Acute Kidney Injury in Toxic Epidermal Necrolysis ...

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Background: Toxic epidermal necrolysis syndrome (TEN) is a rare but life-threatening skin condition. Acute kidney injury (AKI) is a consequence of TEN.


Acute Kidney Injury in Toxic Epidermal Necrolysis Syndrome Ching-Hsuan Hu1, Shiuan-Tzuen Su1, Nai-Jen Chang1, Weng-Hung Chung2, Ya-Chung Tian3, Shiow-Shuh Chuang1, Jui-Yung Yang1 1

Lin Kou Burn Centre, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University Taipei, Taiwan


Department of Dermatology, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taipei, Taiwan


Departments of Nephrology, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taipei, Taiwan

Background: Toxic epidermal necrolysis syndrome (TEN) is a rare but life-threatening skin condition. Acute kidney injury (AKI) is a consequence of TEN. However, the cascade of events leading to renal manifestations secondary to TEN is not so clear. Aim and Objectives: This study, evaluates the severity of AKI using the RIFLE criteria (Risk, Injury, Failure, Loss of function and End stage) in patients with toxic epidermal necrolysis. We also present the overall incidence, risk factors and elements that influenced survival. Materials and Methods: A retrospective review of medical records was performed on 101 cases presenting with TEN all of which were admitted to the Linkou Chang Gung Intensive Care Burn Unit from 1992 to 2009. Results: Out of all the patients that presented TEN; AKI occurred in 38 (37.6%) the distribution of these patients using the RIFLE criteria was the following: Patients with Risk were 11 (10.9%), Injury 8 (7.9%) and Failure 19 (18.8%) patients. Mortality was higher among patients with AKI. Old age, larger skin detachment, and a higher SCORTEN score on admission, sepsis, multiple organ failure and comorbidity such as chronic kidney disease are risk factors for developing AKI. Among the thirty-eight patients, thirty-one patients were classified as early AKI and seven as late AKI. Infection and sepsis are the main reasons that contribute to late AKI.

Ching-Hsuan Hu, Shiuan-Tzuen Su, Nai-Jen Chang, Weng-Hung Chung, Ya-Chung Tian, Shiow-Shuh Chuang, Jui-Yung Yang


Conclusion: In our observation AKI is common in TEN patients. RIFLE criteria help to predict the degree of kidney injury and overall outcome. The highest class of AKI tends to have the lowest survival rate. Infection control are the upmost important in later period of TEN. (J Taiwan Soc of Plast Surg 2013;22:10~19) Key words: acute kidney injury, RIFLE, toxic epidermal necrolysis syndrome, SCORTEN

Introduction Toxic epidermal necrolysis syndrome (TEN) is a rare life-threatening skin condition with a mortality rate reported to be as high as 30%-50%1. In our previous study, we determine acute renal insuffuency/ failure is a marker for predicting a poor outcome in Asian TEN patients2, however, the renal manifestation in TEN is still not so clear. That is, if renal function decreasing is observed in a TEN patient, how much, how severe and what a consequence will there be? The Risk, Injury, Failure, Loss, and End-stage kidney (RIFLE) classification system2 (Table 1) was recently developed to categorize the severity of renal dysfunction and enabled investigators to examine the impact of acute kidney dysfunction in critically ill patients. According to the international classification RIFLE, acute kidney injury can be categorized into: Risk, Injury, Failure, Loss of kidney function based on changes in either serum creatinine or urine output, and two outcome categories (loss and end-stage kidney disease). Recent studies in burn patients have revealed that a higher RIFLE class during hospitalization, was correlated to a worst prognosis3, however, the use of RIFLE as a tool to identify AKI in TEN patients during hospitalization has not yet been evaluated. In view of the above, we carried out a retrospective study to investigate manifestations and risk factors that lead to acute renal failure (ARF) and its impact on TEN patients.

