Improvement of the Ocular Prognosis of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A National Survey in Japan.

PURPOSE: To investigate the incidence and prognostic factors of ocular sequelae in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) cases arising between 2016 and 2018 in Japan, and compare the findings with those presented in the previous 2005-2007 survey. DESIGN: Retrospective, national trend survey . METHODS: Dermatological case report forms (CRFs) (d-CRFs) were sent to 257 institutions that treated at least 1 SJS/TEN case, and 508 CRFs were collected from 160 institutions. Ophthalmological CRFs (o-CRFs) regarding patient demographic data, onset date, ocular findings (first appearance, day of worst severity, and final follow-up), topical treatment (betamethasone), outcome (survival or death), and ocular sequelae (visual disturbance, eye dryness) were sent to the ophthalmologists in those 160 institutions. The results of this survey were then compared with that of the previous 2005-2007 survey. RESULTS: A total of 240 cases (SJS/TEN: 132/108) were included. The incidence of ocular sequelae incidence was 14.0%, a significant decrease from the 39.2% in the previous survey (SJS/TEN: 87/48). In 197 (82.1%) of the cases, systemic treatment was initiated within 3 days after admission, an increase compared to the previous survey (ie, treatment initiated in 82 [60.7%] of 135 cases). Of the 85 cases with an Acute Ocular Severity Score of 2 and 3, 62 (72.9%) received corticosteroid pulse therapy and 73 (85.9%) received 0.1% betamethasone therapy; an increase compared to the 60.0% and 70.8%, respectively, in the previous survey. Ocular-sequelae-associated risk factors included Acute Ocular Severity Score (P < 0.001) and specific year in the survey (P < 0.001). CONCLUSIONS: The ophthalmologic prognosis of SJS/TEN has dramatically improved via early diagnosis, rapid assessment of acute ocular severity, and early treatment.

Development and Validation of a Novel Score to Predict Mortality in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: CRISTEN.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, severe mucocutaneous adverse reactions. Severity prediction at early onset is urgently required for treatment. However, previous prediction scores have been based on data of blood tests. OBJECTIVE: This study aimed to present a novel score that predicts mortality in patients with SJS/TEN in the early stages based on only clinical information. METHODS: We retrospectively evaluated 382 patients with SJS/TEN in a development study. A clinical risk score for TEN (CRISTEN) was created according to the association of potential risk factors with death. We calculated the sum of these risk factors using CRISTEN, and this was validated in a multinational survey of 416 patients and was compared with previous scoring systems. RESULTS: The significant risk factors for death in SJS/TEN comprised 10 items, including patients' age of ≥65 years, ≥10% body surface area involvement, the use of antibiotics as culprit drugs, the use of systemic corticosteroid therapy before the onset, and mucosal damage affecting the ocular, buccal, and genital mucosa. Renal impairment, diabetes, cardiovascular disease, malignant neoplasm, and bacterial infection were included as underlying diseases. The CRISTEN model showed good discrimination (area under the curve [AUC] = 0.884) and calibration. In the validation study, the AUC was 0.827, which was statistically comparable to those of previous systems. CONCLUSION: A scoring system based on only clinical information was developed to predict mortality in SJS/TEN and was validated in an independent multinational study. CRISTEN may predict individual survival probabilities and direct the management and therapy of patients with SJS/TEN.

Risk factors for sepsis and effects of pretreatment with systemic steroid therapy for underlying condition in SJS/TEN patients: Results of a nationwide cross-sectional survey in 489 Japanese patients.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse reactions (SCARs). Sepsis has been shown to be the main cause of death in SJS/TEN. The European SCAR study reported that 14.8 % of SJS/TEN patients were receiving systemic steroid therapy for their underlying condition prior to onset. However, it remained unclear whether this factor affected the mortality rate. OBJECTIVE: This study was performed to identify risk factors for sepsis in SJS/TEN patients. In addition, we compared patients who had and had not received systemic steroid therapy for their underlying condition. METHODS: A primary survey regarding the numbers of SJS/TEN patients between 2016 and 2018 was sent to 1205 institutions in Japan. A secondary survey seeking more detailed information was sent to institutions reporting SJS/TEN patients. We analyzed 315 SJS patients and 174 TEN patients using a logistic regression model, Wilcoxon's rank-sum test, χ2 test, and Fisher's exact test. RESULTS: Significant risk factors for sepsis included TEN, diabetes, and intensive care unit (ICU) admission. The mortality rate was significantly higher among patients with sepsis. Patients who had received systemic steroid therapy had a lower incidence of fever, and showed a higher mortality rate. CONCLUSION: Based on a nationwide epidemiological survey of SJS/TEN in Japan, we identified risk factors for sepsis and found that patients who had received steroid therapy for their underlying condition had a lower incidence of fever and a higher mortality rate.

The nationwide epidemiological survey of Stevens-Johnson syndrome and toxic epidermal necrolysis in Japan, 2016-2018.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse reactions (SCARs). The first national epidemiological survey of SJS/TEN was carried out in 2008. We conducted a new survey to identify changes from the previous survey. OBJECTIVE: The present survey aimed to estimate the number of SJS/TEN patients in Japan between 2016 and 2018 (primary survey) and to clarify clinical epidemiological profiles (secondary survey). METHODS: A primary survey asking for numbers of SJS/TEN patients during the study period was sent to 1205 institutions nationwide. A secondary survey was sent to institutions reporting SJS/TEN patients, seeking detailed information. RESULTS: Yearly prevalence per million was 2.5 for SJS and 1 for TEN. The secondary survey allowed analysis of 315 SJS cases and 174 TEN cases from 160 institutions. Mean age was 53.9 years in SJS, and 61.8 years in TEN. Mortality rate was 4.1 % for SJS and 29.9 % for TEN. In TEN, mean age and mortality rates had increased from the previous survey. The ratio of expected to observed mortality calculated by SCORTEN score was lowest with high-dose steroid therapy (0.40), followed by steroid pulse therapy (0.52). CONCLUSION: The present findings suggest that the mortality rate of TEN has increased because of increases in mean ages of patients and patients with malignant neoplasm as underlying disease. When comparing the ratio of expected mortality to actual mortality, high-dose steroid therapy achieved the greatest reduction in mortality.

Associations between normal weight central obesity and cardiovascular disease risk factors in Japanese middle-aged adults: a cross-sectional study.

BACKGROUND: Several studies have shown that normal weight central obesity (NWCO) is associated with cardiovascular disease (CVD) risk factors. However, studies conducted in the Japanese population have been very limited. Thus, the relationships between normal weight central obesity, classified using body mass index (BMI), the waist-to-height ratio (WHtR), and CVD risk factors in middle-aged Japanese adults were investigated. METHODS: The participants were Japanese adults aged 40-64 years who had undergone periodic health examinations in Japan during the period from April 2013 to March 2014. The participants were categorized into the following four groups: normal weight (BMI 18.5-24.9 kg/m2) and no central obesity (WHtR < 0.5) (NW); normal weight and central obesity (WHtR ≥ 0.5) (NWCO); obesity (BMI ≥ 25 kg/m2) and no central obesity (OB); and obesity and central obesity (OBCO). Hypertension was defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or taking medication for hypertension. Dyslipidemia was defined as LDL-C ≥ 140 mg/dl, HDL-C < 40 mg/dl, triglyceride ≥ 150 mg/dl, or taking medication for dyslipidemia. Diabetes was defined as fasting plasma glucose ≥ 126 mg/dl, random plasma glucose ≥ 200 mg/dl, HbA1c ≥ 6.5%, or receiving medical treatment for diabetes mellitus. A logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for hypertension, dyslipidemia, and diabetes. RESULTS: A total of 117,163 participants (82,487 men and 34,676 women) were analyzed. The prevalence of NWCO was 15.6% in men and 30.2% in women. With reference to NW, the ORs for hypertension (adjusted OR 1.22, 95% CI 1.17-1.27 in men, 1.23, 1.16-1.31 in women), dyslipidemia (1.81, 1.74-1.89 in men, 1.60, 1.52-1.69 in women), and diabetes (1.35, 1.25-1.46 in men, 1.60, 1.35-1.90 in women) were significantly higher in NWCO. CONCLUSIONS: Normal weight with central obesity was associated with CVD risk factors, such as hypertension, dyslipidemia, and diabetes, compared with normal weight without central obesity, regardless of sex. It is important to focus on normal weight with central obesity for the prevention of CVD in Japanese middle-aged adults.

Effects of eating dinner alone on overweight in Japanese adolescents: a cross-sectional survey.

BACKGROUND: The decrease in the frequency of family meals among Asian youth is often lamented. In Japan, adolescents who eat breakfast alone might have an unhealthy diet, which increases the risk of overweight or obese. However, there are few studies on the relationship between eating dinner alone and overweight in Japanese adolescents. Here, we investigated if eating dinner alone is associated with being overweight in Japanese adolescents of each sex. METHODS: The participants consisted of 890 seventh graders (12-13 years of age) from the junior high schools of Ina, Japan who were recruited from 2011 to 2012. Information about eating dinner alone was obtained using a self-reported questionnaire, which was given to each participant. The participants were classified into the following three groups: does not eat alone, eats alone 1-2 times/week, or eats alone ≥3 times/week. A logistic regression model was used to examine the relationship between eating dinner alone and being overweight. The height and weight of each participant were measured. Childhood overweight status was defined using the body mass index cutoff points proposed by the International Obesity Task Force. RESULTS: When compared with girls who did not eat dinner alone, a significantly increased odds ratio (OR) was observed among girls who ate dinner alone ≥1 time/week (adjusted OR = 2.78; 95% confidence interval = 1.21-6.38). In contrast, there was no statistically significant difference between eating dinner alone and being overweight among boys. CONCLUSION: The present study found that eating dinner alone is associated with being overweight among adolescent girls in this community in Japan. Therefore, reducing the frequency of eating dinner alone might contribute to decreasing the risk for becoming overweight or obese among adolescent girls.