Toxic epidermal necrolysis carbamazepine

Dermatologic Severe dermatologic reactions, including toxic epidermal necrolysis (Lyell syndrome) and Stevens-Johnson syndrome, have been reported with carbamazepine. These reactions have been extremely rare however, a few fatalities have been reported. 

Oxcarbazepine is typically started at a dosage of 150 mg twice a day and titrated by 300 mg/day at weekly intervals. Therapeutic dosages are in the range of 450 mg twice a day to 1,200 mg twice a day. The conversion from carbamazepine to oxcarbazepine is approximately 1 to 1.5. Oxcarbazepine has a higher risk of hyponatremia than does carbamazepine. Serum sodium should be monitored in patients at risk for hyponatremia, such as the elderly or patients who are also taking diuretics. Stevens-Johnson syndrome and toxic epidermal necrolysis may occur between 3 and 10 times more frequently in oxcarbazepine-treated patients than in the general population. Median time from starting treatment to the development of these serious reactions is 19 days. 

Toxic epidermal necrolysis occurs when the skin epidermis is destroyed by the action of toxicants and becomes detached from the dermis. This condition severely disrupts the ability of skin to regulate the release of heat, fluids, and electrolytes. Metabolites of the anticonvulsive drug carbamazepine have been implicated in toxic epidermal necrolysis. 

A 55-year-old man who had been treated for a manic-depressive disorder for about 5 years developed toxic epidermal necrolysis after being given carbamazepine and haloperidol (35). 

Hypersusceptibility reactions to carbamazepine are relatively common and range from cutaneous reactions (including Stevens-Johnson sjmdrome and toxic epidermal necrolysis, severe forms of erythema multiforme) to systemic reactions with fever, lymphadenopathy, and/or involvement of the bone marrow, the liver, the heart, the gastrointestinal system, the lungs, and other organs. 

A skin rash occurs in 5-20% of patients started on carbamazepine, and is a common cause of early drug withdrawal. The rash is usually erythematous or maculopapular and may accompany systemic manifestations of hypersensitivity. Exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis are relatively rare (SED-13, 148) (55,56). 

Breathnach SM, McGibbon DH, Ive FA, Black MM. Carbamazepine ( Tegretol ) and toxic epidermal necrolysis report of three cases with histopathological observations. Qrn Exp Dermatol 1982 7(6) 585-91. 

Friedmann PS, Strickland I, Pirmohamed M, Park BK (1994) Investigation of mechanisms in toxic epidermal necrolysis induced by carbamazepine. Arch Dermatol 130 598-604 Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y (2003) Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52 65-70 Ganey PE, Luyendyk JP, Maddox JF, Roth RA (2004) Adverse hepatic drug reactions inflammatory episodes as consequence and contributOT. Chem Biol Interact 150 35-51 Gao B (2005) Cytokines, STATs and liver disease. Cell Mol Immunol 2 92—100... 

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... 

An isolated report describes a 26-year-old woman with cerebral palsy who had been taking phenobarbital 15 mg with carbamazepine 400 mg daily for 12 years to control epilepsy, and who developed fatal toxic epidermal necrolysis 2 weeks after starting oral terbinafine 250 mg daily for tinea corporis. The reasons are not understood, but the authors point out that all three drugs can cause adverse skin reactions (erythema multiforme) and suggest that some synergism may have occurred. It is uncertain whether this was a true interaction or a terbinafine adverse effect. 

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-B 1301, Cw 0801, and DRB1 1602 also showed an association with phenytoin. The authors concluded that HLA-B 1502 is a susceptibility factor for Stevens-Johnson syndrome/toxic epidermal necrolysis in patients taking these aromatic antiepileptic drugs, as has previously been shown with carbamazepine. 

Skin Several further cases of Stevens— Johnson syndrome/toxic epidermal necrolysis associated with carbamazepine have been described [120, 121 ], sometimes evolving to septic shock and multiple organ failure followed by death [122 ]. 

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... 

Serious, sometimes fatal dermatological reactions have been reported, including Stevens-Johnson syndrome and toxic epidermal necrolysis. The risk is 10 times greater in some Asian countries due to a strong association with the HLA-B 1502 allele, which is found almost exclusively in Asian patients. Genetically at-risk patients should be screened prior to receiving carbamazepine, and carbamazepine should not be given to patients who test positive for the allele. 

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 ]. 

Carbamazepine-induced toxic epidermal necrolysis has been reported in a child [91 ]. 

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 ]. 

The risk of erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis in 72 patients with bipolar disorder taking carbamazepine, valproate, or other medications has been analysed using a large... 

In a young patient with carbamazepine-induced toxic epidermal necrolysis, blister fluid was analysed for protein, chemical, and mineral contents [95 ]. There was a threefold increase in albumin and protein compared with bums blisters. 

In a large database study, treatment with valproic acid was significantly associated with erythema multiforme, Stevens—Johnson syndrome, or toxic epidermal necrolysis among patients with bipolar disorder [94 ] (see Carbamazepine for details). 

Ferrell Jr. PB, McLeod HL. Carbamazepine, HLA-B 1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis US FDA recommendations. Pharmacogenomics 2008 9(10) 1543-6. 

Sevketoglu E, Hatipoglu S, Akman M, Bicer S. Toxic epidermal necrolysis in a child after carbamazepine dosage increment. Pediatr Emerg Care 2009 25(2) 93-5. 

Kaniwa N, Saito Y, Aihara M, Matsunaga K, Tohkin M, Kurose K, et al. HLA-B 1511 is a risk factor for carbamazepine-induced Steveirs-Johnson syndrome and toxic epidermal necrolysis in Japanese patients. Epilepsia 2010 51 2461-5. 

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