Analysis of StevensJohnson syndrome and toxic epidermal necrolysis using the Japanese Adverse Drug Event Report database. Plasmapheresis. 2011;71(5):67283. These patches tend to spread until, after a matter of days or weeks, most of the skin surface is covered with an erythematous, pruritic eruption. 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]. The time interval between the appearance of exfoliative dermatitis and the appearance of cutaneous T-cell lymphoma lesions can vary from months to years or even decades. Fritsch PO. 2. Some anti-seizure medicines have also been known to cause exfoliative dermatitis. tion in models of the types of systemic disease for S. aureus pathogenesis research is also expected to receive which anti-virulence drugs would be most desirable. Chemicals and Drugs 61. Adapted from Ref. (in Chinese) . Once established the percentage of the involved skin, lactate Ringer infusion of 12mL/Kg/% of involved skin must be started during the first 24h [91]. Kavitha Saravu. Khalaf D, et al. 2012;66(6):e22936. Am J Infect Dis. Comprehensive survival analysis of a cohort of patients with StevensJohnson syndrome and toxic epidermal necrolysis. Exfoliative dermatitis is also a risk factor for epidemic spread of methicillin-resistant Staphylococcus aureus.6,20. 2014;70(3):53948. These levels could reflect the interaction between culprit drugs and aldehyde dehydrogenase that is the enzyme which metabolizes retinoid acid. Goulden V, Goodfield MJ. Pemphigus vulgaris usually starts in the oral mucosa followed by blistering of the skin, which is often painful. Careers. It should be used only in case of a documented positivity of cultural samples. J Invest Dermatol. Heat loss is another major concern that accompanies a defective skin barrier in patients with exfoliative dermatitis. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. Huang YC, Li YC, Chen TJ. CAS PubMed Pharmacogenet Genom. Hydration and hemodynamic balance. Toxic epidermal necrolysis (Lyell syndrome). 3. Talk to our Chatbot to narrow down your search. J Invest Dermatol. Hospitalization is usually necessary for initial evaluation and treatment. Robyn A. McMenamin, L M. Davies and P. W. Craswell, Aust. It recommended to used G-CSF in patients with febrile neutropenia [94, 95]. Gynecologist consultation is required for avoiding the appearance of vaginal phimosis or sinechias. De Araujo E, et al. They usually have fever, are dyspneic and cannot physiologically feed. Br J Dermatol. Patients must be cleaned in the affected areas until epithelization starts. Toxic epidermal necrolysis: Part II Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. Patients can be extremely suffering because of the pain induced by skin and mucosal detachment. Br J Dermatol. Tumor necrosis factor : TNF- seems also to play an important role in TEN [41]. Mortality rate of patients with TEN has shown to be directly correlated to SCORTEN. Schwartz RA, McDonough PH, Lee BW. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. CAS This hypermetabolic state is also furtherly increased by the inflammation present in affected areas. Case Rep Dermatol. Volume 8, Issue 1 Pages 1-90 (August 1994). Br J Dermatol. J Popul Ther Clin Pharmacol. PubMed It was used with success in different case reports [114116]. In this study, 965 patients were reviewed. J Allergy Clin Immunol. Lonjou C, et al. It is not completely clear whether EM and SJS are separate clinical entities or if they represent two different expressions of a single disease process. J Am Acad Dermatol. Federal government websites often end in .gov or .mil. Generalized bullous fixed drug eruption is distinct from StevensJohnson syndrome/toxic epidermal necrolysis by immunohistopathological features. In patients with this disorder, the mitotic rate and the absolute number of germinative skin cells are higher than normal. In contrast with DRESS, eosinophilia and atypical lymphocytes are not described in patients with SJS or TEN. Drug-induced hypersensitivity syndrome (DiHS) or drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe adverse drug-induced reaction characterized by various symptoms: skin rash, fever, lymph node enlargement and internal organ involvement, which starts within 2 weeks to 3 months after drug initiation. A case of toxic epidermal necrolysis with involvement of the GI tract after systemic contrast agent application at cardiac catheterization. Since cutaneous function as a multiprotective barrier is so disrupted in exfoliative