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A clinicoetiological analysis of patients with Stevens–Johnson syndrome and toxic epidermal necrolysis treated at Sohag University Hospital, Egypt

El-Hamd, Mohammed Abu; El-Dawla, Reham Ezz; Elmagid, Wafaa Abd

Journal of the Egyptian Women's Dermatologic Society: January 2017 - Volume 14 - Issue 1 - p 37–44
doi: 10.1097/01.EWX.0000491262.03254.04
Original articles
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Background Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are characterized by widespread epidermal necrosis and mucosal involvement secondary to keratinocyte apoptosis induced mostly by drugs and associated with high mortality.

Objective To examine the prevalence, etiology, clinical presentations, and outcome of SJS/TEN in patients admitted in the Department of Dermatology, Venereology, and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt.

Patients and methods This observational study included all patients with SJS/TEN admitted in the Department of Dermatology, Venereology, and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt, between September 2013 and September 2014. All patients with SJS/TEN were subjected to complete medical history and examinations to evaluate the extent of skin and mucous membrane involvement, complications, and other system affections. They also underwent complete laboratory investigations. The severity-of-illness score for toxic epidermal necrolysis was used to evaluate all patients within the first 24 h of admission.

Results Of the 500 patients admitted, 21 (4.2%) were diagnosed with SJS/TEN (six men and 15 women; mean age 30.4 years). Fourteen patients were diagnosed with SJS (n=14; 66.7%), three with SJS/TEN overlap (n=3; 14.3%), and four with TEN (n=4; 19%). Nineteen patients (90.5%) had a history of drug intake. The most common causative drugs were carbamazepine (33.3%) and antibiotics+NSAIDs (28.57%).

Limitations The main limitations of our study were the small sample size.

Conclusion SJS and TEN are uncommon diseases. Most of the cases of SJS/TEN were drug-induced. The most common offending drugs were carbamazepine, NSAIDs, and antibiotics.

Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt

Correspondence to Mohammed Abu El-Hamd, MD, Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt Tel: +20 100 413 9060; e-mail: mohammedadva@yahoo.com

Received February 24, 2016

Accepted July 26, 2016

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Introduction

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute life-threatening skin diseases characterized by extensive epidermal sloughing at the dermoepidermal junction resulting from keratinocyte apoptosis 1. Both TEN and SJS are rare, affecting approximately one or two individuals per 1 000 000 populations annually, and are considered medical emergencies, as they are potentially fatal 2.

The exact molecular pathogenesis of TEN and SJS are not fully understood. TEN patients appear to have an increased incidence of the haplotype HLA-B12, demonstrating an inability to detoxify intermediate reactive drug metabolites 3. SJS and TEN are characterized by massive keratinocyte apoptosis. Fas–Fas ligand-induced apoptosis in keratinocytes is one of the most thoroughly studied immune mechanisms in SJS/TEN 4.

At least 80% of TEN cases are believed to be drug-induced, whereas the proportion of SJS cases attributable to drugs is lower, with the estimates ranging from 50 to 80% 5. The commonly associated drugs include antibacterial sulfonamides, anticonvulsant agents, NSAIDs, aminopenicillins, and quinolones 6.

Both SJS and TEN are characterized by erythematous skin and extensive detachment of the epidermis and erosions of mucous membranes 7. The two diseases are differentiated based on the extent of skin detachment, which is limited to at least 10% of the body surface area (BSA) in SJS, 10–30% of the BSA in SJS/TEN overlap, and up to 30% of the BSA in TEN 8.

TEN is associated with a higher mortality rate (30–35%) compared with SJS (5–15%) 9. To assess the prognosis of patients with SJS/TEN, the severity-of-illness score of TEN (SCORTEN) was used. This scoring system takes into consideration important prognostic factors, including age, the presence of underlying malignancy, heart rate, percentage loss of BSA, blood urea nitrogen level, serum glucose level, and bicarbonate level 10.

The prevalence, etiology, clinical presentations, and outcome of SJS/TEN in Egypt have not been reported yet.

