Increased prevalence of erythema multiforme in patients with COVID-19 infection or vaccination.

Several reports stated that erythema multiforme (EM) was associated with COVID-19 with detrimental outcomes in patients. However, since most of these are case reports, it is challenging to quantitively assess their associations. Therefore, our study aims to determine the prevalence of EM in the context of COVID-19. The study was designed as a retrospective cross-sectional hospital-based study of registered patients at the University of Florida Health Hospital. The ICD-10 codes for EM, COVID-19 infection, and COVID-19 vaccines were searched in the database. The odds ratio was calculated to assess the risk of EM after COVID-19 infection or vaccination. Our study included 43,547 patients with a history of COVID-19 infection, of whom 92 developed EM. Patients with COVID-19 infection were 6.68 times more likely to have EM than those without COVID-19 (P < 0.0001). Similarly, the risk of developing EM after COVID-19 vaccination was 2.7, significantly higher than the general population (P < 0.0001). The prevalence of EM following COVID-19 infection or vaccination significantly differs from the general population, highlighting the importance of monitoring patients for EM after COVID-19 infection and/or vaccination. It is imperative to disseminate awareness to clinicians and patients regarding the impact of COVID-19 on EM.

Background rates for severe cutaneous reactions in the US: Contextual support for safety assessment of COVID-19 vaccines and novel biologics.

The global COVID-19 public health crisis has resulted in extraordinary collaboration to expeditiously develop vaccines and therapeutics. The safety of these biologics is closely monitored by the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC). Novel products may have limited safety data, and although serious medical outcomes associated with vaccination are rare, knowledge of background incidence rates of medical conditions in the US population puts reported adverse events (AEs) in perspective for further study. Although relatively minor vaccination skin reactions are common, rare instances of severe delayed hypersensitivity reactions such as erythema multiforme (EM), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome may occur. To aid in the assessment of these events, we performed a literature search in PubMed and Web of Science on the background incidence of EM, SJS, SJS/TEN, and TEN in the US population and on published reports of these conditions occurring post-vaccination. The US background annual incidence rates per million individuals of all ages ranged from 5.3 to 63.0 for SJS, from 0.4 to 5.0 for TEN, and from 0.8 to 1.6 for SJS/TEN. Since these conditions may overlap, some studies reported rates for EM/SJS/TEN combined, however we did not find studies with exclusive EM incidence rates. The published literature, including studies of reports submitted to the FDA/CDC Vaccine Adverse Event Reporting System (VAERS), describes post-vaccination EM, SJS, SJS/TEN and/or TEN as rare occurrences. The vaccines most frequently associated with these conditions were measles, mumps, and rubella; diphtheria, tetanus, and pertussis; and varicella. The majority of VAERS reports of EM, SJS, SJS/TEN, or TEN occurred in children within 30 days of vaccination. This review summarizes background rates of these disorders in the general population and published AEs among vaccine recipients, to support safety surveillance of COVID-19 vaccines and other biologics.

Reality of drug-induced erythema multiforme: A French pharmacovigilance study.

BACKGROUND: Since the 2002 SCAR study, erythema multiforme (EM), a post-infectious disease, has been distinguished from Stevens-Johnson syndrome (SJS), drug-induced. Nevertheless, EM cases are still reported in the French pharmacovigilance database (FPDB). OBJECTIVES: To describe EM reported in the FPDB and to compare the quality and the characteristics of the reports. METHODS: This retrospective observational study selected all EM cases reported in the FPDB over two periods: period 1 (P1, 2008-2009) and period 2 (P2, 2018-2019). Inclusion criteria were 1) a diagnosis of clinically typical EM and/or validated by a dermatologist; 2) a reported date of onset of the reaction; and 3) a precise chronology of drug exposure. Cases were classified confirmed EM (typical acral target lesions and/or validation by a dermatologist) and possible EM (not-otherwise-specified target lesions, isolated mucosal involvement, doubtful with SJS). We concluded possible drug-induced EM when EM was confirmed, with onset ranging from 5 to 28 days without an alternative cause. RESULTS: Among 182 selected reports, 140 (77%) were analyzed. Of these, 67 (48%) presented a more likely alternative diagnosis than EM. Of the 73 reports of EM cases finally included (P1, n=41; P2, n=32), 36 (49%) had a probable non-drug cause and 28 (38%) were associated with only drugs with an onset time ≤4 days and/or ≥29 days. Possible drug-induced EM was retained in 9 cases (6% of evaluable reports). Etiological work-up was more often performed in period 2 than 1 (53.1% vs 29.3%, P=0.04), and the time to onset from 5 to 28 days was more frequent in period 2 (59.2% vs 40%, P=0.04). CONCLUSIONS: This study suggests that possible drug-induced EM is rare. Many reports describe "polymorphic" rashes inappropriately concluded as EM or post-infectious EM with unsuitable drug accountability subject to protopathic bias.

