An extremely rare mucocutaneous adverse reaction following COVID-19 vaccination: Toxic epidermal necrolysis. ALDEN, an algorithm for assessment of drug causality in StevensJohnson Syndrome and toxic epidermal necrolysis: comparison with case-control analysis. A recently published meta-analysis by Huang [110] and coworkers on IVIG in SJS/SJS-TEN/TEN reviewed 17 studies with 221 patients and compared the results obtained with high-dosage IVIG (>2g/kg) compared to lower-dosage IVIG (<2g/kg). Do this 2 to 3 times a week. In ED increased levels of FasL have been detected in patients sera [33]. Cite this article. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Erythema multiforme (EM), StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Ann Intern Med. StevensJohnson syndrome and toxic epidermal necrolysis. Huang YC, Li YC, Chen TJ. -. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Read this article to find out all its symptoms, causes and treatments. Even though exfoliative dermatitis is a complex disorder involving many factors, the underlying disease is usually the key determinant of the course and prognosis. Copyright 1999 by the American Academy of Family Physicians. Not responsive to therapy. Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involving skin and usually occurring from days to several weeks after drug exposure. National Library of Medicine Mucosal involvement could achieve almost 65% of patients [17]. Nassif A, et al. Erythema multiforme. J Am Acad Dermatol. This is due to a reaction to certain medicines, a pre-existing skin condition, and sometimes cancer. Epub 2022 Mar 9. J Am Acad Dermatol. J Invest Dermatol. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti-PD-1/PD-L1 treatments. Orton PW, et al. Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal necrolysis. Toxic epidermal necrolysis associated with severe cytomegalovirus infection in a patient on regular hemodialysis. Ned Tijdschr Geneeskd. The drug level peaks after 1- 4 h in plasma after ingestion with 95% protein binding. Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis. Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involving skin and usually occurring from days to several weeks after drug. 2008;53(1):28. PubMed . Some of these patients undergo spontaneous resolution. 2013;69(2):173174. In: Eisen AZ, Wolff K, editors. Int J Dermatol. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis. 2013;27(5):65961. The clinical course of patients with malignancies depends on the type of malignancy and the response to appropriate therapy. Am J Infect Dis. After 24 hours, split formation was evident in hematoxylin and eosin-stained sections of HOSCs treated . Aminoglutethimide: Aminoglutethimide may lead to a loss of corticosteroid-induced adrenal suppression. Possible involvement of CD14+CD16+monocyte lineage cells in the epidermal damage of StevensJohnson syndrome and toxic epidermal necrolysis. Clipboard, Search History, and several other advanced features are temporarily unavailable. The diagnosis of GVDH requires histological confirmation [87]. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. The erythrodermic form of mycosis fungoides and the Szary syndrome may also be difficult to distinguish from benign erythroderma. Exfoliative dermatitis is characterized by generalized erythema with scaling or desquamation affecting at least 90% of the body surface area. Exfoliative dermatitis (ED) is defined as diffuse erythema and scaling of the skin involving more than 90% of the total body skin surface area. Allergol Immunopathol (Madr). 2015;13(7):62545. Acute generalized exanthematous pustulosis (AGEP) is characterized by acute erythematous skin lesions, generally arising in the face and intertriginous areas, subsequently sterile pinhead-sized nonfollicular pustules arise and if they coalesce, may sometimes mimic a positive Nikolskys sign and in this case the condition may be misinterpreted as TEN [86]. Diagnosis in a routine setting is based on patch test (PT) while skin test (prick and intradermal tests) with a delayed reading are contraindicated in these patients [72]. CAS Ganciclovir and cidofovir should be used when polymerase-chain reactions (PCR) on peripheral blood or other biological sample identifies a viral reactivation (HHV6, HHV7, EBV and CMV). Arch Dermatol. . Erythema multiforme and toxic epidermal necrolysis. Hepatobiliary: jaundice, hepatitis, including . Patch testing in severe cutaneous adverse drug reactions, including StevensJohnson syndrome and toxic epidermal necrolysis. Mayo Clin Proc. 1997;22(3):1467. Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involving skin and usually occurring from days to several weeks after drug exposure. Fischer M, et al. 8600 Rockville Pike Recombinant granulocyte colony-stimulating factor in the management of toxic epidermal necrolysis. In EMM lesions typically begin on the extremities and sometimes spread to the trunk. In patients with this disorder, the mitotic rate and the absolute number of germinative skin cells are higher than normal. 