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Year : 2022  |  Volume : 6  |  Issue : 3  |  Page : 285-287

Oxcarbazepine-induced stevens johnson syndrome and toxic epidermal necrolysis overlap

Department of Psychiatry, AIIMS, Raipur, Chhattisgarh, India

Date of Submission01-Jun-2021
Date of Decision20-Jun-2021
Date of Acceptance27-Jun-2021
Date of Web Publication31-Oct-2022

Correspondence Address:
Dr. Puneet Kumar Soni
Department of Psychiatry, AIIMS, Raipur, Chhattisgarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aip.aip_68_21

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Drug-induced skin reactions are familiar with older epileptic drugs such as phenytoin, lamotrigine, and carbamazepine (CBZ); the newer antiepileptic drugs are less likely to cause. Oxcarbazepine (OXC), the successor of CBZ, has a better safety profile with respect to side effects and adverse drug reactions (ADRs). The StevensJohnson syndrome (SJS), an ADR, is less common with OXC, and there are few case reports in the literature. Here, we report a case of OXC-induced SJS/toxic epidermal necrolysis overlap in line with CARE guidelines.

Keywords: Adverse drug reaction, oxcarbazepine, skin reaction, Stevens–Johnson syndrome, toxic epidermal necrolysis

How to cite this article:
Godi SM, Nandan NK, Soni PK. Oxcarbazepine-induced stevens johnson syndrome and toxic epidermal necrolysis overlap. Ann Indian Psychiatry 2022;6:285-7

How to cite this URL:
Godi SM, Nandan NK, Soni PK. Oxcarbazepine-induced stevens johnson syndrome and toxic epidermal necrolysis overlap. Ann Indian Psychiatry [serial online] 2022 [cited 2022 Dec 4];6:285-7. Available from: https://www.anip.co.in/text.asp?2022/6/3/285/360081

  Introduction Top

Drug-induced cutaneous reactions can be mild or severe based on morbidity and mortality it possesses. While drug exanthem is the most common skin reaction to medications, it is not uncommon for serious cutaneous drug reactions to ensue.[1] StevenJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are idiosyncratic drug reactions, which are type IV hypersensitivity reactions triggered by drug antigens in keratinocytes that induce T-cell-mediated cytotoxic reaction.[2] SJS is characterized by skin lesions that can range from erythematous or purpuric papules to flaccid bullae and confluent erosions and can affect both mucosal and nonmucosal surfaces, predisposing the patient to superadded infections and toxic state. This potentially lethal drug reaction if involves >10% of body surface area (BSA) is called SJS syndrome while when involving more than 30% of BSA is called TEN.[3]

Sulfonamides, nonsteroidal anti-inflammatory drugs, anticonvulsants, and antibiotics are the commonly implicated drugs in SJS and TEN. And among antiepileptics, carbamazepine (CBZ) is one of the culpable agents implicated.[4] The 10-keto analog of CBZ, oxcarbazepine (OXC), has better safety profile compared to predecessor and hence preferred in elderly and children. The SJS, an adverse drug reaction (ADR), was found to be less common with OXC and there were only a few case reports in the literature.[1],[2],[5],[6],[7] Most of ADRs are underreported, thus resulting in no evaluation of the expectedness, severity, and causality of these reactions.[8] Thus, it is important to report such drug reactions as it will further help in estimating the incidence of OXC-induced SJS. Here, we report a case of OXC-induced SJS/TEN overlap.

