Toxic epidermal necrolysis associated with pembrolizumab

2019 ◽  
Vol 26 (5) ◽  
pp. 1259-1265 ◽  
Author(s):  
Zhuo Ran Cai ◽  
Julie Lecours ◽  
Jean-Philippe Adam ◽  
Isabelle Marcil ◽  
Normand Blais ◽  
...  

Introduction Stevens-Johnson syndrome and toxic epidermal necrolysis are severe cutaneous drug eruptions characterized by epidermal detachment. Pembrolizumab is a monoclonal antibody that binds to the programmed death-1 receptor, and it has been associated with numerous cutaneous adverse side-effects, including Stevens-Johnson syndrome. Case report We describe a 63-year-old male with metastatic lung adenocarcinoma who developed a rapidly progressing maculopapular rash three days after a first dose of pembrolizumab. On day 16, the rash affected more than 80% of body surface area with detachment of large sheets of necrolytic epidermis in 30–40% of body surface area. However, the patient only presented with mild mucosal involvement. Histopathologic examination of a skin biopsy showed a subepidermal blister with overlying prominent full thickness epidermal keratinocytic necrosis and a superficial perivascular infiltrate of lymphocytes. A toxic epidermal necrolysis secondary to pembrolizumab was then diagnosed. Management and outcome: In addition to supportive cares, the patient received corticosteroids and cyclosporine. The patient responded rapidly to the immunosuppressant therapy, and nearly complete re-epithelialization was achieved 24 days after the start of the reaction. Discussion In our review of the literature, 15 other cases of Stevens-Johnson syndrome/toxic epidermal necrolysis were reported with programmed death-1/programmed cell death ligand-1 inhibitors. To our knowledge, this is the first case of toxic epidermal necrolysis secondary to pembrolizumab published in the literature. The American Society of Clinical Oncology guidelines suggest that cyclosporine, in addition to corticosteroids, be initiated when toxic epidermal necrolysis is suspected. Clinicians should be aware of this rare dermatological emergency with the increasing use of pembrolizumab in oncology.

2020 ◽  
Vol 88 (3) ◽  
pp. 160-162
Author(s):  
Ajay Kumar ◽  
Mandar Ramchandra Sane ◽  
Amandeep Singh ◽  
Dasari Harish

Toxic epidermal necrolysis is a rapidly progressive exfoliating dermatosis which simulates second degree burns. The authors describe a fatal case reported as due to burns. Around 95% of the deceased’s total body surface area was affected, with epidermolysis over face, chest, abdomen, limbs and associated with mucosal involvement. Histopathological findings revealed epidermal necrolysis and confirmed the autopsy suspicion. Because of its sudden onset and rapid progression, toxic epidermal necrolysis often arises suspicion of burns by investigators. We emphasise the differentiating features between toxic epidermal necrolysis and burns and its implications.


1994 ◽  
Vol 111 (3P1) ◽  
pp. 236-242 ◽  
Author(s):  
Michael G. Stewart ◽  
Newton O. Duncan ◽  
Daniel J. Franklin ◽  
Ellen M. Friedman ◽  
Marcelle Sulek

Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis are related disorders of skin and mucous membranes, which are typically associated with antecedent medication use or infection. We review 108 cases of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis from Texas Children's Hospital, Houston, Texas, from 1981 to 1991, and illustrate the characteristic skin and mucosal lesions. In addition, we describe in detail two unusual cases requiring intensive airway management. Head and neck manifestations were present in 4 of 79 patients (5%) with erythema multiforme and 26 of 28 patients (93%) with Stevens-Johnson syndrome. In Stevens-Johnson syndrome, mucosal involvement of the lip (93%), conjunctiva (82%), oral cavity (79%), and nose (36%) were most common. Antecedent medication use was identified in 59% of erythema multiforme patients and 68% of Stevens-Johnson syndrome patients. We note a striking increase in the number of cases in our series caused by cephalosporins. Fifty percent of Stevens-Johnson syndrome patients required supplemental hydration or alimentation because of the severity of the oral cavity involvement. The head and neck mucosal manifestations largely respond to local care, and the routine use of prophylactic antibiotics or systemic steroids is not recommended.


2020 ◽  
Vol 8 (B) ◽  
pp. 381-388
Author(s):  
Tran Thi Huyen ◽  
Pham Dinh Hoa ◽  
Trinh Minh Trang ◽  
Riichiro Abe ◽  
Nguyen Van Thuong ◽  
...  