dermatitis, the body loses heat, water, protein and electrolytes, and renders itself much more vulnerable to infection. SJS/TEN syndrome is associated with severe blistering, mucocutaneous peeling, and multi-organ damage and could be life threatening. Schwartz RA et al. Stevens-Johnson syndrome and toxic epidermal necrolysis due to anticonvulsants share certain clinical and laboratory features with drug-induced hypersensitivity syndrome, despite differences in cutaneous presentations. Drug reactions are one of the most common causes of exfoliative dermatitis. TNF- has a dual role: interacts with TNF-R1 activating Fas pathway and activates NF-B leading to cell survival. exfoliative dermatitis. Allergol Immunopathol (Madr). The most important actions to do are listed in Fig. 2010 Oct;35(7):723-8. doi: 10.1111/j.1365-2230.2009.03718.x. Epilepsia. ADRJ,2015,17(6):464-465. Insidious development of the erythroderma, progressive debilitation of the patient, absence of previous skin disease and resistance to standard therapy are features that may suggest an underlying malignancy.6,11, Erythroderma is also associated with disorders that cannot easily be classified into groups. Disasters. The administration of a single dose of 5mg/kg was able to stop disease progression in 24h and to induce a complete remission in 614days. Google Scholar. Fritsch PO. Etoricoxib-induced toxic epidermal necrolysis: successful treatment with infliximab. Accurate eye cleaning with saline solution is fundamental for the prevention of synechiae and for reducing corneal damage. 2008;23(5):54750. Targeting keratinocyte apoptosis in the treatment of atopic dermatitis and allergic contact dermatitis. Erythema multiforme (EM), StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. EMM is a clinically severe, potentially life-threatening, extensive sloughing of epidermis, generally involving mucosal tissue. Supportive and specific care includes both local and systemic measures, as represented in Fig. Early sites of skin involvement include trunk, face, palms and soles and rapidly spread to cover a variable extension of the body. eCollection 2018. Patients should be educated to avoid any causative drugs. Clinical and Molecular Allergy Br J Dermatol. Law EH, Leung M. Corticosteroids in StevensJohnson Syndrome/toxic epidermal necrolysis: current evidence and implications for future research. Barbaud A. New York: McGraw-Hill; 2003. pp. Among the anti-tubercular drugs exfoliative dermatitis is reported with rifampicin, isoniazid, ethambutol, pyrazinamide, streptomycin, PAS either singly or in combination of two drugs in some cases. Roujeau JC, et al. Amphotericin B injection and potassium-depleting agents: When corticosteroids are administered concomitantly with potassium-depleting agents (ie, amphotericin B, diuretics), patients should be observed closely for development of hypokalemia.There have been cases reported in which concomitant . The velocity of infusion should be regulated according to patients arterial pressure with the aim of 30mL/h urinary output (1mL/kg/h in case of a child). Before 2007;62(12):143944. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Adverse cutaneous drug reaction. Exfoliative dermatitis may happen as a complication of other skin issues. Erythema multiforme to amoxicillin with concurrent infection by Epstein-Barr virus. 2015;13(7):62545. -, Schwartz RA, McDonough PH, Lee BW. Nassif A, et al. Several authors reported also an increased incidence for aminopenicillins, cephalosporins, and quinolones [61, 62]. It is a reaction pattern and cutaneous manifestation of a myriad of underlying ailments, including psoriasis and eczema, or a reaction to the consumption of . Jang E, Park M, Jeong JE, Lee JY, Kim MG. Sci Rep. 2022 May 12;12(1):7839. doi: 10.1038/s41598-022-11505-0. Temporary tracheostomy may be necessary in case of extended mucosal damage. A serious cutaneous adverse drug reaction namely exfoliative dermatitis (erythroderma) is associated with isoniazid use . Hung S-I, et al. An extremely rare mucocutaneous adverse reaction following COVID-19 vaccination: Toxic epidermal necrolysis. Other clinical findings include lymphadenopathy, hepatomegaly, splenomegaly, edema of the foot or ankle4,6 and gynecomastia.19, The scaling that occurs in exfoliative dermatitis can have severe metabolic consequences, depending on the intensity and the duration of the scaling. FDA Drug information Dupixent Read time: 6 mins Marketing start date: 04 Mar 2023 . Fischer M, et al. In