American Journal of Therapeutics 23, e916–e919 (2016)
Rapidly Progressing Severe Cutaneous Adverse Reaction With Acute Kidney Injury After Drug Exposure: An Uncommon Presentation Bradley K. Rodgers, MD and Avinash B. Kumar, MD, FCCP, FCCM*
Toxic epidermal necrolysis syndrome (TEN) is a rare severe cutaneous adverse drug reaction that involves skin and mucous membranes. We describe a case of TEN presenting with stage III acute kidney injury, rhabdomyolysis, and acute respiratory failure likely triggered by allopurinol for recently diagnosed gout. Prompt diagnosis, multidisciplinary management, including aggressive resuscitation, cardiorespiratory support, intravenous immunoglobulin therapy, and daily wound care resulted in a positive outcome despite a predicted mortality greater than 60%. Although allopurinol is a known triggering agent, TEN presenting with rhabdomyolysis and acute kidney injury is rare. Keywords: toxic epidermal necrolysis syndrome, allopurinol, acute kidney injury, acute, respiratory failure
INTRODUCTION Severe cutaneous adverse reactions or SCARs are uncommon but life-threatening complications that are usually iatrogenic in nature (frequently secondary to drug reactions). The spectrum of conditions encompassed includes toxic epidermal necrolysis syndrome (TEN), Stevens–Johnson syndrome (SJS), and drug reaction with eosinophilia and systemic symptoms. These conditions can involve cutaneous hematologic abnormalities and complications secondary to superinfection of the exposed lesions. TEN is a severe cutaneous drug reaction that involves the skin and mucous membranes estimated incidence of 0.4–1.9
Department of Anesthesiology, Vanderbilt University, Nashville, TN. The authors have no conflicts of interest to declare. B. K. Rodgers and A. B. Kumar helped to write the article, provided patient care, and approved the final article. IRB: none; consent obtained from patient family. *Address for correspondence: Associate Professor of Anesthesiology and Critical Care, Anesthesiology and Critical Care, Vanderbilt University Medical Center, 1211 21st Avenue S, Suite 526, Nashville, TN 37212. Email: [email protected]
per million people annually worldwide, with an overall mortality approaching 30%.1,2 We present a complex case of TEN presenting with stage III acute kidney injury (AKI), rhadomyolysis, and acute respiratory failure.
CASE DESCRIPTION After obtaining informed consent, we present the case of a 60-year-old woman who was transported by emergency medical services to our tertiary medical center. She presented with rapidly evolving skin eruptions covering 75%–80% total body surface area with mucosal and ocular involvement (see Figures 1 and 2). She was febrile to 102.9°F, with an altered sensorium and fresh bleeding sites around the oropharynx and was urgently intubated for impending respiratory failure complicated by mucosal sloughing and copious bloody secretions. Additional history (from family members and emergency medical services) included a diagnosis of congestive heart failure, hypertension, hyperlipidemia, and diabetes mellitus type II. She had seen per primary care physician about 3 weeks before arthritis and was prescribed allopurinol for gout. She had no recent
1075–2765 Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
www.americantherapeutics.com
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Rapidly Progressing Cutaneous Adverse Reaction and Acute Kidney Injury
e917
FIGURE 1. Patient with severe toxic epidermal necrolysis presenting with significant mucocutaneous lesions to the ICU.
history of steroid exposure. Family denied any history of HIV. Baseline laboratory values are remarkable for CPK .10,000 U/L, urine myoglobin .17,000 U/L, serum creatinine of 8.68 mg/dL (last known baseline serum creatinine was 1.4 mg/dL), and BUN of 92 mg/dL (Table 1). Toxic epidermal necrolysis was suspected. Allopurinol was the likely triggering agent. Aggressive fluid management was initiated after obtaining additional intravenous access for suspected hypovolemia and rhabdomyolysis complicating AKI. Broad-spectrum antibiotics for suspected infected skin lesions were initiated on admission. A bedside transthoracic echocardiogram showed a hyperdynamic and underfilled left ventricle, preserved contractility, and significant respiratory collapse of the inferior vena cava reflecting hypovolemia. Skin biopsies were sent to pathology and intravenous www.americantherapeutics.com
immunoglobulin therapy (1 g$kg21$d21) was initiated and continued for 3 days after consulting with dermatology. The patient ocular lesions were treated with tobramycin/dexamethasone ointment and lubricating eye drops. The concern for worsening AKI complicated by rhabdomyolysis was high. Serum chemistries, acid base balances, and potassium continued to be monitored closely with continuous venovenous hemodialysis on standby if indicated. Aggressive wound care included hydrotherapy and daily dressing changes by the burn care team (Figure 1). The patient stage III AKI was managed with aggressive rehydration and diuresis after rescuscitation (after intensive care unit [ICU] day 3) with normalization of serum chemistries without the need for renal replacement therapy. American Journal of Therapeutics (2016) 23(3)
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e918
Rodgers and Kumar
FIGURE 2. Showing the extent of involvement of lesions in the same patient. The arrows point to the areas of epidermal–dermal separation.
The patient underwent an open tracheostomy after repeatedly failing liberation trails from mechanical ventilation. The patient was supported from a cardiorespiratory perspective in the ICU and her mucocutaneous and ocular lesions gradually improved over the course of 2 weeks. The patient was discharged to a skilled nursing facility after a 20-day ICU stay and continues to improve over time.
DISCUSSION TEN and SJS are currently viewed as 2 ends of a disease spectrum that differ in their extent of epidermal detachment with less than 10% considered SJS and greater than 30% as TEN.3 The hallmark of TEN being epidermal–dermal separation (Figure 1, 2) and subsequent sequelae has been described as acute skin failure.2 It is common in TEN to have multiple organ systems involved, with erosion and necrosis occurring in the conjunctivae, trachea, bronchi, gut, and kidney.2
The immunopathogenesis of TEN is incompletely understood. The lynchpin mechanism seems to be cytotoxic CD8+ T lymphocyte–mediated keratinocyte apoptosis (through granzyme and Fas ligand pathways) leading to dermal–epidermal separation.4 Specific HLA alleles have been linked with TEN including the HLA-B*1502 allele for carbamazepine-induced TEN and HLA-B*5801 for allopurinol-associated severe cutaneous adverse reactions.5 The majority of cases of TEN are pharmacologically triggered, with allopurinol, anticonvulsants, sulfonamide antibiotics, and oxicam NSAIDS being frequent offenders.6,7 Other nonpharmacologic triggers include Mycoplasma pneumoniae, dengue virus, cytomegalovirus, and contrast medium.2 The time of medication exposure to skin manifestations is between 3 and 6 weeks. Cutaneous manifestations can range from generalized macules with purpuric centers to large confluencing blisters with subsequent epidermal detachment. Nikolsky sign (epidermal detachment by applied tangential pressure on erythematous zones) can be present but is not specific for TEN. Our patient had a positive Nicholsky sign. Early ocular involvement is common and can range from conjunctivitis to corneal ulceration. Histologic examination of a skin biopsy is vital in the diagnosis of TEN. Immunofluorescence analysis is a key in ruling out diagnoses such as autoimmune blistering diseases, bullous fixed drug eruptions, and acute generalized exanthematic pustulosis. Our patient biopsy confirmed TEN. The SCORTEN score is a prognostic score that incorporates 7 clinical variables: age, extent of involved body surface area, heart rate, presence of malignancy, and serum urea, glucose and bicarbonate levels to predict mortality in TEN (Table 2).8 Our patient had 4 risk factors with a predicted mortality of about 58% without factoring in AKI and rhabdomyolysis. Treatment of TEN consists of immediate recognition of the syndrome, withdrawal of the offending drug, aggressive supportive ICU care, and prevention of secondary complications.1 Therapies that can potentially stop epithelial apoptosis (eg, intravenous immunoglobulin) are useful during the initial phase of the
