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Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis in northeastern Malaysia

Kamaliah MD, Zainal D, Mokhtar N, Nazmi N

Int J Dermatol, 1998 Jul;37(7):520-3.
PMID: 9679693

BACKGROUND: Previous studies have reported that drugs and infections are common causes of erythema multiforme (EM) and Stevens-Johnson syndrome (SJS). Toxic epidermal necrolysis (TEN) is mainly related to drugs. No study has been conducted in Kelantan, the northeastern state of Malaysia, to assess these cutaneous reactions.
METHODS: A retrospective study of all hospitalized cases of EM, SJS, and TEN was conducted covering an 8-year period from 1987 to 1994.
RESULTS: There were four cases (13.8%) of EM, 22 cases (75.9%) of SJS, and three cases (10.3%) of TEN. Drugs as a definitive cause was observed in one case (25%) of EM, 12 cases (54.5%) of SJS, and two cases (66.7%) of TEN. Drugs as a probable cause was observed in seven cases (31.8%) of SJS and one case (33.3%) of TEN. The male to female ratio was equal in EM and SJS. Antiepileptics were the commonest culprits, followed by antibiotics. One patient died of SJS and one patient died of TEN, giving mortality rates of 4.5% and 33.5% respectively. Fever was noted in 18 patients (62.1%). Leukocytosis was noted in 10 patients (34.5%), and nine patients (31.0%) had elevated liver transaminase enzymes. No significant correlation was noted between these biochemical changes and cutaneous eruption. Secondary infections were observed in 11 patients (37.9%): Staphylococcus aureus was the commonest isolated organism.
CONCLUSIONS: This study shows that drugs remain the commonest culprit in SJS and TEN. Despite adequate treatment, the mortality rate remains high, especially in TEN. These findings are similar to those of other reported studies.

Matched MeSH terms: Stevens-Johnson Syndrome/etiology
Drug eruptions from phenylbutazone in Jamu

Giam YC, Tham SN, Tan T, Lim A

Ann Acad Med Singap, 1986 Jan;15(1):118-21.
PMID: 2939787

Drug eruptions from indeginous medicine is often difficult to diagnosis and confirm. It is known that a number of these now supplied by bomohs and Chinese sinsehs contain known drugs and are dispensed as tablets and capsules. We report 3 cases of adverse drug eruption to "Jamu", a Malay herb. A particular brand, "Jamu Indonesia, Toko Air Pancur", from Johor Bahru, Malaysia, is especially recommended for "sakit pinggang" or backache. The cases occurred between January and February 1985, and all had taken brown kidney shaped tablets. The adverse reactions were moderately severe. Two had erythroderma with hepatitis, and one, Steven Johnson Syndrome. Analysis of this jamu for analgesics led to the discovery of adulteration with phenylbutazone and diazepam. Records from local cases from 1974-1984 showed that 8 other patients, all Chinese had adverse cutaneous eruptions from phenylbutazone, oxybutazone and propyphenazone. The skin manifestations were erythroderma (2 cases), vasculitis (2 cases) and toxic epidermal necrolysis (4 cases). Those with toxic epidermal necrolysis had 100% mortality.

Matched MeSH terms: Stevens-Johnson Syndrome/etiology
Fulltext Toxic epidermal necrolysis in Malaysian adults. A retrospective study

Ting HC, Adam BA

Singapore Med J, 1985 Oct;26(6):456-9.
PMID: 2937150

We report a retrospective study of all cases of toxic epidermal necrolysis admitted to the adult medical wards of the University Hospital in Kuala Lumpur over a 16 year period from 1967 to 1983. Over this period of time only 7 cases were encountered, suggesting the condition is rare in adults in our country. All the cases were females and the age ranged from 21 to 41 years. Four cases were due to drugs, 2 were idiopathic and one was attributed to Staphylococcal infection. One patient died. The other patients recovered completely with no sequelae.

