Improvement of Mortality Prognostication in Patients With Epidermal Necrolysis: The Role of Novel Inflammatory Markers and Proposed Revision of SCORTEN (Re-SCORTEN).

IMPORTANCE: Epidermal necrolysis is a severe cutaneous adverse reaction in which severe systemic inflammation results in extensive epithelial keratinocyte necrosis. The most commonly used prognostic score in epidermal necrolysis, the Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN), was recently found to overestimate mortality in contemporary cohorts. Identification of independent prognostic markers may help to stratify risk more accurately. OBJECTIVE: This study evaluates the association between novel inflammatory markers and in-hospital mortality in patients with epidermal necrolysis to study the incremental prognostic value of these markers in combination with SCORTEN. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted over a 17-year period from 2003 to 2019. Patients were enrolled from Singapore General Hospital, the national referral center for epidermal necrolysis. A total of 196 patients with epidermal necrolysis were recruited, 4 (2%) of whom were excluded owing to incomplete data. MAIN OUTCOMES AND MEASURES: The main outcome assessed was the in-hospital mortality rate. Discrimination and calibration of risk scores were assessed using the area under the receiver operating characteristic curve (AUC) and calibration plot, respectively. Evaluation of the incremental prognostic value of these markers was done by comparing the AUC between the old and new risk score, and the use of net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: Among 192 total patients (median [IQR] age 56 [42-70] years; 114 [59.4%] women), there were 43 (22.4%) who did not survive to discharge. Of the novel inflammatory markers, only red cell distribution width to hemoglobin ratio was significant in predicting in-hospital mortality (odds ratio [OR] 3.55; 95% CI, 1.76-7.16; P < .001) after adjusting for SCORTEN. The RDW/Hb as applied in 4 risk groups showed similar discrimination to SCORTEN (AUC [95% CI]: RDW/Hb in 4 groups, 0.76 [0.69-0.84], vs SCORTEN, 0.78 [0.70-0.85], P = .89). When RDW/Hb was added to SCORTEN, the composite score Re-SCORTEN showed significantly better discrimination than SCORTEN alone (AUC [95% CI]: Re-SCORTEN, 0.83 [0.77-0.89], vs SCORTEN, 0.78 [0.70-0.85], P = .02). The overall NRI was 0.94 (95% CI, 0.68-1.20), P < .001. The IDI was 0.06 (95% CI 0.03-0.08), P < .001. Re-SCORTEN showed good calibration based on the calibration plot. CONCLUSIONS AND RELEVANCE: In this cohort of patients, RDW/Hb, an inexpensive and readily available marker, showed similar predictive accuracy with SCORTEN. Furthermore, when used in combination with SCORTEN, it also helped augment prognostic ability.

Assessment and Comparison of Performance of ABCD-10 and SCORTEN in Prognostication of Epidermal Necrolysis.

Importance: Epidermal necrolysis is a rare severe cutaneous drug reaction associated with high mortality. The ABCD-10 score (age, bicarbonate, cancer, dialysis, 10% body surface area), a new prognostic score for mortality in epidermal necrolysis, was recently developed and validated in the US. However, to our knowledge, it remains to be externally validated in other cohorts. Objective: To assess ABCD-10 among patients in a contemporary Asian cohort and compare its performance with the Score of Toxic Epidermal Necrosis (SCORTEN) and study the associations of time and immunomodulatory therapy with the performance of ABCD-10 and SCORTEN. Design, Setting, and Participants: This retrospective cohort study was conducted over a 17-year period from January 2003 to March 2019 and included 196 patients with epidermal necrolysis who were recruited from Singapore General Hospital, the national referral center for epidermal necrolysis. Main Outcomes and Measures: In-hospital mortality. Discrimination and calibration of each risk score were assessed and compared using the area under the receiver operating characteristic curve and calibration plot, respectively. Results: Among 196 patients (median [interquartile range] age, 56 [42-70] years; 116 women [59.2%]), 45 (23.0%) did not survive to discharge. All risk factors in ABCD-10 were significantly associated with in-hospital mortality. However, dialysis before admission, the most heavily weighted factor in ABCD-10, performed weaker in this cohort (odds ratio, 3.7; 95% CI, 1.0-13.2, P = .04). Although the discrimination of ABCD-10 and SCORTEN did not differ (area under the curve: ABCD-10, 0.78; 95% CI, 0.72-0.85; vs SCORTEN, 0.77; 95% CI, 0.69-0.84; P = .53), the calibration of ABCD-10 was poorer compared with SCORTEN. From graphical analysis of the calibration plots, ABCD-10 showed mortality underestimation at lower score ranges and overestimation at higher score ranges. By contrast, SCORTEN was generally well calibrated, although at higher score ranges mortality may be overestimated. Assessment of calibration plots showed that there was increasing overestimation of mortality by SCORTEN during the later period or when immunomodulatory therapy was used compared with patients treated with supportive care alone. Calibration of ABCD-10 remained poor even during the later period or among patients treated with immunomodulatory therapy. Conclusions and Relevance: In this cohort of patients, the performance of SCORTEN was superior to ABCD-10 in mortality prognostication in epidermal necrolysis. However, it did display time-associated deterioration in calibration leading to overestimation of mortality risk. Future studies may consider revising the existing SCORTEN given its current good discrimination.