The aim of this study was to examine the prevalence, etiology, clinical presentations, and outcome of SJS/TEN among patients admitted in the Department of Dermatology, Venereology, and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt.

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Patients and methods

This observational study included all patients with SJS/TEN among patients admitted in the Department of Dermatology, Venereology, and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt, from September 2013 and September 2014. It is the only tertiary medical center for admission and management of patients with SJS/TEN in Sohag government, and it contains 24 beds in public section and indeterminate number in private section. Informed consent was obtained from all patients.

According to the criteria of Bastuji-Garin et al.8, the patients were diagnosed as having SJS/TEN, based on the extent of skin detachment (≤10% of BSA in SJS, 10–30% of the BSA in SJS/TEN overlap, and ≥30% of the BSA in TEN). A complete detailed history was taken from all patients with SJS/TEN with regard to their demographics, causative offending drugs, the onset of skin eruption from drug intake, the pattern of involvement, the clinical presentations of the disease, the underlying medical diseases, and the complications. All drugs received within the previous 4 weeks from the onset of skin eruption were investigated.

All patients underwent complete general examination (pulse, blood pressure, and temperature) and local examination, including the extent of skin and mucous membrane involvement, complications, and other system affections.

All patients underwent complete laboratory investigations, including complete blood picture, erythrocyte sedimentation rate, blood glucose level, electrolyte levels, and renal and liver function tests.

SCORTEN was used to evaluate all patients within the first 24 h of admission.

On the basis of the SCORTEN score, expected mortality and expected death were calculated. The SCORTEN includes the following seven clinical variables: (a) age up to 40 years, (b) presence of malignancy, (c) tachycardia up to 120/min, (d) involvement of up to 10% of BSA, (e) serum urea level up to 28 mg/dl, (f) serum glucose level up to 252 mg/dl, and (g) bicarbonate level less than 20 mEq/l 10.

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Statistical analysis

SPSS software, version 16.0 (SPSS Inc., Chicago, Illinois, USA) was used for statistical analysis. The data were descriptive statistics. The data were presented as frequencies, percentages, mean±SD. No analytic test was used.

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Results

Between September 2013 and September 2014, 500 patients were admitted in the Department of Dermatology, Venereology, and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt. Of these patients, 21 (4.2%) were diagnosed with SJS/TEN (6 men and 15 women; age: mean 30.4 years; range, 3.5–60 years; Table 1). Fourteen patients were diagnosed with SJS (n=14; 66.7%), three with SJS/TEN overlap (n=3; 14.3%), and four with TEN (n=4, 19%; Figs 1, 2a, b and 3a, b).

Table 1

Table 1

Figure 1

Figure 1

Figure 2

Figure 2

Figure 3

Figure 3

Nineteen (90.5%) patients had underlying diseases: epilepsy in seven (33.3%) patients, headache in two (9.5%), stuttering in one (4.8%), sinusitis in two (9.5%), tonsillitis in two (9.5%), musculoskeletal diseases in three (14%), cystitis in one (4.8%), and skin burn in one (4.8%) patient (Table 1).

The most common causative drugs were carbamazepine in seven (33.3%) patients for epilepsy. Six (28.57%) patients received antibiotics+NSAIDs for sinusitis, tonsillitis, cystitis, and skin burn. Three (14.9%) patients received NSAIDs for musculoskeletal diseases. Three (14.9%) patients received lamotrigen for tension headache and stuttering. Two (9.5%) patients did not receive medications (Table 1).

The period between relevant drug intake and the onset of skin eruption in 19 patients who received medications ranged from 2 to 20 days, with a mean of 8.84±5.72 days. In SJS (n=13), the period ranged from 2 to 20 days, with a mean of 9.3±5.6 days. In SJS/TEN overlap (n=2), it ranged from 5 to 20 days, with a mean of 12.5±10.6 days. In TEN (n=4), it ranged from 2 to7 days with a mean of 5.5±2.38 days.