Table 1. Laboratory values on presentation to the ICU. Complete blood counts Basic metabolic profile Cardiac enzymes Arterial blood gas Urine analysis
White blood cells, 2.5; hemoglobin, 12.2 g/dL; platelets, 108 Sodium, 141; potassium, 3.7; chloride, 104; BUN, 92; serum creatinine, 8.68 CPK, 11048; troponin I, 1.01; BNP, 72; myoglobin, 17,928 pH, 7.27; pCO2, 48; pO2, 67; O2 saturation, 93.8; bicarbonate, 22; BE, 25.1; and lactate, 1.3 Color: brown; character: turbid; specific gravity: 1.021; protein: 100; blood: large amounts of red blood cells: 2245; myoglobin: positive
American Journal of Therapeutics (2016) 23(3)
www.americantherapeutics.com
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Rapidly Progressing Cutaneous Adverse Reaction and Acute Kidney Injury
e919
Table 2. The SCORTEN score for predicting in-hospital mortality in TEN. SCORTEN parameter
Individual score
Age .40 Malignancy Tachycardia (.120 bpm) Total body surface area .10% BUN .10 mmol/L Serum glucose .14 mmol/L Bicarbonate .20 mmol/L
Yes Yes Yes Yes Yes Yes Yes
5 5 5 5 5 5 5
1; 1; 1; 1; 1; 1; 1;
No No No No No No No
disease.4 Corticosteroids in TEN are controversial at best and are currently not considered the standard of care. Further studies are needed to assess the role of tumor necrosis factor alpha antagonists, plasmapheresis, and cyclophosphamide in future treatment of TEN.9 It is rare for TEN to present with rhabdomyolysis and stage III AKI. Rare cases of TEN with rhabdomyolysis have been reported in association with carbamazepine and statins but not with allopurinol to the best of our knowledge.10,11 It is postulated that TENmediated cellular and immune responses impair mitochondrial function, thereby altering sodium–calcium homeostasis, leading to skeletal muscle breakdown.12 We speculate that this maybe a contributing factor to the rhabdomyolysis in addition to the period of immobility before admission to the ICU. Previous reports of microalbuminuria and tubular enzymuria have been reported in TEN suggesting proximal tubular damage. However, they do not seem to correlate to the severity of disease.13 We speculate that the cause for AKI in our patient was multifactorial. We believe that early recognition of the syndrome, aggressive ICU interventions, and supportive care resulted in a good outcome, despite multiple predictors of high ICU mortality.
REFERENCES 1. Fernando SL. The management of toxic epidermal necrolysis. Australas J Dermatol. 2012;53:165–171. 2. Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: Part I. Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad Dermatol. 2013;69:173 e1–13; quiz 85–6.
www.americantherapeutics.com
5 5 5 5 5 5 5
0 0 0 0 0 0 0
SCORTEN
Predicted mortality
0–1 2 3 4 .5
3.2 12.1 35.8 58.3 90
3. Gerull R, Nelle M, Schaible T. Toxic epidermal necrolysis and Stevens-Johnson syndrome: a review. Crit Care Med. 2011;39:1521–1532. 4. Abe R. Toxic epidermal necrolysis and StevensJohnson syndrome: soluble Fas ligand involvement in the pathomechanisms of these diseases. J Dermatol Sci. 2008;52:151–159. 5. Hung SI, Chung WH, Liu ZS, et al. Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010;11:349–356. 6. Mockenhaupt M, Viboud C, Dunant A, et al. StevensJohnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol. 2008;128:35–44. 7. Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med. 1995;333:1600–1607. 8. Bastuji-Garin S, Fouchard N, Bertocchi M, et al. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol. 2000;115:149–153. 9. Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis. 2010;5:39. 10. Huang LY, Lin CM, Chiou CC, et al. Rhabdomyolysis as a potential complication of carbamazepine-induced toxic epidermal necrolysis. Clin Biochem. 2012;45: 1531–1532. 11. Noordally SO, Sohawon S, Vanderhulst J, et al. A fatal case of cutaneous adverse drug-induced toxic epidermal necrolysis associated with severe rhabdomyolysis. Ann Saudi Med. 2012;32:309–311. 12. Paquet P, Pierard GE. New insights in toxic epidermal necrolysis (Lyell’s syndrome): clinical considerations, pathobiology and targeted treatments revisited. Drug Saf. 2010;33:189–212. 13. Hung CC, Liu WC, Kuo MC, et al. Acute renal failure and its risk factors in Stevens-Johnson syndrome and toxic epidermal necrolysis. Am J Nephrol. 2009;29:633–638.
American Journal of Therapeutics (2016) 23(3)
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Rapidly Progressing Severe Cutaneous Adverse Reaction With Acute Kidney Injury After Drug Exposure: An Uncommon Presentation Bradley K. Rodgers, MD and Avinash B. Kumar, MD, FCCP, FCCM*
Toxic epidermal necrolysis syndrome (TEN) is a rare severe cutaneous adverse drug reaction that involves skin and mucous membranes. We describe a case of TEN presenting with stage III acute kidney injury, rhabdomyolysis, and acute respiratory failure likely triggered by allopurinol for recently diagnosed gout. Prompt diagnosis, multidisciplinary management, including aggressive resuscitation, cardiorespiratory support, intravenous immunoglobulin therapy, and daily wound care resulted in a positive outcome despite a predicted mortality greater than 60%. Although allopurinol is a known triggering agent, TEN presenting with rhabdomyolysis and acute kidney injury is rare. Keywords: toxic epidermal necrolysis syndrome, allopurinol, acute kidney injury, acute, respiratory failure
INTRODUCTION Severe cutaneous adverse reactions or SCARs are uncommon but life-threatening complications that are usually iatrogenic in nature (frequently secondary to drug reactions). The spectrum of conditions encompassed includes toxic epidermal necrolysis syndrome (TEN), Stevens–Johnson syndrome (SJS), and drug reaction with eosinophilia and systemic symptoms. These conditions can involve cutaneous hematologic abnormalities and complications secondary to superinfection of the exposed lesions. TEN is a severe cutaneous drug reaction that involves the skin and mucous membranes estimated incidence of 0.4–1.9
Department of Anesthesiology, Vanderbilt University, Nashville, TN. The authors have no conflicts of interest to declare. B. K. Rodgers and A. B. Kumar helped to write the article, provided patient care, and approved the final article. IRB: none; consent obtained from patient family. *Address for correspondence: Associate Professor of Anesthesiology and Critical Care, Anesthesiology and Critical Care, Vanderbilt University Medical Center, 1211 21st Avenue S, Suite 526, Nashville, TN 37212. Email: [email protected]
per million people annually worldwide, with an overall mortality approaching 30%.1,2 We present a complex case of TEN presenting with stage III acute kidney injury (AKI), rhadomyolysis, and acute respiratory failure.
CASE DESCRIPTION After obtaining informed consent, we present the case of a 60-year-old woman who was transported by emergency medical services to our tertiary medical center. She presented with rapidly evolving skin eruptions covering 75%–80% total body surface area with mucosal and ocular involvement (see Figures 1 and 2). She was febrile to 102.9°F, with an altered sensorium and fresh bleeding sites around the oropharynx and was urgently intubated for impending respiratory failure complicated by mucosal sloughing and copious bloody secretions. Additional history (from family members and emergency medical services) included a diagnosis of congestive heart failure, hypertension, hyperlipidemia, and diabetes mellitus type II. She had seen per primary care physician about 3 weeks before arthritis and was prescribed allopurinol for gout. She had no recent
1075–2765 Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
www.americantherapeutics.com
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Rapidly Progressing Cutaneous Adverse Reaction and Acute Kidney Injury
e917
FIGURE 1. Patient with severe toxic epidermal necrolysis presenting with significant mucocutaneous lesions to the ICU.
history of steroid exposure. Family denied any history of HIV. Baseline laboratory values are remarkable for CPK .10,000 U/L, urine myoglobin .17,000 U/L, serum creatinine of 8.68 mg/dL (last known baseline serum creatinine was 1.4 mg/dL), and BUN of 92 mg/dL (Table 1). Toxic epidermal necrolysis was suspected. Allopurinol was the likely triggering agent. Aggressive fluid management was initiated after obtaining additional intravenous access for suspected hypovolemia and rhabdomyolysis complicating AKI. Broad-spectrum antibiotics for suspected infected skin lesions were initiated on admission. A bedside transthoracic echocardiogram showed a hyperdynamic and underfilled left ventricle, preserved contractility, and significant respiratory collapse of the inferior vena cava reflecting hypovolemia. Skin biopsies were sent to pathology and intravenous www.americantherapeutics.com
immunoglobulin therapy (1 g$kg21$d21) was initiated and continued for 3 days after consulting with dermatology. The patient ocular lesions were treated with tobramycin/dexamethasone ointment and lubricating eye drops. The concern for worsening AKI complicated by rhabdomyolysis was high. Serum chemistries, acid base balances, and potassium continued to be monitored closely with continuous venovenous hemodialysis on standby if indicated. Aggressive wound care included hydrotherapy and daily dressing changes by the burn care team (Figure 1). The patient stage III AKI was managed with aggressive rehydration and diuresis after rescuscitation (after intensive care unit [ICU] day 3) with normalization of serum chemistries without the need for renal replacement therapy. American Journal of Therapeutics (2016) 23(3)
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e918
Rodgers and Kumar
FIGURE 2. Showing the extent of involvement of lesions in the same patient. The arrows point to the areas of epidermal–dermal separation.
The patient underwent an open tracheostomy after repeatedly failing liberation trails from mechanical ventilation. The patient was supported from a cardiorespiratory perspective in the ICU and her mucocutaneous and ocular lesions gradually improved over the course of 2 weeks. The patient was discharged to a skilled nursing facility after a 20-day ICU stay and continues to improve over time.
DISCUSSION TEN and SJS are currently viewed as 2 ends of a disease spectrum that differ in their extent of epidermal detachment with less than 10% considered SJS and greater than 30% as TEN.3 The hallmark of TEN being epidermal–dermal separation (Figure 1, 2) and subsequent sequelae has been described as acute skin failure.2 It is common in TEN to have multiple organ systems involved, with erosion and necrosis occurring in the conjunctivae, trachea, bronchi, gut, and kidney.2
The immunopathogenesis of TEN is incompletely understood. The lynchpin mechanism seems to be cytotoxic CD8+ T lymphocyte–mediated keratinocyte apoptosis (through granzyme and Fas ligand pathways) leading to dermal–epidermal separation.4 Specific HLA alleles have been linked with TEN including the HLA-B*1502 allele for carbamazepine-induced TEN and HLA-B*5801 for allopurinol-associated severe cutaneous adverse reactions.5 The majority of cases of TEN are pharmacologically triggered, with allopurinol, anticonvulsants, sulfonamide antibiotics, and oxicam NSAIDS being frequent offenders.6,7 Other nonpharmacologic triggers include Mycoplasma pneumoniae, dengue virus, cytomegalovirus, and contrast medium.2 The time of medication exposure to skin manifestations is between 3 and 6 weeks. Cutaneous manifestations can range from generalized macules with purpuric centers to large confluencing blisters with subsequent epidermal detachment. Nikolsky sign (epidermal detachment by applied tangential pressure on erythematous zones) can be present but is not specific for TEN. Our patient had a positive Nicholsky sign. Early ocular involvement is common and can range from conjunctivitis to corneal ulceration. Histologic examination of a skin biopsy is vital in the diagnosis of TEN. Immunofluorescence analysis is a key in ruling out diagnoses such as autoimmune blistering diseases, bullous fixed drug eruptions, and acute generalized exanthematic pustulosis. Our patient biopsy confirmed TEN. The SCORTEN score is a prognostic score that incorporates 7 clinical variables: age, extent of involved body surface area, heart rate, presence of malignancy, and serum urea, glucose and bicarbonate levels to predict mortality in TEN (Table 2).8 Our patient had 4 risk factors with a predicted mortality of about 58% without factoring in AKI and rhabdomyolysis. Treatment of TEN consists of immediate recognition of the syndrome, withdrawal of the offending drug, aggressive supportive ICU care, and prevention of secondary complications.1 Therapies that can potentially stop epithelial apoptosis (eg, intravenous immunoglobulin) are useful during the initial phase of the
Table 1. Laboratory values on presentation to the ICU. Complete blood counts Basic metabolic profile Cardiac enzymes Arterial blood gas Urine analysis
White blood cells, 2.5; hemoglobin, 12.2 g/dL; platelets, 108 Sodium, 141; potassium, 3.7; chloride, 104; BUN, 92; serum creatinine, 8.68 CPK, 11048; troponin I, 1.01; BNP, 72; myoglobin, 17,928 pH, 7.27; pCO2, 48; pO2, 67; O2 saturation, 93.8; bicarbonate, 22; BE, 25.1; and lactate, 1.3 Color: brown; character: turbid; specific gravity: 1.021; protein: 100; blood: large amounts of red blood cells: 2245; myoglobin: positive
American Journal of Therapeutics (2016) 23(3)
www.americantherapeutics.com
