Risk Factors and Management of Mood Stabilizer-associated Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A Mini-review

Transcription

1 140 Taiwanese Journal of Psychiatry (Taipei) Vol. 25 No Overview Risk Factors and Management of Mood Stabilizer-associated Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A Mini-review Gen-Tang Lin, M.D. Objectives: In this brief review, I am dealing with the management and risk of mood stabilizers associated Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Methods: I conducted a comprehensive review of 27 published articles on SJS/TEN management and the risk of mood stabilizer-induced SJS/TEN. Results: Mood-stabilizing agents such as carbamezapine, lithium carbonate, valproic acid, topiramate, lamotrigine, gabapentin, and oxcarbazepine have the highest incidence of SJS/TEN. Han Chinese who have the HLA-B*1502 allele are at a much increased risk of developing SJS/TEN when exposed to carbamazepine. Stopping the suspected drug and rapid initiation of supportive and symptomatic management remains the mainstay of SJS/TEN management. Females, substance abusers, and new users with an early or sudden high combined dosage of mood stabilizers have increased risk of SJS/TEN. Carbamazepine-induced SJS/TEN in Taiwan exhibits a 98.3% sensitivity rate for HLA-B*1502. Given the availability of other effective medications for similar indications, avoiding carbamazepine is likely prudent when patients have tested HLA-B*1502 screening positive. Conclusion: Early diagnosis is important and early treatment requirs optimal SJS/TEN management. Key words: Management, risk, mood stabilizers, Stevens-Johnson syndrome (SJS) (Taiwanese Journal of Psychiatry [Taipei] 2011; 25: 140-4) Introduction I have searched the published articles dealing with mood stabilizers and Stevens-Johnson syndrome/toxic epidermal necrolysis in the Pub-med website. In this review, I have chosen 27 articles dealing with the Han people on this topic. Those 27 articles cover SJS/TEN clinical symptoms, diagnosis, treatment, risk factors to the associated mood stabilizers, and possible related genes. SJS is accompanied by fever, inflammation of the buccal mucosa, and severe purulent conjunctivitis. Cutaneous lesions often become con- Taichung Armed Forces General Hospital Received: January 12, 2011; revised: February 21, 2011; accepted: March 28, 2011 Address correspondence to: Dr. Gen-Tang Lin, No.42, Taizhong Peaceful Area Suitable Joyful Street, Taichung 411, Taiwan

2 Lin GT 141 fluent and show a positive Nikolsky sign and epidermal detachment. In SJS, epidermal detachment involves less than 10% of the total body skin area. Transitional SJS/TEN is defined by an epidermal detachment between 10% and 30%, and TEN is defined by a detachment greater than 30%. Impaired skin defense probably contributes to the high incidence of infection. SJS/TEN is essentially drug-induced. Graft versus host disease is another well-established cause, independent of drugs. A few cases are related to infections such as from Mycoplasma pneumoniae, and few other cases remain unexplained. The most extensive study of medication use and SJS/TEN mainly pointed to antibacterial sulfonamides, anticonvulsant agents, some nonsteroidal anti-inflammatory drugs and allopurinol [1]. HIV infection dramatically increases the risk. A predisposing effect of autoimmune disorders such as systemic lupus, and an HLA-linked, genetic susceptibility have been also suggested [2]. Common infections are gramnegative pneumonias and septicemias. Respiratory failure is associated with mucus retention and sloughing of the tracheobronchial mucosa. Conjunctivitis is the most frequent ocular complication. This purulent conjunctivitis causes the eyelids to become swollen, crusted, and ulcerated, with ensuing pain and photophobia [3]. Oral lesions, commonly beginning as vesicles, rupture, forming a gray-white membrane. The oropharyngeal cavity is involved, with erosion and sloughing possibly extending the entire length of the gastrointestinal tract, resulting in malnutrition, pain, and bleeding. The most severe gastrointestinal complication is bleeding [4]. Gastrointestinal and tracheobronchial epithelial involvement may lead to increased mortality while immunologic and epidermal disruption often leads to infection and sepsis [5]. Most often used pharmacologic therapies are aimed at altering the immune response, such as the use of corticosteroids, cyclosporin, and intravenous immunoglobulin [6]. Risk of Mood Stabilizerassociated SJS-TEN Carbamazepine Carbamazepine is used to treat seizure disorders, bipolar disorder, trigeminal neuralgia, and chronic pain. But, carbamazepine is also associated with hypersensitivity reactions that range from benign urticaria to life-threatening cutaneous disorders, including SJS/TEN [7]. Recently generated data implicate HLA allele B*1502 as a marker for carbamazepine-induced SJS/TEN in Han Chinese. Chung et al. were the first to identify an association between carbamazepine-induced SJS/ TEN and HLA-B*1502 allele [8]. Assuming a 0.25% incidence of carbamazepine-sjs/ten in newly prescribed carbamazepine patients in Taiwan and 98.3% sensitivity rate for HLA- B*1502 [9]. Prevalence of HLA-B*1502 allele in Asian populations is also much higher than in Caucasian and African populations [10]. Combined mood stabilizers Carbamazepine and valproate also increase the risk for SJS/TEN [11]. The rate of an antiepileptic drug (AED) rash such as carbamazepine and lamotrigine rash is about five times greater in patients with another (AED) rash [12]. Concomitant use of lamotrigine and aripiprazole increases risk of SJS/TEN [13]. A rapid dose escalation of lamotrigine, even a single higher dose, could expose patients to an unacceptable risk of SJS/TEN, particularly in patients taking valproate [14]. Valproate is known to augment lamotrigine availability through reduced glucuronidation, increasing the risk of serious rash if patients are concomitantly given lamotrigine [15].