Pulse and blood pressure were normal in all patients. In this study, fever on admission was found in eight (38%) patients with SJS/TEN, three of 14 (21.4%) patients with SJS, two of three (66.7%) patients with SJS/TEN overlap, and three of four (75%) patients with TEN. Fever was mild in two (9.5%) patients, moderate in four (19%), and high in two (9.5%) patients.

Of the patients, 20 (95.2%) presented with oral ulcerations, lip erosion, and crustations, eight (38.1%) with nasal erosion and crustations, five (23.8%) with genital erosions and crustations, 13 (62%) with eye affections such as conjunctivitis in 11 (52.4%) [seven (33.3%) with SJS, two (9.5%) with SJS/TEN overlap, and two (9.5%) with TEN], ulcer on the inner canthus in one (4.8%) with TEN, and early papilledema in one (4.8%) with TEN (Table 2 and Fig. 4).

Table 2

Table 2

Figure 4

Figure 4

In laboratory investigations, hypocalcemia was found in 18 (85.7%) patients [11 of 14 (78.5%) with SJS, three of three (100%) with SJS/TEN overlap, and four of four (100%) with TEN]. Hyponatremia was found in 12 (57%) patients [six (28.5%) with SJS, two (9.5%) with SJS/TEN, and four (19%) with TEN]. Hypokalemia was found in 10 patients (47.6%) [six of 14 (42.86%) with SJS, one of three (33.3%) with SJS/TEN overlap, and three of four (75%) with TEN] (Table 3).

Table 3

Table 3

Anemia was found in 10 (47.6%) patients [five of 14 (35.7%) with SJS, two of three (66.6%) with SJS/TEN overlap, and three of four (75%) with TEN]. Erythrocyte sedimentation rate (first and second hours) was elevated in all patients. White blood cell and platelet counts were normal in all patients. Liver and renal function tests at the time of admission were normal in all patients. However, during hospital stay, liver function abnormality was observed in about 38% of the patients (8/21).

All patients received systemic steroids at a dose of 0.5 mg/kg and antibiotics (macrolides).

The mean hospitalization duration for the 21 patients with SJS and TEN was 15–30 days, with a mean of 19.6±4.5 days. Disease duration was 15–24 (mean 17.8±2.7) days, 15–24 (mean 18. 37±2.9) days, and 20–30 (26.3±4.8) days in patients with SJS (n=14), SJS/TEN overlap (n=3), and TEN (n=4), respectively.

SCORTEN scores of 0 or 1, 2, and 3 were seen in 17 (81%), three (14.3%), and one (4.8%) patients with SJS (n=14), SJS/TEN overlap (n=3), and TEN (n=4), respectively (Table 4).

Table 4

Table 4

As regards systemic complications, respiratory tract infections were found in two (9.5%) patients, in one with SJS/TEN and the other with TEN.

Nineteen (90.5%) patients recovered, but two (50%) patients with TEN (n=4) died from electrolyte disturbance.

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Discussion

This study found that the incidence of SJS/TEN was 4.2% (n=21) in relation to all admitted cases (n=500). The annual incidence of SJS/TEN in the general population of Southern Taiwan was 2.8 cases per million individuals according to a retrospective study 11. In particular, the annual incidences of SJS and TEN were ∼1–7 cases and 0.4–1.2 cases per million people, respectively 12–14.

Fourteen (n=14; 66.7%) patients were diagnosed with SJS, three with SJS/TEN overlap (n=3; 14.3%), and four (n=4; 19%) with TEN in this study.

The mean age of the patients was 30.4±18.4 years with marked female predominance (female-to-male ratio 2.5 : 1). This observation was consistent with earlier studies that showed that women are two times more susceptible to SJS/TEN compared with men 15,16 In contrast, another study found that men and women were equally affected 17.