more severe cases antiviral therapies should be given together with intravenous immunoglobulins [93]. Article In patients who develop complications (i.e., infection, fluid and electrolyte abnormalities, cardiac failure), the rate of mortality is often high. Terms and Conditions, 2009;182(12):80719. official website and that any information you provide is encrypted It could also be useful to use artificial tears and lubricating antiseptic gels. In ED increased levels of FasL have been detected in patients sera [33]. The most common causes of death in patients with exfoliative dermatitis are pneumonia, septicemia and heart failure. All Rights Reserved. MRY, MGS, EN and GC designed the study, selected scientifically relevant information, wrote and revised the manuscript. ), Phenolphthalein (Agoral, Alophen, Modane), Rifampin (Rifadin, Rimactane; also in Rifamate), Trimethoprim (Trimpex; also in Bactrim, Septra). HLA-A* 3101 and carbamazepine-induced hypersensitivity reactions in Europeans. Shiga S, Cartotto R. What are the fluid requirements in toxic epidermal necrolysis? Gastrointest Endosc. Rabelink NM, Brakman M, Maartense E, Bril H, Bakker-Wensveen CA, Bavinck JN. Med J Armed Forces India. StevensJohnson syndrome and toxic epidermal necrolysis: a review of the literature. McCormack M, et al. Clinical, etiologic, and histopathologic features of StevensJohnson syndrome during an 8-year period at Mayo Clinic. For carbamazpine, several studies have found a common link between specific HLAs and different kinds of cutaneous adverse reactions, as for HLA-A*3101 in Japanese [30] and Europeans [31]. Poor relevance of a lymphocyte proliferation assay in lamotrigine-induced StevensJohnson syndrome or toxic epidermal necrolysis. Growth-factors (G-CSF). A recent review [111] on 33 pediatric cases of TEN and 6 cases of SJS/TEN overlap showed that therapy with IVIG with a dosage of 0.251.5g/kg for 5days resulted in 0% mortality rate and faster epithelization. Exfoliative dermatitis, also known as erythroderma, is an uncommon but serious skin disorder that family physicians must be able to recognize and treat appropriately. Arch Dermatol. Four cases are described, two of which were due to phenindione sensitivity. Schneck J, et al. Garza A, Waldman AJ, Mamel J. Nutritional support. J Allergy Clin Immunol. In: Eisen AZ, Wolff K, editors. exfoliative conditions. EM is a self-limited skin condition mainly associated with infections and drugs [53, 54]. Gastrointestinal: pancreatitis, glossitis, dyspepsia. erythroderma, exfoliative dermatitis, and fixed drug reactions) 4, 5 and . Grosber M, et al. Moreover, after granulysin depletion, they observed an increase in cell viability. loss of taste Derm: stevens-johnson syndrome, toxic epidermal necrolysis, rash, exfoliative dermatitis, hair . In fact, it was demonstrated that the specificity of the TCR is a required condition for the self-reaction to occur. Ann Intern Med. Curr Allergy Asthma Rep. 2014;14(6):442. Clin Pharmacol Ther. Erythema multiforme and latent herpes simplex infection. 2023 BioMed Central Ltd unless otherwise stated. 2011;364(12):113443. Chem Immunol Allergy. Int J Dermatol. One of the most common malignancies associated with exfoliative dermatitis is cutaneous T-cell lymphoma, which may not manifest for months or even years after the onset of the skin condition. Reticuloendothelial neoplasms, as well as internal visceral malignancies, can produce erythroderma, with the former being the more predominant cause. Toxic epidermal necrolysis: review of pathogenesis and management. 2012;27(4):21520. Nat Med. PubMed Central and transmitted securely. In particular, a specific T cell clonotype was present in the majority of patients with carbamazepine-induced SJS/TEN and that this clonotype was absent in all patients tolerant to the drug who shared the same HLA with the SJS/TEN patients [45]. 2011;20(5):103441. Lymphocyte transformation test (LTT) performed as described by Pichler and Tilch [77] shows a lower sensitivity in severe DHR compared to less severe DHR [78] but, if available, should be performed within 1week after the onset of skin rash in SJS and TEN [79]. 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. 1991;97(4):697700. 