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The role of prior corticosteroid use on the clinical course of Stevens-Johnson syndrome and toxic epidermal necrolysis: A case-control analysis of patients selected from the multinational EuroSCAR and RegiSCAR studies
Abstract
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are immunologically mediated, severe cutaneous adverse reactions involving cytotoxic T cells, natural killer cells and various mediators. In large studies, up to 15% of SJS/TEN occurred in patients with chronic corticosteroid use. It is unclear if this prior exposure to corticosteroids modified the disease course.
To evaluate whether systemic corticosteroid usage prior to the onset of SJS/TEN modified the clinical course and outcome. If a disease-modifying effect is present, information from such an analysis may have implications on the therapeutic use of corticosteroids in SJS/TEN.
This is a case-control study based on data collected in the EuroSCAR and RegiSCAR studies. Ninety-two cases of SJS/TEN with exposure to corticosteroids prior to the onset of disease, and 321 randomly selected SJS/TEN patients without prior exposure were included. Primary outcomes included progression of disease, disease severity and mortality. A secondary analysis of latency between the beginning of drug use and the onset of disease, based on exposure to a single high-risk drug, was also performed.
On multivariate analysis, cases with prior exposure to corticosteroids had a longer progression of disease by 2·2 days [95% confidence interval (CI) 1·1-3·2]. The disease severity and mortality outcome were unaffected. In addition, there is evidence that corticosteroids delayed the onset of SJS/TEN in patients with exposure to high-risk drugs by 7·1 days (CI -0·2 to 14·5).
The prior use of corticosteroids prolonged the period of disease progression without influencing the disease severity or mortality. In addition, when SJS/TEN is preceded by use of a single high-risk drug, the latency between the drug intake and the onset of SJS/TEN may also be increased. These findings suggest that corticosteroids have a mild impact on the course of SJS/TEN, and further studies are required to clarify any potential therapeutic effects.
... 16 Later, a second case-control surveillance (EuroSCAR study, 1997(EuroSCAR study, -2001 was undertaken that could confirm results on drug risk of the previous study and provide new data on recently marketed drugs. [17][18][19][20] These studies were followed by a multinational registry (RegiSCAR study) that was founded to systematically collect biological samples of patients with SCAR and patients were followed longitudinally after hospital discharge. [20][21][22][23] These studies required that investigators establish and maintain a network of hospitals and departments likely to treat SCAR, determine precise definitions of clinical entities (phenotypes), and determine methods for systematic case ascertainment, standardized case validation, and data management and statistical analysis. ...
... [17][18][19][20] These studies were followed by a multinational registry (RegiSCAR study) that was founded to systematically collect biological samples of patients with SCAR and patients were followed longitudinally after hospital discharge. [20][21][22][23] These studies required that investigators establish and maintain a network of hospitals and departments likely to treat SCAR, determine precise definitions of clinical entities (phenotypes), and determine methods for systematic case ascertainment, standardized case validation, and data management and statistical analysis. Case ascertainment was done by trained investigators (health care professionals) using a standardized questionnaire in direct conversation with the patient and in cases of severe illness, the patient's relatives, treating physicians, family physician, and medical records. ...
... The RegiSCAR project is a registry of SCAR cases in several European and non-European countries that combines a protocol for systematic blood sampling and centralized biobanking of PBMCs, plasma, and DNA and cohort studies investigating outcome, sequelae, and treatment. 20,21 Earlier studies focused on SJS/TEN, whereas RegiSCAR includes a broader spectrum of reactions including drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, and generalized bullous fixed drug eruption (GBFDE). Continuous surveillance of SJS/TEN in this cohort shows that approximately 67% of strictly validated cases had a probable or very probable drug cause as determined by the algorithm for assessment of drug causality in epidermal necrolysis score (Table II ; M. Mockenhaupt, MD, unpublished data, March 2017), 20% were secondary to a possible drug cause, and 13% were unlikely or not at all drug-induced. ...
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening, immunologically mediated, and usually drug-induced disease with a high burden to individuals, their families, and society with an annual incidence of 1 to 5 per 1,000,000. To effect significant reduction in short- and long-term morbidity and mortality, and advance clinical care and research, coordination of multiple medical, surgical, behavioral, and basic scientific disciplines is required. On March 2, 2017, an investigator-driven meeting was held immediately before the American Academy of Dermatology Annual meeting for the central purpose of assembling, for the first time in the United States, clinicians and scientists from multiple disciplines involved in SJS/TEN clinical care and basic science research. As a product of this meeting, this article summarizes the current state of knowledge and expert opinion related to SJS/TEN covering a broad spectrum of topics including epidemiology and pharmacogenomic networks; clinical management and complications; special populations such as pediatrics, the elderly, and pregnant women; regulatory issues and the electronic health record; new agents that cause SJS/TEN; pharmacogenomics and immunopathogenesis; and the patient perspective. Goals include the maintenance of a durable and productive multidisciplinary network that will significantly further scientific progress and translation into prevention, early diagnosis, and management of SJS/TEN.
... The pathogenesis is believed to be a drug-specific, immunemediated response that is characterized by epidermal necrosis with detachment and erosion of the mucous membranes [8]. Common culprits are nonsteroidal anti-inflammatory drugs, antimicrobials, carbamazepine, phenytoin, fluoroquinolones, and sulfonamides [9]. ...
... The best medical intervention to improve patient survival is still undetermined. Cyclosporine, systemic corticosteroids, intravenous immunoglobin (IVIG), plasmapheresis, N-acetylcysteine (NAC), and TNF-α inhibitors have all been used to hasten disease recovery (Table 1) [7,8,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Because of the rarity of the disease and the difficulty in performing a randomized control trial, there is no universally accepted gold standard treatment for SJS/TEN. ...
Purpose of Review
Hospitalized patients are at risk of skin injury from drugs and procedures. These complications carry a high risk of morbidity, mortality, and internal organ involvement. This review examines updates in the treatment of drug eruptions and diagnosis of newly reported iatrogenic skin injuries that accompany novel procedures.
Recent Findings
Drug eruptions are a common cause of iatrogenic injury and they vary in presentation and severity. Recent research suggests that medications such as cyclosporine and etanercept may improve mortality in patients with epidermal necrosis although a randomized controlled trial is still needed. Innovative non-invasive procedures can have cutaneous complications such as radiation injury and microemboli. In immunocompromised patients, seemingly banal clinical manipulation such as application of medical tape can lead to cutaneous infection.
Summary
Physicians should maintain a high index of suspicion for iatrogenic injury when caring for the hospitalized patient. It is crucial to obtain a thorough medication and procedural history when evaluating these patients.
... In their study, the mortality rate was 34% in the group treated with IVIG alone, but 18% in the group treated with IVIG and steroids. In another study, Lee et al. [6] found that the odds ratio of death for patients treated with steroids compared with patients treated with supportive care alone was 0.6 (95% confidence interval: 0.3-1.0), suggesting a potential benefit for treatment with steroids. ...
... In our case, the appearance of TEN symptoms dated from the causative drug intake, is relatively late compared with symptom presentation in published literature (Table 1). It is possible that the exposure to steroids before the onset of TEN prolonged the latency and progression of the disease [6]. ...
Background
Toxic epidermal necrolysis (TEN) is a rare life-threatening condition almost exclusively attributed to drugs. The main etiologic factors for TEN are sulphonamides, anticonvulsants, and antibiotics; however, there are no published reports of warfarin causing TEN.
Case presentation
We present the case of a 3-year-old patient who developed TEN while receiving treatment for Henoch–Schönlein purpura nephritis (HSPN). With multiple-drug therapy comprising prednisolone, mizoribine, dipyridamole, and warfarin, it is difficult to detect which drug is the causative agent. While in most cases, diagnosis of the causative drug is based on clinical history without a lymphocyte transformation test (LTT), we performed the test three times and identified the causative drug as warfarin at the late phase. We continued HSPN treatment without warfarin, and results showed good renal function without life-threatening complications.
Conclusion
To our knowledge, this is the first report about TEN caused by warfarin. Repeated LTTs could be useful for identifying TEN-causative drugs even in the late phase.
... Since other potentially protective therapies, such as corticosteroid [30], are often used concomitantly in clinical practice, the true impact of IVIG on SJS/TEN cases may be influenced. It is important to evaluate the differences between the solo and the combined regimen to facilitate clinicians to make optimized decisions. ...
... Since most of these studies recruited individuals treated with the combination of IVIG and corticosteroid as case group and steroid applied cases as control group, only this kind of studies were selected. In addition, steroid therapy is widely used as a standard way to heal SJS/TEN [30], so it was reasonable to set it as a baseline and investigate the additive protective effect of IVIG. Two common variables, the time to arrest progression and the hospitalization length, were utilized to measure the improvements of patients. ...
Background
Intravenous immunoglobulin (IVIG) treatment is commonly used to treat Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with controversial therapeutic effect.
Methods
We conducted a comprehensive meta-analysis through combining the published eligible studies to evaluate the effectiveness of IVIG on SJS and TEN treatment.
Results
A total of 26 studies were selected from public available databases. The combination of IVIG and corticosteroid markedly reduced the recovery time (by 1.63 days, 95% CI: 0.83–2.43, P < 0.001), compared with solo corticosteroid group. The favorable effects were greater in Asian (2.19, 95% CI: 1.41–2.97, P < 0.001), TEN (2.56, 95% CI: 0.35–4.77, P = 0.023) and high-dose IVIG treated individuals (1.78, 95% CI: 0.42–3.14, P = 0.010). The hospitalization length reduced by 3.19 days (95% CI: 0.08–6.30, P = 0.045), though the outcome was proven to be unstable. We found heterogeneities, which sources were probably regional factors. Besides, IVIG was inclined to decrease SJS/TEN mortality (SMR: 0.84, 95% CI: 0.66–1.08, P = 0.178). This impact was possibly more profound when patients were treated with high dose IVIG (SMR: 0.74, 95% CI: 0.50–1.08, P = 0.116), or when patients were diagnosed as TEN (SMR: 0.68, 95% CI: 0.45–1.01, P = 0.058).
Conclusions
Our current meta-analysis suggests that IVIG combined with corticosteroid could reduce recovery time for SJS and TEN. This effect is greater among Asian patients. Whereas, its impact on reducing mortality is not significant.
... Los pulsos de corticoides sistémicos se han utilizado en forma empírica, sin sustento de ECA. Un estudio caso-control analizó la influencia del uso previo de corticoides en el cuadro de SSJ/NET, hallando que prolongan el tiempo entre exposición y aparición de los síntomas, y el tiempo al pico del cuadro clínico, aunque sin modificar la gravedad y la mortalidad del cuadro (22). Una revisión Cochrane 2022 sólo encuentra estudios observacionales con pocos pacientes, en los que el uso de corticoides se asocia a un aumento no significativo de mortalidad (20). ...
Los efectos adversos cutáneos de los fármacos (EACF) son una experiencia frecuente en la práctica del médico general, tanto en el ámbito ambulatorio como en el de internación. El especialista en Dermatología, por su parte, investiga siempre los antecedentes de medicamentos recibidos como posibles responsables de una gran variedad de afecciones cutáneas. Identificar al agente responsable permite suspender su uso y orienta el tratamiento de la lesión cutánea.
La enorme mayoría de los ingredientes farmacéuticos activos (IFA) y de los excipientes que los acompañan en la preparación del medicamento son sustancias extrañas para el organismo y, por este motivo, capaces de disparar la respuesta inmunitaria frente a una molécula que no se reconoce como propia. Los diferentes tipos de reacción de hipersensibilidad constituyen el mecanismo subyacente a las formas más frecuentes de los EACF, abarcando desde cuadros banales a síndromes con alta letalidad.
Pero existen también otros mecanismos de EACF, como la atrofia cutánea generada por el uso crónico de corticoides, los cambios en la coloración de la piel, fotosensibilidad, alopecia e incluso carcinogénesis, que no están mediados por mecanismos de hipersensibilidad.
En este número de la FoliaDOC se pasará revista a los cuadros clínicos más importantes, sus probables desencadenantes, el modo de identificarlos, evaluarlos y tratarlos. Se abordarán tanto los eventos frecuentes de baja gravedad como aquellos síndromes de rara presentación pero que implican un riesgo de vida significativo.