  Case Report Top

A 76-year-old female was brought to the Emergency Department of AIIMS, with chief complaints of dusky red macules all over body, including perioral skin with erosion in buccal and palatal mucosa with white exudate and erosions on bilateral eyelids. She has had a history of insomnia and agitation 1 month back for which escitalopram, lorazepam, and amantadine were prescribed, which was taken for a week and was discontinued because of worsening of agitation, increased talkativeness, and psychomotor activity. And after 2 weeks, she was further taken to a private practitioner for the same symptoms and was prescribed OXC in 600 mg dosage, following which there was resolution of symptoms. Post 1 week of starting of the above medication, she developed mild fever and macular rash over trunk with perioral rashes. The next day, the patient's attendants noticed blister formation on sides of mouth and macular eruptions on thigh, spreading to all over body and face with redness of eyes and painful mouth ulcers with difficulty in eating food over the next 3 days, for which they discontinued the medication and visited the casualty and the patient was admitted. Dermatological examination revealed 20% BSA involvement with erosions in oral mucosa, bilateral eyelids, and back and confluent macular eruptions over trunk and thighs as shown in [Figure 1], [Figure 2], [Figure 3]. She had no history of any allergies, drug reactions. There was no associated swelling of the joints or any other tissue involvement. There was mild local raise of temperature with stable vitals and others systematic examinations were within the normal limits. There was no history of any recent use of cosmetic products or any local application of cream/lotions on face or food changes or any other medication. Laboratory investigations showed significantly anemia, increased erythrocyte sedimentation rate, raised blood glucose levels, neutrophilia, lymphocytopenia, normal liver function tests, and renal function tests but low serum sodium.
Figure 1: Erosions and crusting of bilateral eyelids and purulent discharge from eyes

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Figure 2: The erosions in perioral area with crusting extending to neck

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Figure 3: The red macules all over the trunk with sloughing and positive Nikolsky sign

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During the course in hospital, the patient was started on cyclosporin and tapering dose of dexamethasone. She had an episode of disorientation which was managed with low-dose haloperidol. She was given adequate antibiotic coverage with blood sugar and pain management. She responded well to treatment and was discharged on the 5th day of admission with dried erosions and healing lesions.

This case had a Naranjo score of +8 based on available clinical information that points toward probable ADRs, as we did not attempt to re-challenge with the OXC for any reappearance of the rash.[9] It was an ADR that required admission increasing length of stay in hospital with the treatment and stoppage of suspected drug as per the assessment with Hartwig's Severity Scale that revealed a level-4 severity.[10] The WHO-UMC criteria for causality revealed this ADR as being probable/likely due to OXC intake.[11] A SCORTEN scoring system for SJS/TEN predicts the prA “SCORTEN” scoring system for SJS/TEN, which predicts the probability of hospital mortality, was calculated within the first 24 hours of admission, and it revealed a score of 3 (age >40, epidermal detachment >10% at the time of admission, blood glucose >300 mg/dl).[12]

  Discussion Top

There are two types of ADR based on the expectedness of ADRs, Type A ADRs which are pharmacologically predictable and Type B ADRs which are idiosyncratic.[8] They are described and classified by the percentage of BSA involvement with <10% in SJS, 10%–30% in SJS/TEN overlap, and more than 30% in TEN.[12] This case with 10%–30% BSA involvement is an SJS/TEN overlap due to OXC and a Type B ADR and also defined as a severe cutaneous ADR. The pathophysiological mechanism behind SJS/TEN is conceptualized to be a Type IV hypersensitivity reaction due to binding of drug to major histocompatibility complex I that results in cytotoxic CD8+ T-cell-mediated destruction of lower layer epidermis.[13] The activated antigen-driven CD8+ T-cells in the epidermis produce cytolytic peptides such as granulysin, a cytolytic peptide that leads to keratinocyte death.[13],[14] There is a strong genetic association with HLA-B*1502 allele and CBZ SJS/TEN, which is widely seen in Southeast Asia population led to recommending the individuals of Asian ethnicity to be genotyped for the presence of the risk allele before receiving CBZ by the Food and Drug Administration. However, HLA-B*15:02 is less strongly associated with OXC SJS/TEN with a significantly lower positive predictive value of 0.73 and >5000 patients would need to be tested to prevent one case of SJS/TEN.[13]

There had been a lesser incidence of SJS reported with OXC, but there is reportedly more incidence of drug rashes and SJS in patients who are hypersensitive to CBZ pointing toward cross-sensitivity. This cross-sensitivity may be due to the dibenzazepine ring which is the common structure in CBZ and OXC.[15] In our patient, there was no previous recorded hypersensitivity to any drugs. Here, it is also interesting to note that our patient had SJS within 1 week of starting the incriminated drug which may be due to her older age.