2011;38(3):23645. A significant number of these patients eventually progress to cutaneous T-cell lymphoma.8, Clinically, the first stage of exfoliative dermatitis is erythema, often beginning as single or multiple pruritic patches, involving especially the head, trunk and genital region. Even though there is a strong need for randomized trials, anti-TNF- drugs, in particular a single dose of infliximab 5mg/kg ev or 50mg etanercept sc should be considered in the treatment of SJS and TEN, especially the most severe cases when IVIG and intravenous corticosteroids dont achieve a rapid improvement. Br J Dermatol. Retrospective review of StevensJohnson syndrome/toxic epidermal necrolysis treatment comparing intravenous immunoglobulin with cyclosporine. Still, treatment indication, choice and dosage remain unclear, and efficacy yet unproven. Erythema multiforme and toxic epidermal necrolysis. Hypervolemia can also occur in patients with exfoliative dermatitis, contributing to the likelihood of cardiac failure.2124, In most patients with erythroderma, skin biopsies show nonspecific histopathologic features, such as hyperkeratosis, parakeratosis, acanthosis and a chronic perivascular inflammatory infiltrate, with or without eosinophils. Basal-cell carcinoma; Other names: Basal-cell skin cancer, basalioma: An ulcerated basal cell carcinoma near the ear of a 75-year-old male: Specialty Ayangco L, Rogers RS 3rd. 2012;167(2):42432. Considered variables in SCORTEN are shown in Table2. Abe R, et al. Fas-FasL interaction: Fas is a membrane-bound protein that after interaction with Fas-ligand (FasL) induces a programmed cell death, through the activation of intracellular caspases. Read this article to find out all its symptoms, causes and treatments. Also, physicians should be vigilant about possible secondary infection, whether cutaneous, pulmonary or systemic. Erythema multiforme and toxic epidermal necrolysis: a comparative study. Bourgeois GP, et al. The most common causes of exfoliative dermatitis are best remembered by the mnemonic device ID-SCALP. oboda J, Dudzik A, Chomyszyn-Gajewska M. Ramirez GA, Ripa M, Burastero S, Benanti G, Bagnasco D, Nannipieri S, Monardo R, Ponta G, Asperti C, Cilona MB, Castagna A, Dagna L, Yacoub MR. Microorganisms. SSSS is characterized by periorificial face scabs, de-epithelialization of friction zones and conspicuous desquamation after initial erythroderma. 1. EMM is characterizes by target lesions, circular lesions of 1-2cm of diameter, that are defined as typical or atypical that tends to blister. Epub 2022 Mar 9. Google Scholar. Yamada H, Takamori K. Status of plasmapheresis for the treatment of toxic epidermal necrolysis in Japan. In approximately 25% of people, there is no identifiable cause. J Immunol. Even though exfoliative dermatitis is a complex disorder involving many factors, the underlying disease is usually the key determinant of the course and prognosis. Ramirez GA, Yacoub MR, Ripa M, Mannina D, Cariddi A, Saporiti N, Ciceri F, Castagna A, Colombo G, Dagna L. Biomed Res Int. Viard I, et al. Sekula P, et al. Mockenhaupt M, et al. The epidermal-dermal junction shows changes, ranging from vacuolar alteration to subepidermal blisters [20]. Drug reaction with Eosinophilia and systemic symptoms (DRESS) syndrome can mimic SJS and TEN in the early phases, since ED can occur together with the typical maculo-papular rash. Toxic epidermal necrolysis and StevensJohnson syndrome. 2008;52(3):1519. Severe adverse cutaneous reactions to drugs. 1999;48(5):21726. 543557. Oral hygiene with antiseptic and painkiller mouthwash (chlorhexidine+lidocaine+aluminum hydroxide) together with aerosol therapy with saline and bronchodilators can reduce upper airways symptoms. 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 . Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED. Correspondence to 1990;126(1):437. Man CB, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Exanthematous drug eruptions. A useful sign for differential diagnosis is the absence of mucosal involvement, except for conjunctiva. The taper of steroid therapy should be gradual [93]. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Toxic epidermal necrolysis treated with cyclosporin and granulocyte colony stimulating factor. 2008;59(5):8989. 12 out of 17 studies concluded for a positive role of IVIG in ED. Please enable it to take advantage of the complete set of features! 