Skin conditions. 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. These studies have confirmed an association between carbamazepine-induced SJS/TEN with HLA-B*1502 allele among Han Chinese [27], carbamazepine and HLA-A*3101 and HLA-B*1511 [16], phenytoin and HLA-B*1502 [28], allopurinol and HLA-B*5801 [29]. 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. Rheumatology (Oxford). Erythroderma is the term used to describe intense and usually widespread reddening of the skin due to inflammatory skin disease. [117] described a cohort of ten patients affected by TEN treated with a single dose of etanercept 50mg sc with a rapid and complete resolution and without adverse events. 2005;102(11):41349. Morel E, et al. Br J Dermatol. PubMed Central Malignancies are a major cause of exfoliative dermatitis. Mediterr J Hematol Infect Dis. Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involv ing skin and usually occurring from days to several weeks after drug exposure. Epilepsia. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. 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]. The strength of association with the development of SJS/TEN may vary among countries and historical periods, reflecting differences in ethnicities and prescription habits among the studied populations [6164]. In any case all authors concluded that the blockage of FasL prevents keratinocyte apoptosis [35]. SJS/TEN syndrome is associated with severe blistering, mucocutaneous peeling, and multi-organ damage and could be life threatening. Fritsch PO. Toxic epidermal necrolysis associated with severe cytomegalovirus infection in a patient on regular hemodialysis. 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. 2013;69(2):187. In order to rule out autoimmune blistering diseases, direct immune fluorescence staining should be additionally performed to exclude the presence of immunoglobulin and/or complement deposition in the epidermis and/or the epidermal-dermal zone, absent in ED. Barbaud A. Rarely, Mycoplasma pneumoniae, dengue virus, cytomegalovirus, and contrast media may be the causative agent of SJS and TEN [22, 6567]. Br J Dermatol. 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). Granulysin: Granulysin is a pro-apoptotic protein that binds to the cell membrane by means of charge interaction without the need of a specific receptor, producing a cell membrane disruption, and leading to possible cell death. Terms and Conditions, 2018 Feb;54(1):147-176. doi: 10.1007/s12016-017-8654-z. 2012;66(6):9951003. Reticuloendothelial neoplasms, as well as internal visceral malignancies, can produce erythroderma, with the former being the more predominant cause. Gastrointestinal: pancreatitis, glossitis, dyspepsia. Antibiotics: amoxicillin, ampicillin, ciprofloxacin, demeclocycline , doxycycline , minocycline, nalidixic acid, nitrofurantoin, norfloxacin, penicillin , rifampicin, streptomycin, tetracycline , tobramycin, trimethoprim, trimethoprim + sulphamethoxazole, vancomycin Anticonvulsants : barbiturates, carbamazepine 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. 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]. FDA Drug information Dupixent Read time: 6 mins Marketing start date: 04 Mar 2023 . Please enable it to take advantage of the complete set of features! Adapted from Ref. 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. Oral manifestations of erythema multiforme. 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]. Erythema multiforme StevensJohnson syndrome and toxic epidermal necrolysis. of Internal Medicine, University of Bari, Bari, Italy, Andrea Nico,Elisabetta Di Leo,Paola Fantini&Eustachio Nettis, You can also search for this author in 2013;27(5):65961. 2013;168(3):53949. exfoliative conditions. Association between HLA-B* 1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. It should be considered only once the patient is stable and if the skin damage is still ongoing and doesnt respond to other conventional therapies (corticosteroids or IVIG). Minerva Stomatol. Ayangco L, Rogers RS 3rd. In this study, 965 patients were reviewed. Yacoub, MR., Berti, A., Campochiaro, C. et al. Arch Dermatol. 1999;48(5):21726. No uniformity of opinion exists concerning the best treatment for cutaneous T-cell lymphoma. In acute phase it is crucial to assess the culprit agent, in particular when the patient was assuming several drugs at time of DHR. 2001;108(5):83946. 2008;12(5):3559. 2012;43:10115. Huang SH, et al. 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;81(1):1521. Drug-induced Exfoliative Dermatitis & Eosinophils Increased Symptom Checker: Possible causes include Exfoliative Dermatitis. Combination of infliximab and high-dose intravenous immunoglobulin for toxic epidermal necrolysis: successful treatment of an elderly patient. An official website of the United States government. 2008;159(4):9814. (in Chinese) . 2005;94(4):41923. Nutr Clin Pract. Curr Allergy Asthma Rep. 2014;14(6):442. Interstitial nephritis is common in DRESS syndrome, occurring roughly in 40% of cases, whereas pre-renal azotemia may occur in SJS and TEN. In contrast with DRESS, eosinophilia and atypical lymphocytes are not described in patients with SJS or TEN. 2006;34(2):768. Infliximab: chimeric IgG monoclonal anti-TNF- antibody. Drugs.com provides accurate and independent information on more than . 