... Большинство авторов считают, что ведущее место в лечении пациентов с ССД-ТЭН занимают системные ГКС, которые способны подавить иммунную реакцию организма и предотвратить прогрессирование патологического процесса. Однако дозы ГКС, рекомендуемые для лечения, отличаются от невысоких (обычных) до пульс-терапии высокими дозами уже в начале заболевания [1,4,5,13,[15][16][17]. ...
... A larger meta-analysis has not found any statistically significant positive effect of systemic corticosteroid monotherapy [60]. Interestingly, people taking systemic corticosteroids for other diseases still develop SJS/TEN [61]. Moreover, corticosteroids seem to be associated with higher rates of mortality and infections [62]. ...
The aim of our review article was to summarize the current literature on Stevens-Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN). SJS/TEN is a serious, rare multi-system, immune-mediated, mucocutaneous disease with a significant mortality rate that can lead to severe ocular surface sequelae and even to bilateral blindness. Restoration of the ocular surface in acute and chronic SJS/TEN is challenging. There are only limited local or systemic treatment options for SJS/TEN. Early diagnosis, timely amniotic membrane transplantation and aggressive topical management in acute SJS/TEN are necessary to prevent long-term, chronic ocular complications. Although the primary aim of acute care is to save the life of the patient, ophthalmologists should regularly examine patients already in the acute phase, which should also be followed by systematic ophthalmic examination in the chronic phase. Herein, we summarize actual knowledge on the epidemiology, aetiology, pathology, clinical appearance and treatment of SJS/TEN.
... They are differentiated by the severe of skin detachment, involving <10% of body surface area (BSA) in SJS, 10-30% of BSA in SJS/TEN overlap, and >30% of BSA in TEN (10). According to the RegiSCARs study, SJS has a mortality rates in the range from about 10% and more than 40% for TEN (11). The main causes of SJS-TEN are medicines and risk factors such as HIV infection, renal disease, liver disease, and active systemic autoimmune disease (12). ...
HLA-B*13:01 allele has been identified as the genetic determinant of dapsone hypersensitivity syndrome (DHS) among leprosy and non-leprosy patients in several studies. Dapsone hydroxylamine (DDS-NHOH), an active metabolite of dapsone, has been believed to be responsible for DHS. However, studies have not highlighted the importance of other genetic polymorphisms in dapsone-induced severe cutaneous adverse reactions (SCAR). We investigated the association of HLA alleles and cytochrome P450 (CYP) alleles with dapsone-induced SCAR in Thai non-leprosy patients. A prospective cohort study, 16 Thai patients of dapsone-induced SCARs (5 SJS-TEN and 11 DRESS) and 9 Taiwanese patients of dapsone-induced SCARs (2 SJS-TEN and 7 DRESS), 40 dapsone-tolerant controls, and 470 general Thai population were enrolled. HLA class I and II alleles were genotyped using polymerase chain reaction-sequence specific oligonucleotides (PCR-SSOs). CYP2C9, CYP2C19, and CYP3A4 genotypes were determined by the TaqMan real-time PCR assay. We performed computational analyses of dapsone and DDS-NHOH interacting with HLA-B*13:01 and HLA-B*13:02 alleles by the molecular docking approach. Among all the HLA alleles, only HLA-B*13:01 allele was found to be significantly associated with dapsone-induced SCARs (OR = 39.00, 95% CI = 7.67–198.21, p = 5.3447 × 10−7), SJS-TEN (OR = 36.00, 95% CI = 3.19–405.89, p = 2.1657 × 10−3), and DRESS (OR = 40.50, 95% CI = 6.38–257.03, p = 1.0784 × 10−5) as compared to dapsone-tolerant controls. Also, HLA-B*13:01 allele was strongly associated with dapsone-induced SCARs in Asians (OR = 36.00, 95% CI = 8.67–149.52, p = 2.8068 × 10−7) and Taiwanese (OR = 31.50, 95% CI = 4.80–206.56, p = 2.5519 × 10−3). Furthermore, dapsone and DDS-NHOH fit within the extra-deep sub pocket of the antigen-binding site of the HLA-B*13:01 allele and change the antigen-recognition site. However, there was no significant association between genetic polymorphism of cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) and dapsone-induced SCARs (SJS-TEN and DRESS). The results of this study support the specific genotyping of the HLA-B*13:01 allele to avoid dapsone-induced SCARs including SJS-TEN and DRESS before initiating dapsone therapy in the Asian population.
... Jelenleg a TEN-diagnózis felállítását követően mielőbb magas dózisú IVIG adása javasolt [19,20]. Nagy dózisú szteroid alkalmazása a frissebb vizsgálatok szerint lassítja a sebgyógyulást, és nem csökkenti a mortalitást [21]. Más tanulmányok szerint a szteroid és az IVIG együtt adva jobban képes csökkenteni a mortalitást a csak szteroid-, illetve csak IVIG-terápia alkalmazásához képest [22]. ...
Összefoglaló. Két fiatal nőbetegnél a valproátról lamotriginre történő gyógyszerátállítás során a 3–4. héten influenzaszerű prodromalis tüneteket követően toxikus epidermalis necrolysis (TEN), más néven Lyell-szindróma alakult ki. Mindkét beteg 5 napja kezdődött bőr- és nyálkahártyatünetekkel, kiterjedt hámleválást okozó hámnekrózissal került felvételre a Debreceni Egyetem Bőrgyógyászati Klinikájának Égési Intenzív Osztályára. Multidiszciplináris szupportív terápia mellett nagy dózisú szteroid- és immunglobulin-terápiát alkalmaztunk. A 37 éves nőbetegnél 3 hét után a kórkép fatális kimenetellel végződött. A 19 éves nőbeteg tünetei 4 hét intenzív terápia után szövődményekkel gyógyultak. A TEN ritka, gyógyszer által okozott, életet veszélyeztető, késői hiperszenzitivitási reakció. Patogenezisében a gyógyszermolekula, a humán leukocytaantigén (HLA) I. osztályú molekula és a T-sejt-receptor kóros interakciója szerepel. Kezelésében a legfontosabb a kiváltó gyógyszer elhagyása, valamint az azonnal kezdett komplett szupportív terápia alkalmazása. A specifikus kezelést illetően nincsenek egységes szakmai irányelvek. A veszélyes gyógyszerek titrált bevezetése csökkentheti a kialakuló hiperszenzitivitás súlyosságát, ezenfelül a beteg szoros követése és az adverz tünetek korai felismerése javíthatja a TEN kimenetelét. Orv Hetil. 2020; 161(46): 1959–1965.
Summary. After switching from valproate to lamotrigine, on the 3rd–4th weeks, two young female patients developed flu-like prodromal symptoms, followed by the development of toxic epidermal necrolysis (TEN), also known as Lyell syndrome. Both patients were admitted to the Burn Intensive Care Unit of the Department of Dermatology, University of Debrecen with skin and mucosa symptoms; extensive epithelial death and detachment started 5 days earlier. In addition to multidisciplinary supportive treatment, high-dose corticosteroid and immunoglobulin therapy were administered. In the case of the 37-year-old female patient, the disease resulted in a fatal outcome. The 19-year-old patient healed with some sequelae. TEN is a rare, life-threatening delayed-type hypersensitivity reaction caused by drugs. Its pathogenesis involves an interaction between small-molecule drug, human leukocyte antigen class I molecule and T-cell receptor. The most important treatment is immediate withdrawal of potentially causative drugs and prompt application of supportive therapy. There is no standard guidance on specific treatment. Slow dose escalation of dangerous drugs can be beneficial in avoiding severe reactions, furthermore, close patient follow-up and early detection of the possible adverse reactions contribute to a more favourable outcome of TEN. Orv Hetil. 2020; 161(46): 1959–1965.
... 49,50 Systemic corticosteroids are the most common treatment option, but the use of corticosteroids has not shown a definite survival benefit. [51][52][53] Cyclosporine has been found to reduce mortality. 54 Intravenous immunoglobulin is another commonly used treatment for SJS/TEN, especially for pediatric patients. ...
Background
Patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) had high mortality rates. Disseminated intravascular coagulation (DIC) has been reported in SJS/TEN patients. The influence of this lethal complication in patients with SJS/TEN is not well known.
Objective
This study aimed to investigate the risk and outcomes of DIC in patients with SJS/TEN.
Methods
We analyzed the DIC profiles of patients diagnosed with SJS/TEN between 2010 and 2019.
Results
We analyzed 150 patients with SJS/TEN (75 SJS, 22 overlapping SJS-TEN, and 53 TEN) and their complete DIC profiles. DIC was diagnosed in 32 patients (21.3%), primarily those with TEN. DIC was significantly associated with systemic complications, including gastrointestinal bleeding, respiratory failure, renal failure, liver failure, infection, and bacteremia. Additionally, SJS/TEN patients with DIC had elevated procalcitonin. Among patients with SJS/TEN, DIC was associated with a >10-fold increase in mortality (78.1% vs. 7%).
Limitations
The study limitations include small sample size and single hospital system
Conclusion
DIC is a potential complication of SJS/TEN and associated with higher mortality. Early recognition and appropriate management of this critical complication are important for patients with SJS/TEN.
... Trong số đó, corticoid to|n th}n l| phương ph{p duy nhất được sử dụng trong nghiên cứu của chúng tôi. Mặc dù phổ biến và chi phí thấp, hiệu quả của phương ph{p n|y vẫn còn đang b|n cãi vì đi kèm nguy cơ nhiễm trùng huyết (11) . Nghiên cứu của chúng tôi ghi nhận sự khác biệt rõ rệt về kết cục lâm sàng: dị ứng nhẹ đa số chỉ biểu hiện thoáng qua trong vòng 14 ngày và hồi phục hoàn toàn; dị ứng nặng có thời gian điều trị kéo dài, có thể để lại di chứng sau hồi phục và tỷ lệ tử vong 20%. ...
Background: Gout is one of the most popular inflammatory arthritis. Allopurinol is the mainstay drugs in chronic gout management, otherwise the leading cause of severe cutaneous adverse drug reactions (SCAR). Many risk factors for this condition have been identified. However, no clinical features investigation has been conducted in Vietnamese gout patients.
Objectives: This study aimed to demonstrate the clinical manifestations, treatments and outcome of gout patients with skin reactions to allopurinol.
Materials and methods: We prospectively enrolled and examined 161 gout patients included 10 SCARs, 23 mild skin reactions and 128 allopurinol-tolerant controls. Demographic data, drug usage, clinical presentations, laboratory findings, treatment and outcome were analyzed.
Results: A majority of skin reactions manifested within 60 days, but no sooner than 7 days after exposure. Factors associated with SCAR included female, renal insufficiency, initiated with high dosage and concomitant diuretic use. All the mild cases experienced transient skin rash and full recovery, whereas SCAR patients had prolonged hospitalization, severe skin lesions, critical laboratory abnormalities, increased risk of complication after recovery (50%) and high mortality rate (20%).
Conclusion: This study confirmed several risk factors for allopurinol-induced SCAR in Vietnamese gout population, along with significant difference in clinical presentations and outcome between mild skin reactions and SCAR due to this agent.
Keywords: allopurinol, gout, skin reaction, drug hypersensitivity, SCAR
... However it is still controversial how much benefit patients would get from this treatment. Some case series have concluded that the use of systemic steroids were beneficial in reducing morbidity and mortality 34,35 , whereas others suggesting minimal or no benefit in terms of outcome [36][37][38] . Some earlier observational studies even indicated an increased mortality and a higher frequency of complications for TEN patients treated with systemic steroids [39][40][41] . ...
Background:
Severe cutaneous adverse reactions (SCAR) to drugs are a crucial public health issue and the use of systemic corticosteroids in SCAR has been controversial.
Objective:
To analyze clinical features, causative drugs, treatment, outcomes, and prognostic factors of SCAR in the case-series of 173 patients, and add more information to the debate of using systemic corticosteroids in SCAR management.
Methods:
A retrospective study of 173 SCAR patients diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) or acute generalized exanthematous pustulosis (AGEP) at a tertiary care institution in China between January 2014 and December 2017 was conducted.
