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]. b. Atopic dermatitis. Erythema multiforme (EM), StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. 2012;53(3):16571. Su SC, Hung SI, Fan WL, Dao RL, Chung WH. 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]. The incidence of cutaneous adverse drug reactions (CADRs) is high in HIV-infected persons; however, there are large gaps in knowledge about several aspects of HIV-associated CADRs in Africa, which carries the biggest burden of the disease. 2010;163(4):84753. Google Scholar. Mucosal involvement could achieve almost 65% of patients [17]. Google Scholar. Dent Clin North Am. Yamada H, Takamori K. Status of plasmapheresis for the treatment of toxic epidermal necrolysis in Japan. If cutaneous pathology also mimics cutaneous T-cell lymphoma, it can be very difficult to differentiate a drug-induced skin condition from exfoliative dermatitis associated with a malignancy.2,9. Barbaud A, et al. Supportive and specific care includes both local and systemic measures, as represented in Fig. The most common causes of exfoliative dermatitis are preexisting dermatoses, drug reactions, malignancies and other miscellaneous or idiopathic disorders. See permissionsforcopyrightquestions and/or permission requests. [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. Mediterr J Hematol Infect Dis. Br J Dermatol. Tumor necrosis factor : TNF- seems also to play an important role in TEN [41]. A catabolic state thus ensues, which is often responsible for significant weight loss. 1996;44(2):1646. McCormack M, et al. 2012;42(2):24854. Clin Exp Dermatol. Would you like email updates of new search results? Downey A, et al. 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 . Painkiller therapy. Von Hebra first described erythroderma (exfoliative dermatitis) in 1868. J Am Acad Dermatol. Exfoliative dermatitis is also a risk factor for epidemic spread of methicillin-resistant Staphylococcus aureus.6,20. Goulden V, Goodfield MJ. 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. 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). Before Manage cookies/Do not sell my data we use in the preference centre. 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]. 2011;3(1):e2011004. Volume 8, Issue 1 Pages 1-90 (August 1994). Harr T, French LE. Toxic epidermal necrolysis and StevensJohnson syndrome. Mardani M, Mardani S, Asadi Kani Z, Hakamifard A. Dermatol Ther. [16] Drug-induced Liver Disease Study Group,Chinese Society of Hepatology,Chinese Medical Association. Oral manifestations of erythema multiforme. 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. Barbaud A. Australas J Dermatol. Hydration and hemodynamic balance. The scales may be small or large, superficial or deep. Clin Mol Allergy 14, 9 (2016). ADRJ,2015,17(6):464-465. This content is owned by the AAFP. 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]. Rabelink NM, Brakman M, Maartense E, Bril H, Bakker-Wensveen CA, Bavinck JN. Drug rashes are the body's reaction to a certain medicine. Erythema multiforme (EM), StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Immune-histopathological features allow to distinguish generalized bullous drug eruption from SJS/TEN [36]. If after 4days there is not an improvement it is advised to consider the association of steroid or its replacement with one of the following drugs [49, 93]: Intravenous immunoglobulins (IVIG): play their role through the inhibition of FasFas ligand interaction that it is supposed to be the first step in keratinocytes apoptosis [33]. Australas J Dermatol. Toxic epidermal necrolysis (Lyell syndrome). 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. Nassif A, et al. Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED. Acute processes usually favor large scales, whereas chronic processes produce smaller ones. J Am Acad Dermatol. Drug induced exfoliative dermatitis: state of the art. All non-indispensable drugs have to be stopped because they could alter the metabolism of the culprit agent. 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. 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. Overall, T cells are the central player of these immune-mediated drug reactions. Pehr K. The EuroSCAR study: cannot agree with the conclusions. It is necessary to obtain as soon as possible a central venous access and to start a continuous monitoring of vital signs. Grosber M, et al. 2013;133(5):1197204. This hypermetabolic state is also furtherly increased by the inflammation present in affected areas. 2013;168(3):55562. J Eur Acad Dermatol Venereol. An epidemiologic study from West Germany. 1990;126(1):437. The type of rash that happens depends on the medicine causing it and your response. Garza A, Waldman AJ, Mamel J. 2012;366(26):2492501. 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. 