1998;37(7):5203. Bourgeois GP, et al. The timing of the rash can also vary. Samim F, et al. Erythema multiforme (photo reproduced with, Erythema multiforme (photo reproduced with permission of Gary White, MD): typical target lesions, Mortality rate of patients with TEN has shown to be directly correlated to, Management of patients with a suspected drug induced exfoliative dermatitis, MeSH Several authors report the incidence of hospitalization for EM ranging from 0.46 cases per million people per year of northern Europe [11] to almost 40 cases per million people per year of United States [12]. Roujeau JC, et al. When it precedes cutaneous T-cell lymphoma lesions, exfoliative dermatitis becomes the presenting sign of the underlying malignancy. Morel E, et al. Google Scholar. Hydration and hemodynamic balance. Initial symptoms could be aspecific, as fever, stinging eyes and discomfort upon swallowing, occurring few days before the onset of mucocutaneous involvement. Check the full list of possible causes and conditions now! Rare dermatological side effects such as alopecia, exfoliative dermatitis, xeroderma, pruritus have been reported. In: Eisen AZ, Wolff K, editors. Pehr K. The EuroSCAR study: cannot agree with the conclusions. The SJS histology is characterized by a poor dermal inflammatory cell infiltrate and full thickness necrosis of epidermis [20, 49]. A drug eruption may start as a rash but eventually progress to more generalized exfoliative dermatitis. 2004;428(6982):486. Combination of infliximab and high-dose intravenous immunoglobulin for toxic epidermal necrolysis: successful treatment of an elderly patient. Patient must be placed in an antidecubitus fluidized bed and room temperature must be kept at 3032C in order to slow catabolism and reduce the loss of calories through the skin [89]. Wolkenstein P, et al. While nearly any medication can, in theory, cause a reaction if you're sensitive, medications linked to exfoliative dermatitis include: sulfa drugs; penicillin and certain other antibiotics . These include a cutaneous reaction to other drugs, exacerbation of a previously existing condition, infection, metastatic tumor involvement, a paraneoplastic phenomenon, graft-versus-host disease, or a nutritional disorder. Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involving skin and usually occurring from days to several weeks after drug exposure. The authors concluded that they couldnt demonstrate corticosteroids efficacy in monotherapy, but the use of steroid alone is not linked to an increased risk of mortality due to infective complications [108, 109]. 2008;58(1):3340. The prognosis of cases associated with malignancy typically depends on the outcome of the underlying malignancy. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. The balance of fluids and electrolytes should be closely monitored, since dehydration or hypervolemia can be problems. Fitzpatricks dermatology in general medicine. Overall, incidence of SJS/TEN ranges from 2 to 7 cases per million person per year [9, 1820], with SJS the commonest [21]. Science. 2010;2(3):18994. Clinical and Molecular Allergy Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens-Johnson syndrome. Bastuji-Garin S, et al. Gastrointest Endosc. A patch testing and cross-sensitivity study of carbamazepine-induced severe cutaneous adverse drug reactions. Medicines have been linked to every type of rash, ranging from mild to life-threatening. Prevalence is low, with mortality of roughly 512.5% for SJS and 50% for TEN [1, 2]. Antibiotics: amoxicillin, ampicillin, ciprofloxacin, demeclocycline , doxycycline , minocycline, nalidixic acid, nitrofurantoin, norfloxacin, penicillin , rifampicin, streptomycin, tetracycline , tobramycin, trimethoprim, trimethoprim + sulphamethoxazole, vancomycin Anticonvulsants : barbiturates, carbamazepine ALDEN has shown a good accuracy to assess drug causality compared to data obtained by pharmacovigilance method and casecontrol results of the EuroSCAR casecontrol analysis for drugs associated with TEN. Huff JC. Mawson AR, Eriator I, Karre S. StevensJohnson syndrome and toxic epidermal necrolysis (SJS/TEN): could retinoids play a causative role? These levels could reflect the interaction between culprit drugs and aldehyde dehydrogenase that is the enzyme which metabolizes retinoid acid. N Engl J Med. 2012;42(2):24854. (See paras 3 - 42 and 3- 43.) Therefore, it is important to identify and treat any underlying disease whenever possible and to remove any contributing external factors.2, Most published studies of exfoliative dermatitis have been retrospective and thus do not address the issue of overall incidence. Cyclosporine A (Cys A): Cys A works through the inhibition of calcineurin, that is fundamental for cytotoxic T lymphocytes activation. 2018 Feb;54(1):147-176. doi: 10.1007/s12016-017-8654-z. f. This has been called the nose sign.18, Once the erythema is well established, scaling inevitably follows (Figure 1). Br J Dermatol. 2010;31(1):1004. Exfoliative dermatitis is also a risk factor for epidemic spread of methicillin-resistant Staphylococcus aureus.6,20. AB, CC, ET, GAR, AN, EDL, PF performed a critical revision on the current literature about the described topic, wrote and revised the manuscript. 