Results:
Of 173 patients, allopurinol, carbamazepine, and antibiotics are the most frequently implicated drugs for DRESS (40.4%), SJS/TEN (26.0%), and AGEP (40.0%) respectively. Moreover, there is a strongly negative correlation between early corticosteroids use and the progression (p=0.000) and severity (p=0.01) of skin lesions. However, there is no association between early corticosteroids use and the mortality of SCAR (odds ratio: 1.01, 95% confidence interval: 0.95~1.08). In addition, lymphadenopathy, eosinophilia, and interval from onset to corticosteroids treatment were correlated with SCAR prognosis.
Conclusion:
Prompt short-course systemic corticosteroids use is associated with early-stage skin lesions remission without influencing the disease mortality. Lymphadenopathy and eosinophilia were the independent poor prognostic factors of SCAR.
... ×àùå âñåãî ëå÷åíèå äàííîé ïàòîëîãèè âêëþ÷àåò ïðèìåíåíèå ñèñòåìíûõ ãëþêîêîðòèêîèäîâ, öèêëîñïîðèíà, èììóíîãëîáóëèíîâ è ïëàçìàôåðåçà, îäíàêî èñòèííàÿ ýôôåêòèâíîñòü äàííûõ ìåòîäîâ îñòàåòñÿ íåèçâåñòíîé. Áûëî ïðîâåäåíî î÷åíü îãðàíè÷åííîå êîëè÷åñòâî ðàíäîìèçèðîâàííûõ èññëåäîâàíèé, êîòîðûå ìîãëè áû ñëóaeèòü îñíîâîé äëÿ ôîðìèðîâàíèÿ ðóêîâîäñòâà ïî ëå÷åíèþ òÿaeåëûõ ôîðì ËÃ× [29,31]. ...
Побочные нежелательные реакции на лекарственные средства принято классифицировать как реакции типа А и реакции типа Б. К реакциям типа А относятся предсказуемые, дозозависимые эффекты, обусловленные преимущественно фармакологическим действием препарата. К реакциям типа Б относятся непредсказуемые, не связанные с фармакологическим действием препарата нежелательные реакции, как правило, дозонезависимые. К реакциям типа Б принято относить и гиперчувствительные реакции на лекарственные средства, включающие лекарственную аллергию. Аллергия к лекарственным средствам имеет в своей основе иммунологически опосредованные реакции гиперчувствительности с различными механизмами и клиническими проявлениями. Реакции гиперчувствительности на лекарства непредсказуемы и могут клинически проявляться в виде нетяжелых синдромов, как правило, ограничивающихся кожными проявлениями, преимущественно в виде макулопапулезной сыпи. К тяжелым реакциям гиперчувствительности на лекарственные средства относятся такие синдромы, как анафилаксия, токсический эпидермальный некролиз. Первым и основным шагом в лечении лекарственной гиперчувствительности является прекращение приема причинно-значимого лекарственного средства. При лечении нетяжелых форм лекарственной гиперчувствительности применяются антигистаминные препараты, в том числе в сочетании с глюкокортикоидами, как местными, так и системными. Более серьезные проявления лекарственной гиперчувствительности, помимо назначения системных глюкокортикоидов, могут потребовать назначения посиндромной терапии. В этой статье приводится обзор современных данных по механизму развития лекарственной гиперчувствительности и подходам к терапии лекарственной аллергии.
... The previous results from a RegiSCAR cohort could not confirm the beneficial effects of systemic corticosteroids on reducing mortality in SCARs. 38 A recent meta-analysis, however, showed that corticosteroids and cyclosporine were associated with a decreased mortality rate as compared to a supportive treatment in SJS/TEN. 39 In the present study, the majority of patients were treated with systemic corticosteroids, and a total of 13.2% of patients were treated with IVIG. ...
Purpose:
Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) to antiepileptic drug (AED), are rare, but result in significant morbidity and mortality. We investigated the major culprit drugs, clinical characteristics, and clinical course and outcomes of AED-induced SCARs using a nationwide registry in Korea.
Methods:
A total of 161 patients with AED-induced SCARs from 28 referral hospitals were analyzed. The causative AEDs, clinical characteristics, organ involvements, details of treatment, and outcomes were evaluated. We compared the clinical and laboratory parameters between SJS/TEN and DRESS according to the leading causative drugs. We further determined risk factors for prolonged hospitalization in AED-induced SCARs.
Results:
Carbamazepine and lamotrigine were the most common culprit drugs causing SCARs. Valproic acid and levetiracetam also emerged as the major causative agents. The disease duration and hospital stay in carbamazepine-induced SJS/TEN were shorter than those in other AEDs (P< 0.05, respectively). In younger patients, lamotrigine caused higher incidences of DRESS than other drugs (P= 0.045). Carbamazepine, the most common culprit drug for SCARs, was associated with a favorable outcome related with prolonged hospitalization in SJS (odds ratio, 0.12; 95% confidence interval, 0.02-0.63, P= 0.12), and thrombocytopenia was found to be a risk factor for prolonged hospitalization in DRESS.
Conclusion:
This was the first large-scale epidemiological study of AED-induced SCARs in Korea. Valproic acid and levetiracetam were the significant emerging AEDs causing SCARs in addition to the well-known offending AEDs such as carbamazepine and lamotrigine. Carbamazepine was associated with reduced hospitalization, but thrombocytopenia was a risk factor for prolonged hospitalization. Our results suggest that the clinical characteristics and clinical courses of AED-induced SCARs might vary according to the individual AEDs.
... 9 It has been reported that prior treatment with steroids delays the onset and progression of the disease but does not modify the severity or mortality. 10 In our patient it is difficult to know the role played by variations of cortisol levels in the disease; however, severe hypercortisolism was present before and after the onset of toxic epidermal necrolysis. This latter fact could have had a positive impact on the course of the disease. ...
We report a case of a patient with Cushing's disease with oseltamivir-induced toxic epidermal necrolysis, who was treated with cyclosporine with favorable evolution. There is only one case reported of Cushing's disease and toxic epidermal necrolysis and very few oseltamivir-induced toxic epidermal necrolysis cases in literature. This report also discusses the role that the preexisting hypercortisolism condition may have played in the development and favorable resolution of the toxic epidermal necrolysis.
... However, in spite of more recent data that finds a favorable outcome from cyclosporine on SCAR progression 31 and mortality rates, 23,32 cyclosporine was introduced in only 1 case, which keeps parallel to the fact that no SJS/TEN cases adopted the cyclosporine treatment in the large pediatric study. 10 Considering that conflicting results and the possible risk associated with systemic corticosteroids in SCARs cases, [33][34][35] further studies are warranted to verify the safety and the efficacy of cyclosporine as the primary option for SCAR treatment. ...
Purpose
Although severe cutaneous adverse drug reactions (SCARs) are rare, they are associated with high morbidity and mortality, and thus early diagnosis and treatment are critical for improving prognoses. However, few studies have reported the characteristics of SCARs in children. Thus, we aimed to evaluate the clinical characteristics, current management and prognosis of pediatric SCARs.
Methods
We analyzed pediatric data in the Korean SCARs registry, which was built retrospectively in 2016 with SCAR cases treated in 34 tertiary referral university hospitals during 2010–2015. Using these cases, we descriptively analyzed detailed data regarding etiology, clinical and laboratory features, treatment strategies, and prognosis.
Results
Forty-seven pediatric SCAR cases from 15 tertiary referral hospitals were included. The median patient age was 10 (interquartile range, 3-15.5) years and 68.1% (n = 32) were males. The culprit drug was identified in 95.7% (n = 45) of the patients; antibiotics (44.7%) and antiepileptic drugs (19.1%) were the most common and second most common culprits, respectively. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) cases presented with the largest area of skin involvement without permanent sequelae. Stevens-Johnson syndrome (SJS) cases involved relatively small areas of skin but serious sequelae in two children. Of 4 patients with toxic epidermal necrolysis (TEN), 1 died. Of all patients assessed, 36 (76.6%) received systemic steroids and 21 (44.7%) received intravenous immunoglobulin (IVIG). Thirteen (27.7%) received both systemic steroids and IVIG. Cyclosporine was administered to only 1 patient along with a systemic steroid.
Conclusions
In patients with pediatric SCARs, including those with DRESS, SJS and TEN, clinical presentations were variable. Thus, there was no clear continuous disease spectrum. Although the mortality rate was low (2.1%), clinical suspicion may be the best tool for proactive SCAR management.
... The high crude incidence associated with dexamethasone might also be explained by a protopathic bias (use of steroids to treat early symptoms of SJS/TEN), but in our series, the time since starting the drug to the onset of reaction was 24 days [21] which is not compatible with a protopathic bias. An interesting hypothesis raised by Lee et al. [30] and supported by our data [21] is that the prior or concomitant use of corticosteroids may have delayed the onset of reaction. ...
Purpose
To estimate the specific incidences of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) among new users of drugs frequently reported to be associated with this serious event.
Methods
We performed a case-population approach, which combined data from a registry of SJS/TEN cases from the Madrid region (numerator) during the study period 2005–2015 and a primary healthcare database from the same catchment population. The proportion of new users of drugs estimated in the primary healthcare database was stratified by calendar year, sex and age (5-year bands), and then applied to the same strata of Madrid’s population census to compute the number of new users (denominator). Incidences were re-estimated using only cases in which the concerned drug had a probable or very probable causal relationship.
Results
A total of 44 SJS/TEN cases aged > 14 years were registered during the study period. The highest SJS/TEN incidence was found for phenytoin with 68.9 per 100,000 new users (95% CI 27.7–141.9), followed by dexamethasone (5.48; 1.49–14.03), allopurinol (3.29; 1.07–7.67) and cotrimoxazole (3.19; 0.87–8.16). Considering only probable and very probable cases, the incidences hardly changed, except for dexamethasone, which was left without cases. Pantoprazole, levofloxacin and lorazepam showed incidences between 1 per 100,000 and 1 per 1,000,000 new users. Ibuprofen, amoxicillin-clavulanic acid, metamizole, amoxicillin, paracetamol and omeprazole showed incidences around 1 per one million new users.
Conclusions
Phenytoin was the drug with the highest incidence of SJS/TEN, followed by allopurinol and cotrimoxazole. For the rest of the drugs, the estimated incidences were below 1 in 100,000 new users.
... Nutritional support with good nursing care should be started as soon as possible. These paired with a multidisciplinary approach improves survival and reduces infection and long-term sequelae (Lee et al., 2012, Magina et al., 2003, Mockenhaupt, 2011, Mockenhaupt and Roujeau, 2010, Sheridan et al., 2002, Yip et al., 2007. ...
Background: There is limited data on anxiety and depression in subjects with severe cutaneous adverse drug reactions (SCADR), in a predominantly HIV - infected population. The aim of the study was to prospectively investigate the prevalence of anxiety and depression and quality of life in patients with SCADR. Methods: In this prospective study, SJS, SJS - TEN, TEN and DRESS patients were assessed for anxiety and depression using validated scoring systems, the Hospital Anxiety and Depression Scale (HAD S), and the Dermatology Life Quality Index (DLQI). This was done at six weeks post discharge and again at six months follow - up. Results: Forty - eight patients with SCADR were enrolled at six weeks and 37/48 (77%) completed the study at six months. The populations were similar demographically at six weeks and six months. At six weeks anxiety or borderline anxiety symptoms/caseness was identified in 25/48 (52%) SCADR patients and depression or borderline depression symptoms/caseness in 24/48 (50%). Of those with symptoms, 18 were assessed as having co - morbid anxiety and depression with only 2 cases of pure anxiety and 4 of pure depression. At six months only 37 patients with SCADR returned for follow - up. Four of them had died in the interim while the other seven relocated. Of the cases of pure anxiety; one resolved and one was lost to follow - up. Of the cases of pure depression; one resolved, one persisted, one converted to comorbid anxiety and depression and one was lost to follow - up. Of those with co - morbid anxiety and depression 10 persisted, 2 converted to pure depression, 3 normalised and 2 were lost to follow - up. One previously normal patient developed anxiety symptoms and one case developed comorbid anxiety and depression. In 9/13 (69%) of the patients with SJS, SJS - TEN and TEN, co - morbid anxiety and depression persisted from week six to 6 months. In contrast in only 1/5 (20%) of the patients with DRESS, co - morbid anxiety and depression persisted from week six to 6 months. The cases of pure anxiety and depression were too small for meaningful comment. The overall SJS, SJS - TEN and TEN had median DLQI 8.4 relative to DRESS (DLQI 7.5) at six weeks. However, TEN (DLQI 14) had a greater impact on the quality of life compared to SJS (DLQI 3) and DRESS (DLQI 7.5). This pattern was maintained at six months. Conclusion: Anxiety and depression in patients with SCADR in a predominantly HIV - infected population is present. In the majority of cases, depression and anxiety coexist in patients with SCADR. These are sustained for at least 6 months post discharge. SCADR has a negative impact on quality of life. Our findings should help to improve the awareness of the impact of severe cutaneous adverse drug reactions on mental health especially as this may impact on future treatment adherence.