Orf Nodule with Erythema Multiforme during a Monkeypox Outbreak, France, 2022.

A 26-year-old patient in France who worked as a butcher sought care initially for erythema multiforme. Clinical examination revealed a nodule with a crusty center, which upon investigation appeared to be an orf nodule. Diagnosis was confirmed by PCR. The patient was not isolated and had a favorable outcome after basic wound care.

Childhood epidermal necrolysis and erythema multiforme major: a multicentre French cohort study of 62 patients.

INTRODUCTION: The distinction between epidermal necrolysis [EN; including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and overlap syndrome] and erythema multiforme major (EMM) in children is confusing. We aimed to better describe and compare these entities. MATERIALS AND METHODS: This French retrospective multicentre study included children ≤18 years old referred for EN or EMM between 1 January 2008 and 1 March 2019. According to pictures, children were reclassified into TEN/overlap, SJS or EMM/unclassified (SJS/EMM) groups and compared for epidemiological and clinical data, triggers, histology and follow-up. RESULTS: We included 62 children [43 boys, median age 10 years (range 3-18)]: 16 with TEN/overlap, 11 SJS and 35 EMM. The main aetiologies were drugs in EN and infections (especially Mycoplasma pneumoniae) in EMM (P < 0.001), but 35% of cases remained idiopathic (TEN/overlap, 47%; SJS, 24%; EMM, 34%). The typical target lesions predominated in EMM (P < 0.001), the trunk was more often affected in EN (P < 0.001), and the body surface area involved was more extensive in EN (P < 0.001). Mucosal involvement did not differ between the groups. Two patients with idiopathic TEN died. Histology of EMM and EN showed similar features. The recurrence rate was 42% with EMM, 7% with TEN/overlap and 0 with SJS (P < 0.001). Sequelae occurred in 75% of EN but involved 55% of EMM. CONCLUSION: Clinical features of EN and EMM appeared well demarcated, with few overlapping cases. Idiopathic forms were frequent, especially for EN, meaning that a wide and thorough infectious screening, repeated if needed, is indicated for all paediatric cases of EN/EMM without any trigger drug. We propose a comprehensive panel of investigations which could be a standard work-up in such situation. Sequelae affected both EN and EMM.

Erythema multiforme, Stevens Johnson syndrome, and toxic epidermal necrolysis reported after vaccination, 1999-2017.

BACKGROUND: Since the last review of vaccine safety surveillance data for erythema multiforme (EM), Stevens Johnson syndrome (SJS), SJS/TEN, and toxic epidermal necrolysis (TEN) (EM/SJS/TEN), over 37 new vaccines have been introduced in the United States. We sought to describe reported EM/SJS/TEN after vaccines during 1999-2017. METHODS: We identified U.S. reports of EM/SJS/TEN received by the Vaccine Adverse Event Reporting System (VAERS) during 1999-2017. We stratified analysis by condition (EM, SJS, or TEN), and analyzed reports by serious or non-serious status, sex, age group, time from vaccination to symptom onset, exposure to known causes of EM/SJS/TEN, and vaccines administered. We used Empirical Bayesian data mining to detect vaccine-AE pairs reported more frequently than expected. RESULTS: Of 466,027 reports to VAERS during 1999-2017, we identified 984 reports of EM, 89 reports of SJS, 6 reports of SJS/TEN, and 7 reports of TEN. Few reports of EM (9%), and most reports of SJS (52%), SJS/TEN (100%), and TEN (100%) were serious. Overall, 55% of reports described males, 48% described children aged < 4 years; 58% of EM/SJS/TEN occurred ≤ 7 days after vaccination. Few reports (≤5%) described exposure to known causes of EM/SJS/TEN. Overall, childhood vaccines (e.g., combined measles, mumps, and rubella vaccine) were most commonly reported. We identified 6 deaths; 4 were exposed to medications associated with EM/SJS/TEN. EM after smallpox vaccine was reported disproportionately among people aged 19-49 years. CONCLUSIONS: EM/SJS/TEN were rarely reported after vaccination; data mining identified a known association between EM and smallpox vaccine.

