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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 10  |  Issue : 2  |  Page : 115-117

Stevens–Johnson syndrome/toxic epidermal necrolysis overlap syndrome due to oral phenytoin


1 Department of Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
2 Dermatology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
3 Adverse Drug Reaction Monitoring Centre, Pharmacovigilance Programme of India, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Date of Submission28-Sep-2018
Date of Decision07-Jan-2019
Date of Acceptance02-May-2019
Date of Web Publication17-Jul-2021

Correspondence Address:
Alladi Mohan
Professor (Senior Grade) and Head, Department of Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati 517 507, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCSR.JCSR_15_18

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  Abstract 


Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but lethal manifestation of hypersensitivity reaction precipitated by certain drugs and viral infections. Among the drugs, it is more common with antibiotics, antiepileptics and nonsteroidal anti-inflammatory drugs. We report the case of a 14-year-old male who presented to the medicine out-patient department with a history of fever since the previous day. Four days before this, he had developed an episode of generalised tonic–clonic seizures and was initiated on oral phenytoin since then. Following admission to the medical intensive care unit, fever persisted on the 2nd day as well. The patient developed a maculopapular rash over face and trunk, ulceration over lips and skin peeling involving >10% <30% body surface area suggestive of SJS/TEN overlap syndrome. Oral phenytoin was stopped, and he was started on oral levetiracetam. He was treated with intravenous corticosteroids, topical antibiotics and symptomatic management. The patient recovered, skin lesions subsided and he discharged in a stable condition after 2 weeks of in-hospital stay. The present case documents the rare occurrence of SJS/TEN overlap syndrome as an adverse drug reaction caused by phenytoin. Early identification and stopping of offending drug will aid in better management of the patient.

Keywords: Phenytoin, Stevens–Johnson syndrome, toxic epidermal necrolysis


How to cite this article:
Harikrishna J, Pradeep V, Reddy V D, Kumar M K, Surekha A, Surya Durga Devi PS, Mohan A. Stevens–Johnson syndrome/toxic epidermal necrolysis overlap syndrome due to oral phenytoin. J Clin Sci Res 2021;10:115-7

How to cite this URL:
Harikrishna J, Pradeep V, Reddy V D, Kumar M K, Surekha A, Surya Durga Devi PS, Mohan A. Stevens–Johnson syndrome/toxic epidermal necrolysis overlap syndrome due to oral phenytoin. J Clin Sci Res [serial online] 2021 [cited 2021 Aug 3];10:115-7. Available from: https://www.jcsr.co.in/text.asp?2021/10/2/115/321696




  Introduction Top


Adverse drug reactions (ADR) constitute an important cause of in-hospital morbidity and mortality accounting for 6% of total hospital admissions.[1] They may vary from mild cutaneous drug reactions to life-threatening reactions such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The SJS and TEN are two variants of the same condition varying only in the percentage of body surface area involvement.[2] These reactions are characterised by maculopapular rash along with ulceration of mucocutaneous regions, ultimately leading to multi-organ failure and death.[3] The most common complication and the major contributor towards mortality in SJS/TEN is sepsis syndrome.[4] In this report, we document the occurrence of SJS/TEN overlap syndrome due to oral phenytoin usage.


  Case Report Top


A 14-year-old male patient presented to the medicine out-patient department at our tertiary care teaching hospital with a history of fever since the preceding day. Four days prior to this, he had developed an episode of generalised tonic–clonic seizures and was prescribed oral phenytoin (200 mg/day) by the treating doctor at his place of domicile. On general physical examination, he was looking sick, febrile (temperature 100.6°F); bilateral conjunctival congestion was evident. He was admitted to the medical intensive care unit for further management.

In this scenario of an episode of generalised tonic–clonic seizures followed by onset of fever, differential diagnosis included viral fever, including swine flu (influenza A [H1N1 pdm09]), scrub typhus, leptospirosis, malaria, drug-induced fever and among others. Nasopharyngeal swab tested negative for H1N1 pdm09. Peripheral blood smear for malarial parasite, serological testing for scrub typhus, leptospirosis, non-contrast computed tomography and magnetic resonance imaging of the head was normal.

On the next day, fever persisted. Further, he developed a diffuse erythematous rash on face and trunk with macular lesions [Figure 1]a, mucocutaneous ulcers over lips [Figure 1]b and skin peeling involving >10%–<30% body surface area suggestive of SJS/TEN overlap syndrome.[5] TEN specific severity of illness score (SCORTEN) on day 2 was 3 (indicating 58% mortality).[6] Oral phenytoin was stopped, and he was started on oral levetiracetam (500 mg bid). Dermatology consultation was sought. He was started on topical and oral antihistaminics and other conservative measures. However, as they were no significant improvement with above measures even after 48 h, he was started on intravenous corticosteroids. In the subsequent 2 days, the maculopapular rash subsided, ulcers over lips healed and the patient became afebrile. He was discharged in a stable condition after 2 weeks of in-hospital stay. He was instructed to return for follow-up after 1 week. On follow-up at 1 week [Figure 2], he was doing well.
Figure 1: Clinical photograph showing maculopapular rash with target such as lesions involving face, trunk and ulceration of the surface of lips with haemorrhagic crusting (a). Conjunctival congestion is also evident (b)

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Figure 2: Clinical photograph of the same patient at 1-week follow-up after discharge showing significant resolution or lesions over the trunk (a) and improvement in ocular involvement (b)

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  Discussion Top


SJS and TEN are lethal manifestations of Type IV hypersensitivity reaction with an overall incidence of 1–2/million/year in the United States.[3] Granulysin, a cytolytic and pro-inflammatory marker secreted by cytotoxic T cells and natural killer cells, is thought to be the key mediator for disseminated keratinocyte death, as its serum levels are high in patients with SJS/TEN.[7] SJS has a mortality rate of 1%–5%, and when TEN also occurs, mortality increases to 25%–35%.[2] Among antiepileptics carbamazepine and phenytoin are the most often implicated drugs causing SJS in the Asian population.[8] The maximum risk of SJS occurs within the first 2 months of therapy with phenytoin.[9] In the present case, SJS occurred within 5 days of therapy with phenytoin.

Sometimes, patients with SJS/TEN present with fever[10] followed by mucocutaneous involvement as it occurred in the present case. Early sites of cutaneous involvement include presternal area of trunk and face; a maculopapular rash is usually evident. The involvement of oral, genital and ocular mucosa in the form of erythema and erosions occurs in more than 90% of patients, and in some cases, the respiratory and gastrointestinal tracts are also affected.[11] Ocular involvement ranges from acute conjunctivitis, erythema, eyelid oedema and ocular discharge, to conjunctival membrane or corneal erosion and in severe cases, to cicatrize lesions and corneal ulceration.[12] Other manifestations that have been rarely documented include glomerulonephritis and hepatocellular necrosis, cholestasis.[13]

The role of systemic corticosteroids remains controversial in the treatment of SJS/TEN.[14] However, our patient symptomatically improved following corticosteroid administration. The decision regarding the use of corticosteroids should be considered based on clinical response and possible adverse effects associated with their use on a case-to-case basis.

The present case highlights the importance of having a vigilant approach while prescribing anti-epileptics and further careful monitoring for any ADR during the follow-up. It also highlights the fact that in any case of SJS, early identification and stopping of offending drug will help in better management.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Svensson CK, Cowen EW, Gaspari AA. Cutaneous drug reactions. Pharmacol Rev 2001;53:357-79.  Back to cited text no. 1
    
2.
Sun J, Liu J, Gong QL, Ding GZ, Ma LW, Zhang LC, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: A multi-aspect comparative 7-year study from the people's republic of China. Drug Des Devel Ther 2014;8:2539-47.  Back to cited text no. 2
    
3.
Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis 2010;5:39.  Back to cited text no. 3
    
4.
Chowdhury S, Podder I, Saha A, Bandyopadhyay D. Inpatient mortality resulting from dermatological disorders at a tertiary care center in Eastern India: A record-based observational study. Indian J Dermatol 2017;62:626-9.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol 1993;129:92-6.  Back to cited text no. 5
    
6.
Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P. SCORTEN: A severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol 2000;115:149-53.  Back to cited text no. 6
    
7.
Wong KC, Kennedy PJ, Lee S. Clinical manifestations and outcomes in 17 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis. Australas J Dermatol 1999;40:131-4.  Back to cited text no. 7
    
8.
Yang CY, Dao RL, Lee TJ, Lu CW, Yang CH, Hung SI, et al. Severe cutaneous adverse reactions to antiepileptic drugs in Asians. Neurology 2011;77:2025-33.  Back to cited text no. 8
    
9.
Patel PP, Gandhi AM, Desai CK, Desai MK, Dikshit RK. An analysis of drug induced Stevens-Johnson syndrome. Indian J Med Res 2012;136:1051-3.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
Paulmann M, Mockenhaupt M. Fever in Stevens-Johnson syndrome and toxic epidermal necrolysis in pediatric cases: Laboratory work-up and antibiotic therapy. Pediatr Infect Dis J 2017;36:513-5.  Back to cited text no. 10
    
11.
Lebargy F, Wolkenstein P, Gisselbrecht M, Lange F, Fleury-Feith J, Delclaux C, et al. Pulmonary complications in toxic epidermal necrolysis: A prospective clinical study. Intensive Care Med 1997;23:1237-44.  Back to cited text no. 11
    
12.
Chang YS, Huang FC, Tseng SH, Hsu CK, Ho CL, Sheu HM. Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis: Acute ocular manifestations, causes, and management. Cornea 2007;26:123-9.  Back to cited text no. 12
    
13.
Morelli MS, O'Brien FX. Stevens-Johnson syndrome and cholestatic hepatitis. Dig Dis Sci 2001;46:2385-8.  Back to cited text no. 13
    
14.
Law EH, Leung M. Corticosteroids in Stevens-Johnson syndrome/toxic epidermal necrolysis: Current evidence and implications for future research. Ann Pharmacother 2015;49:335-42.  Back to cited text no. 14
    


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