2023 Jan 30;11(2):346. doi: 10.3390/microorganisms11020346. Erythema multiforme (EM), Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. In acute phase it is crucial to assess the culprit agent, in particular when the patient was assuming several drugs at time of DHR. Allergy. Some anti-seizure medicines have also been known to cause exfoliative dermatitis. It is a clinical manifestation and usually associated with various underlying cutaneous disorders, drug induced reactions and malignancies. 1994;331(19):127285. Kostal M, et al. (in Chinese) . It is necessary to obtain as soon as possible a central venous access and to start a continuous monitoring of vital signs. Recent advances in the genetics and immunology of StevensJohnson syndrome and toxic epidermal necrosis. Drug-induced LPP. 1993;129(1):926. Clinical classification of cases of toxic epidermal necrolysis, StevensJohnson syndrome, and erythema multiforme. Tohyama M, et al. Neoplastic conditions (renal and gastric carcinoma), autoimmune disease (inflammatory bowel disease), HIV infection, radiation, and food additives/chemicals have been reported to be predisposing factor [59]. Ozeki T, et al. Etoricoxib-induced toxic epidermal necrolysis: successful treatment with infliximab. New York: McGraw-Hill; 2003. pp. Toxic epidermal necrolysis: Part I Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. 2012;27(4):21520. Linear IgA dermatosis most commonly presents in patients older than 30years. Chung WH, et al. Robyn A. McMenamin, L M. Davies and P. W. Craswell, Aust. Tang YH, et al. Fritsch PO. Other dermatoses associated with erythroderma are listed in Table 1.2,3,68. Analysis of StevensJohnson syndrome and toxic epidermal necrolysis using the Japanese Adverse Drug Event Report database. Article Mardani M, Mardani S, Asadi Kani Z, Hakamifard A. Dermatol Ther. 2008;12(5):3559. In particular, drug induced exfoliative dermatitis (ED) are a group of rare and more severe drug hypersensitivity reactions (DHR) involving skin and mucous membranes and usually occurring from days to several weeks after drug exposure [2]. In vitro diagnostic assays are effective during the acute phase of delayed-type drug hypersensitivity reactions. 1996;44(2):1646. Interferon alfa (Roferon-A, Intron A, Alferon N), Isoniazid (Laniazid, Nydrazid; also in Rifamate, Rimactane), Isosorbide dinitrate (Isordil, Sorbitrate), Para-amino salicylic acid (Sodium P.A.S. It often precedes or is associated with exfoliation (skin peeling off in scales or layers), when it may also be known as exfoliative dermatitis (ED). Exanthematous drug eruptions. Clinical features; Delayed type hypersensitivity; Drug hypersensitivity; Erythema multiforme; Exfoliative dermatitis; Lyells syndrome; Pathogenesis; StevensJohnson syndrome; Therapy; Toxic epidermal necrolysis. Bullous FDE. Case Rep Dermatol Med. Exfoliative dermatitis accounts for about 1 percent of all hospital admissions for dermatologic conditions.3, Although the disease affects both men and women, it is more common in men, with an average male-to-female ratio of 2.3:1. The most common causes of death in patients with exfoliative dermatitis are pneumonia, septicemia and heart failure. First of all, Sassolas and coauthors proposed an algorithm of drug causality (ALDEN) in order to improve the individual assessment of drug causality in TEN and SJS [71]. Article 2008;159(4):9814. 2010;62(1):4553. Immunol Allergy Clin North Am. Orphanet J Rare Dis. Br J Dermatol. Detection of a herpes simplex viral antigen in skin lesions of erythema multiforme. Both hyperthermia and hypothermia are reported. Man CB, et al. Hospitalization is usually necessary for initial evaluation and treatment. Intravenous administration is recommended. Schwartz RA, McDonough PH, Lee BW. Google Scholar. It is challenging to diagnose this syndrome due to the variety . 2016;2:14. 543557. The authors concluded for a potential beneficial effect of Cys A and a possible improvement in survival compared to IVIG. Gout and its comorbidities: implications for therapy. Medical genetics: a marker for StevensJohnson syndrome. Immunophenotypic studies with the use of advanced antibody panels may be useful in the differential diagnosis of these two forms.10 Reticulum cell sarcoma is another form of cutaneous T-cell lymphoma that may cause exfoliative dermatitis. In most severe cases the suggested dosage is iv 11.5mg/kg/day. Clinicians using antivirals for mpox should be alert for drug-drug interactions with any antiretrovirals used to prevent 16, 17 or treat 18 HIV infection as well as with any other medications used to prevent or treat HIV-related opportunistic infections. The management of toxic epidermal necrolysis. In spared areas it is necessary to avoid skin detachment. The Nikolskys sign is not specific for SJS/TEN, in fact it is present also in auto-immune blistering diseases like pemphigus vulgaris. Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involving skin and usually occurring from days to several weeks after drug. Drug-induced exfoliative dermatitis is usually short-lived once the inciting medication is withdrawn and appropriate therapy is administered.