Risk factors and diagnostic markers of bacteremia in Stevens-Johnson syndrome and toxic epidermal necrolysis: A cohort study of 176 patients.

BACKGROUND: Sepsis is the main cause of death in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). OBJECTIVES: Our aim was to identify admission risk factors predictive of bacteremia and the accompanying clinical or biochemical markers associated with positive blood cultures. METHODS: A retrospective cohort study over a 14-year period (2003-2016) was performed. RESULTS: The study included 176 patients with SJS (n = 59), SJS-TEN overlap (n = 51), and TEN (n = 66). During hospitalization, bacteremia developed in 52 patients (29.5%), who experienced poorer outcomes, including higher intensive care unit admission (P < .0005), longer length of stay (P < .0005), and higher mortality (P < .0005). There were 112 episodes of bacteremia, and isolates included Acinetobacter baumannii (27.7%, n = 31) and Staphylococcus aureus (21.4%, n = 24). On multivariate analysis, clinical factors present at admission that were predictive of bacteremia included hemoglobin ≤10 g/dL (odds ratio [OR] 2.4, confidence interval [CI] 2.2-2.6), existing cardiovascular disease (OR 2.10, CI 2.0-2.3), and body surface area involvement ≥10% (OR 14.3, CI 13.4-15.2). The Bacteremia Risk Score was constructed with good calibration. Hypothermia (P = .03) and procalcitonin ≥1 µg/L (P = .02) concurrent with blood culture sampling were predictive of blood culture positivity. LIMITATIONS: This is a retrospective study performed in a reference center. CONCLUSION: Hemoglobin ≤10 g/dL, cardiovascular disease, and body surface area involvement ≥10% on admission were risk factors for bacteremia. Hypothermia and elevated procalcitonin are useful markers for the timely detection of bacteremia.

Comparison of Outcomes of Fasciocutaneous Free Flaps and Jejunal Free Flaps in Pharyngolaryngoesophageal Reconstruction: A Systematic Review and Meta-Analysis.

BACKGROUND: The literature reports a wide variety of reconstructive methods for pharyngolaryngoesophageal (PLO) defects, the most widely used being anterolateral thigh (ALT), radial forearm (RFF), and jejunal free flaps (JFF). However, there is a lack of uniform agreement among head and neck surgeons as to which technique offers the best results. With an increasing number of salvage PLO extirpations, determining the role of radiotherapy in influencing postoperative complication rates is becoming ever more important. Hence, this study aims to provide an up-to-date comparison of surgical and functional outcomes of the fasciocutaneous ALT and RFF versus the intestinal JFF for circumferential and partial PLO defects and determine whether radiotherapy, both preoperative and postoperative, influences the postoperative fistula and stricture rates in circumferential defects. METHODS: A systematic review and meta-analysis were performed using PubMed for reports published in the most recent 10 years between 2007 and 2017. RESULTS: A total of 33 articles comprising 1213 patients were reviewed. For circumferential defects, fistula and stricture rates were significantly lower in JFF than ALT and RFF. Of note, there was no statistical difference in tracheoesophageal speech and oral alimentation rates between JFF and the FC flaps. For near-circumferential and partial defects, ALT has a significantly lower fistula rate than RFF. There was no statistical difference in stricture and oral alimentation rates between ALT and RFF [corrected]. Fistula rates were significantly higher in patients who had preoperative radiotherapy than those without. However, there was no significant difference in fistula and stricture rates for postoperative radiotherapy. CONCLUSIONS: Jejunal free flaps still remain an excellent first choice for PLO reconstruction of circumferential defects. For near-circumferential and partial defects, ALT seems to have a better performance than RFF. Preoperative radiotherapy was associated with an increased risk of fistula formation in circumferential PLO defects but not postoperative radiotherapy.