PURPOSE: Although severe cutaneous adverse drug reactions (SCARs) are rare, they are associated with high morbidity and mortality, and thus early diagnosis and treatment are critical for improving prognoses. However, few studies have reported the characteristics of SCARs in children. Thus, we aimed to evaluate the clinical characteristics, current management and prognosis of pediatric SCARs. METHODS: We analyzed pediatric data in the Korean SCARs registry, which was built retrospectively in 2016 with SCAR cases treated in 34 tertiary referral university hospitals during 2010–2015. Using these cases, we descriptively analyzed detailed data regarding etiology, clinical and laboratory features, treatment strategies, and prognosis. RESULTS: Forty-seven pediatric SCAR cases from 15 tertiary referral hospitals were included. The median patient age was 10 (interquartile range, 3-15.5) years and 68.1% (n = 32) were males. The culprit drug was identified in 95.7% (n = 45) of the patients; antibiotics (44.7%) and antiepileptic drugs (19.1%) were the most common and second most common culprits, respectively. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) cases presented with the largest area of skin involvement without permanent sequelae. Stevens-Johnson syndrome (SJS) cases involved relatively small areas of skin but serious sequelae in two children. Of 4 patients with toxic epidermal necrolysis (TEN), 1 died. Of all patients assessed, 36 (76.6%) received systemic steroids and 21 (44.7%) received intravenous immunoglobulin (IVIG). Thirteen (27.7%) received both systemic steroids and IVIG. Cyclosporine was administered to only 1 patient along with a systemic steroid. CONCLUSIONS: In patients with pediatric SCARs, including those with DRESS, SJS and TEN, clinical presentations were variable. Thus, there was no clear continuous disease spectrum. Although the mortality rate was low (2.1%), clinical suspicion may be the best tool for proactive SCAR management.
Anti-Bacterial Agents ; Anticonvulsants ; Child ; Cicatrix ; Cyclosporine ; Drug Eruptions ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Early Diagnosis ; Hospitals, University ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Korea ; Male ; Mortality ; Prognosis ; Referral and Consultation ; Retrospective Studies ; Skin ; Steroids ; Stevens-Johnson Syndrome ; Tertiary Care Centers

Despite their being uncommon, severe cutaneous adverse drug reactions (SCARs) result in a very great burden of disease. These reactions not only carry with them a high mortality (10%–50%) and high morbidity (60%) with severe ocular complications, alopecia, oral and dental complications and development of autoimmune diseases, but also create a substantial economic burden for patients' families and society. SCARs are, therefore, an important medical problem needing a solution in many countries, especially in Asia. The clinical spectrum of SCARs comprises Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS (drug rash with eosinophilia and systemic symptoms) (also known as drug hypersensitivity syndrome or drug-induced hypersensitivity syndrome) and acute generalised exanthematous pustulosis. Recent crucial advances in determining genetic susceptibility and understanding how T cells recognise certain medications or their metabolites via the major histocompatibility complex and the effects of cofactors, have led to the implementation of cost-effective screening programs enabling prevention in a number of countries, and to further understanding of the patho-mechanisms involved in SCARs and their significance. In this review, we document comprehensively the journey of SCARs from bedside to bench and outline future perspectives in SCARs research.
Alopecia ; Asia ; Autoimmune Diseases ; Cicatrix ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Eosinophilia ; Exanthema ; Genetic Predisposition to Disease ; Humans ; Hypersensitivity ; Leukocytes ; Major Histocompatibility Complex ; Mass Screening ; Mortality ; Stevens-Johnson Syndrome ; T-Lymphocytes