The strong female predominance observed in the SJS cases in the present study and other studies suggests sex-specific predisposing factors. Estrogen deficiency has been found to be a predisposing factor for SJS. This was supported by the fact that in most of the patients the disease was expressed in the premenopausal period of life of women 18. Studies in normal mice have shown that estrogen suppresses the development of SJS, whereas ovariectomy leads to a condition that mimics SJS 19. In the present study, 46.6% of the female patients (7/15) were older than 35 years. This female predominance can be explained by estrogen level.

In this study, 90.5% of the SJS/TEN cases were apparently drug related. The most commonly implicated drugs were anticonvulsants (48.2%). Among the anticonvulsants, carbamazepine and lamotrigen were the causative agents in 33.3 and 14.9% of the cases, respectively. Meanwhile, NSAIDS and antibiotics (aminopenicillins and ciproflaxacin) caused 42.9 and 28.6% of cases, the latter percentage including six patients who received NSAID and antibiotics in the present study.

This study is in agreement with many other studies that showed that anticonvulsants were the most common culprit agents implicated 20–23. Retrospective studies in Southeast Asia also reported that the major culprit drugs were carbamazepine (17%), allopurinol (15%), β-lactam antibiotics (13%), sulfonamide antibiotics (12%), phenytoin (9%), NSAIDs (8%), lamotrigene (2%), and phenobarbitol (1%) 24.

A unique and strong association between HLA, drug hypersensitivity, and ethnic background was discovered by Tassaneeyakul et al.25, who showed a strong association between the HLA-B*1502, SJS, and carbamazepine in Han Chinese. Another study by Huang et al. 26 confirmed the susceptibility of individuals with HLA-B*1502 to carbamazepine in a Thai population. The authors found that phenytoin, lamotrigine, and oxcarbazepine, which possess an aromatic ring similar to that of carbamazepine, share a common risk allele. They suggested that aromatic antiepileptic drugs should be avoided in the B*1502 carrier and caution should also be exercised for lamotrigine.

These results were different from the results obtained in another study by Yeung et al.27 who reported that allopurinol was the most frequently responsible drug in 31% of patients, followed by anticonvulsants (13%). Another study showed that the most common causative agents were NSAIDs (54.5%), followed by allopurinol, prednisolone, and carbamazepine 28.

In this study, the mean duration of drug exposure before the onset of symptoms was 2–20 days, with a mean of 8.84±5.72 days. Our study showed a mean period of drug exposure of 7.7 days for antibiotics and a slightly longer duration of 11.2 days for anticonvulsants. Yim et al.28 reported shorter time for appearance of skin lesions, with a mean of 4.27 days. Two studies reported a slightly longer duration between drug intake and onset of symptoms as the mean was 14 and 15 days, respectively 17,27.

For many drugs, the risks for SJS and TEN were highest during the first weeks of use, particularly for antibiotics, as shown by Tan and Tay 17. For most high-risk drugs that were intended for long-term use, the risk of developing SJS and TEN were elevated during the initial 2 months of use 29.

Fever has been found to be a commonly reported prodromal symptom, with variations among SJS patients and occurs in almost 100% of TEN patients. The highest body temperature could reach 40°C in drug hypersensitivity syndrome but usually subsides within a few days 30.

In this study, fever on admission was found in many patients with SJS/TEN.

Fever in patients with SJS/TEN has been found to be related to the drug themselves or the release of some pyogenes from the necrotic epidermis rather than the infection itself 30. Thus, prophylactic antibiotics are generally not recommended in the literature 31. However, another study suggested that prophylactic antibiotics may decrease the mortality rate by lowering the infectious threat in SJS and TEN patients 32.

Involvement of the buccal, genital, and/or ocular mucosa (erythema and erosions) occurs in more than 90% of patients with SJS/TEN 33.

In this study, the oral, nasal, genital, and/or ocular mucosa affections were found in most of the patients with SJS/TEN.

Routine ophthalmic consultation with lubrication, steroids, and antibiotic eye drops was well established in our department.

Many studies showed that ocular involvement at the onset of disease was frequent and can range from acute conjunctivitis, eyelid edema, erythema, crusts, and ocular discharge to conjunctival membrane or pseudomembrane formation or corneal erosion, and, in severe cases, to cicatrizing lesions, symblepharon, fornix foreshortening, and corneal ulceration 34,35.

