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.

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.

J-curve association between alcohol intake and varicose veins in Japan: The Shimane CoHRE Study.

The effect of alcohol intake on varicose veins (VV) has not been determined by its consumption level. The aim of this study was to investigate the association between alcohol intake and VV in an elderly general population. Using a cross-sectional approach, the Shimane CoHRE Study data, comprising a total of 1060 participants, were analyzed. By multivariate regression analysis adjusted with basic characteristics, past work history, lifestyle-related factors and medical history, compared with non-drinkers, mild drinkers (<20.0 g/day) showed a significantly lower adjusted odds ratio (aOR) of VV (aOR = 0.64, P = 0.036). In a similar way, regular drinkers (1-5 days/week) showed a significantly lower aOR of VV when compared with occasional drinkers (aOR = 0.57, P = 0.032). VV and alcohol intake showed J-curve relationships. In a stratified analysis by alcohol consumption levels, the association of smoking and VV were also observed in moderate to heavy drinkers and habitual drinkers. These findings can provide better understanding of pathophysiological mechanism and be used for evidence-based patient education.

Surgical methods and clinical results of subfascial endoscopic perforator surgery in Japan.

OBJECTIVES: To clarify the surgical methods and the clinical results of subfascial endoscopic perforator surgery in Japan. METHODS: This study included 1287 limbs of 1091 patients who underwent subfascial endoscopic perforator surgery in 14 hospitals. Simultaneous saphenous vein treatment was performed in 1079 limbs (83.8%), and 118 limbs (9.2%) had deep venous lesions. The venous clinical severity score was calculated before and 6 to 12 months after surgery. The ulcer healing rate and ulcer recurrence rate were calculated cumulatively. RESULTS: Preoperative venous clinical severity score was significantly decreased from 10.0 ± 6.6 to 3.1 ± 3.4 ( P < .0001) postoperatively. The primary ulcer healing rate was 96.2% (332/345 C6 limbs) at an average follow-up of 47.7 months, and the ulcer recurrence rate was 12.0% (49/393 C5, C6 limbs) at the average follow-up of 46.0 months after the ulcer healed. CONCLUSION: These results indicate that subfascial endoscopic perforator surgery is an alternative to improve the long-lasting disease severity and/or clinical outcome.

Neutrophil Depletion Attenuates Muscle Injury after Exhaustive Exercise.

PURPOSE: The infiltration of macrophages in skeletal muscle during exhaustive exercise promotes inflammation, myofiber lesion, and muscle injury. Although neutrophils upregulate macrophage infiltration in skeletal muscles during exercise, the role of neutrophils in promoting muscle injury after exhaustive exercise remains unclear. In this study, we investigated the effects of preexercise neutrophil depletion with antineutrophil antibody treatment on muscle injury, inflammation, and macrophage infiltration after exhaustive exercise. METHODS: Male C57BL/6J mice were randomly assigned to four groups, namely, sedentary with control antibody (n = 10), sedentary with antineutrophil antibody (n = 10), exhaustive exercise with control antibody (n = 10), and exhaustive exercise with antineutrophil antibody (n = 10). The mice were given intraperitoneal injection of the antineutrophil antibody (anti-Ly-6G, clone 1A8) or the control antibody (anti-Ly-6G, clone 2A3), and remained inactive or performed exhaustive exercise on a treadmill 48 h after the injection. Twenty-four hours after the exhaustive exercise, the gastrocnemius muscles were removed for histological and polymerase chain reaction (PCR) analyses. Infiltration of neutrophils and macrophages was evaluated with Ly-6G and F4/80 immunohistochemistry staining procedures. Muscle fiber injury was detected based on the number of IgG staining fiber. The mRNA expression levels of proinflammatory cytokines and chemokines were evaluated with real-time reverse transcription PCR. RESULTS: Exhaustive exercise increased neutrophil infiltration into the gastrocnemius muscle substantially by 3.1-fold and caused muscle injury, but these effects were markedly suppressed by preexercise treatment with antineutrophil antibody (neutrophil infiltration, 0.42-fold, and muscle injury, 0.18-fold). Treatment with antineutrophil antibody also decreased macrophage infiltration (0.44-fold) and mRNA expression of tumor necrosis factor-α (0.55-fold) and interleukin-6 (0.51-fold) in the skeletal muscle after exhaustive exercise. CONCLUSION: These results suggest that neutrophils contribute to exacerbating muscle injury by regulating inflammation through the induction of macrophage infiltration.