In conclusion, SJS due to OXC is rare but still happens nevertheless. SJS being a life-threatening adverse effect, clinicians should be aware and vigilant about the same while starting a patient on OXC and should be prompt in withdrawing the agent at first sight of any cutaneous reaction. Patients should also be informed in detail about the same and encouraged to report back in case of adverse effects. Thus, studying and reporting of ADRs associated with any drug is also vital for estimating their incidence, expectedness, severity, morbidity, and mortality in clinical practice and further determining the predisposing risk factors.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Maitra A, Bhattacharyya S, Mukherjee S, Era N. A rare case of oxcarbazepine induced Stevens Johnson Syndrome: Toxic epidermal necrosis overlap. Int J Basic Clin Pharmacol 2017;6:466-8.  Back to cited text no. 1
Beken B, Can C, Örencik A, Can N, Yazıcıoğlu M. Oxcarbazepine-induced Stevens–Johnson syndrome: a pediatric case report. Oxf Med Case Reports. 2017;(6):79-81.  Back to cited text no. 2
Auquier-Dunant A, Mockenhaupt M, Naldi L, Correia O, Schröder W, Roujeau JC, et al. 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;138:1019-24.  Back to cited text no. 3
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;71:325-8.  Back to cited text no. 4
[PUBMED]  [Full text]  
Guleria VS, Sharda C, Rana T, Sood AK. Oxcarbazepine induced toxic epidermal necrolysis-A rare case report. Indian J Pharmacol 2015;47:459-61.  Back to cited text no. 5
[PUBMED]  [Full text]  
Lin LC, Lai PC, Yang SF, Yang RC. Oxcarbazepine-induced Stevens-Johnson syndrome: A case report. Kaohsiung J Med Sci 2009;25:82-6.  Back to cited text no. 6
Trivedi BS, Darji NH, Malhotra SD, Patel PR. Antiepileptic drugs-induced Stevens-Johnson syndrome: A case series. J Basic Clin Pharm 2016;8:42-4.  Back to cited text no. 7
Petrova G, Stoimenova A, Dimitrova M, Kamusheva M, Petrova D, Georgiev O. Assessment of the expectancy, seriousness and severity of adverse drug reactions reported for chronic obstructive pulmonary disease therapy. SAGE Open Med. 2017;5:1-8.  Back to cited text no. 8
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 9
Hartwig SC, Siegel J, Schneider PJ. Preventability and severity assessment in reporting adverse drug reactions. Am J Hosp Pharm 1992;49:2229-32.  Back to cited text no. 10
World Health Organization. The Use of the WHO-UMC System for Standardized Case Causality Assessment. Uppsala: The Uppsala Monitoring Centre; 2005.  Back to cited text no. 11
Dinulos JG, Habif TP. Hypersensitivity syndromes and vasculitis. In: Dinulos JG, editor. Habif's Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 7th ed., Ch. 18. Philadelphia: Elsevier; 2020. p. 713-47.  Back to cited text no. 12
Burks AW, Holgate ST, O'Hehir RE, Bacharier LB, Broide DH, Hershey GK, et al. Drug allergy. In: Solensky R, Phillips EJ, editors. Middleton's Allergy: Principles and Practice. 9th ed., Ch. 77. Amsterdam: Elsevier; 2020. p. 1261-82.  Back to cited text no. 13
Chung WH, Hung SI, Yang JY, Su SC, Huang SP, Wei CY, et al. Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis. Nat Med 2008;14:1343-50.  Back to cited text no. 14
Schmidt D, Elger CE. What is the evidence that oxcarbazepine and carbamazepine are distinctly different antiepileptic drugs? Epilepsy Behav 2004;5:627-35.  Back to cited text no. 15


  [Figure 1], [Figure 2], [Figure 3]


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