At the time of admission, liver function test results were normal in all patients. During hospital stay, liver function abnormalities were observed in about 38% (8/21) of the patients. This finding concurs with that from the study of Huang et al. 11 who reported liver function abnormalities in 50% of patients with SJS and TEN.

Drug-mediated hepatitis is an idiosyncratic toxicity in which unusual drug metabolites and immune-mediated hepatocyte injury are the main pathogenetic mechanisms 36.

Liver function abnormalities did not correlate with disease severity or hospitalization duration in our observation; this finding matched with that of Huang et al.11.

It is reasonable to say that transaminase level is influenced by many factors such as inflammatory reactions, fatty liver, and underlying virus hepatitis status. This observation is compatible with that previously documented based on the severe-of-illness score system (SCORTEN), in which liver functions were found to be a poor predictor of disease severity in cases of SJS-TEN 37.

The present study showed that the mean duration of hospital care to complete skin healing was 9–21 days, with a mean of 14.1 days, and the mean hospitalization duration was 15–30 days, with a mean of 19.6 days. These results concur with those from the study of Kim et al.38 who reported a hospital stay of 19.7 days. Another study reported a slightly longer stay of 20.6 days 39; two studies reported slightly shorter mean hospital stay durations of 17 and 16.9 days 27,40.

In contrast, Yim et al.28 reported that treatment of their patients in a burn intensive care unit shortened the time to complete reepithelialization to 9 days and shortened the mean hospital stay to 14.66 days.

Many studies reported that the mortality rate in SJS/TEN patients ranged from 5 to 40% 11,22,41. The present study recorded a high mortality rate of 50% for the TEN patients and 9.5% for the SJS/TEN patients. Similar to the present study results, the results obtained by Mockenhaupt 7 showed that the mortality was almost 10% for patients with SJS, ∼30% for patients with SJS/TEN overlap, and almost 50% for patients with TEN. For SJS, SJS/TEN overlap, and TEN the overall mortality rate was almost 25%.

Huang et al.11 reported a mortality of 20% for TEN (2/10) and 0% for SJS in their retrospective study. Gravante et al.42 reported a higher mortality rate of 34% in SJS/TEN patients (11/32).

The causes of death in the present study were electrolyte disturbances, as in the study of Haung et al.11. This finding contradicts another study that found that septicemia was an important mortality factor 42.

This study had many limitations, including its small sample size and the need for a genetic analysis to explain HLA association.

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Conclusion

Prevention and early detection are critical to treat this disease. Differences in disease severity and morbidity mainly influenced the course and outcome. The most common causative drugs in the present study were carbamazepine, NSAIDs, and antibiotics, and thus these should be considered by physicians.

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Acknowledgements

The authors are grateful to all faculty and postgraduates in the department for their invaluable help in conducting this study.

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Conflicts of interest

There are no conflicts of interest.

