalized Exanthematous Pustulosism, AGEP, Histopathological overview, pathology, review

COVID-19 vaccine-induced acute generalized exanthematous pustulosis.

COVID-19 vaccine-induced acute generalized exanthematous pustulosis.

Drug Patch Test as a Diagnostic Test to Determine the Culprit Drug of Cutaneous Adverse Drug Reaction (CADR)

Background: Cutaneous Adverse Drug Reaction (CADR) is a frequent problem in clinical practice since there were new drugs or drug misuse, which leads to high morbidity and mortality rate. It is often difficult to determine the offending drug only from the history. Provocation test, intradermal test or skin prick test are of significant value, but having higher risk to re-precipitate life-threatening reaction. Drug patch test (DPT) is a test, which is performed to CADR patient to determine the culprit drug. The main advantages of DPT are, it gives rarely adverse reaction and any commercialized form of drugs can be used.Methods: This is a retrospective study, aimed to analize the clinical relevance between anamnesis and DPT result in patient with history of CADR. All patient, who were performed with DPT in one year period in Dr. Soetomo General Academic Hospital Surabaya Indonesia, were evaluated in this study. Results: There were 14 patients with history of CADR, who performed DPT; consist of 7 maculopapular eruption cases, 4 Stevens-Johnson Syndrome (SJS) cases, 1 Fixed Drug Eruption (FDE) case, 1 Acute Generalized Exanthematous Pustulosis (AGEP) case and 1 Drug Reaction with Eosinophilia and Systemic Reaction (DRESS) case. There were 9 patients (64.3 %), who got positive result of DPT. The relevance between anamnesis and positive result of DPT were shown in 8 patient (88.9%) of 9 patient with positive DPT result. Conclusion: DPT has important role in identifying the culprit drug in CADR, especially when multiple drugs are involved.

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合糖皮质激素治疗急性泛发性发疹性脓疱病一例

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合糖皮质激素治疗急性泛发性发疹性脓疱病一例

A ten-day-old newborn with acute generalized exanthematous pustulosis

Acute generalized exanthematous pustulosis (AGEP) is a rare reaction related to various causes; in most cases, it is a drug-induced reaction. AGEP can occur at any age but is seldom described in children. In this article, we describe an AGEP case in a ten-day-old patient suspected to be caused by erythromycin, cefotaxime and ampicillin. Until now, according to our knowledge, this is the first pulished case of AGEP in a newborn.

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

Drug reactions with eosinophilia and systemic symptoms (DRESSs) and acute generalized exanthematous pustulosis (AGEP) are potentially severe cutaneous adverse drug reactions. To describe the clinical findings and sensitization profiles of DRESS and AGEP patients who had been administered iodinated contrast media (ICM). 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. 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. 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.

Evaluation of drug patch tests in children.

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.

Hydroxychloroquine-induced acute generalized exanthematous pustulosis: a series of seven patients and review of the literature.

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. 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. Seven female patients were included. The mean age was 47years old, and the average time from HCQ start to onset of symptoms was 40days. All patients received topical steroids with a full resolution of the rash within an average of 39days 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. 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.

The safety profile of hydroxychloroquine: major cutaneous and extracutaneous adverse events.

Hydroxychloroquine is an established therapy for several rheumatological disorders, and very recently it has been proposed as a possible treatment for the new coronavirus disease 2019 even if recent randomised trials did not prove any benefit. Notably, hydroxychloroquine has been associated with a heterogeneous range of cutaneous and extra-cutaneous adverse events. We carried out a narrative review of the literature up to November 1st, 2020, related to the safety of hydroxychloroquine. In particular, cutaneous and extra-cutaneous adverse events associated with hydroxychloroquine were reviewed. The following databases were consulted: PubMed, Embase, Google Scholar and ResearchGate. The research of articles was conducted by using the following search terms: ''hydroxychloroquine," ''adverse event/effect,'' "cutaneous", "skin", "cardiotoxicity", "retinopathy", gastrointestinal and neurological toxicity". The main indication for which hydroxychloroquine was used in the reports was an immune mediated disorder. Adverse events were described mostly in females over 50 years of age. The most common cutaneous adverse effect was maculopapular and erythematous rash occurring within 4 weeks of initiating hydroxychloroquine and disappearing within few weeks of discontinuation. Gastrointestinal symptoms and headache were the most frequent extracutaneous manifestations. Rarer cutaneous manifestations include hyperpigmentation, psoriasiform dermatitis, photodermatitis, stomatitis, melanonychia and hair loss. More severe conditions were acute generalised exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome/toxic epidermal necrolysis, and among extra-cutaneous adverse events cardiotoxicity and retinopathy. Since hydroxychloroquine is widely prescribed in rheumatology, it is important for rheumatologists to be familiar with its safety profile.