2006;34(2):768. New York: McGraw-Hill; 2003. pp. The syndrome has been described previously in association with phenindione administration, leptospirosis and heavy metal poisoning. When it precedes cutaneous T-cell lymphoma lesions, exfoliative dermatitis becomes the presenting sign of the underlying malignancy. Infliximab was used in cases refractory to high-dosage steroid therapy and/or IVIG. Generalized. Allergol Int. Part of Immunol Allergy Clin North Am. Hepatobiliary: jaundice, hepatitis, including . Am J Clin Dermatol. However, according to a consensus definition [54], EMM syndrome has been separated from SJS/TEN spectrum. Ann Pharmacother. FOIA Indian J Dermatol. Theoretically, any drug may cause exfoliative dermatitis. Usually, but not always, the palms of the hands, the soles of the feet and the mucous membranes are spared. Medicines have been linked to every type of rash, ranging from mild to life-threatening. 1984;101(1):4850. Exposure to anticonvulsivants (phenytoin, phenobarbital, lamotrigine), non-nucleoside reverse transcriptase inhibitors (nevirapine), cotrimoxazole and other sulfa drugs (sulfasalazine), allopurinol and oxicam NSAIDs [2] confers a higher risk of developing SJS/TEN. Burns. 2002;109(1):15561. Skin testing and patch testing in non-IgE-mediated drug allergy. Mayo Clin Proc. A heterogeneous pathologic phenotype. In acute phase it is crucial to assess the culprit agent, in particular when the patient was assuming several drugs at time of DHR. Antipyretic therapy. 5% silver nitrate compresses have antiseptic properties. 1992;11(3):20710. J Am Acad Dermatol. Article Jarrett P, et al. J Am Acad Dermatol. Clin Exp Allergy. 2012;43:10115. FDA Drug information Palynziq Read time: 10 mins Marketing start date: 04 Mar 2023 . A central role in the pathogenesis of ED is played by CD8+ lymphocytes and NK cells. . 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. 1996;135(1):611. The authors concluded for a potential beneficial effect of Cys A and a possible improvement in survival compared to IVIG. 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. 2018 Feb;54(1):147-176. doi: 10.1007/s12016-017-8654-z. Mucosal involvement could achieve almost 65% of patients [17]. J Invest Dermatol. Erythema multiforme. Kirchhof MG, et al. 2008;14(12):134350. IBUPROFENE ZENTIVA is indicated for the symptomatic treatment of headaches, migraines, dental pain, back pain, dysmenorrhea, muscle pain, neuralgia . More recently, carcinomas of the fallopian tube,12 larynx13 and esophagus14 have been reported as causes of exfoliative dermatitis. Unable to load your collection due to an error, Unable to load your delegates due to an error, 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 SCORTEN. Recent advances in the genetics and immunology of StevensJohnson syndrome and toxic epidermal necrosis. Some of these patients undergo spontaneous resolution. Unauthorized use of these marks is strictly prohibited. Department of Allergy and Clinical Immunology, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy, Mona-Rita Yacoub,Maria Grazia Sabbadini&Giselda Colombo, Vita-Salute San Raffaele University, Milan, Italy, Mona-Rita Yacoub,Alvise Berti,Corrado Campochiaro,Enrico Tombetti,Giuseppe Alvise Ramirez,Maria Grazia Sabbadini&Giselda Colombo, Section of Allergy and Clinical Immunology, Dept. Australas J Dermatol. 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. Orton PW, et al. Gout and its comorbidities: implications for therapy. Erythema multiforme StevensJohnson syndrome and toxic epidermal necrolysis. Options include use of PUVA light therapy, total-body electron beam irradiation, topical nitrogen mustard, systemic chemotherapy and extracorporeal photopheresis. Ko TM, et al. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Focus on the Pathophysiological and Diagnostic Role of Viruses. The overall mortality rate is roughly 30%, ranging from 10% for SJS to more than 30% for TEN, with the survival rate worsening until 1year after disease onset [9, 1821]. Erythema multiforme: a review of epidemiology, pathogenesis, clinical features, and treatment. Samim F, et al. statement and Fluid balance is a main focus. Association of HLA-B*1502 allele with carbamazepine-induced toxic epidermal necrolysis and StevensJohnson syndrome in the multi-ethnic Malaysian population. Case Rep Dermatol Med. Hematologic: anemia, including aplastic and hemolytic. Management of patients with a suspected drug induced exfoliative dermatitis, acute generalized exanthematous pustulosis, algorithm of drug causality for epidermal necrolysis, European registry of severe cutaneous adverse reactions to drugs. Epidemiological studies on EM, SJS and TEN syndromes report different results, probably related to several biases, such as ethnical differences, diagnostic criteria and drug consumption patterns in different socio-economic systems.