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute, life-threatening drug reactions, which lead to massive epidermal necrolysis. Granulysin plays an important role as a key mediator for keratinocyte apoptosis in these conditions. Erythema multiforme (EM) may have skin manifestation similar to SJS/TEN. AIMS: The aim of the study was to compare serum granulysin levels in patients with SJS/TEN and EM as well as to investigate a possible association between serum granulysin levels and the severity of SJS/TEN. METHODS: In total, 48 patients with SJS/TEN, 43 patients with EM, and 20 health controls (HCs) were enrolled. We measured serum granulysin levels using enzyme-linked immunosorbent assay. RESULTS: The average level of serum granulysin in the SJS/TEN patients was 23.0 ng/ml (range 1.2–144.6 ng/ml), significantly higher than that of EM group (20.1 ng/ml; range 8.5–121 ng/ml, p < 0.05) and HCs group (20.8 ng/ml; range 10.1–46.7 ng/ml, p < 0.05). Of 48 SJS/TEN patients, the 25 samples collected <6 days after onset showed higher level of serum granulysin (27.7 ng/ml; range 2.5–144.6 ng/ml) than those collected ≥6 days after onset (17.9 ng/ml; range 1.2–59 ng/ml; p > 0.05). No significant correlation was found between serum granulysin levels and the body surface area affected and the modified-SCORTEN. At the day of re-epithelialization, serum granulysin levels were not different compared with those at the day of hospitalization. CONCLUSIONS: Serum granulysin levels are significantly higher in SJS/TEN group than in EM group. After the onset, serum granulysin levels in patients with SJS/TEN are not a good biomarker to evaluate the severity of the diseases.


Author(s):  
Rahima S. ◽  
Abdul Latheef E. N. ◽  
Pavithran K. ◽  
Saleem P. M.

<p class="abstract"><strong>Background:</strong> Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered as the severest end of spectrum of erythema multiforme. Various etiologies like infections, drugs and malignancies have been proposed. The aim of the present study was to know the incidence, common causes, clinical course of SJS and TEN and to estimate the morbidity and mortality<span lang="EN-IN">.</span></p><p class="abstract"><strong>Methods:</strong> A 2 year study of patients presenting with SJS and TEN was carried out. A detailed examination to know the cutaneous and mucosal involvement was done. Biopsy was done in 3 patients.<strong></strong></p><p class="abstract"><strong>Results:</strong> There were fifty patients of SJS-TEN spectrum. Of which 31 were SJS, 3 had SJS-TEN overlap and 16 had TEN.  Anticonvulsants were implicated in causing these reactions in 24 patients (48%) with carbamazepine being the most common i.e. in 16 patients (32%). Sparing of pressure areas like the strap area of brassier and waist was noticed in two patients (4%). The most common complication was due to eye involvement seen in 20 patients (40%). 46 patients were treated with steroids and of the remaining, 3 were children and one was HIV positive. Only three patients with TEN (6%) died<span lang="EN-IN">. </span></p><p class="abstract"><strong>Conclusions:</strong> To conclude, TEN was less common than SJS, had more sequelae and more mortality compared to SJS<span lang="EN-IN">.</span></p><p class="abstract"> </p>


Author(s):  
Rodrigo Banegas Ruiz ◽  
Alan I. Valderrama Treviño ◽  
Gómez Mendoza F. F. ◽  
Baca Domínguez C. R. ◽  
Campos Angulo G. ◽  
...  

Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are considered a single entity with variability in the extent of the lesions, characterized by erythema multiforme that may involve mucosa. Severe cutaneous reactions secondary to medications are classified according to the area of epidermal detachment. The activation of cytotoxic T cells and macrophages is mediated mainly by IL-2 and interferon gamma secreted by Th1 lymphocytes, and the activation of eosinophils and B lymphocytes in IgE is mediated by secreted IL-4, IL-5, IL-10 and IL13 by B lymphocytes. The topography of SJS is predominantly central, affecting the trunk and sometimes a generalized dissemination is shown that affects a body surface area of less than 10%, characterized by irregular violaceous erythematous macules of target shooting, which can form confluent blisters. TEN is characterized by a skin detachment greater than 30% of the body surface, whose predominant lesion is diffuse erythema with individual macules, which give rise to detachment surfaces greater than 5 cm. The treatment is symptomatic, nonspecific, and aimed at avoiding complications, carried out in specialized intensive care units, due to ignorance of the pathogenesis. Integral management with different therapeutic alternatives can represent a crucial part in the multisystemic management of SJS and TEN.


2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Carlos Saavedra ◽  
Paola Cárdenas ◽  
Héctor Castellanos ◽  
Kateir Contreras ◽  
J. R. Castro

Toxic epidermal necrolysis is the most severe form of drug-induced skin reaction and includes denudation of >30% of total body surface area. The mechanism of disease is not completely understood, but immunologic mechanisms, cytotoxic reactions, and delayed hypersensitivity seem to be involved. We report a case of cephazolin-induced toxic epidermal necrolysis treated with intravenous immunoglobulin and N-acetylcysteine with excellent response.


2016 ◽  
Vol 19 (2) ◽  
pp. 154-159
Author(s):  
Dewi Puspasari ◽  
Irna Sufiawati

Stevens–Johnson syndrome (SJS)/ Toxic Epidermal Necrolysis (TEN) are acute, self-limited, potentially life-threatening mucocutaneous disease. Oral mucosal involvement manifest as extensive erosions and haemorrhagic crusting, which can interfere oral functions causing odynophagia, inability to tolerate solid foods, and increased aspiration risk. A 40-year-old female patient was referred from Dermatology and Venereology department with diagnosis SJS/TEN overlap. The patient complained mouth opening difficulty due to mouth and lip sores. Drug history revealed positive intake of carbamazepine. Extraoral examination revealed multiple diffuse discrete facial lesions, conjunctival hyperemia, erosions and hemorrhagic crusting lips. Intraoral examination revealed white yellowish plaque, and erosions on buccal mucosa, palate, floor of the mouth, dorsal, ventral, and lateral tongue. Laboratory investigation revealed decrease of haemoglobin, hematocrite, Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), thrombocyte, eosinophil, band of eosinophil, lymphocyte, natrium, potassium, and calcium. Oral lesions associated with SJS/TEN overlap diagnosis was made. Chlorhexidine gluconate 0,1%, nystatin oral suspension, vitamin B12, folic acid, and corticosteroid unguent compounding were given, which showed improvement of oral lesions in 3 weeks. SJS/TEN are the same disease spectrum of delayed hypersensitivity reaction leading to keratinocyte apoptosis through cytotoxic T-cell mediated Fas-Fas ligand, perforin/ granzyme B, and granulysin, which distinguished primarily by severity and percentage of total body surface area involved.Currently, an optimal treatment standard for SJS/TEN patients remains unavailable. Oral lesions management play significant role in enhancing patients’ quality of life and achieving better prognosis in SJS/TEN overlap patients through multidisciplinary approach.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Carlo Maria Rossi ◽  
Flavio Niccolò Beretta ◽  
Grazia Traverso ◽  
Sandro Mancarella ◽  
Davide Zenoni

Abstract Background Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is the most Serious Cutaneous Adverse Reaction (SCAR) often with a fatal outcome. Coronavirus Disease (COVID-19) is caused by Severe Acute Respiratory Syndrome–Coronavirus—2 (SARS-COV2) and is an emergent pandemic for which no cure exist at the moment. Several drugs have been tried often with scant clinical evidence and safety. Case presentation Here we report the case of 78-years-old woman with cardiometabolic syndrome and COVID-19. A multidrug regimen including others hydroxychloroquine, antibiotics, dexamethasone and paracetamol, low-molecular-weight-heparin and potassium canrenoate was started. After almost 3 weeks, the patient started to display a violaceous rash initially involving the flexural folds atypical targetoid lesions and showing a very fast extension, blister formation and skin detachments of approximately 70% of the total body surface area and mucous membranes involvement consistent with toxic epidermal necrolysis (TEN). The ALDEN algorithm was calculated inserting all drugs given to the patient in the 28 days preceding the onset of the skin manifestations. The highest score retrieved was for hydroxychloroquine. Other less suspicious drugs were piperacillin/tazobactam, ceftriaxone and levofloxacin. Conclusions To our knowledge, this is the first case of TEN in a patient suffering from COVID-19 probably associated with hydroxychloroquine. Given the activation of the immune system syndrome induced by the virus and the widespread off-label use of this drug, we suggest a careful monitoring of skin and mucous membranes in all COVID-19 positive patients treated with hydroxychloroquine in order to early detect early signs of toxicities.


2012 ◽  
Vol 21 (2) ◽  
pp. 74-76
Author(s):  
Md. Rokon Uddin ◽  
Motahar Hossain Bhuiyan ◽  
Farjana Akhter ◽  
Md. Abu Baker ◽  
AKM Akramuzzaman

Medicine Today 2009 Volume 21 Number 02 Page 74-76 DOI: http://dx.doi.org/10.3329/medtoday.v21i2.12552


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