Materials and methods 101 patients admitted to the burn intensive care unit with TEN over 18 years from January 1992 to

December 2009 were retrospective reviewed. The demographic data including sex, age, total body surface area involved, laboratory data, and outcome were obtained where available. The follow up was until December 2011. The survival was considered from the date of diagnosis to the last day of follow up. We assessed patients developing AKI in TEN patients using RIFLE classification as well as sepsis and organ failure using conventional criteria and definitions4,5. SCORTEN scores were calculated on the first day of admission to the burn intensive care unit to predict mortality rate. The SCORTEN score is an illness severity index used exclusively for TEN developed by Roujeau JC in 2000 and is defined by Euro-SCAR group6,7. The score is designed to predict the mortality rate through seven independent factors (age>40 years; presence of malignancy; body surface area involved> 10%; serum urea nitrogen level>28 mg/dL ; glucose level >252 mg/dL ; bicarbonate [HCO3] level 120 beats per minute that are scored within 24 h from patient admission. Each factor contributes one point to the overall SCORTEN level with scores ranging from 0 to 7 and a higher score correlating with a higher mortality rate. To evaluate the prognosis of our patients with TEN, we used the SCORTEN score.

Definition According to the glomerular filtration rate or urine output criteria, patients were placed into risk, injury, failure, loss of kidney function, and end-stage kidney disease by RIFLE criteria (table1). No patients met the criteria for loss of kidney function or end-stage renal disease at time of ICU admission in our study.

JTSPS 2013. Vol 22‧No.1


Acute Kidney Injury in Toxic Epidermal Necrolysis Syndrome

We evaluated mortality rate of patients diagnosed with TEN using the SCORTEN scores. Sepsis was defined according to modified American College of Chest Physicians and Society of Critical Care Medicine consensus criteria (table 2)4,8. Patients with proven or suspected infection, two or more systemic inflammatory response syndrome criteria were classified as having sepsis. Early AKI was defined by patients reaching the level for Risk within the first 7 days, and late AKI was beyond 8 days5

Statistical analysis Values were expressed as mean ± standard deviation. Categorical and continuous variables were compared with means and normal distribution using the chi-square, one way ANOVA and Mann-Whitney U Test. P values < 0.05 were considered statistically significant.

Results A total of 101 patients were included in this study (Figure 1), of whom 38(37.6%) patients developed AKI (10.9% Risk, 7.9% Injury, and 18.8% Failure). Overall mortality was 52.5%. Patients’ demographic and clinical characteristics are shown in table 3. Old age, larger area of skin detachment, higher

SCORTEN scores on admission, and sepsis were associated with the patient developing AKI. Comorbidity such as chronic kidney disease is associated patient developing AKI. Sex and length of ICU stay had no significant difference between these two groups. Patients diagnosed with AKI had a higher multiple organ failure rate and mortality rate since cumulative survival rate showed a statistical significance (p < 0.05) between non-AKI and AKI patients. These findings are in line with previous studies analyzing kidney injury and outcome4-8,11,12. The characteristics and outcome of patients classified into the RIFLE categories are shown in Table 4. There was a greater sepsis, multiple organ failure, time period of mechanical ventilation and mortality rate in the severe types of AKI (P 0.5 mg/dl

< 0.3 ml/kg/hour × 24 hours, or anuria × 12 hours


Persistent acute renal failure = complete loss of kidney function > 4 weeks

End-stage kidney disease

End-stage kidney disease > 3 months

RIFLE criteria is determined based on the worst of either glomerular filtration criteria or urine output criteria. Glomerular filtration criteria are calculated as an increase of serum creatinine above the baseline serum creatinine level.

臺灣整形外科醫誌:民國 102 年/22 卷/1 期

Ching-Hsuan Hu, Shiuan-Tzuen Su, Nai-Jen Chang, Weng-Hung Chung, Ya-Chung Tian, Shiow-Shuh Chuang, Jui-Yung Yang

Table 2.


Definition of Sepsis4.8

Known Infection Focus and 2 or More of Following Criteria: 1.Temperature>38℃ or 90 beats per minute 3.Respiratory rate >20 breaths per minute or PaCO2< 4.3kPa 4.White blood cell count>12x109/L or

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