... Medical management includes steroids, imunomodulaters. 34 Surgical management includes debridement and coverage with non-adherent cutaneous dressings. 35 ...
Drug induced adverse reactions are a major health problem. Drug hyper sensitivity reactions manifest themselves in many diseases, of which some are very severe. The most common allergic reactions occur in the skin. Stevens-Johnson syndrome is mainly caused by drugs (antimicrobials e.g.: penicillin’s, sulphonamides and cephalosporin’s e.g.: cefixime, antiepileptic’s, NSAIDS), infections and also by other risk factors not yet identified. The most common allergic reactions occur in the skin. These reactions ranging from simple pruritic eruptions to potentially life threatening events are a significant cause of iatrogenic morbidity and mortality. Identification of the cause, withdrawal of the trigger and supportive management is crucial to improve the patient state. Despite of all therapeutic efforts, mortality is high and increases with disease severity, patient’s age and underlying medical conditions. Survivors may suffer from long-term squeal such as strictures of mucous membranes including severe eye problems.
... Prior exposure to steroids has been shown to increase the duration of healing, but with no beneficial impact on mortality [50]. High doses of methylprednisolone during the acute phase have no significant impact on mortality [46]. ...
Epidermal necrolysis (EN) encompasses Stevens-Johnson syndrome (SJS, < 10% of the skin affected), Lyell syndrome (toxic epidermal necrolysis, TEN, with ≥30% of the skin affected) and an overlap syndrome (10 to 29% of the skin affected). These rare diseases are caused, in 85% of cases, by pharmacological treatments, with symptoms occurring 4 to 28 days after treatment initiation. Mortality is 20 to 25% during the acute phase, and almost all patients display disabling sequelae (mostly ocular impairment and psychological distress).
The objective of this French national diagnosis and care protocol (protocole national de diagnostic et de soins; PNDS), based on a critical literature review and on a multidisciplinary expert consensus, is to provide health professionals with an explanation of the optimal management and care of patients with EN. This PNDS, written by the French National Reference Center for Toxic Bullous Dermatoses was updated in 2017 (https://www.has-sante.fr/portail/jcms/c_1012735/fr/necrolyse-epidermique-syndromes-de-stevens-johnson-et-de-lyell). The cornerstone of the management of these patients during the acute phase is an immediate withdrawal of the responsible drug, patient management in a dermatology department, intensive care or burn units used to dealing with this disease, supportive care and close monitoring, the prevention and treatment of infections, and a multidisciplinary approach to sequelae. Based on published data, it is not currently possible to recommend any specific immunomodulatory treatment. Only the culprit drug and chemically similar molecules must be lifelong contraindicated.
... Moreover, it led to an increase in the rate of infective complications associated with SJS-TEN. [58][59][60] Thus, the role of systemic corticosteroids in the management of TEN is controversial [61] • Cyclosporine: As per the survey, cyclosporine is the second most commonly used immunomodulator in the treatment of SJS-TEN. It specifically targets granulysin, an important mediator of apoptosis of keratinocytes; and thus, leads to arrest of disease progression. ...
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions, which are mainly caused by drugs; and these are usually associated with high degree of morbidity and mortality. Recently, two detailed guidelines were published on the management of SJS/TEN, Indian guidelines and UK guidelines. Still, there is no consensus on the management of SJS/TEN. In this article, our aim is to conceptualize the management aspect of SJS/TEN considering Indian setup. Early discontinuation of all medicines, supportive measures (hydration, electrolytes, and care of denuded skin), corticosteroids and cyclosporine has been found to be useful. Oral provocation test is reserved for patients, who undergo complete remission and this is to be done after hospitalization, under strict vigilance. As there is no consensus, the treatment should be individualized on case to case basis.
... Bazıları da puls steroid tedavisini bazı durumlarda denemiş ve faydasını bildirmişlerdir [21] . Yine hastalık başlangıcı öncesinde kortikosteroid kullanımının hastalığın başlangıcını geciktirdiği ama hastalık seyir ve şiddetini değiştirmediği bildirilmiştir [26] . Hastamız da metilprednizolon 7 gün kadar düşük dozda kullanılmış ve fayda görmüştür. ...
Stevens-Johnson syndrome (SJS) is an acute, self-limiting but life-threatening skin condition, in which cell death causes the epidermis to separate from the dermis. The syndrome is thought to be an immune-complex-mediated hypersensitivity that affects the skin and mucous membranes. SJS is most often an adverse effect of medication, and frequently occur two weeks after use. There is an oral medication called as Scholl solution, which has different formulations, correcting base deficit in renal tubular acidosis (RTA). It is made of pure citric acid and salt of sodium citrate or salt of sodium and potassium citrate in distilled water. SJS is not reported to be related to Scholl solution till now. Since a patient, with cystinosis using Scholl solution for years, who developed SJS after receiving Scholl solution with different formula is presented, we want to increase awareness on this issue. Three-year-old-female presented to us with complaints of maculo-papular rash on her face and over the trunk. She has been taking cysteamine, carnitine, calcitriol, neutral phosphate and Scholl solution. After consanguineous marriage, she has two siblings having cytinosis and one sibling required renal transplantation. Physical examination showed erythematous maculo-papular rash on her face and over the trunk and extremities, later skin lesions were resulted in exfoliation. C-reactive protein, CBC, with differential, biochemistry and blood gas were normal. Following dermatology consultation, she was diagnosed with SJS after biopsy, but the patient was thought to be inclined to develop toxic epidermal necrolysis (TEN). Methylprednisolone, pheniramine, desloratadin, and intravenous immunoglobulin were given to prevent developing TEN. Skin lesions regressed after discontinuing medications. Since the etiology was uncertain, when medications restarted, the skin lesions recurred after Scholl solution containing pure citric acid. This patient shows that physicians keep Scholl solution in mind as a cause for SJS in RTA patient.
... The efficacy of systemic immunosuppressants or immunomodulatory treatments (e.g., corticosteroids, cyclosporine, intravenous immunoglobulins (IVIg), and plasmapheresis) still remains controversial. Systemic corticosteroids could be the most common treatment option, but the prior use of corticosteroids was found to prolong disease progression with no definite benefit in terms of survival [60,[201][202][203]. IVIg is one of the most commonly utilized therapies for SJS/TEN and is frequently the adjunctive therapy used for severe cases or pediatric patients [204]. ...
Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR) molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity.
... This same study, moreover, suggested that the use of corticosteroids in these patients prevents ocular complications. On the other hand, a separate study by Lee et al. (2012) suggested that it is necessary to undertake controlled clinical trials in order to assess the real benefits of corticosteroid use in patients with SJS and TEN. ...
... In case of prior use of glucocorticoids for treatment of other diseases, the time to stabilization was longer by 2.2 days. Other parameters such as morbidity and fatality did not differ in patients with or without prior use of glucocorticoids [225]. ...
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered a delayed-type hypersensitivity reaction to drugs. They represent true medical emergencies and an early recognition and appropriate management is decisive for the survival. SJS/TEN manifest with an “influenza-like” prodromal phase (malaise, fever), followed by painful cutaneous and mucous membrane (ocular, oral, and genital) lesions, and other systemic symptoms. The difference between SJS, SJS/TEN overlap, and TEN is defined by the degree of skin detachment: SJS is defined as skin involvement of < 10%, TEN is defined as skin involvement of > 30%, and SJS/TEN overlap as 10–30% skin involvement. The diagnosis of different degrees of epidermal necrolysis is based on the clinical assessment in conjunction with the corresponding histopathology. The mortality rates for SJS and TEN have decreased in the last decades. Today, the severity-of-illness score for toxic epidermal necrolysis (SCORTEN) is available for SJS/TEN severity assessment. Drugs with a high risk of causing SJS/TEN are anti-infective sulfonamides, anti-epileptic drugs, non-steroidal anti-inflammatory drugs of the oxicam type, allopurinol, nevirapine, and chlormezanone. Besides conventional drugs, herbal remedies and new biologicals should be considered as causative agents. The increased risk of hypersensitivity reactions to certain drugs may be linked to specific HLA antigens. Our understanding of the pathogenesis of SJS/TEN has improved: drug-specific T cell-mediated cytotoxicity, genetic linkage with HLA- and non-HLA-genes, TCR restriction, and cytotoxicity mechanisms were clarified. However, many factors contributing to epidermal necrolysis still have to be identified, especially in virus-induced and autoimmune forms of epidermal necrolysis not related to drugs. In SJS/TEN, the most common complications are ocular, cutaneous, or renal. Nasopharyngeal, esophageal, and genital mucosal involvement with blisters, erosions as well as secondary development of strictures also play a role. However, in the acute phase, septicemia is a leading cause of morbidity and fatality. Pulmonary and hepatic involvement is frequent. The acute management of SJS/TEN requires a multidisciplinary approach. Immediate withdrawal of potentially causative drugs is mandatory. Prompt referral to an appropriate medical center for specific supportive treatment is of utmost importance. The most frequently used treatments for SJS/TEN are systemic corticosteroids, immunoglobulins, and cyclosporine A.
... Systemic treatments, including systemic steroids, intravenous immunoglobulin (IVIg), and cyclosporine, have been studied for SJS and TEN. Due to an increased risk of complications associated with corticosteroid use, 8,9 treatment with IVIg or cyclosporine has increased among clinicians. Studies on the effect of IVIg on mortality rates have reported conflicting results 10,11 ; however, several case reports and series on cyclosporine have reported its ability to halt disease progression and reduce mortality rates. ...
Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening reactions, mainly to drug, characterized by epidermal necrosis and mucous membrane ulceration. SCORTEN-predicted mortality has been used to assess the efficacy of treatments comparing with actual mortality. Several literatures about cyclosporine have shown its ability to halt disease progression and decrease mortality.
Objectives: This study was aimed to provide a more evidence-based review by conducting a meta-analysis of cyclosporine for the treatment of SJS/TEN.
Methods: We conducted a systemic review of articles published before Jan 31, 2017. The outcomes were mortality rate and SCORTEN-based standardized mortality ratio (SMR). The pooled odds ratio (OR) and SMR ratio were analyzed from these extracted data.
Results: There were 7 observational controlled studies (1 historical controlled study) which met the inclusion criteria. The overall mortality rate for patients receiving cyclosporine was 7.1%. The observed mortality was significantly lower than predicted mortality in patients receiving cyclosporine (pooled SMR: 0.42; 95% CI, 0.19–0.95). The pooled estimate of ORs for 4 studies describing observed mortality in cyclosporine to intravenous immunoglobulins (IVIg) group was 0.40 (95%CI, 0.06–2.69). Comparison of SMR between cyclosporine and IVIg was presented with the pooled SMR ratio, which showed no significant difference in SMR ratio between two treatments (SMR ratio, 0.49, 95% CI, 0.08–2.89).
Conclusion: We have provided the first meta-analysis study regarding the efficacy on mortality of cyclosporine for treatment of SJS/TEN. From the existing research, cyclosporine has a beneficial effect on mortality. And there is a trend that cyclosporine demonstrated better survival whether in pooled OR or SMR ratio than IVIg. Due to the limitations of current studies, a double-blind randomized controlled trial is still urged.
... Steroid pulse therapy has recently been proposed with initial encouraging results, although the experience is still limited. Interestingly, the exposure to corticosteroids before the onset of SJS/TEN did not affect the disease severity and mortality; however, corticosteroids prolonged the latency period from drug initiation to onset and progression of the disease [106]. ...
Opinion Statement
Severe cutaneous adverse drug reactions (SCARs) can occur at any age and can be life threatening, although some drugs have been more frequently reported than others. The spectrum of SCARs includes acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome (DiHS) or hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Immediate withdrawal of the offending drug is the mainstay treatment in SCARs, and rechallenge often leads to recurrent reactions. Cross reactivity and multiple sensitivities have also been reported. The identification of the offending medication at the onset of the disease is therefore essential to avoid future exposures to the same or chemically related compounds. Various algorithms can be useful to identify the culprit drug in the acute stage. Delayed onset from the initiation of treatment differs in the various clinical entities. Therefore, a prompt, accurate diagnosis is crucial for proper identification of the offending agent. After resolution of the disease, cutaneous tests and in vitro tests can be useful for confirmation of drug causality and investigation of possible cross-reactivity. SCARs are rare diseases, given the incidence is extremely low. Multidisciplinary and international teams are required to study these diseases. Further research is needed to fully understand etiopathogenesis and for the development of specific treatments.
... Malignancy was further Dermatology Online Journal || Original Article shown to be associated with a higher mortality rate of SJS in a recent study that also demonstrated the effect of malignancy-related risk factors, such as chemotherapy treatment [34]. A recent jointinstitutional study demonstrated some evidence that corticosteroids, which are prevalent in use, may increase the time until onset for SJS and prolong duration of symptoms, but did not affect severity or mortality [35]. Our study has many implications for patients and practicing dermatologists, from preventative and therapeutic standpoints. ...
Background:
Stevens Johnson Syndrome (SJS) is a life threatening skin condition with an overall mortality rate of 5%. Although the causes and pathology of the disease have been well studied, the factors that significantly contribute to mortality remain unclear.
Objective:
To determine relevant risk factors that increase the likelihood of inpatient mortality after diagnosis of SJS.
Methods:
A retrospective cohort study of the 2010-2011 Healthcare Costs and Utilization Project (HCUP) Nationwide InpatientSample (NIS) database was conducted. This study included 1,811 patients who encountered inpatient hospital stays with a discharge diagnosis of SJS.
Results:
The primary outcome of our study was inhospital mortality. We analyzed the prevalence and associated inpatient mortality of underlying critical illness in patients with SJS. Three age ranges of patients in this study showed significantly increased rates of inpatient mortality by odds-ratio with a 95% CI: 70-79 years (10.91% mortality, OR=4.57, p=0.001),80-89 years (10.67% mortality, OR=4.48, p=0.001), and 90+ years (9.30% mortality, OR=4.22, p=0.028). Two comorbid conditions showed significant association with increased inpatient mortality in SJS by odds-ratio with a 95% CI: cirrhosis (14.58% mortality, OR=2.79,p=0.028) and metastatic disease (10.62% mortality,OR=1.87, p=0.031).
Interpretation:
Age (70+ years), cirrhosis, and metastatic disease were identified as significantly associated with inpatient mortality after diagnosis with SJS. These findings enhance current understanding of the pathology of this disease, as well as help improve clinical management of high-risk patients to reduce inpatient mortality.
... Reportes más recientes sugieren que la utilización temprana de altas dosis de corticosteroides con terapia pulsada de dexametasona podría ser un tratamiento efectivo. Sin embargo, esto refuerza aún más la necesidad de un estudio prospectivo y aleatorizado para pruebas concluyentes (14) . ...
El Sindrome de Stevens Johnson, la Necrolisis Epidermica Toxica y el Sindrome Estafilococico de la piel escaldada corresponden a patologias dermatologicas que cursan con perdida de piel en grandes areas corporales, por lo que ameritan un manejo similar al de las quemaduras de segundo grado y recomendablemente controlado en una Unidad de Quemados.
Background:
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, severe mucocutaneous adverse reactions. Severity prediction at early onset is urgently required for treatment. However previous prediction scores have been based on data of blood tests.
Objective:
This study aimed to present a novel score that predicts mortality in patients with SJS/TEN in the early stages, based on only clinical information.
Methods:
We retrospectively evaluated 382 patients with SJS/TEN in development study. A clinical risk score for TEN (CRISTEN) was created according to the association of potential risk factors with death. We calculated the sum of these risk factors using CRISTEN, and this was validated in a multinational survey of 416 patients and was compared to previous scoring systems.
Results:
The significant risk factors for death in SJS/TEN comprised of 10 items, including patients' age of ≥65 years, ≥10% BSA involvement, the use of antibiotics as culprit drugs, the use of systemic corticosteroid therapy prior to the onset, and mucosal damage affecting ocular, buccal, and genital mucosa. Renal impairment, diabetes, cardiovascular disease, malignant neoplasm, and bacterial infection were included as underlying diseases. The CRISTEN model showed good discrimination (AUC=0.884) and calibration. In the validation study, the AUC was 0.827, which was statistically comparable to those of previous systems.
Conclusion:
A scoring system based on only clinical information was developed to predict mortality in SJS/TEN and was validated in an independent multinational study. CRISTEN may predict individual survival probabilities and direct the management and therapy of patients with SJS/TEN.
Background:
Epidermal necrolysis (SJS/TEN) is a rare but acute severe drug reaction associated with high morbidity and mortality rates.
Aims:
To describe the clinical, molecular, biochemical, and therapeutic profile of these patients.
Methods:
A total of 24 acute SJS/TEN patients were recruited during their hospital stay and detailed clinical history and treatment course recorded. Blood samples collected were subjected to DNA and serum separation for molecular and biochemical analysis.
Results:
Of 24 patients, 18 (75%) were females and six (25%) were males with six SJS, six SJS-TEN overlap, and 12 TEN cases. The inciting drugs were non-steroidal anti-inflammatory (87.50%; n = 21) followed by antibiotics (66.67%; n = 16), antiepileptics (37.50%; n = 9), and others (37.50%; n = 9). Seventeen patients (77.2%) showed skin eruptions within 7 days after drug intake. Different co-morbidities were observed in 22 (91.6%) and 20 (83.3%) patients showed ocular manifestations. Length of hospital stay ranged from 8 to 55 days, 20 (83.3%) patients were treated with corticosteroids, and four (16.6%) received antimicrobial therapy. Interleukin polymorphisms revealed significantly low frequency of IL-4 in the patients, HLA-A locus typing revealed higher frequency of HLA-A*3301 (20.8%), HLA-A*02 (25%), HLA-A*2402 (14.6%), and sera showed raised levels of granulysin and sFas L in the patients compared to controls.
Conclusions:
The preliminary study illustrates the clinical, molecular, and biochemical features of acute SJS/TEN and provides a better understanding that helps to improve patient care at an earlier stage. It also highlights the use of corticosteroids and antimicrobial therapy for effective treatment of patients.
Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are manifestations of a drug-induced mucocutaneous epithelial necrolysis syndrome. The two entities represent either end of a severity spectrum with SJS at the milder end (<10% body surface area epidermal detachment) and TEN at the severe end (>30% epidermal detachment). During the acute phase, SJS/TEN is associated with multiple morbidities and a high mortality (15–30%). There are a number of commonly implicated drugs including the antibacterial sulfonamides, allopurinol, aromatic anticonvulsants, nonsteroidal anti-inflammatory drugs of the oxicam family, and nevirapine. Granulysin appears to be the major cytotoxic molecule responsible for keratinocyte necrosis. Two or more mucous membranes are involved in almost all cases; initial skin lesions are purpuric macules and atypical targets. Ultimately SJS/TEN progresses to blistering and detachment of epidermal sheets. Patients with SJS/TEN should be admitted to a unit with specialist expertise in the management of skin loss syndromes and acute skin failure (specialized intensive care unit or burns unit). Survival is associated with an early diagnosis and supportive care directed at treating acute skin failure. There is no unambiguous evidence for significant benefit from any of the active interventions used in SJS/TEN (systemic corticosteroids, IVIg, ciclosporin). After the acute phase, survivors of SJS/TEN are commonly troubled by long-term mucocutaneous, ocular, and psychological sequelae.
Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe mucocutaneous bullous disorders characterized by widespread skin and mucosal necrosis and detachment, which are most commonly triggered by medications. Despite their rarity, these severe cutaneous adverse drug reactions will result in high mortality and morbidity as well as long-term sequela. The immunopathologic mechanisms is mainly cell-mediated cytotoxic reaction against keratinocytes leading to massive skin necrolysis. Subsequent studies have demonstrated that immune synapse composed of cytotoxic T cells with drug-specific human leukocyte antigen (HLA) class I restriction and T cell receptors (TCR) repertoire is the key pathogenic for SJS/TEN. Various cytotoxic proteins and cytokines such as soluble granulysin, perforin, granzyme B, interleukin-15, Fas ligand, interferon-γ, tumor necrosis factor-α have been as mediators involved in the pathogenesis of SJS/TEN. Early recognition and immediate withdrawal of causative agents, and critical multidisciplinary supportive care are key management of SJS/TEN. To date, there is yet to be a sufficient consensus or recommendation for the immunomodulants of the treatment in SJS/TEN. Systemic corticosteroids remain one of the most common treatment options for SJS/TEN, though the efficacy remain uncertain. Currently, there is increasing evidence showing that cyclosporine and TNF-α inhibitors decrease the mortality of SJS/TEN. Further multicenter double-blinded, randomized, placebo-controlled trials are required to confirm the efficacy and safety.
Относящийся к типу В неблагоприятных побочных реакций на лекарственные средства по классификации ВОЗ синдром Стивенса-Джонсона (ССД) является тяжелой системной аллергической реакцией, в основе которой лежит клеточно-опосредованный патогенез, и представляет собой тяжелый вариант течения многоформной эритемы, при которой наряду с поражением кожи отмечается поражение слизистых оболочек как минимум двух органов. Приведены литературные данные современного взгляда на этиологию, патогенез и лечение ССД. описан клинический случай у женщины 24 лет с возникновением ССД после перорального применения ципрофлоксацина с выраженной гипертермической реакцией. Представлен вариант ведения пациентки в терапевтическом стационаре с проведением дифференциальной диагностики и с назначением интенсивной кортикостероидной терапии с положительным эффектом.
Introduction: The clinical manifestations of cutaneous adverse drug reactions are variable with different severity. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse reactions (SCARs) majorly caused by drugs and mediated by cytotoxic T cells.
Areas covered: In this review, we focus on risk factors that contribute to the development of SJS/TEN and review the updated immune mechanism, preventive strategies as well as current therapeutic approaches for SJS/TEN.
Expert opinion: SJS/TEN research to date has revealed that cytotoxic T cells
majorly activated by drugs interacting with the human leukocyte antigen and T
cell receptors play an important role in the immune mechanism of SJS/TEN. Several
clinical assessment tools and in vitro drug-T cells activation tests have been
developed to identify the causality of SJS/TEN. New therapeutic approaches and
biologics such as TNF-alpha antagonists have been conducted to improve the
prognosis of SJS/TEN.
Background and objective:
Severe cutaneous adverse reactions to drugs (SCARs), have a high morbidity, mortality and present sequelae. Objective: To characterize patients with SCARs in eight health care institutions in Latin America.
Methods:
Cross-sectional, descriptive, multicenter, Latin American study of patients diagnosed with SCARs, between January 2009 and December 2018. The analysis was made from a database in BD Clinic.
Results:
Seventy cases were reported. Forty-two (60%) were women. The average age was 38.7 years. Forty-two (60%) had DRESS-DIHS, 12 (17.1%) TEN, 5 (7.1%) SJS, 6 (8.5%) AGEP, 4 (5.7%) other, not classified SCARs, and 1 (1.4%) overlapping TEN/SJS. The main causative drugs were aromatic anticonvulsants in 31 cases (44.3%), beta lactam antibiotics in 11 cases (15.7%) and non-beta lactam antibiotics in 6 cases (8.6%). In all of cases, the suspected drug was withdrawn at the first sign of a SCAR. Sixty-six patients (94.2%) received anti-inflammatory treatment, mostly systemic corticosteroids. Complications occurred in 53 cases (75.7%) and death in three patients (4.3%). Thirteen patients (18.6%) had some type of sequelae.