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References

1. Fromowitz JS, Ramos-Caro FA, Flowers FP. Practical guidelines for the management of toxic epidermal necrolysis and Stevens–Johnson syndrome. Int J Dermatol 2007; 46:1092–1094.
2. Harr T, French LE. Toxic epidermal necrolysis and Stevens–Johnson syndrome. Orphanet Rare 2010; 5:39.
3. Roujeau JC, Huynh TN, Bracq C, Guillaume JC, Revuz J, Touraine R. Genetic susceptibility to toxic epidermal necrolysis. Arch Dermatol 1987; 123:1171–1173.
4. Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science 1998; 282:490–493.
5. Bachot N, Roujeau JC. Differential diagnosis of severe cutaneous drug eruptions. Am J Clin Dermatol 2003; 4:561–572.
6. Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T, et al. Medication use and the risk of Stevens–Johnson syndrome or toxic epidermal necrolysis. N Engl J Med 1995; 333:1600–1607.
7. Mockenhaupt M. Burgdorf WHC, Plewig G, Wolff HH, Landthaler M. Severe cutaneous adverse reactions. Braun-Falco’s dermatology, 3rd ed. Heidelberg, Germany: Springer Medizin Verlag; 2009. 473–484.
8. Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens–Johnson syndrome, and erythema multiforme. Arch Dermatol 1993; 129:92–96.
9. Ghislain PD, Roujeau JC. Treatment of severe drug reactions: Stevens–Johnson syndrome, toxic epidermal necrolysis and hypersensitivity syndrome. Dermatol Online J 2002; 8:5.
10. Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol 2000; 115:149–153.
11. Huang CH, Ho JC, Cheng YW, Wu WM, Huang SL. Epidemiological Study of Stevens–Johnson syndrome and toxic epidermal necrolysis: retrospective analysis of Southern Taiwanese population during 2002–2007. Dermatol Sini 2009; 27:15–26.
12. Kim KJ, Jee MS, Han MH, Choi JH, Sung KJ, Moon KC, et al. The effect of high-dose intravenous immunoglobulin for the treatment of toxic epidermal necrolysis. Korean J Dermatol 2002; 40:766–771.
13. Lohmeier K, Megahed M, Schulte KW, Stannigel H, Mayatepek E, Schroten H. Toxic epidermal necrolysis in a premature infant of 27 weeks’ gestational age. Br J Dermatol 2005; 152:150–151.
14. Chan HL, Stern RS, Arndt KA, Langlois J, Jick SS, Jick H, Walker AM. The incidence of erythema multiforme, Stevens–Johnson syndrome, and toxic epidermal necrolysis. A population-based study with particular reference to reactions caused by drugs among outpatients. Arch Dermatol 1990; 126:43–47.
15. Fritsch P. European Dermatology Forum: skin diseases in Europe. Skin diseases with a high public health impact: toxic epidermal necrolysis and Stevens–Johnson syndrome. Eur J Dermatol 2008; 18:216–217.
16. Yamane Y, Aihara M, Ikezawa Z. Analysis of Steven–Johnson syndrome and toxic epidermal necrolysis in Japan from 2000–2006. Allergol Int 2007; 56:419–425.
17. Tan SK, Tay YK. Profile and pattern of Stevens–Johnson syndrome and toxic epidermal necrolysis in a general hospital in Singapore: treatment outcomes. Acta Derm Venereol 2012; 92:62–66.
18. Leimola-Virtanen R, Salo T, Toikkanen S, Pulkkinen J, Syrjänen S. Expression of estrogen receptor (ER) in oral mucosa and salivary glands. Maturitas 2000; 36:131–137.
19. Ishimaru N, Arakaki R, Watanabe M, Kobayashi M, Miyazaki K, Hayashi Y. Development of autoimmune exocrinopathy resembling Sjögren’s syndrome in estrogen-deficient mice of healthy background. Am J Pathol 2003; 163:1481–1490.
20. Yap FB, Wahiduzzaman M, Pubalan M. Stevens–Johnson syndrome and toxic epidermal necrolysis in Sarawak: 4 years‘ review. EDOJ 2008; 4:1.
21. Kamaliah MD, Zainal D, Mokhtar N, Nazmi N. Erythema multiforme, Stevens–Johnson syndrome and toxic epidermal necrolysis in northeastern Malaysia. Int J Dermatol 1998; 37:520–523.
22. Devi K, George S, Criton S, Suja V, Sridevi PK. Carbamazepine – the commonest cause of toxic epidermal necrolysis and Stevens–Johnson syndrome: a study of 7 years. Indian J Dermatol Venereol Leprol 2005; 71:325–328.
23. Huang SH, Wu SH, Sun IF, Lee SS, Lai CS, Lin SD, Lin TM. AQUACEL Ag in the treatment of toxic epidermal necrolysis (TEN). Burns 2008; 34:63–66.
24. Lee HY, Martanto W, Thirumoorthy T. Epidemiology of Stevens–Johnson syndrome and toxic epidermal necrolysis in Southeast Asia. Dermatol Sini 2013; 31:217–220.
25. Tassaneeyakul W, Tiamkao S, Jantararoungtong T, Chen P, Lin SY, Chen WH, et al. Association between HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in a Thai population. Epilepsia 2010; 51:926–930.
26. Hung SI, Chung WH, Liu ZS, Chen CH, Hsih MS, Hui RC, 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.
27. Yeung CK, Ma SY, Hon C, Peiris M, Chan HH. Aetiology in sixteen cases of toxic epidermal necrolysis and Steven–Johnson syndrome admitted within 8 months in a teaching hospital. Acta Derm Venereol 2003; 83:179–182.
28. Yim H, Park JM, Cho YS, Kim D, Hur J, Chun W, et al. A clinical study of Stevens–Johnson syndrome and toxic epidermal necrolysis: efficacy of treatment in burn intensive care unit. J Korean Surg Soc 2010; 78:133–139.
29. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med 1994; 331:1272–1285.
30. Wolf R, Orion E, Marcos B, Matz H. Life-threatening acute adverse cutaneous drug reactions. Clin Dermatol 2005; 23:171–181.
31. Letko E, Papaliodis BS, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Stevens–Johnson syndrome and toxic epidermal necrolysis: a review of the literature. Ann Allergy Asthma Immunol 2005; 94:419–436.
32. Peter OF, Ramon RM. Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz S. Erythema multiforme, Stevens–Johnson syndrome and toxic epidermal necrolysis. Fitzpatrick's Dermatology in General Medicine. 6th ed. New York: McGraw-Hill; 2003. 543–557.
33. Revuz J, Penso D, Roujeau JC, Guillaume JC, Payne CR, Wechsler J, Touraine R. Toxic epidermal necrolysis; clinical findings and prognosis factors in 87 patients. Arch Dermatol 1987; 123:1160–1165.
34. Chang YS, Huang FC, Tseng SH, Hsu CK, Ho CL, Sheu HM. Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis: acute ocular manifestations, causes, and management. Cornea 2007; 26:123–129.
35. Sotozono C, Ueta M, Koizumi N, Inatomi T, Shirakata Y, Ikezawa Z, et al. Diagnosis and treatment of Stevens–Johnson syndrome and toxic epidermal necrolysis with ocular complications. Ophthalmology 2009; 116:685–690.
36. Castell JV. Allergic hepatitis: a drug-mediated organ-specific immune reaction. Clin Exp Allergy 1998; 28 (Suppl 4):13–19.
37. Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol 2000; 115:149–153.
38. Kim YG, Cho KH, Chung JH. A comparative clinical study of toxic epidermal necrolysis and Stevens–Johnson syndrome. Korean J Dermatol 1991; 29:602–609.
39. Kim JW, Kim ST, Song DH. A clinical observation of the patients with Stevens–Johnson syndrome and toxic epidermal necrolysis in Jeju island. Korean J Dermatol 2004; 42:579–591.
40. Kim EJ, Lee JB, Kwon YH, Yun SJ, Kim SJ, Lee SC, et al. A clinical study of Stevens–Johnson syndrome and toxic epidermal necrolysis over the last 5-year period in the Gwangju-Chonnam area. Korean J Dermatol 2006; 44:574–578.
41. Auquier-Dunant A, Mockenhaupt M, Naldi L, Correia O, Schröder W, Roujeau JC. SCAR Study Group. Severe Cutaneous Adverse Reactions. Correlations between clinical patterns and causes of erythema multiforme majus, Stevens–Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study. Arch Dermatol 2002; 138:1019–1024.
42. Gravante G, Delogu D, Marianetti M, Trombetta M, Esposito G, Montone A. Toxic epidermal necrolysis and Steven–Johnson syndrome: 11-years experience and outcome. Eur Rev Med Pharmacol Sci 2007; 11:119–127.
Keywords:

cutaneous drug eruption; Stevens–Johnson syndrome; toxic epidermal necrolysis

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