Matched MeSH terms: Stevens-Johnson Syndrome/etiology*
Association of HLA-B*1502 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome in the multi-ethnic Malaysian population

Chang CC, Too CL, Murad S, Hussein SH

Int J Dermatol, 2011 Feb;50(2):221-4.
PMID: 21244392 DOI: 10.1111/j.1365-4632.2010.04745.x

BACKGROUND: Carbamazepine (CBZ), a frequently used anticonvulsant drug, is one of the most common causes of life-threatening cutaneous adverse drug reactions such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). Recent studies have revealed a strong association between HLA-B*1502 and CBZ-induced TEN/SJS in the Taiwan Han Chinese population.
OBJECTIVES: This study is aimed to investigate the association between human leucocyte antigens (HLA) and CBZ-induced TEN/SJS in the multi-ethnic Malaysian population.
METHODS: A sample of 21 unrelated patients with CBZ-induced TEN/SJS and 300 race-matched, healthy controls were genotyped for HLA-A, -B and -DR using polymerase chain reaction (PCR). Allele frequencies were compared.
RESULTS: HLA-B*1502 was present in 75.0% (12/16) of Malay patients with CBZ-induced TEN/SJS but in only 15.7% (47/300) of normal controls (odds ratio 16.15, 95% confidence interval 4.57-62.4; corrected P-value = 7.87 × 10(-6) ), which suggests a strong association between HLA and CBZ-induced TEN/SJS. Additionally, HLA-B*1502 was found in all three Chinese and two Indian patients. Existing data show that frequencies of the HLA-B*1502 allele are generally much higher in Asian populations than in White European populations, which explains the higher incidences of SJS and TEN in Asian countries.
CONCLUSIONS: HLA-B*1502 is strongly associated with CBZ-induced TEN/SJS in the Malay population in Malaysia, as has been seen in Han Chinese in Taiwan. This indicates that the genetic association apparent in the incidence of CBZ-induced TEN/SJS is linked with the presence of HLA-B*1502, irrespective of racial origin. Screening of patients for this genetic marker can help to prevent the occurrence of TEN/SJS.

Matched MeSH terms: Stevens-Johnson Syndrome/etiology
Frequency of the HLA-B*1502 allele contributing to carbamazepine-induced hypersensitivity reactions in a cohort of Malaysian epilepsy patients

Then SM, Rani ZZ, Raymond AA, Ratnaningrum S, Jamal R

Asian Pac J Allergy Immunol, 2011 Sep;29(3):290-3.
PMID: 22053601

We describe the association of the HLA-B*1502 allele in 27 epilepsy patients (19 Malays, 8 Chinese) treated with carbamazepine (CBZ) at the UKM Medical Center (UKMMC), 6 with CBZ-Steven Johnson Syndrome (CBZ-SJS), 11 with CBZ-induced rash, 2 with suspected phenytoin-induced rash and 8 negative controls. Our study showed that 10 (6 Malay, 4 Chinese) patients were positive for HLA-B*1502. Out of the 10 patients, six were confirmed to have CBZ-SJS (p = 0.0006), while four patients developed a skin rash. However there were 6 Malay patients and 1 Chinese patient that developed a skin rash after CBZ administration who were not positive for the allele, indicating that there might be more that one allele associated with CBZ-induced hypersensitivity. Another 2 patients were suspected of having phenytoin-induced rash, instead of CBZ, and these patients did not have HLA-B*1502. In conclusion, this study confirmed the association of HLA-B*1502 with CBZ-SJS among Malaysian epilepsy patients, however there might be other genes that could be responsible for the CBZ-induced rash.

Matched MeSH terms: Stevens-Johnson Syndrome/etiology
HLA-A*31: 01 and HLA-B*15:02 association with Stevens-Johnson syndrome and toxic epidermal necrolysis to carbamazepine in a multiethnic Malaysian population

Khor AH, Lim KS, Tan CT, Kwan Z, Tan WC, Wu DB, et al.