Clinical and histologic features of Mycoplasma pneumoniae-related erythema multiforme: A single-center series of 33 cases compared with 100 cases induced by other causes.

BACKGROUND: Mycoplasma pneumoniae infection has been documented in erythema multiforme (EM) and Stevens-Johnson syndrome-toxic epidermal necrosis (SJS-TEN). Clinical aspects of M pneumoniae-related EM have been poorly described in the literature. OBJECTIVE: To highlight differences between M pneumoniae EM and non-M pneumoniae EM. METHODS: This single-center, retrospective cohort study included all patients admitted to our dermatology department for EM during 2000-2015. We compared epidemiologic, clinical, and histologic data and follow-up for M pneumoniae EM and non-M pneumoniae EM cases. RESULTS: Thirty-three patients with M pneumoniae EM were compared with 100 patients with non-M pneumoniae EM. Disease onset in winter was more frequent with M pneumoniae EM (P = .003). Acrally distributed lesions (32% vs 88%, P < .0001) and typical targets (45% vs 74%, P = .01) were less common in M pneumoniae EM than non-M pneumoniae EM. Multiple (≥2) mucousal membrane involvement was more frequent in M pneumoniae EM than non-M pneumoniae EM (97% vs 60%; P < .0001), as were mucosal and respiratory tract sequelae (P < .05). The mean hospital stay was longer with M pneumoniae EM patients: 9.5 days versus 5.1 days (P = .0002). A TEN-like pattern was observed in all 14 (100%) M pneumoniae EM skin biopsies versus 10 of 27 (48%) non-M pneumoniae EM biopsies (P < .001). LIMITATIONS: The retrospective design. CONCLUSION: M pneumoniae EM has a distinctive presentation compared with non-M pneumoniae EM, with more diffuse and atypical targets, more mucositis and respiratory tract sequelae. Histologic data show a TEN-like pattern in all M pneumoniae EM skin samples.

Characteristics of pediatric recurrent erythema multiforme.

BACKGROUND: Erythema multiforme (EM) is an acute condition characterized by distinctive target lesions of the skin often accompanied by mucosal ulcers. A subset of individuals experience frequent episodes of recurrent EM, which is rare and poorly understood, especially in children. OBJECTIVE: To characterize clinical features, laboratory findings, and treatment responses of pediatric recurrent EM. METHODS: A retrospective chart review was conducted at the Children's Hospital of Wisconsin in Milwaukee, Wisconsin (2000-2015) and the Mayo Clinic in Rochester, Minnesota (1990-2015). Inclusion criterion was a diagnosis before age 18 years with recurrent EM, defined as a symmetrically distributed, fixed eruption, including target lesions, with or without mucous membrane involvement, occurring on at least three occasions. A literature review was conducted to include individuals who met the inclusion criterion. RESULTS: Twenty-six patients were included, of whom 16 (62%) were male. The median age of onset was 9.1 years (range 0-15.7 years). Nine patients (35%) required hospitalization. Herpes simplex virus testing was positive in 9 of 17 (65%) patients. Remission was achieved in 5 of 16 (31%) patients while taking suppressive antivirals. Eight patients received continuous anti-inflammatory treatment, two (25%) of whom experienced remission. CONCLUSION: This study of pediatric recurrent EM found a greater male predominance, more hospitalizations, fewer cases caused by herpes simplex virus, and a lower response to immunosuppression in children than in the general population.

Paediatric Erythema Multiforme: Epidemiological, Clinical and Laboratory Characteristics.

Erythema multiforme (EM) is an immune-mediated reaction presenting as acrofacial target lesions. Most studies utilize the outdated classification, which includes EM, Stevens-Johnson syndrome and toxic epidermal necrolysis as related entities. We describe here epidemiological, aetiological, clinical, laboratory and treatment characteristics of paediatric EM. This is a retrospective single-centre study, performed between 2000 and 2013. Of 119 children given a diagnosis of EM, only 30 met clinical criteria and were included in this study. Most misdiagnosed cases were non-specific eruptions and urticaria multiforme. Mean age was 11.3 years. Fifty percent had mucosal involvement. An aetiology was observed in half of the patients. Seventy percent of patients were admitted to hospital, 46.7% were treated with systemic steroids. Sixteen percent had recurrent EM. The most common identified infectious agent associated with EM in this study was Mycoplasma pneumonia and the cases associated with this infection may represent the recent entity, mycoplasma-induced rash and mucositis. Association with herpes simplex virus was not observed. Despite being a benign, self-limiting condition, children were over-treated in terms of hospitalization and therapy.