PURPOSE: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) to antiepileptic drug (AED), are rare, but result in significant morbidity and mortality. We investigated the major culprit drugs, clinical characteristics, and clinical course and outcomes of AED-induced SCARs using a nationwide registry in Korea. METHODS: A total of 161 patients with AED-induced SCARs from 28 referral hospitals were analyzed. The causative AEDs, clinical characteristics, organ involvements, details of treatment, and outcomes were evaluated. We compared the clinical and laboratory parameters between SJS/TEN and DRESS according to the leading causative drugs. We further determined risk factors for prolonged hospitalization in AED-induced SCARs. RESULTS: Carbamazepine and lamotrigine were the most common culprit drugs causing SCARs. Valproic acid and levetiracetam also emerged as the major causative agents. The disease duration and hospital stay in carbamazepine-induced SJS/TEN were shorter than those in other AEDs (P< 0.05, respectively). In younger patients, lamotrigine caused higher incidences of DRESS than other drugs (P= 0.045). Carbamazepine, the most common culprit drug for SCARs, was associated with a favorable outcome related with prolonged hospitalization in SJS (odds ratio, 0.12; 95% confidence interval, 0.02-0.63, P= 0.12), and thrombocytopenia was found to be a risk factor for prolonged hospitalization in DRESS. CONCLUSION: This was the first large-scale epidemiological study of AED-induced SCARs in Korea. Valproic acid and levetiracetam were the significant emerging AEDs causing SCARs in addition to the well-known offending AEDs such as carbamazepine and lamotrigine. Carbamazepine was associated with reduced hospitalization, but thrombocytopenia was a risk factor for prolonged hospitalization. Our results suggest that the clinical characteristics and clinical courses of AED-induced SCARs might vary according to the individual AEDs.
Anticonvulsants ; Carbamazepine ; Cicatrix ; Drug Hypersensitivity Syndrome ; Epidemiologic Studies ; Hospitalization ; Humans ; Incidence ; Korea ; Length of Stay ; Mortality ; Referral and Consultation ; Risk Factors ; Stevens-Johnson Syndrome ; Thrombocytopenia ; Valproic Acid

BACKGROUND: Severe cutaneous adverse reactions (SCAR) to drugs are a crucial public health issue and the use of systemic corticosteroids in SCAR has been controversial. OBJECTIVE: To analyze clinical features, causative drugs, treatment, outcomes, and prognostic factors of SCAR in the case-series of 173 patients, and add more information to the debate of using systemic corticosteroids in SCAR management. METHODS: A retrospective study of 173 SCAR patients diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) or acute generalized exanthematous pustulosis (AGEP) at a tertiary care institution in China between January 2014 and December 2017 was conducted. RESULTS: Of 173 patients, allopurinol, carbamazepine, and antibiotics are the most frequently implicated drugs for DRESS (40.4%), SJS/TEN (26.0%), and AGEP (40.0%) respectively. Moreover, there is a strongly negative correlation between early corticosteroids use and the progression (p=0.000) and severity (p=0.01) of skin lesions. However, there is no association between early corticosteroids use and the mortality of SCAR (odds ratio: 1.01, 95% confidence interval: 0.95~1.08). In addition, lymphadenopathy, eosinophilia, and interval from onset to corticosteroids treatment were correlated with SCAR prognosis. CONCLUSION: Prompt short-course systemic corticosteroids use is associated with early-stage skin lesions remission without influencing the disease mortality. Lymphadenopathy and eosinophilia were the independent poor prognostic factors of SCAR.
Acute Generalized Exanthematous Pustulosis ; Adrenal Cortex Hormones ; Allopurinol ; Anti-Bacterial Agents ; Carbamazepine ; China ; Cicatrix ; Drug Hypersensitivity Syndrome ; Eosinophilia ; Humans ; Lymphatic Diseases ; Mortality ; Prognosis ; Public Health ; Retrospective Studies ; Skin ; Stevens-Johnson Syndrome ; Tertiary Healthcare