Usefulness of sentinel lymph node biopsy for the detection of metastasis in the early stage of extramammary Paget's disease.

BACKGROUND: Invasive cases of extramammary Paget's disease have a poor prognosis, owing to its rapid progression and resistance to irradiation and chemotherapy. Morton et al. introduced a technique to identify sentinel lymph nodes by local injection of vital dyes and reported its benefit for managing the progress of malignant melanoma. OBJECTIVES: Since the rate of lymph node metastasis of extramammary Paget's disease is not uncommon (reported from 8.5% to 26%), this study tested the hypothesis that sentinel lymph node biopsy would be useful to detect lymph node metastasis in the clinically early stage of extramammary Paget's disease. MATERIALS & METHODS: Eighteen patients with primary extramammary Paget's disease were enrolled in the study. The precise location of sentinel lymph nodes was visualized using either intraoperative patent blue dye injection or indocyanine green dye injection in combination with a hand-held gamma-detecting probe after a 99mTc phytate injection. RESULTS: Of the 18 patients, sentinel lymph node metastasis was identified in 2 (Cases 2 and 15) of the 2 patients with deep invasion and in 1 (Case 12) of the 7 patients with minimal dermal invasion, however, it was absent in 9 patients who had been categorized into the intraepidermal group. CONCLUSION: This study demonstrates that extramammary Paget's disease possibly causes metastasis via regional lymphatic systems to which the lesion belongs, even in the early stages of no nodule or tumor formation, and that sentinel lymph node biopsy is useful to detect lymph node metastasis.

Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR).

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse drug reaction caused by specific drug. It is characterized by visceral organ involvement and reactivation of various human herpesviruses. Although sporadic reports have documented certain conditions that appear after the resolution of DIHS/DRESS, little information is available on sequelae after resolution of DIHS/DRESS in a large patient population. The Asian Research Committee on Severe Cutaneous Adverse Reactions, comprised of doctors from Japan and Taiwan, conducted a survey on sequelae and deterioration of the underlying disease in patients with DIHS/DRESS. This was achieved by directly interviewing patients who had been followed-up by experts or through a questionnaire mailed to patients. Questions were asked about new onset cardiovascular disease, collagen disease or autoimmune disease, gastrointestinal disease, renal disease, respiratory disease, neoplasms, and other diseases such as herpes zoster and diabetes mellitus, as well as deterioration of the underlying disease. A total of 145 patients were analyzed in this study. The following newly developed diseases after recovery from DIHS/DRESS were observed: Graves' disease (n = 2), Hashimoto's disease (n = 3), painless thyroiditis (n = 2), fulminant type 1 diabetes mellitus (n = 5), and infectious diseases (n = 7). Several DIHS/DRESS patients with pre-existing renal dysfunction required lifelong hemodialysis. DIHS/DRESS is a condition that increases the risk of new onset of disease. Long-term observation of DIHS/DRESS can provide an opportunity to investigate substantial diseases from onset to the full-blown stage. Patients with DIHS/DRESS require careful long-term follow-up.

Fluorescence navigation with indocyanine green for detecting sentinel nodes in extramammary Paget's disease and squamous cell carcinoma.

The radioisotope navigation method, which has usually been used for identification of sentinel nodes, is less useful in locating sentinel nodes close to primary lesions in cases of extramammary Paget's disease because of overlapping radioactivity from the primary site. We applied fluorescence navigation with indocyanine green (ICG) in two patients with skin cancer to cover this defect. The use of a charge-coupled device camera enabled real-time visualization of dynamic lymph flow without skin incision. The inguinal skin over the identified sentinel node with a handheld gamma probe was in accordance with the point detected by ICG fluorescence in a patient with squamous cell carcinoma of the foot. Sentinel node biopsy using fluorescence navigation with ICG proved to be easy and reliable.