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Toxic epidermal necrolysis/Stevens-Johnson syndrome overlap syndrome. A 14-month-old girl was presented with TEN/SJS overlap syndrome after 20 days of initiation of phenobarbital for complex febrile convulsion (a). She was treated with 3 days of IVIG in addition to supportive care (b).
Source publication
Background:
Different epidemiologic aspects of drug-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in children are scarce.
Aim:
To compare the clinical and epidemiological features of patients with drug-induced SJS and TEN in children and adults.
Method:
This retrospective study was conducted at two academic referr...
Similar publications
Objective
To summarise the clinical characteristics of patients with Stevens–Johnson syndrome/toxic epidermal necrolysis syndrome (SJS/TEN) and analyse the efficacy and safety of systemic glucocorticoid therapy.
Methods
This study was a retrospective study of 56 patients with SJS/TEN who had been systematically treated with glucocorticoids in the...
Citations
... The comparison of the structure of suspected drugs in the pediatric and general populations revealed the dramatic predominance of N group drugs (36.1% vs. 28.8% in general population), with antiepileptics accounting for up to 26.9% of the total drugs involved in SJS and TEN in children. Our results are in line with the published data: antiepileptics were the main culprit drugs, reported in 45.2% of the cases of SJS and TEN in the pediatric population analyzed in Iran (retrospective study of patients' data from two hospitals for 5 year period) [54]. The identification of pediatric patients with SJS and TEN at the Shriner's Burn Hospital in Galveston, Texas, USA (period from 1990 to 2015) revealed phenytoin and lamotrigine used concomitantly with valproic acid among the most common culprit drugs, and antiepileptics approved after 1990 (lamotrigine, clobazam, and zonisamide) were the cause in 25.5% of the cases [55]. ...
(1) Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are extremely severe cutaneous adverse drug reactions which are relatively rare in routine clinical practice. An analysis of a national pharmacovigilance database may be the most effective method of obtaining information on SJS and TEN. (2) Methods: Design—a retrospective descriptive pharmacoepidemiologic study of spontaneous reports (SRs) with data on SJS and TEN retrieved from the Russian National Pharmacovigilance database for the period from 1 April 2019 to 31 December 2023. Descriptive statistics was used to assess the demographic data of patients and the structure of suspected drugs. (3) Results: A total of 170 SRs on SJS and TEN were identified, of which 32.9% were SJS and 67.1%—TEN. In total, 30% were pediatric SRs, 21.2%—SRs of the elderly. There were 12 lethal cases, and all cases were TEN. The leading culprit drugs were anti-infectives for systemic use and nervous system agents. The top 10 involved drugs are as follows: lamotrigine (23.5%), ibuprofen (12.9%), ceftriaxone (8.8%), amoxicillin and amoxicillin with beta-lactam inhibitors (8.8%), paracetamol (7.6%), carbamazepine (5.9%), azithromycin (4.1%), valproic acid (4.1%), omeprazole (3.5%), and levetiracetam (3.5%). (4) Conclusions: Our study was the first study in Russia aimed at the assessment of the structure of the drugs involved in SJS and TEN on the national level.
... Another study by our team showed that phenobarbital was the most frequent cause of SJS/TEN in children with epilepsy. 16 Similar to previous studies on DHRs, 17 most of the affected children in our study were males. The study by Oh et al. on Korean pediatric patients revealed that about 70% of children with SCARs were boys. ...
... This agrees with the previous studies. [15][16][17][18][19]25,26 According to a French systematic review of 49 pediatric patients with DRESS, lymphadenopathy was the third most common manifestation observed in nearly 70% of cases. 25 In our study, the highest rate of abnormal peripheral blood smear (PBS) was observed in children with DRESS. ...
There are limited data on severe cutaneous adverse reactions (SCARs) associated with antiepileptic medications. The current study aims to investigate the clinical and epidemiological characteristics of antiepileptic medication-induced SCARs in hospitalized children. This five-year retrospective study was conducted at Isfahan University of Medical Sciences, Iran. The study included all children with a diagnosis of SCARs secondary to antiepileptic medications as defined by the World Health Organization (WHO). In our study SCARs were categorized into three groups: drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and a group with symptoms overlapping between maculopapular eruptions (MPE) and DRESS. Among 259 children with SCARs induced by antiepileptic medications, 199 (76.83%), 42 (16.22%), and 18 (6.95%) had overlapping MPE/DRESS, DRESS, and SJS/TEN, respectively. Phenobarbital was the most common offending drug among SCARs. The multinomial logistic regression model revealed that lymphadenopathy increased DRESS occurrence by 35 times compared to overlapping MPE/DRESS. Girls were at risk of SJS/TEN approximately 6 times more than boys. Age, weight, and mucosal involvement affected hospitalization duration in children with SCARs related to antiepileptic medication. There are some similarities and differences in the clinical and epidemiological features of Iranian children suffering from antiepileptic medication-induced SCARs.
... Levetiracetam was also consistently found to induce severe cADRs, specifically SJS [20][21][22][23][24], with more than 90% of SJS developing within the first 2-4 months of antiepileptic drug use [19,25]. HLA-B*15: 02 and HLA-A*31: 01 and carbamazepine associations were found in Han Chinese and Thai populations and Europeans, respectively but no HLA allele susceptibility has been reported to date [15]. ...
Patient: Male, 51-year-old
Final Diagnosis: Stevens-Johnson syndrome
Symptoms: Cutaneous adverse drug reactions namely Stevens-Johnson syndrome
Clinical Procedure: Punch biopsy of the skin
Specialty: General and Internal Medicine
Objective
Unusual clinical course
Background
Trimethoprim/sulfamethoxazole and levetiracetam are commonly prescribed medications in the treatment of infections and seizures, respectively. Despite their known efficacy, each has a reputation for triggering severe and sometimes life-threatening cutaneous adverse drug reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Although the mechanism of such cutaneous adverse drug reactions cannot be fully explained, it is thought to be a type IV T cell and NK cells-mediated hypersensitivity reaction that leads to keratinocyte apoptosis and epidermal necrosis. It is also thought that cutaneous adverse drug reactions are also linked to a patient’s genetic predispositions, especially the human leukocyte antigens profiles and the N-acetyl transferase 2 phenotypic variation.
Case Report
We describe a case of Stevens-Johnson syndrome in a severely ill 51-year-old man who was treated in an outside health care facility simultaneously with Trimethoprim/sulfamethoxazole and levetiracetam. The patient presented to our Emergency Department with Stevens-Johnson syndrome believed to possibly be related to the combination of these 2 agents.
Conclusions
The concomitant use of Trimethoprim/sulfamethoxazole and levetiracetam might have been responsible for heightening the potential of these 2 medications to trigger an unfortunate adverse drug reaction, but no formal culprit was able to be identified and no in vivo study was performed, due to ethical considerations. Thus, through this case report we strive to increase awareness of the potential risk of simultaneously prescribing these 2 medications.
... SJS is a disease known as a rare occurrence in the world (1-3 cases per 1 000 000 persons) [14] . Additionally, the frequency of pediatric SJS/TEN is very low, but a high rate of long-term complications appears in children with SJS/TEN [15] . Clinical manifestations of SJS/TEN are similar to SARS-CoV-2 infections, including mucosal damage and many dermatological complications including oral lesions [16,17] . ...
Introduction and importance
Symptoms similar to diseases such as Stevens–Johnson syndrome (SJS) and multisystemic inflammatory syndrome in children (MIS-C) were reported in pediatric coronavirus infections.
Case presentation
Here, we present a 4-year-old girl with coronavirus disease 2019 (COVID-19), an earlier diagnosis of SJS, and a final diagnosis of MIS-C.
Clinical discussion
Unlike the negative PCR test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the positive serological test confirmed COVID-19.
Conclusion
The monitoring of this case indicated that higher coronavirus infection can delay immune reaction and cause symptoms similar to SJS.
... TMP/SMX may induce maculopapular exanthems as the most common form of drug allergy with sulfonamides. However, they are an established cause of more severe reactions, including Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) [5,6]. It should be noted that drug hypersensitivity has been 100 times more common in those living with HIV [7]. ...
Drug-induced Stevens-Johnson syndrome (SJS) is a rare but life-threatening hypersensitivity reaction. Drug desensitization might be considered in drug-allergic patients with no therapeutic alternative. A 29-year-old man with a recent diagnosis of HIV and HBV (CD4 count: 4 cells/mm3) who has been receiving Trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis pneumonia (PCP) prophylaxis was admitted at Imam Khomeini hospital complex affiliated to Tehran University of Medical Sciences, with the diagnosis of SJS due to TMP/SMX. After 45 days of supportive care, the patient was a candidate for TMP/SMX desensitization due to our region's unavailability of alternative agents. A 9-day desensitization protocol was used, but the patient complained about diarrhea with severe pain in the rectal mucosa, and macules developed over his lips again on the third day. As a result, the desensitization process immediately stopped, and after the signs and symptoms were resolved, the patient was discharged with Clindamycin tablet 600 mg TDS. Unfortunately, two weeks after discharge, the patient experienced acute kidney injury (AKI) and expired after two dialysis sessions.
The treatment of epidermal necrolysis in pediatric patients remains a major challenge. Cyclosporine A has emerged as a promising therapy for epidermal necrolysis in adults; however, its efficacy in children is unclear. We present the case of a boy with Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome who was initially resistant to methylprednisolone monotherapy but improved after receiving the combination of cyclosporine A and methylprednisolone. Published reports on the use of cyclosporine A for pediatric epidermal necrolysis are also briefly reviewed.
Purpose of review:
The concept of Stevens-Johnson syndrome (SJS) in children is evolving. This manuscript reviews recent advances with the lens of new terminology namely infection-triggered reactive infectious mucocutaneous eruption and drug-induced epidermal necrolysis, with the objective of integrating this novel terminology practically.
Recent findings:
Traditionally considered to exist on a spectrum with toxic epidermal necrolysis, SJS in children is more often caused or triggered by infections instead of medications. Proposed pediatric-specific terminology can be applied to literature to gain further insights into blistering severe cutaneous adverse reactions.
Summary:
Distinguishing infection-triggered from drug-triggered blistering reactions is useful for 3 main reasons: (1) early clinically recognizable different features such as isolated or predominant mucositis, (2) different initial management depending on trigger, (3) avoiding the label of a drug reaction on cases triggered by infection.
Aggregated risk of carbamazepine (CBZ)‐induced cutaneous adverse drug reactions (cADRs) with different HLA variants are unclear and limited in terms of the power of studies. This study aimed to assess the aggregated risk of CBZ‐induced cADRs associated with carrying the following HLA variants: HLA‐B*15:02, HLA‐B*15:11, HLA‐B*15:21, HLA‐B*38:02, HLA‐B*40:01, HLA‐B*46:01, HLA‐B*58:01, HLA‐A*24:02, and HLA‐A*31:01. Literature was searched in different databases following PRISMA guidelines. The outcomes were measured as odds ratio (OR) using RevMan software by a random/fixed effects model, where p < 0.05 was set as statistical significance. In total, 46 case–control studies met the inclusion criteria and were included in this analysis consisting of 1817 cases and 6614 controls. It was found that case‐patients who carried the HLA‐B*15:02 allele were associated with a significantly increased risk of CBZ‐induced Stevens−Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) compared to controls (OR 26.01; 95% CI 15.88–42.60; p < 0.00001). The aggregated risk of cADRs was slightly higher in Asian compared to Caucasian patients (Asians: OR 14.84; 95% CI 8.95–24.61; p < 0.00001; Caucasians: OR 11.65; 95% CI 1.68–80.70; p = 0.01). Further, HLA‐B*15:11, HLA‐B*15:21, or HLA‐A*31:01 allele was also associated with significantly increased risk of CBZ‐induced cADRs (HLA‐B*15:11: OR 6.08; 95% CI 2.28–16.23; p = 0.0003; HLA‐B*15:21: OR 5.37; 95% CI 2.02–14.28; p = 0.0008; HLA‐A*31:01: OR 5.92; 95% CI 4.35–8.05; p < 0.00001). Other HLA variants were not found to have any significant associations with CBZ‐induced cADRs. Strong associations between the HLA‐B*15:02, HLA‐B*15:11, HLA‐B*15:21, or HLA‐A*31:01 allele with CBZ‐induced cADRs have been established in this analysis. Pharmacogenetic testing of particular HLA alleles before initiation of CBZ therapy may be beneficial to patients and may help to eradicate cADRs substantially.