3 142 Risk and Management of SJS/TEN Other risks (new users, female and substance abusers ) More than 90% of SJS/TEN cases occur within the first 63 days of mood stabilizer use, and new users are at higher risk [16]. A prospective case series and review of literature showed that lamotrigine induced a higher rate of SJS/TEN in female cases [17]. SJS with transition to TEN after carbamazepine administration, heroin and alcohol abuse [18]. Alcohol abuse alters host immunity which may subsequently increase susceptibility to allergic reactions. Patient s risk factors to develop mood stabilizer-associated SJS/TEN include: HLA-B*1502 positive Female New users Early or sudden high dosage Combined Mood stabilizers Substance abusers Prognosis SJS/TEN is an acute, self-limited disease, with high morbidity, and is potentially life threatening. Mortality rates are 5%-10% with SJS, 30%- 35 % with TEN and 10%-15% with transitional forms [2]. Early diagnosis and withdrawal of all potential causative drugs are essential to a favorable outcome. Morbidity and mortality are increased if the offending drug is withdrawn late. No difference has been seen for drugs with long half-lives [19]. Age, percentage of denuded skin, neutropenia, serum urea nitrogen level, and visceral involvement are prognostic factors. A specific score (SCORTEN) was recently elaborated and validated [20]. After healing, altered pigmentation and corneal lesions are the main long-term complications. Treatments for SJS/TEN Supportive and symptomatic treatments The main types of symptomatic treatment are the same as for patients with burn injury. Essential treatments consist of oral nutrition by nasogastric tube if needed; prevention of stress ulcer; fluid support (which should be based on the percentage of the affected total body surface area, the patient s weight, and an estimation of the volume of fluid lost); and medication administration for pain and anxiety control. If the trachea and bronchi are involved, patients need to receive intubation and mechanical ventilation. Skin lesions and oral ulcers have traditionally been treated with topical antibacterial agents. Liquid ocular lubricants should be applied to dry or photophobic eyes to minimize complications. Clinicians should consult with a dermatologist and an ophthalmologist if needed. Other treatments Administering systemic corticosteroids can prolong wound healing, increase risk of infection, mask early signs of sepsis, cause severe gastrointestinal bleeding, and increased mortality [21]. The use of corticosteroids in SJS-TEN remains controversial. Intravenous immunoglobulin (IVIG) can protect the keratinocytes in patients with SJS-TEN, thereby limiting disease progression [22]. Early infusion of IVIG can convey this protection as soon as the diagnosis is complete, and further limit the massive apoptosis of keratinocytes [23]. A high dose of IVIG (about 3 g/kg) showed increased survival, but was costly [24]. Interleukin-6 and TNF-α are found in higher quantities in lesioned skin in SJS-TEN, anti-tnf-α agents such as infliximab have been used with