Dermoscopic Aspects of Cutaneous Adverse Drug Reactions.

Little is known about the dermoscopic evaluation of cutaneous adverse drug reactions (CADRs). To evaluate the dermoscopic patterns of CADRs and identify those associated with severe cutaneous adverse reactions to drugs (SCARDs). Patients included in this study from May 2015 to April 2016 had presented with CADRs. CADR presentation and classification were based on standard criteria. SCARDs included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), overlap SJS/TEN, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). The dermoscopic features of CADRs were described and compared according to the severity of the reactions. Sixty-nine patients were included. Sixteen patients (23.2%) presented SCARDs. The main dermoscopic findings in SJS, overlap SJS/TEN and TEN were black dots or necrotic areas (100%). Erosion [respectively, 4/6 (66.7%), 3/3 (100%) and 1/1 (100%)], necrotic borders [respectively, 4/6 (66.7%), 3/3 (100%) and 1/1, (100%)] and epidermal detachment [respectively, 5/6 (83.3%); 2/3 (66.7%) and 1/1 (100%)] were also common among these reactions. Erythema and purpuric dots were the main dermoscopic findings [respectively, 5/6 (83.3%) and 4/6 (66.7%)] in DRESS. In non-severe reactions, the most prevalent structures were erythema and purpura in exanthema [respectively, 31/33 (93.9%) and 24/33 (72.7%)] and erythema and vascular structures in urticarial reactions [respectively, 6/6 (100%) and 3/6 (50%)]. Black dots or necrotic areas, epidermal detachment, necrotic borders and erosion were highly associated with SCARDs (P < 0.001). Dermoscopy improves clinical recognition of SCARDs.

A retrospective, 5-year, clinicoepidemiological study of severe cutaneous adverse reactions (SCARs).

A severe cutaneous adverse reaction (SCAR) is a rare, clinically heterogeneous, life-threatening phenomenon that results in serious skin damage, systemic complications, and significant morbidity or mortality comprising of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or SJS-TEN overlap, acute generalized exanthematous pustulosis (AGEP), exfoliative dermatitis, and drug rash with eosinophilia and systemic symptoms (DRESS). A retrospective study was conducted on all cases of SCARs admitted in a tertiary care referral hospital from January 2015 to December 2019. Clinical and epidemiological details were retrieved from the records of patients as per predesigned proforma. The data collected were analyzed and statistically evaluated. A total of 142 patients (67 males, 75 females) with SCARs, constituting 0.08% of total hospital admission and 0.027% of total dermatology outpatient department (OPD), were studied. Age group ranged from 2 to 61years, with the mean age of 33.6years (SD=17.43). Most patients belonged to SJS-TEN complex (75 cases; SJS 48, SJS-TEN 18, TEN nine) followed by exfoliative dermatitis (27 cases/19%), AGEP (26 cases/18.3%), and DRESS (14 cases/9.8%). Anticonvulsants were most commonly implicated (22%) followed by antibiotics (20%), nonsteroidal anti-inflammatory drugs (NSAIDs) (17%), and ayurvedic (7%). There was only single mortality in a DRESS patient. SCAR has considerable disease burden with marginal female preponderance in SJS/TEN and exfoliative dermatitis and can involve even the pediatric population. Anticonvulsants followed by antibiotics, NSAIDs, and ayurvedic medicines are common groups known to cause SCARs. To date, there are no definitive recommendations regarding their optimal treatment regimen, hence early diagnosis, prompt withdrawal of culprit drug, high standard of nursing care, and interdisciplinary consultations are vital steps to avoid disease progression and restore health.

Acute Generalized Exanthematous Pustulosis (AGEP) in 12 Patients Treated for SARS-CoV-2 Positive Pneumonia

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.

The Role of Frozen Section in the Rapid Diagnosis of Severe Cutaneous Adverse Drug Reactions.