Pharmacogenet Genomics, 2017 07;27(7):275-278.
PMID: 28570299 DOI: 10.1097/FPC.0000000000000287

The majority of the carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis CBZ-SJS/TEN are associated with HLA-B*15:02 in Asian populations where this allele is common. In contrast, the association with HLA-A*31:01 is only reported in Japanese and Europeans. This study aimed to further investigate the association with HLA-A*31:01 besides HLA-B*15:02 in a multiethnic Malaysian population. Twenty-eight CBZ-SJS/TEN cases and 227 CBZ-tolerant controls were recruited. Association was tested by comparing carrier frequencies of the alleles between cases and controls. Significant associations were detected between HLA-B*15:02 and CBZ-SJS/TEN in independent ethnic groups: Malays [P=2.00×10; odds ratio (OR): 49.0; 95% confidence interval (CI): 9.36-256.81], Chinese (P=0.0047; OR: 14.3; 95% CI: 2.38-86.03) and Indians (P=0.04; OR: 13.8; 95% CI: 1.51-124.99). Combined analysis of all ethnic groups showed a significant association with OR Cochran-Mantel-Haenszel (ORCMH) of 26.6 (95% CI: 12.80-55.25; PCMH=2.31×10). In Indians, HLA-A*31:01 was found to be associated significantly with CBZ-SJS/TEN (P=0.023; OR: 10.4; 95% CI: 1.64-65.79) and combined analyses of both variants, HLA-A*31:01 and HLA-B*15:02, increased the strength of the association (P=0.0068; OR: 14.3; 95% CI: 2.20-92.9). Besides HLA-B*15:02, our study found a new association between HLA-A*31:01 and CBZ-SJS/TEN in Indians.

Matched MeSH terms: Stevens-Johnson Syndrome/etiology*
Fulltext Cross-reactivity in AED-Induced Severe Cutaneous Adverse Reaction: A Case Report

Khor AH, Lim KS, Tan CT, Kwan Z, Ng CC

J Investig Allergol Clin Immunol, 2016;26(5):329-331.
PMID: 27763865 DOI: 10.18176/jiaci.0085
Matched MeSH terms: Stevens-Johnson Syndrome/etiology
Fulltext An epidemiological and clinical analysis of cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia

Choon SE, Lai NM

Indian J Dermatol Venereol Leprol, 2012 Nov-Dec;78(6):734-9.
PMID: 23075643 DOI: 10.4103/0378-6323.102367

BACKGROUND: The prevalence, clinical patterns, and causative drugs of cutaneous adverse drug reactions (cADR) vary among the different populations previously studied.
AIM: To determine the prevalence, the clinical patterns of drug eruptions, and the common drugs implicated, particularly in severe cADR such as Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophilia and systemic symptoms (DRESS) in our population.
METHODS: We analyzed the database established for all cADR seen by the department of Dermatology from January 2001 till December 2010.
RESULTS: A total of 362 cADR were seen among 42 170 new clinic attendees, yielding an incidence rate of 0.86%. The most common reaction pattern seen was maculopapular eruption (153 cases) followed by SJS/TEN (110 cases) and DRESS (34 cases). Antibiotics was the most commonly implicated drug group (146 cases) followed by anticonvulsants (81 cases) and antigout drugs (50 cases). The most frequently implicated drug was allopurinol (50 cases). Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 21.8%, 20.9%, and 12.7%, respectively, of the 110 cases seen, whereas DRESS was mainly caused by allopurinol (15 cases). Mortality rates for TEN, SJS, and DRESS were 28.6%, 2.2%, and 5.9%, respectively.
CONCLUSIONS: The low rate of cADR with a high proportion of severe reactions observed in this study was probably due to referral bias. Otherwise, the reaction patterns and drugs causing cADR in our population were similar to those seen in other countries. Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN in our population.
Study site: department of dermatology in Hospital Sultanah Aminah

Matched MeSH terms: Stevens-Johnson Syndrome/etiology