4 Lin GT 143 success in a handful of patients [25]. Cyclosporine can inhibit CD8 and reduce extensive epidermal destruction, thereby shortening both the duration of active disease within hours and time to complete re-epithelization [6, 26]. Conclusion For optimal management and risk of mood stabilizers, careful inquiry into drug intake is recommended, especially in cases of SJS/TEN. Recent studies have investigated the role of genetic factors in the development of antiepileptic druginduced cutaneous reactions, as well as the relationship such factors have with carbamazepine and valproate-induced liver toxicity, vigabatrininduced visual field defects, and antiepileptic drug-induced teratogenicity. The greatest progress has involved an improved definition of the role of human leukocyte antigen-related genes as predictors of the risk of serious antiepileptic drug-induced cutaneous reactions. This has led to the recommendation that patients of Asian ancestry be tested for the HLA-B*1502 allele, to identify those with high risk of developing SJS/TEN after administration of carbamazepine and, possibly, phenytoin and other antiepileptic drugs [27]. Advanced human leukocyte antigen-related gene study and future prospective screening may help prevent mood stabilizer-induced SJS/TEN. References 1. 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: Ghislain PD, Roujeau JC: Treatment of severe drug reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis and hypersensitivity syndrome. Dermatol Online J. 2002; 8: Howard GM: The Stevens-Johnson syndrome, ocular prognosis, and treatment. Am J Ophthalmol 1963; 55: Boe J, Dalgaard JB, Scott D: Mucocutaneous-ocular syndrome with intestinal involvement. Am J Med 1958; 25: Wolf R, Wolf D, Davidovici B: In the pursuit of classifying severe cutaneous adverse reactions. Clin Dermatol 2007; 25: Khalili B, Bahna SL: Pathogenesis and recent therapeutic trends in Stevens-Johnson syndrome and toxic epidermal necrolysis. Ann Allergy Asthma Immunol 2006; 97: Tennis P, Stern RS: Risk of serious cutaneous disorders after initiation of use of phenytoin, carbamazepine, or sodium valproate: a record linkage study. Neurology 1997; 49: Chung WH, Hung SI, Hong HS, et al.: Medical genetics: a marker for Stevens-Johnson syndrome. Nature 2004; 428: Hung SI, Chung WH, Jee SH, et al.: Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics 2006; 16: Ferrell PB Jr., McLeod HL: Carbamazepine, HLA- B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics 2008; 9: Gau SS, Chao PF, Lin YJ, Chang CJ, Gau CS: The association between carbamazepine and valproate and adverse cutaneous drug reactions in patients with bipolar disorder: a nested matched case-control study. J Clin Psychopharmacol 2008; 28: Arif H, Buchsbaum R, Weintraub D: Comparison and predictors of rash associated with 15 antiepileptic drugs. Neurology 2007; 68: Shen YC, Chen SJ, Lin CC, Chen CH: Concomitant use of lamotrigine and aripiprazole increases risk of Stevens-Johnson syndrome? Int Clin Psychopharmacol 2007; 22: Famularo G, De Simone C, Minisola G: Stevens- Johnson syndrome associated with single high dose of lamotrigine in a patient taking valproate. Dermatol

5 144 Risk and Management of SJS/TEN Online J 2005; 11: Yalcin B, Karaduman A: Stevens-Johnson syndrome associated with concomitant use of lamotrigine and valproic acid. J Am Acad Dermatol 2000; 43: Mockenhaupt M, Messenheimer J, Tennis P, Schlingmann J: Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptics. Neurology 2005; 64: Aiken CB, Orr C: Rechallenge with lamotrigine after a rash: a prospective case series and review of the literature. Psychiatry (Edgemont) 2010; 7: Petter G, Haustein UF: Stevens-Johnson syndrome with transition to toxic epidermal necrolysis after carbamazepine administration, heroin and alcohol abuse. Hautarzt 1999; 50: Garcia-Doval I, LeCleach L, Bocquet H, Otero XL, Roujeau JC: Toxic epidermal necrolysis and Stevens- Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol 2000; 136: Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P: SCORTEN: a severityof-illness score for toxic epidermal necrolysis. J Invest Dermatol 2000; 115: Cheriyan S, Patterson R, Greenberger PA, Grammer LC, Latall J: The outcome of Stevens-Johnson syndrome treated with corticosteroids. Allergy Proc 1995; 16: Paquet P, Kaveri S, Jacob E, et al.: Skin immunoglobulin deposition following intravenous immunoglobulin therapy in toxic epidermal necrolysis. Exp Dermatol 2006; 15: Yeung CK, Lam LK, Chan HH: The timing of intravenous immunoglobulin therapy in Stevens-Johnson syndrome and toxic epidermal necrolysis. Clin Exp Dermatol 2005; 30: Teo L, Tay YK, Liu TT, Kwok C: Stevens-Johnson syndrome and toxic epidermal necrolysis: efficacy of intravenous immunoglobulin and a review of treatment options. Singapore Med J 2009; 50: Hunger RE, Hunziker T, Buettiker U, Braathen LR, Yawalkar N: Rapid resolution of toxic epidermal necrolysis with anti-tnf-alpha treatment. J Allergy Clin Immunol 2005; 116: Arevalo JM, Lorente JA, Gonzalez-Herrada C, Jimenez-Reyes J: Treatment of toxic epidermal necrolysis with cyclosporin A. J Trauma 2000; 48: Franciotta D, Kwan P, Perucca E: Genetic basis for idiosyncratic reactions to antiepileptic drugs. Curr Opin Neurol 2009; 22: