Stevens-Johnson Syndrome Cases Research Articles

Coronavirus-disease-2019-associated Stevens–Johnsons syndrome in a 15-year-old boy: a case report and review of the literature

BackgroundStevens–Johnson syndrome (SJS) is a life-threatening condition characterized by high fever and severe mucocutaneous lesions, often triggered by drugs or infection. During the coronavirus disease 2019 pandemic, there was a marked increase in Stevens–Johnson syndrome cases, but relatively few cases were reported in children. The present article reports a pediatric case of Stevens–Johnson syndrome due to coronavirus disease 2019 infection and provides a review of the most relevant literature.Case presentationA previously healthy 15-year-old Han Chinese boy from China presented to the hospital with oral ulcers, conjunctival hyperemia, and widespread maculopapular rash. He had a history of fever 9 days prior and tested positive for coronavirus disease 2019 infection. Upon admission, his rash and mucosal lesions worsened, with the development of blisters on the fingertips of both hands, ocular pain, photophobia, and erosive lesions on the genital mucosa with exudation. He was diagnosed with Stevens–Johnson syndrome and received treatment with methylprednisolone, intravenous immunoglobulin, and dermatological and mucosal care. The patient’s condition was managed, and the dosage of high-dose intravenous methylprednisolone was tapered down, followed by a transition to oral prednisolone. He was discharged without sequelae.ConclusionWe should be aware that coronavirus disease 2019 infection is associated with the development of Stevens–Johnson syndrome in children and may lead to a wide spectrum of dermatologic presentations. Although Stevens–Johnson syndrome is a relatively rare condition, given its potentially serious consequences, it is crucial to identify it as early as possible and to take appropriate preventive and therapeutic measures to reduce complications and improve the quality of life for patients.

Severe Ocular Manifestations in Stevens-Johnson syndrome : a case report

Introduction : Stevens-Johnson syndrome (SJS) is a severe mucocutaneous reactions, characterized by cell death in the epidermis, resulting in blistering and sloughing. Hypersensitivity reaction to drug causes the majority of SJS cases. Ocular involvement occurs in 80% of patients in the acute phase.
 Case Illustration m A 38-year-old female was consulted to the ophthalmology department with diagnosis of Stevens- Johnson syndrome (SJS). She complained of bilateral eye redness and blurred vision. She was first admitted to the Emergency Department with complaints of burning sensation, progressive rash, and blistering skin all over her body for the past 2 weeks. Ophthalmology examination revealed a visual acuity of no-light perception (NLP) for both eyes. The anterior segment examination in both eyes showed the palpebra was edema and lagophthalmos, conjunctival hyperemia and corneal ulcer, while the posterior segment could not be identified. The patient was hospitalized in the intensive care unit (ICU) due to her symptoms and clinical findings. She was treated with combination of systemic intravenous antibiotics and steroid, eye drops and eye ointment. After 2 weeks, she was able to blink partially. She was discharged after 20 days of intensive treatment.
 Discussion : 
 Conclusion : Ocular manifestations in SJS are a significant aspect of the disease that can lead to severe visual impairment or even blindness. A multidisciplinary approach to managing SJS is necessary to prevent and treat the ocular manifestations of the disease effectively.

Investigation of Four Cases of Stevens-Johnson Syndrome among Participants in a Mass Drug Administration Campaign with Sulfadoxine-Pyrimethamine and Primaquine in Haiti, 2020.

In 2018, a mass drug administration (MDA) campaign for malaria elimination was piloted in Haiti. The pilot treated 36,338 people with sulfadoxine-pyrimethamine (SP) and primaquine; no severe adverse events were detected. In 2020, another MDA campaign using the same medications was implemented to mitigate an upsurge in malaria cases during the COVID-19 pandemic. Four cases of Stevens-Johnson syndrome (SJS) were identified among the 42,249 people who took the medications. Three of these individuals required hospitalization; all survived. In addition to SP ingestion, an investigation of potential causes for increased SJS cases identified that all four cases had human leukocyte antigens A*29 and/or B*44:03, another known risk factor for SJS. Additionally, three of the four case individuals had antibodies to SARS-CoV-2, and the fourth may have been exposed around the same time. These findings raise the possibility that recent SARS-CoV-2 infection may have contributed to the increased risk for SJS associated with SP exposure during the 2020 campaign.

Long-Term Benefits of Tear Exchangeable Limbal-Rigid Contact Lens Wear Therapy in Stevens-Johnson Syndrome Cases.

To evaluate the long-term benefits of tear-exchangeable, limbal-rigid contact lens (CL) wear therapy in patients with Stevens-Johnson syndrome (SJS)-associated ocular sequelae. This retrospective study evaluated 50 eyes of 41 SJS patients (15 men and 26 women) who underwent limbal-rigid CL wear therapy for more than 2 years post fitting. Ocular sequelae (i.e., conjunctival hyperemia, corneal neovascularization, and upper tarsus scarring) before fitting and at 3 months, 6 months, 12 months, and annually after initiating CL wear therapy were evaluated and then graded on a severity score (range: 0-3, maximum score: 3). Moreover, visual acuity (VA) at immediately post initiating CL wear therapy was evaluated. The mean follow-up period was 4.3±1.1 years. Compared with before fitting, the mean conjunctival hyperemia score improved from 1.14 to 0.86 at 3 months of CL wear therapy ( P <0.01) and was maintained thereafter; the mean corneal neovascularization score improved from 2.10 to 1.98 at 3 months of CL wear therapy, with no deterioration of the score observed in all cases at the final follow-up examination, and mean VA (log of minimum angle of resolution) improved from 1.60 to 1.04 at immediately post initiating CL wear therapy ( P <0.01). Limbal-rigid CL wear therapy can provide long-term ocular surface stabilization and improved VA in SJS patients.

Stevens-Johnson Syndrome Following Non-steroidal Anti-inflammatory Drugs: A Real-World Analysis of Post-marketing Surveillance Data.

Background:The Stevens-Johnson syndrome (SJS) is a severe skin reaction to non-steroidal anti-inflammatory drugs (NSAIDs), and can even be life-threatening. However, there are still few real-world studies to compare the specific differences in the adverse effects of skin and mucosal invasion.MethodsDisproportionality analysis and Bayesian analysis were devoted to data-mining of the suspected SJS after using NSAIDs based on the FDA's Adverse Event Reporting System (FAERS) from January 2004 to March 2021. The times to onset, fatality, and hospitalization rates of antipyretic analgesic-associated SJS were also investigated.ResultsA total of 1,868 reports of SJS adverse events were identified with NSAIDs. Among 5 NSAIDs monotherapies we studied (acetaminophen, ibuprofen, aspirin, diclofenac and celecoxib), ibuprofen had the highest association with SJS based on the highest reporting odds ratio (ROR = 7.06, 95% two-sided CI = 6.59–7.56), proportional reporting ratio (PRR = 6.98, χ2 = 4201.14) and empirical Bayes geometric mean (EBGM = 6.78, 95% one-sided CI = 6.40). However, ibuprofen-associated SJS had the lowest fatality rate (6.87%, p < 0.0001) and the highest hospitalization rate (79.27%, p < 0.0001). Celecoxib-associated SJS had the latest time to onset (317.56 days, p < 0.0001). Diclofenac-associated SJS cases appeared to be associated with the highest risk of death (25.00%, p < 0.0001).ConclusionsThe analysis of FAERS data provides a more accurate profile of the incidence and prognosis of SJS after NSAIDs treatment, enabling continued surveillance and timely intervention in patients at risk of SJS following these NSAIDs.

Stevens-Johnson Syndrome Following Vancomycin and Linezolid: A Real-World Analysis of Post-Marketing Surveillance Data.

Background: Stevens-Johnson syndrome (SJS) has been reported as a serious adverse effect in patients treated with vancomycin or linezolid, and there is currently a lack of real-world studies comparing specific differences in adverse effects of SJS. Methods: According to the FDA’s Adverse Event Reporting System (FAERS), from January 2004 to July 2021, the data of suspected SJS after the use of vancomycin and linezolid were analyzed by imbalance and Bayesian analysis. The onset time, fatality rate and hospitalization rate of vancomycin-associated SJS and linezolid-associated SJS were also investigated. Results: 276 cases of vancomycin-related SJS reports and 63 cases of linezolid-related SJS reports were identified. These two drugs are more common in middle-aged patients (45–64 years) than other age groups, and less common in underage children (<18). Among them, linezolid-related SJS is more common in middle-aged and elderly patients (45–74 years old) than other groups. Except for unspecified data, in vancomycin-associated SJS cases, there are more men than women (49.28% vs 43.84%), while in linezolid-associated SJS cases, the proportion of men and women is almost equal (44.44%). From the point of view of the areas where adverse reactions were reported, about 1/2 of the reports on Vancomycin-related SJS came from North America, and 1/3 of the reports came from Europe. The median onset time of Linezolid-related SJS was 5 days (interquartile range [IQR] 2–7.75), which was significantly earlier than that of Vancomycin-related SJS (12 days, IQR 4–20) (Mann-Whitney test, p < 0.0001). There were no significant differences in mortality and hospitalization rates after vancomycin and linezolid caused SJS. Conclusion: The analysis of faers data provides a comprehensive overview of the adverse reactions of SJS caused by the use of vancomycin and linezolid, and can warn clinical workers to timely intervene and continuously monitor the patients at risk of SJS when using such drugs.

Retrospective analysis of cases with Stevens-Johnson syndrome/toxic epidermal necrolysis: A case series of 20 patients

Background: Stevens-Johnson syndrome (SJS)/ toxic epidermal necrolysis (TEN) are rare, acute, severe cutaneous hypersensitivity reactions usually triggered by medications. They are classified by the extent of the detached skin surface area. Objective: We aimed to retrospectively evaluate the sociodemographic, clinical, therapeutic, and prognostic characteristics of SJS/TEN cases diagnosed between January 2015 and December 2020 in our centre. Materials and Methods: All the data regarding patient characteristics were obtained retrospectively. The SCORe of Toxic Epidermal Necrolysis (SCORTEN) was used to predict disease severity and mortality rates. Results: Out of 20 patients (14 females, 6 males), eight (40%) were evaluated as TEN, three (15%) as SJS/ TEN overlap, and nine (45%) as SJS. The mean age was 39.2 ± 27.92 years. A higher frequency of systemic antibiotic use was found in cases of SJS/TEN overlap or TEN compared to SJS cases during patients’ follow-up after the diagnosis (P = 0.006). The most common responsible drug was allopurinol (25%). While the estimated mortality in patients with SCORTEN values of 4 and 5 was 58.3% and 90.0%, the mortality observed in our cohort was 50% and 100%, respectively. In terms of complications, ocular problems were the most common ones. Ophthalmic sequelae were observed in 15 patients during the follow-up period, the most common belonging to the cornea. Conclusion: In conclusion, early diagnosis, immediate discontinuation of suspected drugs, and good clinical care are among the most crucial treatment steps in the treatment of SJS/TEN. In addition, multidisciplinary management of the disease is vital in preventing the development of long-term sequelae in survivors.

504 Mycoplasma pneumoniae-associated Stevens-Johnson syndrome; clinical and histological features

Mycoplasma pneumoniae (M. pneumoniae) induces various types of skin manifestations and potentially develop extensive mucous/eye lesion consistent with Stevens-Johnson syndrome(SJS). Specifically, in children cases with SJS, M.pneumoniae infection, as well as various drugs, is considered a major cause of SJS. M.pneumoniae-associated SJS cases often show only mucous/eye lesions without skin lesions, whereas typical drug-induced SJS cases show both skin lesions and mucosal lesions. In addition, palatal small vesicles are thought to be characteristic in M.pneumoniae-associated SJS. We aimed to investigate the clinical and histological findings of M.pneumoniae-associated SJS. Furthermore we performed M.pneumoniae staining in mucous lesions to detect M. pneumoniae-infected cells. The cases in our study (n=2) showed mucosal lesions and high fevers, which were suspected to be M.pneumonae-associated SJS. The patients had ocular lesions and severe mucous erosions including palatal small vesicles, however there were no skin lesions. Tests of serology and direct pathogen detection indicated M.pneumonae infection. Lip biopsies revealed sparse mucoepithelial necrotic cells in only basal cells and band-like inflammatory cell infiltrate in upper lamina propria mucosae. On the other hand, drug-induced SJS is widespread-epithelial cell necrosis through mucoepithelium. In M.pneumonae staining, there were positive cells in lamina propria mucosae, whereas there were no positive cells in mucoepithelium. From our study, M.pnumoniae-associated SJS is clearly distinguishable from drug-associated SJS in clinical manifestation and pathological findings. In addition, M.pneumonae infected cells in lamina propria mucosae might influence to basal layer cell death in M.pnumoniae-associated SJS.

Ocular surface cytokine profile in chronic Stevens-Johnson syndrome and its response to mucous membrane grafting for lid margin keratinisation

BackgroundTo study the tear cytokine and the conjunctival and oral mucosal marker profile in chronic ocular Stevens-Johnson syndrome (SJS) and their alteration following mucous membrane grafting (MMG) for lid margin...

Outbreak of Mycoplasma pneumoniae-Associated Stevens-Johnson Syndrome.

Stevens-Johnson syndrome (SJS) is an uncommon, sporadic disease and outbreaks are rare. In November 2013, an outbreak of SJS was identified at Children's Hospital Colorado. Outbreak cases were children aged 5-21 with a discharge diagnosis of SJS admitted from September 1 to November 30, 2013. Medical charts were reviewed using standardized data collection forms. Respiratory specimens were tested for viruses and Mycoplasma pneumoniae (Mp) by polymerase chain reaction (PCR). We conducted a separate 4-year retrospective case-control study comparing hospitalized SJS cases with and without evidence of Mp infection. During the outbreak, 8 children met SJS criteria. Median age was 11.5 years (range 8-16 years); 5 (63%) were boys and 5 (63%) were Mp-PCR-positive. Of the 5 PCR-positive children, none had preceding medication exposure, and all had radiographic pneumonia. All outbreak Mp isolates were macrolide susceptible. The retrospective case-control analysis showed that Mp-associated SJS episodes (n = 17) were more likely to have pneumonia (odds ratio [OR] 7.5, confidence interval [CI] 1.6–35.1), preceding respiratory symptoms (OR 30.0, CI 3.3–269.4) [corrected] an erythrocyte sedimentation rate ≥35 mg/dL (OR 22.8, CI 2.1-244.9), and ≤3 affected skin sites (OR 4.5, CI 1.2-17.4) than non-Mp-associated SJS episodes (n = 23). We report the largest outbreak of SJS in children, which was also predominately associated with Mp infection. Mp-associated SJS was associated with a distinct clinical presentation that included less extensive skin disease, an elevated erythrocyte sedimentation rate, and evidence of a preceding respiratory infection.

Predictive Factors Associated With Acute Ocular Involvement in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

To suggest an objective score for grading the acute ocular severity of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and to determine predictive factors for severe acute ocular involvement such as ocular surface epithelial defect and/or pseudomembrane formation. Retrospective cohort study. The medical records of SJS (n = 87) and TEN (n = 48) patients between 2005 and 2007 were reviewed. An acute ocular severity score was determined on a scale from 0 to 3 (none, mild, severe, and very severe) according to the existence of hyperemia, corneal or conjunctival epithelial defect, and pseudomembrane formation. The associations between the severe acute ocular involvement and factors such as patient age, exposed drugs, systemic severity, and the prevalence of ocular sequelae were examined. The number of cases with score grade 0, 1, 2, and 3 was 19 (21.8%), 31 (35.6%), 22 (25.3%), and 15 (17.2%) in 87 SJS cases and 12 (25.0%), 11 (22.9%), 17 (35.4%), and 8 (16.7%) in 48 TEN cases. Multivariate logistic regression analysis revealed that patient age (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96-0.99; P = .007) and nonsteroidal anti-inflammatory drugs NSAIDs or cold remedies (OR, 2.58; 95% CI, 1.26-5.29; P = .010) were predictive factors for severe acute ocular involvement. The prevalence of visual disturbance and eye dryness increased according to the increase of acute ocular severity (P = .001 and P = .007 in SJS; P = .007 and P = .014 in TEN, respectively). At the onset of SJS/TEN, strict attention should be paid to ocular involvement in young patients and in patients exposed to NSAIDs or cold remedies.

Exome sequencing pilot study in children with carbamazepine‐induced serious skin reactions

Stevens-Johnson syndrome (SJS) and drug-induced hypersensitivity syndrome (HSS, also known as DRESS) are life-threatening drug hypersensitivity reactions. Previous studies on genetic predictors for SJS and HSS were focused on immune-related genes and on known, frequent polymorphisms in the genome. For the anticonvulsant carbamazepine (CBZ), genetic markers for CBZ-induced SJS and HSS have been identified in the HLA region (HLA-B*15:02, HLA-A*31:01). However, many patients carriyng HLA-B*15:02 or HLA-A*31:01 tolerate CBZ, resulting in a low positive predictive value of a predictive test based on these genetic markers alone. In this pilot study, we aimed to identify rare genetic variants potentially associated with CBZ-induced SJS and HSS using whole exome sequencing in seven children with CBZ-induced SJS and five children with CBZ-induced HSS. Whole exome sequencing was performed using Illumina TruSeq exome capture and sequencing technology. Paired-end sequence reads were aligned and variants within 150 bp of the 64 Mb target region were identified using Bowtie, BWA and GATK. DNA samples from 95 CBZ-tolerant Canadian children were pooled and sequenced to a median depth of 300-fold to estimate frequencies of sequence variants identified in the hypersensitivity cases. All study participants were recruited through the Canadian Pharmacogenomics Network for Drug Safety. Children with CBZ-induced SJS or HSS were of European, Asian and First Nations ancestry with three SJS cases of Asian origin carrying HLA-B*15:02 and two HSS patients of European and First Nations origin carrying HLA-A*31:01. No individual rare single nucleotide variant (SNV) was strongly overrepresented in the SJS or HSS cases either in combined or in hypersensitivity reaction-specific analyses. Gene-based analyses revealed several candidate genes with rare nonsynonymous SNVs observed in a majority of SJS or HSS cases, respectively, which require follow-up in additional patients. With a hypothesis-free, comprehensive genetic screening approach, we identified new candidate genes and variants potentially involved in the development of CBZ-induced SJS or HSS for further investigation. The identified genes and pathways may lead to novel hypotheses for the pathomechanisms of these serious dermatologic reactions, potentially opening up new possibilities for prevention and treatment strategies.

Developing a data mining approach to investigate association between physician prescription and patient outcome – A study on re-hospitalization in Stevens–Johnson Syndrome

Stevens–Johnson syndrome (SJS) is a potentially life-threatening skin reaction. Drugs are the major causes for cases of SJS. While treating patients with SJS, the first and most important step is to identify and discontinue any possible responsible drugs. However, potential drugs that may lead to SJS are many and encompass various therapeutic areas. Very few physicians are familiar with the potential risk of all these drugs. If properly treated, most SJS cases are expected to recover without much sequelae. All drugs that have been associated with SJS should be avoided in these patients to prevent recurrence. If the physicians fail to identify and discontinue the drugs causing SJS, or even adding new drugs related to SJS, the patient may get worse or SJS may recur. These conditions can cause SJS patients to be re-hospitalized. Currently the reasons for re-hospitalization of SJS patients in Taiwan are not known. This study uses Taiwan National Health Insurance Research Database to analyze the causes of re-hospitalization for cases of SJS. First, we classified prescription history of re-hospitalized patients through the rule-based classification method. Secondly, by using the basic prescription actions, we identified drug association patterns. Then, by employing A-priori algorithm, pairs of drugs with relatively higher frequency of appearance were identified and their degrees of association were measured by using selected symmetric and asymmetric association mining methods. Finally, by listing and ranking up these pairs of drugs according to the value of support based on their degrees of association, we provide prescribing physicians with possible means of increasing the awareness and reducing re-hospitalization of SJS patients.

Risk of nevirapine-associated Stevens-Johnson syndrome among HIV-infected pregnant women: The Medunsa National Pharmacovigilance Centre, 2007 - 2012

Stevens-Johnson syndrome (SJS) is an acute life-threatening condition often elicited by drugs. The government's indecisiveness in deciding to stop the use of nevirapine (NVP) in HIV-infected pregnant women owing to the increase of SJS among this population group in South Africa prompted this investigation. To investigate if pregnancy is a risk factor for SJS among HIV-infected women taking NVP-containing regimens and registered within the Medunsa National Pharmacovigilance Centre database. A matched case-control study with 5:1 matching was conducted. Women with SJS (cases) taking NVP-containing regimens were matched with women without SJS (controls) taking NVP-containing regimens. Controls were randomly selected and matched to cases by hospital, age, treatment duration and CD4 count. Conditional logistic regression was used to determine if pregnancy was a risk factor for SJS. Six SJS cases were identified and 30 controls selected. The median age of both cases and controls was 29 years and the average CD4 counts were 237 and 234 cells/microl respectively. Subjects were on NVP treatment for 18 - 31 days before the onset of SJS. Controls did not develop SJS after treatment of between 1 and 365 days. Pregnancy increased the chances of developing SJS 14-fold (OR 14.28, p = 0.006, 95% CI 1.54 - 131.82). NVP-containing ARV regimens taken during pregnancy increase the risk of developing SJS. Healthcare workers are advised to offer informed consent to patients and recommend effective contraception methods if NVP treatment is considered. In the light of our findings, further studies of the association between NVP, pregnancy and SJS are necessary before general conclusions can be reached.

Profile and Pattern of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in a General Hospital in Singapore: Treatment Outcomes

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but potentially life-threatening, reactions to medications. Both conditions have significant morbidity and mortality. The aim of this study was to document the epidemiological features, aetiologies, treatment and clinical outcomes of retrospectively reviewed data of all patients with SJS or TEN treated from January 2004 to November 2010 in a general hospital. There were 18 cases of SJS, seven cases of SJS/TEN overlap and three cases of TEN. Mean age was 50.6 years, with a range of 13-85 years. The male/female ratio was 1. Drugs accounted for 26 cases; one case was caused by Neisseria gonorrhoea infection. Anti-convulsants (35.7%) were the most common implicated drugs followed by antibiotics (28.5%), non-steroidal anti-inflammatory drugs (NSAIDS) (14.3%), allopurinol (7.1%) and traditional Chinese medication (7.1%). In seven cases, multiple drugs were implicated. Most SJS cases (88%) were treated with corticosteroids, of which 61% were given high-dose systemic corticosteroids. No infective complications were observed. Six out of the seven SJS/TEN overlap syndrome and all three TEN cases were given intravenous immunoglobulins. One patient with TEN died. In conclusion, anti-convulsants, especially carbamazepine, were the most frequently implicated drugs, followed by antibiotics and NSAIDS. High-dose corticosteroids were effective in SJS, whereas intra-venous immunoglobulin were useful in TEN and SJS/TEN overlap syndrome.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a setting of chemotherapy treatment: An assessment of FDA MedWatch database.

e19519 Background: The association of chemotherapy with potentially fatal adverse events such as SJS/TEN has not been systematically examined. Case reports in association with agents such as imatinib and docetaxel have been published in the literature. We applied data mining algorithms to assess the risk of SJS/TEN to chemotherapy. Methods: FDA Safety Information and Adverse Event Reporting Program MedWatch database was searched for cases of SJS and TEN reported in association with FDA-approved chemotherapy agents through December 2009. Proportional reporting ratios (PRR>2) and empirical Bayes geometric mean (EBGM>2) with a case count threshold ≥3 were considered signals of disproportionate reporting. Cases obtained by searching this database included those in which chemotherapeutic agents were used to treat cancer and non-cancer-related diseases. Results: Using our criteria for selection of cases, we have identified 252 TEN cases associated with 11 FDA-approved drugs. Similarly, 71 SJS cases in association with 4 FDA-approved chemotherapy agents were identified (Table). Conclusions: By identifying disproportionally reported agents we demonstrated that multiple chemotherapy agents may be associated with SJS/TEN. Although data mining may not be sufficient to establish causality, this method may serve as a supplemental tool to identify chemotherapy drugs that may warrant further investigation. Drugs Cases Signal n PRR 95% CI EBGM 95% CI SJS Bendamustine 8 6.67 3.34-13.28 5.54 2.33-10.85 Chlorambucil 10 2.66 1.43-4.93 2.21 1.16-3.92 Ibritumomab tiuxetan 17 4.64 2.48-7.65 3.52 1.88-6.03 Temozolomide 36 2.16 1.56-2.99 2.07 1.47-2.82 Total 71 TEN Bendamustine 5 9.53 3.97-23.32 7.21 2.39-16.38 Busulfan 17 3.85 2.39-6.18 3.29 2.00-5.245 Cytarabine 55 2.67 2.05-3.48 2.56 1.94-3.30 Chlorambucil 12 6.19 3.52-10.88 5.67 3.04-9.69 Dactinomycin 8 3.81 1.90-7.60 2.82 1.36-5.57 Fludarabine 40 3.62 2.65-4.93 3.37 2.44-4.56 Ibritumomab tiuxetan 4 2.96 1.11-7.86 1.93 0.69-4.52 Lomustine 14 17.17 10.23-28.79 14.81 7.49-24.27 Procarbazine 24 5.51 3.69-8.2 5.18 3.3-7.62 Thiotepa 8 4.84 2.42-9.66 3.38 1.59-6.81 Vincristine 65 2.12 1.65-2.7 2.06 1.6-2.6 Total 252

Endothelial cell apoptosis in severe drug-induced bullous eruptions

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are characterized by extensive keratinocyte apoptosis mediated by cytotoxic proteins. Similar features have been found in another severe dysimmune syndrome, allogeneic acute graft-versus-host disease, where endothelial cell apoptosis has been recently characterized. To determine whether endothelial cell apoptosis occurs in dermal vessels of TEN and SJS, and whether it is linked to expression of cytotoxic proteins. Skin biopsies of eight patients with severe drug-induced bullous eruptions (four TEN, four SJS), eight with drug-induced urticaria and eight healthy controls were compared. Blood vessel damage was studied by electron microscopy and quantified by CD31 immunostaining. Apoptotic cells, characterized by electron microscopy, were quantified on terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling assay. Immunohistochemistry was also used to characterize and quantify inflammatory cells and granzyme B, tumour necrosis factor (TNF)-alpha and Fas ligand (FasL) expression. Endothelial cell apoptosis was observed in all TEN and SJS cases: it occurred in 85% of the vessel sections. It occurred in one case of drug-induced urticaria, in 5% of vessel sections, but not in healthy controls. Numbers of CD68+ macrophages and CD8+ T lymphocytes were significantly higher in TEN and SJS compared with both other groups; granzyme B and TNF-alpha but not FasL were expressed. Characterization of endothelial cell apoptosis in TEN and SJS is important to assess a factor worsening skin damage, with possible extension to other organs. It may also be useful for the development of novel therapeutic strategies.

Lamotrigine-induced severe cutaneous adverse reactions.

We systematically reviewed and analyzed published and unpublished cases of Stevens-Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN) associated with lamotrigine (LTG) therapy to identify characteristics of these reactions. We performed a MEDLINE search (January 1985 to April 1998) and citation tracking for published reports. In addition, reports were requested from the Uppsala Monitoring Centre of the World Health Organization (WHO). Published and WHO cases of LTG-associated SJS or TEN were included if the causal relationship was assessed as either possible, probable, or definite. We identified a total of 57 cases (43 cases of SJS, 14 cases of TEN), of which 13 (23%) were published. Cases in the SJS group were significantly younger than in the TEN group (21 years vs. 31 years). The median time to onset (17 days for SJS and TEN) and the median dosage at onset (50 mg vs. 87.5 mg) for SJS and TEN did not differ significantly. Concomitant use of valproate (VPA) was reported in 74% of the SJS cases and 64% of the TEN cases. In three cases, TEN was the cutaneous manifestation of the antiepileptic drug hypersensitivity syndrome (AHS). The main features of severe cutaneous drug reactions, such as dosage, onset, and concomitant VPA use, do not differ in patients with LTG-induced SJS or TEN. SJS or TEN may also be the cutaneous manifestations of LTG-induced AHS. Further epidemiologic studies are needed to identify the incidence of severe LTG-induced cutaneous adverse reactions and the relative risk compared with other AEDs.