Seasonal variations in dermatologic and dermatopathologic diagnoses: a retrospective 15-year analysis of dermatopathologic data.

BACKGROUND: Certain dermatologic conditions are known to show seasonal variations in frequency, the reasons for which are unclear but in some cases may be attributable to changes in ambient weather conditions. OBJECTIVES: The current study was conducted to determine whether seasonal trends might exist for dermatologic conditions including erythema multiforme, guttate psoriasis, erythema dyschromicum perstans (ashy dermatosis), pityriasis lichenoides, and pityriasis rosea. METHODS: Data were derived from a 15-year retrospective review of electronic records from a large dermatopathology laboratory located in the mid-Atlantic region of the USA. Numbers of diagnoses per month and "per season" were determined. Pairwise comparisons of seasonal data were made using two-sample t-tests with significance set at P ≤ 0.05. RESULTS: Perniosis (chilblains) was significantly more common in winter and spring (P = 0.001). Hand, foot, and mouth disease was statistically more prevalent in summer and autumn (P = 0.028). Erythema multiforme was most common in spring and summer (P = 0.004). Grover's disease was most common in winter and spring (P = 0.000039). Guttate psoriasis was non-significantly more common in winter and spring (P = 0.076). No statistically significant seasonal variation was found for erythema dyschromicum perstans (P = 0.899), pityriasis rosea (P = 0.727), or pityriasis lichenoides (P = 0.366). CONCLUSIONS: This study found statistically significant seasonal trends for several dermatologic conditions. The study was primarily epidemiologic and was not intended to address histopathologic differences that might underlie the seasonal variations observed. However, further investigation of seasonal differences in the histopathology of erythema multiforme may prove interesting.

Erythema Multiforme in Children and Mycoplasma pneumoniae Aetiology.

Erythema multiforme (EM) in children is understudied and confused with Stevens-Johnson syndrome (SJS) despite their being separate diseases with unique aetiologies and clinical presentations. The goal of this study was to determine the prevalence of Mycoplasma pneumoniae in paediatric patients with EM minor, EM major (EMM), and SJS. This retrospective cohort at The Hospital for Sick Children accrued all cases of EM minor, EMM, and SJS from 1999 to 2013. Sixty-five cases were identified: 20 of EM minor, 23 of EMM, and 22 of SJS. Aetiologies were attributed in 58% of cases: 79% infection and 21% drug aetiology. Sixty-one percent of patients with EMM were M pneumoniae positive, compared with 14% of those with SJS and 22% of those with EM minor (P < .01). M pneumoniae patients were older at presentation (P = .03) and more frequently had sore throat (P < .01) and atypical targets with central blistering (P < .01). These findings suggest that M pneumoniae should be suspected and treated until laboratory confirmation becomes available in patients presenting with atypical target lesions with central blistering.

Reacciones lepromatosas en pacientes adultos y pediátricos en un centro de referencia. Programa Nacional de Lepra, Paraguay / Lepromatous reactions in adults and pediatric outpatients in a reference center. National Lepra Program, Paraguay

Introducción la lepra, llamada también enfermedad de Hansen, es una afección de la piel y de los nervios periféricos, infectocontagiosa, causada por Mycobacterium leprae. Las reacciones lepromatosas se presentan aún con tratamiento y son expresiones de respuesta inmunitaria. Conocerlas es importante a fin de facilitar el abordaje. Objetivo determinar la frecuencia y tipo de reacciones lepromatosas en pacientes con diagnóstico de lepra que acuden al centro de referencia de Enfermedad de Hansen en el Hospital Distrital de San Lorenzo, de enero 2013 a diciembre 2015. Metodología observacional, descriptivo, retrospectivo de corte transverso. Resultados se incluyeron 217 pacientes, 72% presentaban lepra MB y 63% era de sexo masculino. La prevalencia de reacción lepromatosa fue 44%, siendo más frecuentes las de tipo 2 (65%). Se presentó reacción lepromatosa como debut de la enfermedad en 27 %. Treinta y tres pacientes presentaron de tres a doce episodios de reacción lepromatosa. El tratamiento fue talidomida y corticoides. Conclusiones la prevalencia de leprorreacciones fue cercana al 50%, predominando las de tipo 2. El tratamiento utilizado fue talidomida y/o corticoides dependiendo del tipo de reacción lepromatosa.