Context:Early diagnosis is the mainstay in the management of severe cutaneous adverse reactions (SCARs) to drugs.Aims:To study the role of frozen section in the rapid diagnosis of SCARs and the impact on outcome of the affected patients.Settings and Design:A single-blind, hospital-based study was conducted from December 2014-July 2016.Methods and Material:We biopsied 32 adults with SCARs diagnosed by clinical features and standard criteria. The histopathological features seen on frozen sections were compared to that of paraffin blocks. The impact of rapid diagnosis on the clinical outcome was studied in toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP).Statistical Analysis:Z test was used to compare two proportions. Kappa statistic, sensitivity, specificity, positive predictive value, and negative predictive value of the frozen section diagnosis were calculated in TEN/SJS and DRESS using MedCalc software.Results:Frozen and paraffin sections were done in TEN/SJS spectrum (13), DRESS (17), and AGEP (2). The sensitivity, specificity and kappa values for frozen section diagnosis in SJS/TEN and DRESS were 91.7%, 95%, 0.867 and 94.4%, 100%, 0.937 respectively. The concordance between frozen and paraffin section diagnosis was 100% in TEN, SJS, DRESS and AGEP. All the 6 patients with TEN and 2 with AGEP survived. Taking the worst-case scenario, the mortality in SJS was 28.6%. The mortality among patients with DRESS was 11.8%.Conclusions:Frozen section helps in the rapid diagnosis and early treatment of SCARs and differentiates it from diseases that mimic it.

The Role of In Vitro Detection of Drug-Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions.

ProposeThe purpose of this study was to investigate panels of enzyme-linked immunospot assays (ELISpot) to detect drug-specific mediator releasing cells for confirming culprit drugs in severe cutaneous adverse reactions (SCARs).MethodsFrequencies of drug-induced interleukin-22 (IL-22)-, interferon-gamma (IFN-γ)-, and granzyme-B (GrB)-releasing cells were measured by incubating peripheral blood mononuclear cells (PBMCs) from SCAR patients with the culprit drugs. Potential immunoadjuvants were supplemented to enhance drug-induced mediator responses.ResultsTwenty-seven patients, including 9 acute generalized exanthematous pustulosis (AGEP), 10 drug reactions with eosinophilia and systemic symptoms, and 8 Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) were recruited. The average frequencies of drug-induced IL-22-, IFN-γ-, and GrB-releasing cells were 35.5±16.3, 33.0±7.1, and 164.8±43.1 cells/million PBMCs, respectively. The sensitivity of combined IFN-γ/IL-22/GrB ELISpot was higher than that of IFN-γ ELISpot alone for culprit drug detection in all SCAR subjects (77.8% vs 51.9%, P < 0.01). The measurement of drug-induced IL-22- and IFN-γ releasing cells confirmed the culprit drugs in 77.8% of AGEP. The measurement of drug-induced IFN-γ- and GrB-releasing cells confirmed the culprit drugs in 62.5% of SJS/TEN. Alpha-galactosylceramide supplementation significantly increased the frequencies of drug-induced IFN-γ releasing cells.ConclusionThe measurement of drug-induced IFN-γ-releasing cells is the key for identifying culprit drugs. The additional measurement of drug-induced IL-22-releasing cells enhances ELISpot sensitivity to identify drug-induced AGEP, while the measurement of drug-induced GrB-releasing cells could have a role in SJS/TEN. ELISpot sensitivity might be improved by supplementary alpha-galactosylceramide.Trial RegistrationClinicalTrials.gov Identifier: NCT02574988

Development of Acute Generalized Exanthematous Pustulosis due to Hydroxychloroquine Use for COVID-19 Treatment

Acute generalized exanthematous pustulosis (AGEP) is a cutaneous drug eruption, which is characterized by nonfollicular, sterile pustules, rapidly and severely progresses on an erythematous base. Although antibiotics have been considered to be responsible for most of the development of AGEP, many drugs, such as hydroxychloroquine (HCQ), may also cause it. Recently, HCQ is frequently used in the prophylaxis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection along with antiviral drugs. In our study, we have presented an AGEP reaction case that has been developed in one patient who is being treated for coronavirus disease-19 (COVID-19) and using the HCQ.

Potentially life‑threatening severe cutaneous adverse reactions associated with tyrosine kinase inhibitors (Review).

Tyrosine kinase inhibitors (TKIs) have emerged as a new frontier of cancer therapy. These agents include inhibitors of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor2 (HER2), BRAF, mitogen‑activated protein kinase kinase (also referred to as MEK), bcr‑abl, c‑KIT, platelet‑derived growth factor (PDGFR), fibroblast growth factor receptor(FGFR), anaplastic lymphoma kinase (ALK) and vascular endothelial growth factor (VEGF). Along with the evolving applications of TKIs, there has been an increased recognition of the breadth of potential cutaneous toxicities to these agents. In this review, we provide an overview of potentially life‑threatening severe cutaneous adverse reactions (SCARs) that may occur during therapy with TKIs. These toxicities include Stevens‑Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP).