PubMed Anticoagulation therapy. Fritsch PO. Erythema multiforme (EM), StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. A multidisciplinary team is fundamental in the therapeutic management of patients affected by exfoliative DHR. Fitzpatricks dermatology in general medicine. CAS Erythema multiforme (EM), Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Schwartz RA, McDonough PH, Lee BW. Epilepsia. In more severe cases continuous iv therapy can be necessary. J Am Acad Dermatol. doi: 10.4065/mcp.2009.0379. Dermatologist and/or allergist should confirm the diagnosis, individuate the culprit agent, give indications about skin management and necessity to obtain theconsultationofthe ENT specialist, the gynecologist/urologist, the ophthalmologist and/or the pulmonologist in the case of mucosal involvement. Clinical clues of a drug-induced etiology include: Abrupt onset, previous morbilliform eruption, multiple, varied cutaneous morphologic lesions present together Extensive erythema is followed in 2-6 days by exfoliative scaling Pruritus can be severe, leading to scratching and lichenification in more chronic processes Chang CC, et al. Wolkenstein P, et al. Karnes JH, Miller MA, White KD, Konvinse KC, Pavlos RK, Redwood AJ, Peter JG, Lehloenya R, Mallal SA, Phillips EJ. Chemicals and Drugs 61. The EuroSCAR-study. 2015;64(3):2779. CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. Cookies policy. Mortality rate of patients with TEN has shown to be directly correlated to SCORTEN, as shown in Fig. (adult rickets), anticonvulsant-induced rickets and osteomalacia, osteoporosis, renal osteodystrophy . It is also recommended to void larger vesicles with a syringe. New York: McGraw-Hill; 2003. pp. New York: McGraw-Hill; 2003. p. 585600. 2011;18:e12133. A promising and complementary in vitro tool has been used by Polak ME et al. Next vol/issue During the acute reaction, diagnosis of ED is mainly based on clinical parameters. J. Annu Rev Pharmacol Toxicol. Ramirez GA, Yacoub MR, Ripa M, Mannina D, Cariddi A, Saporiti N, Ciceri F, Castagna A, Colombo G, Dagna L. Biomed Res Int. 1995;14(6):5589. 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]. [16] Drug-induced Liver Disease Study Group,Chinese Society of Hepatology,Chinese Medical Association. The most common causes of exfoliative dermatitis are best remembered by the mnemonic device ID-SCALP. Mediterr J Hematol Infect Dis. 2015;13(7):62545. Huang YC, Li YC, Chen TJ. Google Scholar. Kirchhof MG et al. 1997;22(3):1467. Exp Dermatol. J Am Acad Dermatol. A marked increase in serum soluble Fas ligand in drug-induced hypersensitivity syndrome. Indian J Dermatol. Some anti-seizure medicines have also been known to cause exfoliative dermatitis. In the 5 studies that concluded negatively for IVIG, the dosage was below 0.4g/kg/day and treatment was maintained for less than 5days. Lerch M, Mainetti C, Terziroli Beretta-Piccoli B, Harr T. Clin Rev Allergy Immunol. Diclofenac sodium topical solution, like other NSAIDs, can cause serious systemic skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations . Toxic epidermal necrolysis: Part II Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. 2011;20(2):10712. Rabelink NM, Brakman M, Maartense E, Bril H, Bakker-Wensveen CA, Bavinck JN. Paradisi A, et al. Australas J Dermatol. The authors wish to thank Dr. Gary White for the picture of EM showed in Fig. 2010;31(1):1004. 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. Bullous pemphigoid is characterized by large, tense bullae, but may begin as an urticarial eruption. It is a clinical manifestation and usually associated with various underlying cutaneous disorders, drug induced reactions and malignancies. Morel E, et al. Chung and colleagues found an high expression of this molecule in TEN blister fluid [39] and confirmed both in vitro and in vivo its dose-dependent cytotoxicity [39]. AB, CC, ET, GAR, AN, EDL, PF performed a critical revision on the current literature about the described topic, wrote and revised the manuscript. For SJS/TEN, corticosteroids are the cornerstone of treatment albeit efficacy remains unclear. 2010 Oct;35(7):723-8. doi: 10.1111/j.1365-2230.2009.03718.x. Ann Allergy Asthma Immunol. Tohyama M, Hashimoto K. Immunological mechanisms of epidermal damage in toxic epidermal necrolysis. 2011;50(2):2214. Erythroderma is an intense and widespread reddening of the skin due to inflammation which may often be associated with peeling of skin termed as exfoliative dermatitis. Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Therefore, the clinician should always consider drugs as a possible cause. Adverse cutaneous drug reaction. Accessibility 2002;118(4):72833. Google Scholar. It is challenging to diagnose this syndrome due to the variety . N Engl J Med. Moreover, the time necessary for cells to mature and travel through the epidermis is decreased. 2012;366(26):2492501. The long-term prognosis is good in patients with drug-induced disease, although the course tends to be remitting and relapsing in idiopathic cases. Gueudry J, et al. Von Hebra first described erythroderma (exfoliative dermatitis) in 1868. 2011;364(12):113443. The scales may be small or large, superficial or deep. . Bookshelf 8600 Rockville Pike It is important to take into consideration the mechanism of action of the different drugs in the pathogenesis of ED [104]. Am J Dermatopathol. 2013;69(2):187. Hospitalization and dermatologic consultation are indicated in most cases to ensure that all of the necessary cutaneous, laboratory and radiologic investigations and monitoring are performed. 2012;2012:915314. A patch testing and cross-sensitivity study of carbamazepine-induced severe cutaneous adverse drug reactions. As written before, Sassolas B. et al. Int J Dermatol. Article Clinical features; Delayed type hypersensitivity; Drug hypersensitivity; Erythema multiforme; Exfoliative dermatitis; Lyells syndrome; Pathogenesis; StevensJohnson syndrome; Therapy; Toxic epidermal necrolysis. J Am Acad Dermatol. Systemic corticosteroids: These are the most common used drugs because of their known anti-inflammatory and immunosuppressive effect through the inhibition of activated cytotoxic T-cells and the production of cytokines. Antiviral therapy. Death ligand TRAIL, secreted by CD1a+and CD14+cells in blister fluids, is involved in killing keratinocytes in 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 exposure. Fernando SL. Arch Dermatol. Erythema multiforme and toxic epidermal necrolysis. Barbaud A, et al. Narita YM, et al. exfoliative dermatitis. [49] confirmed these results and even suggested that higher dosage regimen with 2.74g/kg seem to be more effective in survival outcome. Rarely, Mycoplasma pneumoniae, dengue virus, cytomegalovirus, and contrast media may be the causative agent of SJS and TEN [22, 6567]. Mucosal involvement could achieve almost 65% of patients [17]. Adapted from Ref. Toxic epidermal necrolysis (Lyell syndrome). (2.4, 5.6) Embryo-fetal Toxicity: Can cause fetal harm. Erythema multiforme: a review of epidemiology, pathogenesis, clinical features, and treatment. Bastuji-Garin S, et al. Arch Dermatol. J Dermatol Sci. It is important to protect the damaged skin with sterile fat dressing especially in the genital area. Correspondence to The incidence of erythema multiforme, StevensJohnson syndrome, and toxic epidermal necrolysis. . 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]. 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]. Paradisi et al. Heat loss is another major concern that accompanies a defective skin barrier in patients with exfoliative dermatitis. Beneficial effect of plasma exchange in the treatment of toxic epidermal necrolysis: a series of four cases. In the hospital, special attention must be given to maintaining temperature control, replacing lost fluids and electrolytes, and preventing and treating infection. Cutaneous drug eruptions are one of the most common types of adverse reaction to medications, with an overall incidence of 23% in hospitalized patients [1]. Overall, incidence of SJS/TEN ranges from 2 to 7 cases per million person per year [9, 1820], with SJS the commonest [21]. 1995;5(4):2558. 2011;3(1):e2011004. Br J Dermatol. Contact dermatitis from topical antihistamine . HHS Vulnerability Disclosure, Help Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Patients should be educated to avoid any causative drugs. In case of a respiratory failure, oxygen should be administrated and a NIMV may be required. Erythema multiforme and toxic epidermal necrolysis: a comparative study. . Abe R. Toxic epidermal necrolysis and StevensJohnson syndrome: soluble Fas ligand involvement in the pathomechanisms of these diseases. Patch testing in severe cutaneous adverse drug reactions, including StevensJohnson syndrome and toxic epidermal necrolysis. J Am Acad Dermatol. 