Conclusions:
This is the first multicenter report on SCARs in Latin America. DRESS-DIHS was the most frequently reported clinical entity and anticonvulsants were the main triggers. Most of patients received systemic corticosteroids. Complications were frequent and three patients died.
Severe cutaneous drug hypersensitivity reactions consist of different entities, some of which are life-threatening, such as Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, generalized bullous fixed drug eruptions , serum sickness and serum sickness-like reaction and drug-induced vasculitis. These reactions may have substantial morbidity and mortality. In the past years, successive studies have provided new evidence regarding the pathogenesis of some of these severe reactions and revealed that underlying mechanisms are highly variable. Since these reactions have unique presentations and distinct pathomechanisms, the treatment methods and response rates might be different among various entities. Although supportive and local therapies are sufficient in some of these reactions, targeted immunosuppressive treatments and even mechanistic therapies such as plasmapheresis may be required in severe ones. However, there is still insufficient evidence to support the best treatment options for these patients since number of patients and large-scale studies are limited. In this review, conventional and new treatment options for severe cutaneous drug hypersensitivity reactions are presented in detail in order to provide the contemporary approaches to lessen the morbidity and mortality relevant to these severe iatrogenic diseases.
Patients diagnosed with cancer will face various adverse events (AEs) of chemotherapy, radiation, surgery, or stem cell transplants. Numerous dermatological AEs associated with these treatments range from those with minor psychosocial impact to being potentially life-threatening. Adverse events may result in decreased quality of life and dose reduction or treatment interruption, all of which may compromise clinical outcome. A variety of adverse events such as alopecia, mucositis, hand–foot syndrome, and rashes associated with conventional cytotoxic agents have been well-described, but with the advent of novel targeted agents, new dermatologic adverse events and systemic AEs have emerged. AEs affecting the skin and its adnexa (i.e., hair, nails) such as hand–foot skin reaction, acneiform rash, and paronychia may present both diagnostic and management challenges for health-care providers. Although many antitoxicity interventions have not been investigated in randomized studies, there are ways of mitigating these untoward events in clinical practice. This chapter will address multiple skin and nail AEs induced by conventional, targeted chemotherapy agents and immunotherapies and will describe adverse effects associated with radiotherapy. Proposed underlying mechanisms will be reviewed, and special attention will be directed to management strategies that are available to date.
Purpose
The “case‐population” design has been proposed for the surveillance of rare events like Stevens‐Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), wherein a registry of cases is combined with sales data from the source population in order to estimate crude odds ratios (ORs). A major drawback of this method is the inability to distinguish between new and non‐new users of drugs, which for the study of hypersensitivity reactions is of utmost importance.
Methods
We have explored an approach in which the exposure to the drugs of interest in the source population is inferred from a primary health care database (BIFAP), which helped us to identify drug initiators among all users and additionally adjust for potential confounders. A total of 44 SJS/TEN cases from the Registry and 44 000 controls randomly sampled from BIFAP and matched with cases for index date were included. We estimated the adjusted ORs (AORs) and 95% confidence intervals (CI) of SJS/TEN associated with the new use of 13 drugs (for which we had at least two exposed cases) through a conditional logistic regression model.
Results
AORs (95% CI) were estimated for phenytoin, 4618 (434‐49112); cotrimoxazole, 1142 (163‐8015); allopurinol, 160 (36‐709); dexamethasone, 38 (1.33‐1077); ibuprofen, 33 (8.6‐124); lorazepam, 27 (5.8‐124); paracetamol, 13 (2.8‐62); levofloxacine, 12 (1.24‐120); amoxicillin, 6.9 (1.39‐35); pantoprazole, 6.5 (0.10‐420); metamizole, 6.3 (0.69‐57); amoxicillin clavulanic acid, 4.2 (0.53‐34); and omeprazole, 1.34 (0.06‐31). The inclusion of non‐new users dramatically decreased the AORs for all drugs.
Conclusions
The case‐population approach using a registry of cases and a primary health care database proved feasible and efficient for the active surveillance of SJS/TEN.
Background
Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous drug reactions requiring intensive care and protracted hospitalization. Local data on their characteristics, management and outcomes are minimal.
Objectives
Our objective was to identify the complications of SJS/TEN and the management strategies employed and the effect of these on patient mortality.
Methods
We conducted a retrospective cross-sectional study to determine the characteristics, management strategies and patient mortality associated with SJS/TEN in patients admitted to Kenyatta National Hospital from June 2006 to June 2016. Total population sampling was used to identify 115 patients with SJS/TEN. Data on disease complications, management strategies employed and mortality status as an outcome of therapy were extracted.
Results
Patients were predominantly managed using antimicrobials (16.4% of patients, 21.8% of whom received topical mupirocin). Fluid and electrolyte replacement, skin emolliation with liquid paraffin, temperature regulation and corticosteroids were used to treat 15.3, 13.4, 11.1 and 9.4% of patients, respectively. The mortality rate was 21.7%. Significantly (p ≤ 0.05) higher mortality was associated with patients’ area of residence, disease subclass, disease severity score, hypokalaemia, dyspnoea, haematological disturbance, sepsis and dehydration. Conversely, use of total parenteral nutrition, anticoagulants for deep venous thrombosis prophylaxis and prolonged duration of therapy were associated with significantly (p ≤ 0.001) lower mortality. Mortality was not associated with administration of corticosteroids or antibiotics. Independent predictors of mortality were hypokalaemia, dyspnoea, haematological disturbance and sepsis (all p ≤ 0.05).
Conclusion
The main management strategy used to treat SJS/TEN was antimicrobial prophylaxis, but this was not correlated with mortality. Mortality was high and was attributed to distant patient residence, severe disease and complications, suggesting that early recognition of these signs could avert mortality.
We report two rare cases of childhood epilepsy patients who developed ethosuximide-induced Stevens–Johnson syndrome (SJS). Unlike typical SJS, the initial eruption of both patients presented well-demarcated, infiltrating firm papules mainly on the cheeks and the extensor aspects of the arms (case 1), and multiple vesicles on the soles and oral aphthosis (case 2), which closely mimicked viral exanthema. We diagnosed both patients with ethosuximide-induced SJS, based on the dosing period and the positive results of drug-induced lymphocyte stimulation test. Systemic corticosteroids are usually selected as a standard therapy for SJS, despite controversial results regarding their effectiveness. In case 1, an i.v. pulse therapy of methylprednisolone (30 mg/kg, 3 days consecutively) was initiated on day 7 from the onset of illness, and an i.v. immunoglobulin (400 mg/kg, 5 days consecutively) was added the following day. In case 2, an i.v. prednisone treatment (1 mg/kg, for 1 week) was initiated on day 4 from the onset. Eventually, the early therapeutic interventions resulted in good outcomes in both patients.
During the past decade, major advances have been made in the accurate diagnosis of severe cutaneous adverse reactions (SCARs) to drugs, management of their manifestations, and identification of their pathogenetic mechanisms and at-risk populations. Early recognition and diagnosis of SCARs are key in the identification of culprit drugs. SCARS are potentially life threatening, and associated with various clinical patterns and morbidity during the acute stage of Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reactions with eosinophilia and systemic symptoms, and acute generalised exanthematous pustulosis. Early drug withdrawal is mandatory in all SCARs. Physicians' knowledge is essential to the improvement of diagnosis and management, and in the limitation and prevention of long-term sequelae. This Seminar provides the tools to help physicians in their clinical approach and investigations of SCARs.
Background:
Nivolumab is an anti-programmed cell death receptor-1 (PD-1) antibody used in the treatment of metastatic or unresectable melanoma. Cutaneous reactions are the most common adverse events reported with these agents and are rarely severe or life-threatening.
Methods:
Case report describing the clinicopathological findings of a patient with a fatal toxic epidermal necrolysis (TEN) eruption associated with use of nivolumab for treatment of metastatic melanoma.
Results:
The patient developed a pruritic, morbiliform eruption, which slowly progressed over 3 months to a tender, exfoliative dermatosis. Histology initially demonstrated interface dermatitis and subsequently revealed full thickness epidermal necrosis. The diagnosis of TEN was made. From initial biopsy to TEN presentation, there was an increase in the number of CD8+ lymphocytes within the dermal-epidermal junction and programmed death ligand 1 (PD-L1) expression increased in both lymphocytes and keratinocytes. Despite treatment with infliximab, high dose steroids, and intravenous immunoglobulin, the patient expired.
Conclusions:
Herein we describe what we believe is the 2(nd) case of TEN associated with anti-PD1 therapy reported in the literature. Increased expression of PD-L1 by immunohistochemistry was observed as the eruption progressed to TEN. Early diagnosis and treatment is necessary in these fatal TEN reactions secondary to the anti-PD-1 antibody therapies.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening adverse drug reactions characterized by massive epidermal necrosis, in which the specific danger signals involved remain unclear. Here we show that blister cells from skin lesions of SJS-TEN primarily consist of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, and both blister fluids and cells were cytotoxic. Gene expression profiling identified granulysin as the most highly expressed cytotoxic molecule, confirmed by quantitative PCR and immunohistochemistry. Granulysin concentrations in the blister fluids were two to four orders of magnitude higher than perforin, granzyme B or soluble Fas ligand concentrations, and depleting granulysin reduced the cytotoxicity. Granulysin in the blister fluids was a 15-kDa secretory form, and injection of it into mouse skin resulted in features mimicking SJS-TEN. Our findings demonstrate that secretory granulysin is a key molecule responsible for the disseminated keratinocyte death in SJS-TEN and highlight a mechanism for CTL- or NK cell--mediated cytotoxicity that does not require direct cellular contact.
Toxic epidermal necrolysis (TEN, Lyell's syndrome) is a severe adverse drug reaction in which keratinocytes die and large sections of epidermis separate from the dermis. Keratinocytes normally express the death receptor Fas (CD95); those from TEN patients were found to express lytically active Fas ligand (FasL). Antibodies present in pooled human intravenous immunoglobulins (IVIG) blocked Fas-mediated keratinocyte death in vitro. In a pilot study, 10 consecutive individuals with clinically and histologically confirmed TEN were treated with IVIG; disease progression was rapidly reversed and the outcome was favorable in all cases. Thus, Fas-FasL interactions are directly involved in the epidermal necrolysis of TEN, and IVIG may be an effective treatment.
Mortality in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is high. Apart from intensive supportive therapy, no generally accepted specific treatment regimen exists. The role of corticosteroids in SJS/TEN is controversial. It is possible that high-dose pulse therapy with corticosteroids might be an improvement on long-term lower dose therapy, by combining higher efficacy with a diminished risk both of infection and of delayed wound healing. The aim of this study was to evaluate the efficacy of dexamethasone pulse therapy with respect to mortality and healing time of patients with SJS/TEN. A small, uncontrolled series of consecutive inpatients with SJS/TEN was treated with dexamethasone pulse therapy. The efficacy of this treatment was assessed retrospectively using SCORTEN. Twelve patients were included over a period of 10 years. One patient died, while SCORTEN predicted a fatal outcome of 4 patients. Stabilization was reached after 2.3 days on average, total re-epithelialization after 13.9 days. The results of this study bear no statistical relevance due to the small number of patients. In conclusion, short-term dexamethasone pulse therapy, given at an early stage of the disease, may contribute to a reduced mortality rate in SJS/TEN without increasing healing time. A larger controlled trial is warranted to investigate further the use of dexamethasone pulse therapy in SJS/TEN.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse reactions (SCAR) related to a variety of medications. They have a significant public health impact because of high mortality and morbidity. A multinational case-control study conducted in Europe between 1997 and 2001 evaluated the risk of medications to induce SCAR. Cases were actively detected through a hospital network covering more than 100 million inhabitants. Three hospitalized patients per case matched on age, gender, and date of interview were enrolled as controls. After validation by an expert committee blinded to exposures, 379 SCAR cases and 1,505 controls were included. Among drugs recently introduced into the market, strong associations were documented for nevirapine (relative risk (RR)>22) and lamotrigine (RR>14), and weaker associations for sertraline (RR=11 [2.7-46]), pantoprazole (RR=18 [3.9-85]), and tramadol (RR=20 [4.4-93]). Strong associations were confirmed for anti-infective sulfonamides, allopurinol, carbamazapine, phenobarbital, phenytoin, and oxicam-NSAIDs , with some changes in relative numbers of exposed cases. Thus, many cases were still related to a few "old" drugs with a known high risk. Risk was restricted to the first few weeks of drug intake. The use of such drugs as first-line therapies should be considered carefully, especially when safer alternative treatments exist. A number of widely used drugs did not show any risk for SJS and TEN.
Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, sometimes life-threatening skin reaction that are often drug-induced. Unfortunately, the definitions and nomenclature of these severe skin reactions have been confusing, and thus various publications on this issue could be hardly compared. Methods/data base: After several attempts had been made to clarify this situation, a consensus definition published in 1993 suggests the differentiation between erythema exsudativum multiforme majus (EEMM) and SJS, as well as an overlap group of SJS and TEN, whereas TEN with maculae is the most severe type of skin reaction with more than 30% of skin detachment related to the body surface area (BSA). This classification was applied to cases of severe skin reactions in several large studies that have been undertaken over the last years. The incidence of SJS, SJS/TEN overlap and TEN has been estimated to be approximately 1.89 cases per 1 million inhabitants per year. Although SJS and TEN occur very rarely, a mortality rate of more than 40% could be calculated for patients suffering from TEN. One may conclude that mortality increases with age and the amount of skin detachment related to the BSA. Results and Conclusions: A number of drugs have been reported to induce severe skin reactions, e.g., antiinfective sulfonamides, antibiotics, anticonvulsants, and nonsteroidal antiinflammatory drugs. Although a lot is known in the etiology of severe skin reactions, the pathogenetic mechanisms have not yet been clarified. Therefore, a specific therapy aiming to stop the progression of disease does not yet exist.
Background and Design:
The usefulness of steroid therapy in toxic epidermal necrolysis (TEN) remains controversial. Up to 5% of the TEN cases occur in patients who undergo long-term steroid therapy. We, thus, looked for the potential effect of long-term glucocorticosteroid therapy before the onset of TEN on altering the progression of the disease. The records of 179 patients were reviewed. The characteristics of the 13 patients who were undergoing long-term glucocorticosteroid therapy were compared with those of 166 other patients with TEN. The following parameters were studied: age, mortality, delay between the introduction of the suspect drug and the onset of TEN, length of hospital stay, body surface area involved, time elapsed between the first symptom of TEN and hospital admission, number of medications taken by the patients before the onset of TEN, lymphocyte count, granulocyte count, platelet count, glycemia, serum aspartate aminotransferase level, and total disease duration.
Results:
Patients who were undergoing long-term glucocorticosteroid therapy differed from other patients with TEN in the administration of more drugs, longer delay between the introduction of the suspect drug and the onset of TEN, and a longer time elapsed between the first symptom of TEN and hospital admission. We observed no differences for the other parameters that were studied.
Conclusion:
Our study shows that long-term steroid therapy may delay the onset of TEN, but it does not hall its progression.(Arch Dermatol. 1995;131:669-672)
Background and design:
To conduct a prospective case-control study about causative factors of severe bullous erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, we needed to define criteria for classifying the cases and standardize the collection of data so that cases could be reliably diagnosed according to this classification. Based on review of case histories and photographs of patients, a group of experts proposed a classification based on the pattern of erythema multiforme-like lesions (categorized as typical targets, raised or flat atypical targets, and purpuric macules) and on the extent of epidermal detachment. An atlas illustrating this classification that included photographs and schematic drawings was developed. We compared the evaluations of 28 cases by four nonphysicians relying on the atlas with the evaluations of the same cases by five experts not using the atlas to determine the usefulness of this atlas for classifying cases according to our nosologic schema.
Results:
The following consensus classification in five categories was proposed: bullous erythema multiforme, detachment below 10% of the body surface area plus localized "typical targets" or "raised atypical targets"; Stevens-Johnson syndrome, detachment below 10% of the body surface area plus widespread erythematous or purpuric macules or flat atypical targets; overlap Stevens-Johnson syndrome-toxic epidermal necrolysis, detachment between 10% and 30% of the body surface area plus widespread purpuric macules or flat atypical targets; toxic epidermal necrolysis with spots, detachment above 30% of the body surface area plus widespread purpuric macules or flat atypical targets; and toxic epidermal necrolysis without spots, detachment above 10% of the body surface area with large epidermal sheets and without any purpuric macule or target. Using the atlas, the nonexperts showed excellent agreement with the experts.
Conclusion:
This study suggests that an illustrated atlas is a useful tool for standardizing the diagnosis of acute severe bullous disorders that are attributed to drugs or infectious agents. Whether the five categories proposed represent distinct etiopathologic entities will require further epidemiologic and laboratory investigations.
• Five patients with severe drug-induced toxic epidermal necrolysis improved rapidly after one to two plasma exchanges. The improvement of all five patients treated with plasmapheresis contrasts with the disease's mortality rate of up to 50%, as reported in the literature and as observed among our previously treated patients. Since there is no effective treatment for toxic epidermal necrolysis, a controlled clinical trial to evaluate the effectiveness of plasma exchange would seem worthwhile.
(Arch Dermatol 1985;121:1548-1549)
Background Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute mucocutaneous reactions associated with poor prognosis. The treatment is mainly symptomatic, based on supportive care. Until now, several curative treatments have been proposed without evidence of effectiveness.
Objectives To evaluate the effect of ciclosporin on SJS and TEN after a short series had suggested a benefit.
Methods We conducted an open, phase II trial to determine the safety and possible benefit of ciclosporin. Among the 45 consecutive patients admitted for SJS/TEN from March 2005 to September 2007, 29 fulfilled inclusion criteria. Ciclosporin was administered orally (3 mg kg−1 daily for 10 days) and tapered over a month. Clinical and biological evaluations were performed sequentially. Predicted death rate was estimated with a validated prognostic score (SCORTEN).
Results Twenty-nine patients were included at a mean ± SD of 2·8 ± 1·8 days after onset. The final diagnosis was SJS (n = 10), SJS/TEN overlap (n = 12) and TEN (n = 7). One month of treatment was completed in 26. Ciclosporin was stopped after more than 10 days in three cases for side-effects including posterior leucoencephalopathy (n = 1), neutropenia (n = 1) and nosocomial pneumopathy (n = 1). Ciclosporin dosage was tapered earlier than scheduled in two cases for alteration in renal function. The prognostic score predicted 2·75 deaths; none occurred (P = 0·1). Mean epidermal detachment remained stable in 18 of 29 cases (62%). The mean ± SD hospital stay was 16·2 ± 9·1 days.
Conclusions Both the death rate and the progression of detachment seemed lower than expected, suggesting a possible usefulness of ciclosporin in SJS and TEN that needs to be confirmed.
• Eighty-seven patients with toxic epidermal necrolysis were observed at Hôpital Henri Mondor in Créteil, France, over the last 12 years. The mean percentage of body surface area involved was 39%. Erosive mucous membrane lesions, identical to those of Stevens-Johnson syndrome, were present in all but three cases. Necrolysis was sometimes generalized within 24 hours but usually spread progressively after a Stevens-Johnson syndrome—like aspect at the onset. Mortality was 25%. Infection, mainly with Staphylococus aureus and Pseudomonas aeruginosa, was the first cause of death, clearly responsible in ten of 20 cases. Age, extension of necrolysis, idiopathic nature of toxic epidermal necrolysis, ingestion of many drugs, elevation of urea, creatinine, and glucose levels, neutropenia, lymphopenia, and thrombocytopenia were statistically linked to a bad prognosis. A multivariant analysis showed that three of these prognosis factors are of paramount importance, namely: age, area of necrolysis, and serum urea level. Pigmentary changes and sicca syndrome were frequently observed sequelae in survivors.
(Arch Dermatol 1987;123:1160-1165)
Stevens-Johnson syndrome has long been considered to resemble erythema multiforme with mucosal involvement, but is now thought to form a single disease entity with toxic epidermal necrolysis. Although Stevens-Johnson syndrome is less severe, etiology, genetic susceptibility and pathomechanism are the same for Stevens-Johnson syndrome/toxic epidermal necrolysis. The condition is mainly caused by drugs, but also by infections and probably other risk factors not yet identified. Identification of the cause is important for the individual patient and in cases of drug-induced disease withdrawal of the inducing drug(s) has an impact on the patient's prognosis. If an infectious cause is suspected, adequate anti-infective treatment is needed. Besides this, supportive management is crucial to improve the patient's state, probably more than specific immunomodulating treatments. Despite all of the therapeutic efforts, mortality is high and increases with disease severity, patients' age and underlying medical conditions. Survivors may suffer from long-term sequelae such as strictures of mucous membranes including severe eye problems.
Patients relapsing from multiple sclerosis (MS) are treated with high-dose, short-term intravenous injection of glucocorticoid (GC), although its mechanism of action remains only partly understood. We evaluated the ex vivo and in vitro effects of GC on regulatory T cell (T(reg)) function in 14 relapsing-remitting MS (RR-MS) patients in acute phase and 20 healthy controls (HC). T(reg) function was enhanced significantly after 5 days of GC treatment. Furthermore, there was a trend towards increasing proportions of CD4(+)CD25(+)forkhead box P3(+) T cells and interleukin-10 secretion with GC treatment when compared with HC. In conclusion, GC treatment restores the impaired T(reg) function in patients with RR-MS in its acute phase.
Despite the lack of evidence of an immunologically mediated mechanism for Toxic Epidermal Necrolysis (TEN), glucocorticosteroids are frequently used for the treatment of patients afflicted with TEN. We investigated the data of 216 patients with TEN for therapy with glucocorticosteroids prior to the beginning of TEN. The data had been collected between 1984 and 1985 during the epidemiological study on severe skin reactions in West-Germany spanning the years 1981-85. 11/216 (5%) patients could be traced, who had been treated with glucocorticosteroids for at least a week prior to the first dermatological sign of TEN. Glucocorticosteroids had been administered predominantly for neurological or neurosurgical conditions. The period of treatment ranged from 1 week to several months. Doses ranging between 7.5 and 325 mg prednisolone/per day were found. There were no major differences between patients with or without steroid therapy with regard to sex, age and lethality. The observation of TEN in patients receiving therapy with glucocorticosteroids raises questions about the usefulness of treating patients with TEN with glucocorticosteroids.
In this article we describe the immunocytochemical and electron microscopic findings in five patients with toxic epidermal necrolysis. They indicate the occurrence of necrotic keratinocytes with nuclear disintegration associated with apposed dendritic cells with the nuclear chromatin configuration of T lymphocytes. These findings, including the presence of blebbing of the keratinocytes and membrane defects associated with cytoplasmic processes from these apposed lymphoid cells, fit known electron microscopic criteria that suggest the involvement of T lymphocyte-mediated cytolysis of drug-altered target keratinocytes in toxic epidermal necrolysis. The effector cell appears to be a dendritic subset, with the phenotypic characteristics (CD3+, CD4-, CD8+, CD2+, DR+) of a T cell subset. There is some evidence that tumor necrosis factor alpha, secreted by activated macrophages, may play a role in necrolysis of the epidermis. The dramatic response of our patients to cyclophosphamide, which is known to inhibit cell-mediated cytotoxicity by inhibiting both the recognition and lethal hit stages, together with the rapid regrowth of the epidermis within 4 days to a week in patients who received adequate dosage of the drug, supports the preceding concepts.