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. A marker for StevensJohnson syndrome: ethnicity matters. AQUACEL Ag in the treatment of toxic epidermal necrolysis (TEN). 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. Medication use and the risk of StevensJohnson syndrome or toxic epidermal necrolysis. It characteristically demonstrates diffuse erythema and scaling of greater than 90% of the body surface area. Pemphigus vulgaris, paraneoplastic pemphigus, bullous pemphigoid and linear IgA dermatosis have to be considered. It is important to take into consideration the mechanism of action of the different drugs in the pathogenesis of ED [104]. 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. Recently, a meta-analysis based on 6 retrospective studies evaluating the role of corticosteroids alone or together with IVIG has been published [107]. Harr T, French LE. Clinical features; Delayed type hypersensitivity; Drug hypersensitivity; Erythema multiforme; Exfoliative dermatitis; Lyells syndrome; Pathogenesis; StevensJohnson syndrome; Therapy; Toxic epidermal necrolysis. Roujeau JC, Stern RS. Strom BL, et al. Soak for 5 to 10 minutes and rinse off before patting dry. Exfoliative dermatitis is a dangerous form of CADR which needs immediate withdrawl of all the four drugs. Skin manifestations of drug allergy. 1996;35(4):2346. Arch Dermatol. Exfoliative dermatitis is a rare inflammatory skin condition that is characterized by desquamation and erythema involving more than 90% of the body surface area. A slow acetylator genotype is a risk factor for sulphonamide-induced toxic epidermal necrolysis and StevensJohnson syndrome. The dermis shows an inflammatory infiltrate characterized by a high-density lichenoid infiltrate rich in T cells (CD4+ more than CD8+) with macrophages, few neutrophils and occasional eosinophils; the latter especially seen in cases of DHR [5, 50]. In the acute phase, before determination of the etiology, treatment consists of measures to soothe the inflamed skin. doi: 10.4065/mcp.2009.0379. It is a clinical manifestation and usually associated with various underlying cutaneous disorders, drug induced reactions and malignancies. 2013;69(2):1734. Supportive and specific care includes both local and systemic measures, as represented in Fig. Verma R, Vasudevan B, Pragasam V. Severe cutaneous adverse drug reactions. Fitzpatricks dermatology in general medicine. Hematologic: anemia, including aplastic and hemolytic. EMM is characterizes by target lesions, circular lesions of 1-2cm of diameter, that are defined as typical or atypical that tends to blister. Notably, Agr inhibitors have not yet been more rigorous pre-clinical testing using the established analyzed using rigorous testing with systemic applica standards for drug development. Generalized. Su SC, Hung SI, Fan WL, Dao RL, Chung WH. Abe J, et al. J. 2009;29(3):51735. Would you like email updates of new search results? 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. When it precedes cutaneous T-cell lymphoma lesions, exfoliative dermatitis becomes the presenting sign of the underlying malignancy. 22 Abacavir-induced hypersensitivity syndrome is strongly associated with HLA-B*5701 during treatment . Partial to full thickness epidermal necrosis, intraepidermal vesiculation or subepidermal blisters, due to spongiosis and to the cellular damage of the basal layer of the epidermis, can be present in the advanced disease [49] Occasionally, severe papillary edema is also present [20]. Am J Infect Dis. Bullous dermatoses can be debilitating and possibly fatal. [Erythema multiforme vs. Stevens-Johnson syndrome and toxic epidermal necrolysis: an important diagnostic distinction]. J Am Acad Dermatol. J Am Acad Dermatol. Paradisi A, et al. 1991;127(6):8318. 2013;52(1):3444. Adverse cutaneous drug reaction. Main discriminating factors between EMM, SJS, SJS-TEN, TEN and SSSS is summarized in Table3 [84]. 2. Patients must be cleaned in the affected areas until epithelization starts. Article Typical laboratory values include mild anemia, leukocytosis, eosinophilia, elevated erythrocyte sedimentation rate, abnormal serum protein electrophoresis with a polyclonal elevation in the gamma globulin region, and elevated IgE levels.13,68. volume14, Articlenumber:9 (2016) Paul C, et al. Chemicals and Drugs 61. Perforin/granzyme B pathway: Nassif and colleagues have proposed a role for perforin/grazyme B in keratinocyte death [37]. official website and that any information you provide is encrypted Ther Apher Dial. Moreover, after granulysin depletion, they observed an increase in cell viability. In a hemodialysis patient with active pulmonary tuberculosis, early withdrawl followed by prompt rechallenging to identify the causative agent and then to achieve cure of pulmonary tuberculosis is an interesting therapeutic challenge. 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/. 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. 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). Bethesda, MD 20894, Web Policies It recommended to used G-CSF in patients with febrile neutropenia [94, 95]. 2013;133(5):1197204. Prevalence is low, with mortality of roughly 512.5% for SJS and 50% for TEN [1, 2]. 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). Add 1 cup (about 236 milliliters) of vinegar to a bathtub filled with warm water. 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. J Immunol. National Library of Medicine Med Sci Monit. . Cookies policy. CAS Toxic epidermal necrolysis and StevensJohnson syndrome. Li X, et al. J Clin Apher. What are Drug Rashes? PubMed The erythrodermic form of mycosis fungoides and the Szary syndrome may also be difficult to distinguish from benign erythroderma. The induction dosage in EMM is usually 1mg/kg/day that should be maintained until a complete control of the skin is obtained. This content is owned by the AAFP. Many people have had success using a dilute vinegar bath rather than a bleach bath. 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 . In an open trial on cyclosporine in 29 patients with TEN, the use of Cys A for at least 10days led to a rapid improvement without infective complications [112]. J Am Acad Dermatol. sharing sensitive information, make sure youre on a federal It is also extremely important to obtain within the first 24h cultural samples from skin together with blood, urine, nasal, pharyngeal and bronchus cultures. Arch Dermatol. During the acute reaction, diagnosis of ED is mainly based on clinical parameters. J Am Acad Dermatol. Each of these physiologic disruptions is potentially life-threatening. Increased peripheral blood flow can result in high-output cardiac failure. Rzany B, et al. The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Among drug related cases, the main triggering factors are sulfonamides, nonsteroidal anti-inflammatories (NSAIDs), penicillins, and anticonvulsants (Table1) [59]. Clinical, etiologic, and histopathologic features of StevensJohnson syndrome during an 8-year period at Mayo Clinic. Avoid rubbing and scratching. Rifampin, paracetamol, metronidazole, paclitaxel, erythromycin, and ibuprofen have all been reported to cause bullous FDE. 2012;42(2):24854. The former is usually a recurring, localized eruption of the skin characterized by pathognomonic target or iris lesions, with minimal or no mucosal involvement (Fig. 2008;23(5):54750. Google Scholar. 1990;126(1):3742. Immune-histopathological features allow to distinguish generalized bullous drug eruption from SJS/TEN [36]. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. The syndrome has been described previously in association with phenindione administration, leptospirosis and heavy metal poisoning. [81]. Efficacy of plasmapheresis for the treatment of severe toxic epidermal necrolysis: is cytokine expression analysis useful in predicting its therapeutic efficacy? Guidelines for the management of drug-induced liver injury[J]. 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 Intravenous administration is recommended. Szary syndrome, the leukemic variant of mycosis fungoides, is also associated with exfoliative dermatitis. It is necessary to obtain as soon as possible a central venous access and to start a continuous monitoring of vital signs. 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. 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. Eosinophils from Physiology to Disease: A Comprehensive Review. A drug eruption may start as a rash but eventually progress to more generalized exfoliative dermatitis. 2011;38(3):23645. 2012;167(2):42432. 2014;70(3):53948. The exact source of FasL production has not been yet identified as different groups have postulated that the production might be sought in keratinocytes themselves [33] or in peripheral blood mononuclear cells [34]. Allergy. Mona-Rita Yacoub. Expression of alpha-defensin 1-3 in T cells from severe cutaneous drug-induced hypersensitivity reactions. Half-life of the drug is approximately 54 h. Modification of nitisinone in liver and renal dysfunction is yet to be studied. 3. Indian J Dermatol. This has been called the nose sign.18, Once the erythema is well established, scaling inevitably follows (Figure 1). Detection of a herpes simplex viral antigen in skin lesions of erythema multiforme. Fitzpatricks dermatology in general medicine. The site is secure. Contact Dermatitis. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. The diagnosis of GVDH requires histological confirmation [87]. 2011;20(2):10712. In addition to all these mechanisms, alarmins, endogenous molecules released after cell damage, were found to be transiently increased in SJS/TEN patients, perhaps amplifying the immune response, including -defensin, S100A and HMGB1 [47]. 2008;53(1):28. Wetter DA, Camilleri MJ. The serum levels of granulysin were also found to be increased in the early stage of SJS/TEN, but not in other cutaneous DHR [40]. 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]. 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]. Fitzpatricks dermatology in general medicine. 2009;151(7):5145. 2013;69(2):173174. 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. In EM a lymphocytic infiltrate (CD8+ and macrophages), associated with vacuolar changes and dyskeratosis of basal keratinocytes, is found along the dermo-epidermal junction, while there is a moderate lymphocytic infiltrate around the superficial vascular plexus [20]. A useful sign for differential diagnosis is the absence of mucosal involvement, except for conjunctiva. Acute processes usually favor large scales, whereas chronic processes produce smaller ones. Exfoliative dermatitis (ED) is defined as diffuse erythema and scaling of the skin involving more than 90% of the total body skin surface area. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Consultation with an oncologist who is well-versed in treatment of cutaneous T-cell lymphoma is advisable once the disease progresses to the tumor stage. Pregnancy . 2004;428(6982):486. Tohyama M, et al. An increased metabolism is typical of patients with extended disepithelizated areas. Erythema multiforme (EM), StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. On the other hand, it has been demonstrated that genetic predisposition may increase the risk for sulphonamide-induced [24] and carbamazepine-induced TEN and SJS [25]. In ED increased levels of FasL have been detected in patients sera [33]. In fact, it was demonstrated that the specificity of the TCR is a required condition for the self-reaction to occur. If there is a high suspicion of infection without a documented source of infection, broad range empiric therapy should be started. Antipyretic therapy. Correction of hyperthermia or hypothermia Antibiotic administration when underlying infection is suspected or identified as cause of exfoliative dermatitis or when a secondary skin and soft. Am Fam Physician. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. 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. Grosber M, et al. Mayo Clin Proc. Acute interstitial nephritis associated with hepatitis, exfoliative dermatitis, fever and eosinophilia is uncommon. Since the earliest descriptions of exfoliative dermatitis, medications have been known to be important causative agents. Fritsch PO. In: Eisen AZ, Wolff K, editors. Polak ME, et al. Therefore, the clinician should always consider drugs as a possible cause. Patients should be educated to avoid any causative drugs. Download Free PDF. Nayak S, Acharjya B. Painkiller therapy. A correlation between increased levels of perforin/granzyme B and the severity of TEN was also described [38]. The most common causes of death in patients with exfoliative dermatitis are pneumonia, septicemia and heart failure. Epub 2018 Aug 22. Frequently reported adverse events of rebamipide compared to other drugs for peptic ulcer and gastroesophageal reflux disease. Other dermatoses associated with erythroderma are listed in Table 1.2,3,68. 2005;136(3):20516. Erythema multiforme StevensJohnson syndrome and toxic epidermal necrolysis. Mittmann N, et al. Important data on ED have been obtained by RegiSCAR (European Registry of Severe Cutaneous Adverse Reactions to Drugs: www.regiscar.org), an ongoing pharmaco-epidemiologic study conducted in patients with SJS and TEN. PubMed 2009;182(12):80719. 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]. It might be. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). A promising and complementary in vitro tool has been used by Polak ME et al. Bookshelf CAS Eur J Clin Microbiol Infect Dis. Tumor necrosis factor : TNF- seems also to play an important role in TEN [41]. Karnes JH, Miller MA, White KD, Konvinse KC, Pavlos RK, Redwood AJ, Peter JG, Lehloenya R, Mallal SA, Phillips EJ. Beneficial effect of plasma exchange in the treatment of toxic epidermal necrolysis: a series of four cases. 8600 Rockville Pike b. Atopic dermatitis. Unauthorized use of these marks is strictly prohibited. Australas J Dermatol. SJS and TEN are two overlapping syndromes resembling severe burn lesions and characterized by skin detachment. Carbamazepine and phenytoin induced StevensJohnson syndrome is associated with HLA-B* 1502 allele in Thai population. Gonzalez-Delgado P, et al. 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. 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. Skin testing and patch testing in non-IgE-mediated drug allergy. Abe R, et al. Initial symptoms could be aspecific, as fever, stinging eyes and discomfort upon swallowing, occurring few days before the onset of mucocutaneous involvement. FOIA Harr T, French LE. Adverse cutaneous drug reaction. 2023 BioMed Central Ltd unless otherwise stated. 1. Article 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. Am J Dermatopathol. Gastrointest Endosc. PubMed Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. More than moderate, unresponsive to treatment, and which interferes with the Soldier's perfor-mance of duty. 2011;66(3):3607. Archivio Istituzionale della Ricerca Unimi, Nayak S, Acharjya B. Unfortunately, the clinical picture does not contribute to an understanding of the underlying cause. Etoricoxib-induced toxic epidermal necrolysis: successful treatment with infliximab. 2004;114(5):120915. (5.7, 8.1, 8.3) ADVERSE REACTIONS The most commonly reported adverse drug reactions (ADRs), reported in more than 20% of the patients and greater than placebo were skin reactions and diarrhea .