Stevens-Johnson syndrome carbamazepine-induced

Carbamazepine stimulates antidiuretic hormone activity and has been used for the treatment of neurohypophyseal diabetes insipidus. Carbamazepine induces microsomal enzymes and its metabolism is subject to auto-induction. Frequently occurring adverse effects are sedation, dry mouth, dizziness and gastrointestinal disturbances. Photosensitivity reactions, urticaria and Stevens-Johnson syndrome have been described. The elderly are more prone to mental confusion, cardiac abnormalities and problems due to inappropriate ADH secretion. 

Rash risk in 5%-10% Rarely, life-threatening rash (including Stevens-Johnson syndrome) Risk minimized by low starting dose and slow titration Metabolism inhibited by valproate Metabolism induced by carbamazepine... 

Straussberg R, Harel L, Ben-Amitai D, Cohen D, Amir J. Carbamazepine-induced Stevens-Johnson syndrome... 

In a 26-year-old woman who had severe Stevens-Johnson syndrome induced by phenytoin and later by carbamazepine, gabapentin resulted in an erythematous pruriginous skin eruption limited to the legs without mucosal involvement (35). 

Carbamazepine (CBZ) is a widely used anticonvulsant that can cause rashes in up to 10% of patients, and in occasional cases this may be the precursor to the development of a hypersensitivity syndrome characterized by systemic manifestations such as fever and eosinophilia (Feeder 1998 Vittorio and Muglia 1995). Rarely, CBZ can induce blistering skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis, two conditions associated with a high fatality rate (Rzany et al. 1999). There is now increasing laboratory evidence to show that... 

Locharemkul C, Loplumlert J, Limotai C, Korkij W, Desudchit T, Tongkobpetch S, Kangwanshiratada O, Hirankam N, Suphapeetipom K, Shotelersuk V (2008) Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B 1502 allele in Thai population. Epilepsia 49 2087-2091... 

Dhar S, Todi SK. Are carbamazepine-induced Stevens-Johnson syndrome and toxic epider-malnecrolysismore common innonepileptic patients D mia/t)/t) (1999) 199, 194. 

Genetic factors associated with severe adverse skin reactions induced by antiepileptic drugs in different ethnic populations have been discussed [80 , 81" ]. Several studies have shown that Han Chinese patients carrying the HLA-B 1502 are at high risk of Stevens-Johnson syndrome or toxic epidermal necrolysis when exposed to carbamazepine. 

HLA class I has been examined in 15 Japanese patients who fulfilled the diagnostic criteria for carbamazepine-induced cutaneous adverse reactions (mild in 10 and Stevens-Johnson syndrome in 5) [124 ]. HLA-B 1518, HLA-B 5901, and HLA-C 0704 alleles were associated with higher relative risks of severe cutaneous adverse reactions. The haplotype HLA-A 2402-B 5901-C 0102 carried a high relative risk of severe adverse reactions. In patients with severe cutaneous adverse reactions, the frequencies of HLA-A 1101, HLA-A 3303, HLA-B 1501, HLA-B 4403, HLA-B 5101, HLA-B 5201, HLA-C 0702, and HLA-C 1202 alleles were relatively lower than in the general population of Japanese people. The authors suggested that HLA-B 5901 may be a marker of carbamazepine-induced Stevens-Johnson syndrome in Japanese people. 

In a case-control study to determine whether HLA-B 1502 is a valid pharmaco-genetic test for carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Thai patients, 79 with these serious complications carried... 

HLA allele B 1502 is a marker for an increased risk of carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. The FDA has therefore changed the carbamazepine label, recommending genotyping in all Asians [90 ]. 

The possible association between HLA-B 1502 and carbamazepine- or phenytoin-induced Stevens-Johnson syndrome or maculopapular eruptions has been explored in 31 Thai subjects who had these antiepileptic drug-induced complications between 1994 and 2007 and in 50 antiepileptic drug-tolerant controls [92. There was a strong association between HLA-B 1502 and phenytoin- and carbamazepine-induced Stevens-Johnson syndrome. However, some patients with HLA-B 1502 had had carbamazepine-induced Stevens-Johnson syndrome and were tolerant of phenytoin and vice versa, which suggests that other factors contribute to this adverse reaction. 

The association between HLA-B 1502 and carbamazepine-induced Stevens- Johnson syndrome and toxic epidermal necrolysis has been investigated in eight Indian patients, of whom six had the HLA-B 1502 allele, confirming the association in Indian patients [93 ]. 

A 54-year-old woman with carbamazepine-induced Stevens-Johnson syndrome was given intravenous immunoglobulin 1 g/kg/day for 3 days and topical glucocorticoids to the non-erosive skin lesions [65 ]. However, 3 days later she developed multiple non-pruritic vesi-cobullae with clear fluid contents on the palms after most of the previous lesions had resolved. The new lesions resolved spontaneously within 1 week without treatment. 

In the Han Chinese population, genetic polymorphisms at HLA-B 1502 are associated with an increased risk for carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS), while HLA-A 3101 polymorphisms are associated with an increased risk for drug hypersensitivity to CBZ [1 ]. Studies on Caucasian populations did not consistently reproduce the same associations [2,3 ] although a more recent multiethnic study population in Canada demonstrated similar associations to those seen in the Han Chinese population In addition, HLA-A 2402 allele is linked... 

Shi YW, Min FL, Qin B, Zou X, Liu XR, Gao MM, et al. Association between HLA and Stevens-Johnson syndrome induced by carbamazepine in Southern Han Chinese genetic markers besides B 1502 Basic Clin Pharmacol Toxicol July 2012 lll(l) 58-64. 

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