BACKGROUND/AIMS: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions that frequently result in fatal outcomes. We investigated cases of SJS and TEN in a regional hospital. METHODS: From 2008 to 2014, SJS and TEN cases were enrolled retrospectively by allergy and dermatology specialists, and their clinical features and severity-of-illness score for TEN (SCORTEN) were assessed. RESULTS: During the 7-year study period, 56 SJS and 14 TEN cases were recruited. The majority (71%) were 40-70 years of age (mean age of male and female patients, 55 and 54 years, respectively). Regarding drugs, anticonvulsants (42.8%) were the most frequently causative, followed by carbonic anhydrase inhibitors (20.0%), antimicrobials (15.7%), allopurinol (7.1%), and non-steroidal anti-inflammatory drugs (7.1%). No fatal case of SJS was seen. However, 7 of the 14 patients with TEN died (50%; mean age, 67 years; 1 of 5 [20%] males and 6 of 9 females [66.7%]). The mortality rate was reflected in the SCORTEN values. Vancomycin, allopurinol, methazolamide (two cases each) and megestrol (one case) were the causative drugs in the seven fatal TEN cases. Treatment modality did not affect the likelihood of death due to TEN. CONCLUSIONS: The causative drugs of, and frequency of mortality due to, SJS and TEN should be recognized by physicians. Elderly females with TEN are at high risk of mortality. SCORTEN values reflect the mortality rate of TEN patients. Early recognition and proper management of SJS and TEN may reduce the mortality rate.
Aged ; Allopurinol ; Anticonvulsants ; Carbonic Anhydrase Inhibitors ; Dermatology ; Drug-Related Side Effects and Adverse Reactions ; Fatal Outcome ; Female ; Humans ; Hypersensitivity ; Male ; Megestrol ; Methazolamide ; Mortality ; Retrospective Studies ; Specialization ; Stevens-Johnson Syndrome* ; Vancomycin

Drug reaction with eosinophilia and systemic symptom (DRESS) syndrome is a type of severe adverse drug-induced reaction. Dermatologists should make a quick diagnosis and provide appropriate treatment for DRESS syndrome to reduce mortality rates, which can be as high as 10%. We present the case of a 47-year-old man with schizoaffective disorder treated with lamotrigine who developed DRESS syndrome to emphasize the importance of close observation of patients with drug eruption. He was consulted for erythematous maculopapular rashes on the trunk that developed 3 weeks after starting lamotrigine. A few days later, he developed generalized influenza-like symptoms. The skin rashes spread over his entire body, and the sense of itching was rapidly aggravated within a few days. Increased liver enzyme levels and significant eosinophilia were found on laboratory test results. His condition was diagnosed as DRESS syndrome, and he was treated with systemic and topical corticosteroids for 2 weeks.
Adrenal Cortex Hormones ; Anticonvulsants ; Diagnosis ; Drug Eruptions ; Drug Hypersensitivity Syndrome ; Eosinophilia* ; Exanthema ; Humans ; Liver ; Middle Aged ; Mortality ; Pruritus ; Psychotic Disorders

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions to drugs, which carry significant morbidities and mortalities. Although SJS and TEN can be treated by corticosteroids or intravenous immunoglobulin, they may be induced by steroids. We experienced a 36-year-old man who developed whole body erythromatous maculopapular rashes and multiple bullae after ingestion of deflazacort. After avoidance of deflazacort and use of dexamethasone, skin lesions resorbed. We reported a case of TEN diagnosed by characteristic clinical findings with a brief review of the literature.
Adrenal Cortex Hormones ; Adult ; Dexamethasone ; Drug Hypersensitivity Syndrome ; Eating ; Exanthema ; Humans ; Immunoglobulins ; Mortality ; Nephrotic Syndrome ; Skin ; Steroids ; Stevens-Johnson Syndrome*

Despite the fact that any drug can be an impending cause of hypersensitivity reactions, Ibuprofen, an over-the-counter drug used extensively as an analgesic and antipyretic in Asia, is considered to be relatively safe. But herein we report a rare extremely 'rapid onset' occurrence of a severe case of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a 22-year-old male, induced by 3 doses of 400 mg of Ibuprofen taken at 8-hour interval for eye pain, probably the first case report of rapid onset of TEN by nonsteroidal antiinflammatory drugs in Nepal. SJS and TEN are idiosyncratic, delayed hypersensitivity inflammatory adverse drug reactions that are severe adverse cutaneous drug reactions which predominantly involve the skin and mucous membranes and are linked with high morbidity and mortality. Nevertheless, removal of ibuprofen and its metabolites with plasma exchange and treatment with antibiotics and intravenous corticosteroids along with supportive therapy improved the course of the disorder. This rare case report addresses the fact that severe hypersensitivity reactions can occur with Ibuprofen, which can be potentially dangerous and life threatening. It is thus important for the clinicians to be alert to such severe hypersensitivity reactions even with drugs which are deemed to be probably safe.
Adrenal Cortex Hormones ; Anti-Bacterial Agents ; Asia ; Drug-Related Side Effects and Adverse Reactions ; Eye Pain ; Humans ; Hypersensitivity ; Hypersensitivity, Delayed ; Ibuprofen ; Immune System Diseases ; Male ; Mortality ; Mucous Membrane ; Nepal ; Plasma Exchange ; Skin ; Stevens-Johnson Syndrome ; Young Adult

BACKGROUND: Drug allergy (DA) is one of the most important contributors to iatrogenic morbidity and mortality. Currently DA remains a major challenge for healthcare practitioners (HCPs). OBJECTIVE: To assess the knowledge, attitudes and practices of DA among HCPs in Central China. METHODS: A 25-item self-administered DA questionnaire were developed and applied in our study. The questionnaire covered 3 domains: knowledge, attitudes, and practice patterns. From July 2015 to October 2015, HCPs in 7 cities of Central China anonymously participated in the cross-sectional study. RESULTS: A total of 350 HCPs participated the study, 91 questionnaires uncompleted and 259 were analyzed. Among the respondents, 166 (64.1%) were doctors, 55 (21.2%) were nurses and 38 (14.7%) were medical students. The mean knowledge precision was 59.8%. HCPs agreed that drug induced immediate allergic reactions were IgE mediated (83.4%) and happened within 6 hours after drug administration (89.6%), and epinephrine was the first choice for drug induced anaphylaxis (79.5%). They also agreed that penicillin skin test was valuable to predict allergic reaction (88.4%). However, high proportion of HCPs (66.0%) believed glucocorticoids had an impact on drug skin test rather than antihistamines (4.2%), 47.1% never performed positive and negative control during skin test. More than 90% of the respondents would take patients' allergic history before drug administration, 98.8% agreed that they should receive advanced training of DA knowledge and practice. CONCLUSION: The HCPs demonstrated a low level of knowledge regarding DA. Advanced education is urgently needed for better understanding and filling the gaps exist in knowledge and clinical practice of DA.
Anaphylaxis ; Anonyms and Pseudonyms ; China ; Cross-Sectional Studies ; Delivery of Health Care ; Drug Hypersensitivity ; Education ; Epinephrine ; Glucocorticoids ; Histamine Antagonists ; Humans ; Hypersensitivity ; Immunoglobulin E ; Mortality ; Penicillins ; Skin Tests ; Students, Medical ; Surveys and Questionnaires

BACKGROUND: Anaphylaxis is a serious allergic reaction that may cause death. The signs and symptoms of anaphylaxis have not been examined in the Saudi population before. OBJECTIVE: The present study examined the signs, symptoms, triggers, and demographic patterns of patients treated for anaphylaxis at a large tertiary care hospital in Riyadh, Saudi Arabia. METHODS: All the patients who were prescribed new prescriptions of adrenaline auto-injectors (AAs) between February 1, 2010 and December 31, 2011 were included in this study. Information was collected using a standardized form. RESULTS: There were 238 patients who were analyzed. The median age at the time of first AA prescription was 15.5 years. Female to male ratio was 52:48 and 54% of the subjects were more than 18 years of age. There were some differences in the presenting signs and symptoms observed in our study compared with similar studies from around the world. Urticaria and angioedema were the most common at about 70% across all ages, followed by shortness of breath at 28%. Some triggers were found to be more common in our region. Food was the commonest trigger for anaphylaxis including tree nuts, egg, and sesame. Drug allergy was also a common trigger, with penicillins and nonsteroidal anti-inflammatory drugs being the commonest. Regarding insect allergy, samsam ant was the commonest trigger in our study. CONCLUSION: To our knowledge, this is the first study on anaphylaxis in Saudi Arabia. Some of the manifestations of anaphylaxis are significantly different in our population study compared to previously published data from other parts of the world. While managing anaphylaxis, we should be mindful of these differences. This improved understanding should help reduce the morbidity and mortality associated with anaphylaxis in our region.
Anaphylaxis ; Angioedema ; Ants ; Drug Hypersensitivity ; Dyspnea ; Epinephrine ; Female ; Humans ; Hypersensitivity ; Insects ; Male ; Mortality ; Nuts ; Ovum ; Penicillins ; Prescriptions ; Saudi Arabia ; Sesamum ; Tertiary Healthcare ; Trees ; Urticaria