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Rapidly Progressing Cutaneous Adverse Reaction and Acute Kidney Injury
e919
Table 2. The SCORTEN score for predicting in-hospital mortality in TEN. SCORTEN parameter
Individual score
Age .40 Malignancy Tachycardia (.120 bpm) Total body surface area .10% BUN .10 mmol/L Serum glucose .14 mmol/L Bicarbonate .20 mmol/L
Yes Yes Yes Yes Yes Yes Yes
5 5 5 5 5 5 5
1; 1; 1; 1; 1; 1; 1;
No No No No No No No
disease.4 Corticosteroids in TEN are controversial at best and are currently not considered the standard of care. Further studies are needed to assess the role of tumor necrosis factor alpha antagonists, plasmapheresis, and cyclophosphamide in future treatment of TEN.9 It is rare for TEN to present with rhabdomyolysis and stage III AKI. Rare cases of TEN with rhabdomyolysis have been reported in association with carbamazepine and statins but not with allopurinol to the best of our knowledge.10,11 It is postulated that TENmediated cellular and immune responses impair mitochondrial function, thereby altering sodium–calcium homeostasis, leading to skeletal muscle breakdown.12 We speculate that this maybe a contributing factor to the rhabdomyolysis in addition to the period of immobility before admission to the ICU. Previous reports of microalbuminuria and tubular enzymuria have been reported in TEN suggesting proximal tubular damage. However, they do not seem to correlate to the severity of disease.13 We speculate that the cause for AKI in our patient was multifactorial. We believe that early recognition of the syndrome, aggressive ICU interventions, and supportive care resulted in a good outcome, despite multiple predictors of high ICU mortality.
REFERENCES 1. Fernando SL. The management of toxic epidermal necrolysis. Australas J Dermatol. 2012;53:165–171. 2. Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: Part I. Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad Dermatol. 2013;69:173 e1–13; quiz 85–6.
www.americantherapeutics.com
5 5 5 5 5 5 5
0 0 0 0 0 0 0
SCORTEN
Predicted mortality
0–1 2 3 4 .5
3.2 12.1 35.8 58.3 90
3. Gerull R, Nelle M, Schaible T. Toxic epidermal necrolysis and Stevens-Johnson syndrome: a review. Crit Care Med. 2011;39:1521–1532. 4. Abe R. Toxic epidermal necrolysis and StevensJohnson syndrome: soluble Fas ligand involvement in the pathomechanisms of these diseases. J Dermatol Sci. 2008;52:151–159. 5. Hung SI, Chung WH, Liu ZS, et al. Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010;11:349–356. 6. Mockenhaupt M, Viboud C, Dunant A, et al. StevensJohnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol. 2008;128:35–44. 7. Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med. 1995;333:1600–1607. 8. Bastuji-Garin S, Fouchard N, Bertocchi M, et al. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol. 2000;115:149–153. 9. Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis. 2010;5:39. 10. Huang LY, Lin CM, Chiou CC, et al. Rhabdomyolysis as a potential complication of carbamazepine-induced toxic epidermal necrolysis. Clin Biochem. 2012;45: 1531–1532. 11. Noordally SO, Sohawon S, Vanderhulst J, et al. A fatal case of cutaneous adverse drug-induced toxic epidermal necrolysis associated with severe rhabdomyolysis. Ann Saudi Med. 2012;32:309–311. 12. Paquet P, Pierard GE. New insights in toxic epidermal necrolysis (Lyell’s syndrome): clinical considerations, pathobiology and targeted treatments revisited. Drug Saf. 2010;33:189–212. 13. Hung CC, Liu WC, Kuo MC, et al. Acute renal failure and its risk factors in Stevens-Johnson syndrome and toxic epidermal necrolysis. Am J Nephrol. 2009;29:633–638.
American Journal of Therapeutics (2016) 23(3)
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
