|Year : 2022 | Volume
| Issue : 3 | Page : 285-287
Oxcarbazepine-induced stevens johnson syndrome and toxic epidermal necrolysis overlap
Sangha Mitra Godi, Neethu K Nandan, Puneet Kumar Soni
Department of Psychiatry, AIIMS, Raipur, Chhattisgarh, India
|Date of Submission||01-Jun-2021|
|Date of Decision||20-Jun-2021|
|Date of Acceptance||27-Jun-2021|
|Date of Web Publication||31-Oct-2022|
Dr. Puneet Kumar Soni
Department of Psychiatry, AIIMS, Raipur, Chhattisgarh
Source of Support: None, Conflict of Interest: None
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 10];6:285-7. Available from: https://www.anip.co.in/text.asp?2022/6/3/285/360081
| Introduction|| |
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. 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. 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.
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. 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.,,,, Most of ADRs are underreported, thus resulting in no evaluation of the expectedness, severity, and causality of these reactions. 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|| |
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 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. 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. The WHO-UMC criteria for causality revealed this ADR as being probable/likely due to OXC intake. 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).
| Discussion|| |
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. 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. 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. The activated antigen-driven CD8+ T-cells in the epidermis produce cytolytic peptides such as granulysin, a cytolytic peptide that leads to keratinocyte death., 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.
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. 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.
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[Figure 1], [Figure 2], [Figure 3]