Little work has been carried out on the epidemiology of the two serious skin reactions--toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). We collected details of all the hospitalized cases of TEN and SJS in the Federal Republic of Germany for the years 1981 through 1985 inclusive. Inquiries by telephone, letter, and personal visits produced an overall response of 91%; 259 cases of TEN and 315 cases of SJS were identified. From these data, we were able to calculate an overall annual risk of 0.93 and 1.1 per million for TEN and SJS, respectively. The average age group was higher for TEN (63 years) than for SJS (25 years). Women are markedly more at risk for TEN in the ratio of 2:1, these figures being reversed for SJS. The mortality was 34% (87/259) for TEN and only 1% (2/315) for SJS. An association with previous medication defined as "definite, probable, possible" could be established for 89% of cases of TEN and 54% of cases of SJS. The drugs most commonly involved were antibiotics (TEN, 40%; SJS, 34%), followed by the analgesics (TEN, 23%; SJS, 33%). As with the drug groups, the incidences being based on the defined daily doses, were high for sulfonamides, beta-lactam antibiotics, and some nonsteroidal anti-inflammatory drugs.
We looked retrospectively for all cases of toxic epidermal necrolysis that occurred in France over a 5-year period to appreciate the incidence of this disorder and its drug etiology. Of the 399 cases identified, we obtained detailed information on 344 cases and validated 253 cases. From response rates (66% to 98%), we estimated the actual total number of cases to be 333, and the incidence of toxic epidermal necrolysis in France to 1.2 cases per million per year. An independent estimation derived from death certificates gave a figure of 1.3 cases per million per year. When the number of cases with a given drug present were related to the defined daily doses of that drug sold over the 5-year period, the highest ratios were for sulfadiazin (230.10(-8], isoxica (41.10(-8], oxyphenbutazone (18.10(-8], phenytoin (14.10(-8], fenbufen (13.10(-8], and cotrimoxazole (12.10(-8]. This first nationwide study confirmed the rarity of toxic epidermal necrolysis. Within the two main classes of responsible drugs (antibacterial sulfonamides and nonsteroidal anti-inflammatory agents) the risks linked to different drugs appeared quite different, even for closely chemically related products.
Fifteen consecutive patients with toxic epidermal necrolysis or the Stevens-Johnson syndrome managed without corticosteroids after transfer to the burn center (group 2) are compared to a previous consecutive group of 15 who received high doses of these drugs (group 1). Group 2 had a 66% survival, which was a significant improvement compared to the 33% survival in group 1 (p = 0.057). In group 1, mortality was associated with loss of more than 50% of the body surface area skin. In group 2, mortality was related to advanced age and associated diseases. Age, extent of skin loss, progression of skin loss after burn center admission, incidence of abnormal liver function tests, and the incidence of septic complications were not significantly different in the two groups (p greater than 0.10). The incidence of detected esophageal slough was similar in both groups. Nonsteroid (group 2) management was associated with a decreased incidence of ulceration of gastrointestinal columnar epithelium, Candida sepsis, and an increased survival after septic complications. The combined experience of these 30 patients suggests that corticosteroids are contraindicated in the burn center management of toxic epidermal necrolysis and the Stevens-Johnson syndrome.
Five patients with severe drug-induced toxic epidermal necrolysis improved rapidly after one to two plasma exchanges. The improvement of all five patients treated with plasmapheresis contrasts with the disease's mortality rate of up to 50%, as reported in the literature and as observed among our previously treated patients. Since there is no effective treatment for toxic epidermal necrolysis, a controlled clinical trial to evaluate the effectiveness of plasma exchange would seem worthwhile.
The usefulness of steroid therapy in toxic epidermal necrolysis (TEN) remains controversial. Up to 5% of the TEN cases occur in patients who undergo long-term steroid therapy. We, thus, looked for the potential effect of long-term glucocorticosteroid therapy before the onset of TEN on altering the progression of the disease. The records of 179 patients were reviewed. The characteristics of the 13 patients who were undergoing long-term glucocorticosteroid therapy were compared with those of 166 other patients with TEN. The following parameters were studied: age, mortality, delay between the introduction of the suspect drug and the onset of TEN, length of hospital stay, body surface area involved, time elapsed between the first symptom of TEN and hospital admission, number of medications taken by the patients before the onset of TEN, lymphocyte count, granulocyte count, platelet count, glycemia, serum aspartate aminotransferase level, and total disease duration.
Patients who were undergoing long-term glucocorticosteroid therapy differed from other patients with TEN in the administration of more drugs, longer delay between the introduction of the suspect drug and the onset of TEN, and a longer time elapsed between the first symptom of TEN and hospital admission. We observed no differences for the other parameters that were studied.
Our study shows that long-term steroid therapy may delay the onset of TEN, but it does not halt its progression.
This article has no abstract; the first 100 words appear below.
Although the rate of acute severe adverse cutaneous reactions to medications is low, these reactions can affect anyone who takes medications and can result in death or disability¹. Even a small number of cases associated with a particular drug may alter the recommendations for its use²–⁴. Prompt differentiation of severe adverse cutaneous reactions from less serious skin disorders may be difficult. Rapid recognition of severe reactions is essential. Prompt withdrawal of the offending drug is often the most important action to minimize morbidity. Adverse cutaneous reactions to drugs are frequent, affecting 2 to 3 percent of hospitalized . . .
Supported in part by a grant from INSERM (90-0812).
Source Information
From the Department of Dermatology, Henri Mondor Hospital, University of Paris XII, Creteil, France (J.C.R.), and Beth Israel Hospital, Harvard Medical School, Boston (R.S.S.).
Address reprint requests to Dr. Stern at the Department of Dermatology, Beth Israel Hospital, 330 Brookline Ave., Boston, MA 02215.
Toxic epidermal necrolysis (TEN) is a life threatening exfoliative disorder that is most commonly precipitated by the administration of a medication. Efforts to reduce morbidity and improve survival have brought into question the use of corticosteroids and recommend the transfer of patients to a burn center to facilitate wound care.
This study evaluated the correlation of measures of disease severity and impact of treatment strategies on morbidity and mortality in patients with TEN. The records of all patients with TEN admitted to the United States Army Institute of Surgical Research during a 12 year period were reviewed. Patient characteristics, etiologic agents, time to referral of patients to the burn center, corticosteroid therapy, and other demographic features were studied. Univariate and multivariate analyses were used to determine the significance of these factors with respect to outcome.
The sulfonamides and phenytoin were the most frequently identified etiologic agents. Patients at the extremes of age had a higher mortality rate. The period of hospitalization was longer in patients transferred to the burn center more than seven days after skin slough. Percent of epidermalysis, white blood cell count nadir, and corticosteroid administration for more than 48 hours were independently associated with mortality.
These data indicate that the sulfonamides and phenytoin are the most common etiologic agents, expeditious transfer to a burn center reduces morbidity, and corticosteroid administration dramatically increases mortality.
The severe skin reactions erythema exsudativum multiforme majus (EEM with mucosal involvement, EEMM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) are difficult to study as they are very rare diseases with an incidence of about two cases per 1 million inhabitants per year. We report on the structure of a registry with the aim of ascertaining all hospitalized cases of EEMM, SJS, and TEN in western Germany and Berlin. The registry is structured as an intensive reporting system, regularly contacting more than 1500 departments including 100% of the burn units (n = 34), departments of pediatrics (n = 241), departments of dermatology (n = 106), and 100% of all internal medicine departments in hospitals with intensive care facilities or with more than 200 beds (n = 1161). With a coverage rate up to 95% based on the number of responding departments between April 1, 1990 and December 31, 1992, from a total of 767 reported cases 353 patients with EEMM, SJS, and TEN were finally included in the registry. Most of these patients were directly reported to the registry; only 2.54% (9 of 353) were primarily registered by the German spontaneous reporting systems. Assuming an average population of 64.5 million for western Germany and Berlin an incidence up to 1.89 per 1 million inhabitants per year could be calculated for SJS and TEN.
Toxic epidermal necrolysis (TEN) is a severe skin disorder characterized by separation of the dermal-epidermal junction, as is observed in second-degree superficial burns. It has been proposed that immunosuppressive treatment may improve prognosis of patients with TEN.
We report here a case series of patients with TEN treated with cyclosporin A (CSA) without other concomitant immunosuppressive agent. These patients (n = 11) were consecutively admitted to our Intensive Care Burn Unit because of severe TEN, involving a large body surface area (83 +/- 17% [mean +/- SD], median, 90%; range, 35-96%) and were treated with CSA 3 mg/kg per day enterally every 12 hours. We compared the series of patients treated with CSA with a historical series of patients admitted to our Intensive Care Burn Unit before CSA was introduced as part of the treatment protocol These patients (n = 6) were treated with cyclophosphamide (150 mg i.v. every 12 hours) and different doses of corticosteroids (> or =1 mg/kg per day of 6-methyl-prednisolone). Both groups of patients were similar in regard to age, delay from onset of disease to Intensive Care Burn Unit admission, and body surface area involved.
Time from the onset of skin signs to arrest of the disease progression (1.4 +/- 0.3 days, vs. 3.6 +/- 1.5 days) and to complete reepithelialization (12.0 +/- 3.6 days, vs. 17.6 +/- 3.1 days) was significantly shorter in patients treated with CSA compared with those treated with cyclophosphamide and corticosteroids (p = 0.0002, and p = 0.0058, respectively). Significantly fewer patients in the CSA group had > or =4 organs failing (2 of 11 vs. 3 of 6, respectively, p = 0.029), had severe leukopenia (<1,000 cells/microL) (0 of 11 vs. 4 of 6, respectively, p = 0.006), or died (3 of 6 vs. 0 of 11, respectively, p = 0.0029).
We conclude that immunosuppressive treatment with CSA is safe and is associated with a rapid reepithelialization rate and a low mortality rate in patients with severe TEN. Our data suggest that this regimen could be more effective than treatment with cyclophosphamide and corticosteroids. Prospective controlled trials are required to test the hypothesis that CSA is more effective than cyclophosphamide or other immunosuppressive regimens for the treatment of TEN.
A 62-year-old female patient is described who developed toxic epidermal necrolysis (TEN) after medication with phenytoin and oxazepam. Initially phenytoin was discontinued and dexamethasone pulse therapy (1.5 mg/kg on 3 consecutive days) was initiated on the tenth day of skin disease. This resulted in clinical improvement. Histologically re-epithelialization could be demonstrated below the necrotic epidermis. However, on the eighteenth day of skin disease (10 days after discontinuation of phenytoin and 8 days after the start of dexamethasone pulse therapy), a histologically verified rebound-TEN developed with a detachment of 95%. Oxazepam was stopped and a second series of dexamethasone pulse therapy was given. Re-epithelialization began within 24 h of the start of the second series of dexamethasone pulse therapy, and continued to almost complete recovery within 1 week.
THERAPEUTIC STUDIES in toxic epidermal necrolysis (TEN), a rare but dramatic and life-threatening disease, have recently drawn a considerable amount of attention. Despite (or perhaps due to) the fact that a variety of possible therapeutic modalities have been proposed, usually based on a symptomatic approach and tried in single patients or small series, still no proven and widely accepted treatment regimen exists.
The development of a generally accepted treatment strategy has been hampered by the fact that the condition is part of a larger spectrum of reactive inflammatory skin diseases and thus heterogeneous; that it is rare and life threatening and thus precludes placebo-controlled studies; and that our knowledge on the pathogenic mechanisms involved are still only fragmentary.
No treatment modality has been established as standard for patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.
We sought to evaluate the effect of treatment on mortality in a large cohort of patients with Stevens-Johnson syndrome or toxic epidermal necrolysis.
Data on therapy were retrospectively collected from patients in France and Germany enrolled in EuroSCAR, a case-control study of risk factors.
Neither intravenous immunoglobulins nor corticosteroids showed any significant effect on mortality in comparison with supportive care only. Compared with supportive care, odds ratios for death were 1.4 (95% confidence interval: 0.6-4.3) for intravenous immunoglobulins in France and 1.5 (0.5-4.4) in Germany, and 0.4 (0.1-1.7) for corticosteroids in France and 0.3 (0.1-1.1) in Germany.
Such an observational study with retrospective data collection has obvious limitations, including heterogeneity between the countries, supportive care, treatment doses, and durations.
We found no sufficient evidence of a benefit for any specific treatment. The trend for a beneficial effect of corticosteroids deserves further exploration.
Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin
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Viard I, Wehrli P, Bullani R et al. Inhibition of toxic epidermal
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Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin
- Viard