Introduction leprosy, wich is cause by Mycobacterium leprae, also known as Hansen's Disease, affects skin and peripheral nerves. Lepromatous reactions (LRs) are expressions of an immune reaction and remain as a major persistent problem. LRs are present even with appropriated treatment. Emphasis must be made in early diagnosis and prevention of the catastrophic consequences of LRs. Objective to determine the frequency and type of lepromatous reactions in leprosy patients with leprosy attending to reference center of Hansen´s Disease in the District Center Hospital in San Lorenzo, from January 2013 to December 2015. Methodology observational, retrospective cross sectional study. Results 217 patients were included, 72% with multibacillary leprosy. 63% were male. Lepromatous reactions were found in 44%, been more frequent Type II reaction, in 65% of cases. LRs as oset disease occurred in 27%. 33 patients presented from 3 to 12 episodes of lepromatous reaction. The number of LRs episodes per patient were 3 to 12. Thalidomide was used as treatment in Erithema Nodosum Leprosum (ENL) and corticosteroids for the other types de LRs. Conclusions prevalence of PRs were 50%, been more frecuent the type II. Reaction the treatment used was Thalidomide and/or corticosteroids depending on the type of lepromatosus reaction.

Oral erythema multiforme: trends and clinical findings of a large retrospective European case series.

OBJECTIVE: Erythema multiforme (EM) continues to be an underestimated disease with a lack of strict classification and diagnostic criteria. We present the analysis of a case series of 60 oral EM patients from 2 centers and illustrate the range of oral clinical presentations. STUDY DESIGN: Clinical data from 60 EM patients with oral involvement, diagnosed and treated between 1982 and 2014, were retrospectively collected from the archives of 2 independent hospitals. Statistical analyses of the data were performed using the Pearson χ-squared test and the Mann-Whitney U test. RESULT: Thirty-one patients (51.7%) were male and 29 (48.3%) were female, with a mean (±SD) age of 37.9 years (±18.1). The frequency of previous occurrences ranged from 0 to 10 (mean ± SD: 1.4 ± 2.0). Twenty-nine patients (48%) had no previous occurrence. Medications (particularly antipyretics, food additives, and antibiotics) were the suspected precipitants in 28 patients (46.7%), whereas herpes simplex virus infection was suspected in 18 (30.0%). All but 1 patient had involvement of multiple oral sites, with the buccal mucosa being the most commonly involved oral site (75%), followed by the vermillion border (71.7%). CONCLUSIONS: Patients with EM may present initially to oral health care workers. Medications and herpes simplex virus continue to be the most typically involved precipitating factors. Our data highlight the additional role of food-derived antigens. Although laboratory tests can provide support diagnostically, EM diagnosis continues to be based on clinical features. A medication and food diary should be encouraged particularly in patients with recurrent forms.

Erythema Multiforme Associated with Respiratory Disease in a Commercial Breeding Pig Herd.

This study describes an erythema multiforme (EM) in breeding sows, after their mixing in the group housing system. Sows at 30-35 days of gestation showed red and raised skin areas, depression, anorexia, fever, respiratory problems, and increased return to estrus. Blood and nasal samples from diseased sows were examined by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay for respiratory pathogens. Hematological and biochemical analyses were performed on the blood samples. From diseased sows, vaginal swabs for microbiological examinations and samples at slaughterhouse for gross and microscopic examinations were collected. Samples from the complete gestation and lactation feed were examined for mycotoxins. All sampled sows were seropositive for Actinobacillus pleuropneumoniae (App) and porcine reproductive and respiratory syndrome virus (PRRSV). No viremia for PRRSV and porcine circovirus type 2 were detected. All nasal samples were positive for Streptococcus suis, one for Swine Influenza Virus and one for App, Hemophilus parasuis, and S. suis. In all vaginal swabs, Escherichia coli and Streptococcus spp. were detected. Diseased sows had moderate leukocytosis, mild anemia, and thrombocytopenia. No mycotoxins were detected in feed. Histopathological examination revealed increased vascularization of the superficial and middle dermis. EM was likely due to illness caused by viral and bacterial infections. This study suggests that stress caused by the sows' mixing might have triggered the problem.