5% silver nitrate compresses have antiseptic properties. Etanercept therapy for toxic epidermal necrolysis. 2012;167(2):42432. CAS T and NK lymphocytes can produce FasL that eventually binds to target cells. Efficacy of plasmapheresis for the treatment of severe toxic epidermal necrolysis: is cytokine expression analysis useful in predicting its therapeutic efficacy? See this image and copyright information in PMC. [Stevens-Johnson Syndrom and Toxic Epidermal Necrolysis--based on literature]. 2007;48(5):10158. Fournier S, et al. Acute processes usually favor large scales, whereas chronic processes produce smaller ones. Pharmacogenetics studies have found an association between susceptibility to recurrent EM in response to several stimuli and human leukocyte antigen (HLA) haplotypes of class II, in particular HLA DQB1*0301 [23]. 12 out of 17 studies concluded for a positive role of IVIG in ED. Blood counts and bone marrow studies may reveal an underlying leukemia. Am Fam Physician. Kirchhof MG, et al. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Download Free PDF. 2012;66(6):e22936. J Eur Acad Dermatol Venereol. It has a wide spectrum of severity, and it is divided in minor and major (EMM). 2013;27(3):35664. Orphanet J Rare Dis. J Invest Dermatol. PubMed 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). Gastrointest Endosc. Severe Cutaneous Adverse Reactions: The Pharmacogenomics from Research to Clinical Implementation. . Even though exfoliative dermatitis is a complex disorder involving many factors, the underlying disease is usually the key determinant of the course and prognosis. 585600. Downey A, et al. . 2013;133(5):1197204. Volume 8, Issue 1 Pages 1-90 (August 1994). Strom BL, et al. 19 Key critical interactions are discussed below for each mpox antiviral. Plasmapheresis may have a role in the treatment of ED because it removes Fas-L [96], other cytokines known to be implied in the pathogenesis (IL-6, IL-8, TNF-) [97, 98]. Skin testing and patch testing in non-IgE-mediated drug allergy. Defective regulatory T cells in patients with severe drug eruptions: timing of the dysfunction is associated with the pathological phenotype and outcome. 2014;70(3):53948. Arch Dermatol. For the calculation, available values on vital and laboratory parameters within the first 3days after admission to the first hospital are considered when the reaction started outside the hospital (community patients) or at the date of hospitalization for in-hospital patients. In SJS and TEN mucosal erosions on the lips, oral cavity, upper airways, conjunctiva, genital tract or ocular level are frequent [60, 6870]. 2010;62(1):4553. Drug induced exfoliative dermatitis: state of the art, https://doi.org/10.1186/s12948-016-0045-0, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/. 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. The team should include not only physicians but also dedicated nurses, physiotherapists and psychologists and should be instituted during the first 24h after patient admission. PubMedGoogle Scholar. Two Cases in Adult Patients. 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]. 2000;22(5):4137. 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. Drug-induced LPP. Tohyama M, et al. 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]. Despite improved knowledge of the immunopathogenesis of these conditions, immune-modulatory therapies currently used have not been definitively proved to be efficacious [49, 107], and new strategies are urgently needed. Autologous transplantation of mesenchymal umbilical cord cells seems also to be highly efficacious [102]. In this study, 965 patients were reviewed. 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. (scFv) (directed against Dsg1/3) or AK23 (directed against Dsg3) with (as a control) or without exfoliative toxin A (ETA). The diagnosis of GVDH requires histological confirmation [87]. J Am Acad Dermatol. If necessary, it can be repeated every 68h. NSAIDs should be avoided as they can induce ED as well. J Eur Acad Dermatol Venereol. 2010;2(3):18994. Clin Exp Dermatol. When it precedes cutaneous T-cell lymphoma lesions, exfoliative dermatitis becomes the presenting sign of the underlying malignancy. Pharmacogenomics J. Google Scholar. 2008;49(12):208791. [Erythema multiforme vs. Stevens-Johnson syndrome and toxic epidermal necrolysis: an important diagnostic distinction]. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Oral manifestations of erythema multiforme. 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. Patients can be extremely suffering because of the pain induced by skin and mucosal detachment. 2012;51(8):889902. 2013;168(3):53949. Medication use and the risk of StevensJohnson syndrome or toxic epidermal necrolysis. Painkiller therapy. Talk to our Chatbot to narrow down your search. Case Rep Dermatol Med. 2008;58(1):3340. 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. 2014;71(1):1956. Gonzalez-Delgado P, et al. 2014;71(5):9417. 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. Usually, but not always, the palms of the hands, the soles of the feet and the mucous membranes are spared. Soak for 5 to 10 minutes and rinse off before patting dry. 2003 Oct 25;147(43):2089-94. A rare case of toxic epidermal necrolysis with unexpected Fever resulting from dengue virus. 1990;126(1):3742. Jarrett P, et al. By using this website, you agree to our Granulysin is a key mediator for disseminated keratinocyte death in StevensJohnson syndrome and toxic epidermal necrolysis. In most severe cases the suggested dosage is iv 11.5mg/kg/day. Early sites of skin involvement include trunk, face, palms and soles and rapidly spread to cover a variable extension of the body. 2012;43:10115. Abe J, et al. Curr Allergy Asthma Rep. 2014;14(6):442. Journal of Pharmaceutical Research and health Care. ), Phenolphthalein (Agoral, Alophen, Modane), Rifampin (Rifadin, Rimactane; also in Rifamate), Trimethoprim (Trimpex; also in Bactrim, Septra). J Dermatol. Skin and appendages: acne, bruising, erythema multiforme, exfoliative dermatitis, pruritus ani, rash, skin ulceration, Stevens . J Am Acad Dermatol. Comprehensive survival analysis of a cohort of patients with StevensJohnson syndrome and toxic epidermal necrolysis. Epub 2018 Aug 22. Takahashi R, et al. In: Eisen AZ, Wolff K, editors. Not responsive to therapy. Barbaud A. The cutaneous T-cell lymphomas are the lymphomas most commonly associated with exfoliative dermatitis. 2002;146(4):7079. Antiepileptic medications, antihypertensive medications, antibiotics, calcium channel blockers and a variety of topical agents (Table 2)2,3,69 can cause exfoliative dermatitis, but theoretically, any drug may cause exfoliative dermatitis. Its also characterized by a cell-poor infiltrate, where macrophages and dendrocytes with a strong TNF- immunoreactivity predominate [6, 50]. It might be. Br J Dermatol. National Library of Medicine 2015;49(3):33542. Normal epidermis undergoes some exfoliation every day, but the scales that are lost contain little, if any, important viable material, such as nucleic acids, soluble proteins and amino acids.4 In exfoliative dermatitis, however, protein and folate losses may be high.5, The pathogenesis of exfoliative dermatitis is a matter of debate. Exfoliative dermatitis is a rare inflammatory skin condition that is characterized by desquamation and erythema involving more than 90% of the body surface area. Anti-Allergic Agents Immunoglobulin E Allergens Cetirizine Histamine H1 Antagonists, Non-Sedating Histamine H1 Antagonists Loratadine Emollients Nasal Decongestants Dermatologic Agents Leukotriene Antagonists Antigens, Dermatophagoides Ointments Histamine Antagonists Eosinophil Cationic Protein Adrenal Cortex Hormones Terfenadine Antipruritics Antigens, Plant . Erythema multiforme (photo reproduced with permission of Gary White, MD): typical target lesions (white arrows) together with atypical two-zoned lesions (black arrows). 1999;48(5):21726. Wetter DA, Camilleri MJ. Br J Dermatol. These measures include bed rest, lukewarm soaks or baths, bland emollients and oral antihistamines.2527, In patients with chronic idiopathic erythroderma, emollients and topical steroids may be effective. Both hyperthermia and hypothermia are reported. Springer Nature. Infliximab was used in cases refractory to high-dosage steroid therapy and/or IVIG. Abe J, et al. HLA-B* 5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. 2005;136(3):20516. Overall, T cells are the central player of these immune-mediated drug reactions. 2008;159(4):9814. Google Scholar. Ann Intern Med. Poor relevance of a lymphocyte proliferation assay in lamotrigine-induced StevensJohnson syndrome or toxic epidermal necrolysis. CAS Cyclosporine A (Cys A): Cys A works through the inhibition of calcineurin, that is fundamental for cytotoxic T lymphocytes activation.