Erythema multiforme--etiopathogenic, clinical and therapeutic aspects.

AIM: To present the epidemiological, etiopathogenic, clinical and therapeutic aspects in Erythema multiforme (EM). MATERIAL AND METHODS: This is a 3-year retrospective study based on medical records of patients with EM admitted to the Dermatology Clinic. Forty patients were included in this study. The obtained data allowed the classification of patients according to their distribution by sex, age group, area of residence, etiology, clinical aspects, and type of administered treatment. RESULTS: The prevalence of EM during the 3 study years was 0.4%. EM prevailed among the rural population, more frequently in women. The minimum age at which EM was diagnosed was 12 years and maximum age 78 years, with a peak incidence between 20-40 years old (37.5% cases). In 42.50% of the cases EM was drug-induced, and in 17.50% of cases it was caused by infection with herpes simplex virus (HSV). There were 18 cases of erythemotous-papular EM (45%), 14 cases of erythematous--vesiculobullous EM (35%) and 8 cases of recurrent EM (20%). All patients received treatment with antihistamines and nonspecific desensitizing agents. Systemic corticotherapy was used in 22 cases. Three patients received treatment with acyclovir. CONCLUSIONS: Erythema multiforme is a rare skin condition, easily diagnosed based on its characteristic clinical appearance, but remains a challenge for the physician in terms of establishing its causal agent.

Phytodermatitis in eastern Turkey: a retrospective, observational study.

BACKGROUND: Plant life is extremely diverse, with a great deal of geographic and seasonal variation. Consequently, the range of reported adverse reactions is large, and there are important differences worldwide in the incidence and prevalence of these reactions. Systemic ingestion of some plants containing furocoumarins can cause erythema, edema, vesicle and bulla formation and later hyperpigmentation, after exposure to sunlight. They may at times exhibit clinical manifestations that mimic angioedema, and rarely progress to necrosis. This condition is named phyto-phototoxic reaction. OBJECTIVE: Our aim was to identify plant dermatitis such as allergic contact dermatitis, irritant contact dermatitis, and phyto-phototoxic dermatitis in eastern Turkey and to add new data to the literature. METHODS: Thirty patients diagnosed with plant dermatitis were evaluated retrospectively. The demographic and clinical characteristics of the patients (age, gender, the type of dermatitis, and the name of the causative plant) were recorded. CONCLUSIONS: A phyto-phototoxic reaction to Chenopodium album (Chenopodiaceae) developed in 12 cases. Irritant contact dermatitis developed due to Ranunculus kotschyi (Ranunculaceae) in 11 cases. The other plants studied were Malva neglecta Wallr (Malvaceae), Mandragora autumnalis (Solanaceae), Eryngium billardieri (Apiaceae), Ceratocephalus falcatus (Ranunculaceae), Ranunculus damascenus (Ranunculaceae), and Plantago lanceolata (Plantaginaceae).

Erythema multiforme, Stevens Johnson syndrome, and toxic epidermal necrolysis syndrome in patients undergoing radiation therapy: a literature review.

OBJECTIVE: Erythema multiforme (EM), Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis syndrome (TENS) are exfoliative disorders that may present as complications in some patients undergoing radiotherapy. The purpose of this literature review was to determine the reported frequency of these exanthemata in irradiated patients. METHODS: A comprehensive search from 1903 to 2011, identified 89 articles with 165 cases. RESULTS: Of 151 evaluable cases, 57 (38%) described EM; 46 (30.5%) SJS; 14 (9%) SJS/TENS overlap; and 34 (22.5%) TENS. Ninety-three percent underwent radiotherapy for either a primary or metastatic malignancy. A majority of patients were simultaneously treated with medications known to precipitate these exanthemata. Of the 61 patients receiving antiepileptic medications during radiotherapy, 48 were treated prophylactically and 13 for seizures, most frequently with phenytoin or phenobarbital. Amifostine was the second most common medication associated with radiotherapy and these reactions. Fourteen (23%) patients on anticonvulsant medication, and 11 (38%) on other medications died compared with 3 (8%) patients treated with radiotherapy alone (P = 0.002). No deaths occurred among irradiated patients receiving amifostine. CONCLUSIONS: EM, SJS, and TENS were rarely reported in patients undergoing radiotherapy alone. The majority of SJS and TENS occurred in irradiated patients with concomitant prescribed medications.