2014;71(1):1956. Patients can be extremely suffering because of the pain induced by skin and mucosal detachment. Kavitha Saravu. Common acute symptoms include abdominal pain or cramps, nausea, vomiting, and diarrhea, jaundice, skin rash and eyes dryness and therefore could mimic the prodromal and early phase of ED. [49] confirmed these results and even suggested that higher dosage regimen with 2.74g/kg seem to be more effective in survival outcome. 2008;14(12):134350. Recurrent erythema multiforme in association with recurrent Mycoplasma pneumoniae infections. Man CB, et al. Genome-scale investigation of drug-induced termination codon-readthrough in a model system of epidermolysis bullosa . J Am Acad Dermatol. c. Amyloidosis. 1996;135(2):3056. Arch Dermatol. Medication use and the risk of StevensJohnson syndrome or toxic epidermal necrolysis. In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of therapy, but can occur at any time during treatment with diclofenac. 2023 Jan 30;11(2):346. doi: 10.3390/microorganisms11020346. Malignancies are a major cause of exfoliative dermatitis. 2004;59(8):80920. 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. Ardern-Jones MR, Friedmann PS. [81]. -. If there is a high suspicion of infection without a documented source of infection, broad range empiric therapy should be started. Recurrent erythema multiforme: clinical characteristics, etiologic associations, and treatment in a series of 48 patients at Mayo Clinic, 2000 to 2007. Fritsch PO. Erythema multiforme StevensJohnson syndrome and toxic epidermal necrolysis. Patients present an acute high-grade of skin and mucosal insufficiency that obviously leads to great impairment in the defenses against bacteria that normally live on the skin, increasing the high risk of systemic infections. Ann Pharmacother. The more common forms of erythroderma, such as eczema or psoriasis, may persists for months or years and tend to relapse. Other patients may warrant PUVA (psoralen plus ultraviolet A) phototherapy, systemic steroids (if psoriasis has been ruled out), retinoids (for exfoliative dermatitis secondary to psoriasis and pityriasis rubra pilaris), or immunosuppressive agents such as methotrexate (Rheumatrex) and azathioprine (Imuran).2527, When used as adjunctive therapy, behavior modification designed to eliminate persistent scratching has been successful in reducing the rate of excoriation and increasing the rate of healing.28. 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]. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis. Other dermatoses associated with erythroderma are listed in Table 1.2,3,68. Antitumour necrosis factor-alpha antibodies (infliximab) in the treatment of a patient with toxic epidermal necrolysis. Int J Dermatol. doi: 10.4065/mcp.2009.0379. 2002;118(4):72833. Therefore, the clinician should always consider drugs as a possible cause. Privacy 00 Comments Please sign inor registerto post comments. Talk to our Chatbot to narrow down your search. PubMed 2014;81(1):1521. Pharmacogenet Genom. 1995;14(6):5589. Mayo Clin Proc. Schwartz RA et al. PubMed All authors read and approved the final manuscript. 2023 BioMed Central Ltd unless otherwise stated. Pharmacogenomics J. The balance of fluids and electrolytes should be closely monitored, since dehydration or hypervolemia can be problems. Skin conditions. J Pharm Health Care Sci. The most common causes of exfoliative dermatitis are best remembered by the mnemonic device ID-SCALP. In more severe cases corneal protective lens can be used. Students also viewed Nostra aetate - Summary Theology: the basics Principles of Risk Management and Insurance Chapters 1-4 Adapted from Ref. Antiviral therapy. A promising and complementary in vitro tool has been used by Polak ME et al. 2007;48(5):10158. 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 Am J Clin Dermatol. Google Scholar. 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. Exfoliative dermatitis is characterized by generalized erythema with scaling or desquamation affecting at least 90% of the body surface area. 2000;115(2):14953. 22 Abacavir-induced hypersensitivity syndrome is strongly associated with HLA-B*5701 during treatment . 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. 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. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. MalaCards based summary: Exfoliative Dermatitis is related to holocarboxylase synthetase deficiency and dermatitis, and has symptoms including exanthema An important gene associated with Exfoliative Dermatitis is SPINK5 (Serine Peptidase Inhibitor Kazal Type 5). Infectious agents are the major cause of EM, in around 90% of cases, especially for EM minor and in children. 2013;27(3):35664. Continue Reading. If it is exfoliative dermatitis that's drug induced, it's easy to treat . J Am Acad Dermatol. In: Eisen AZ, Wolff K, editors. d. Cysts and tumors. 2011;71(5):67283. Ibuprofen Zentiva is a drug based on the active ingredient ibuprofen (DC.IT) (FU), belonging to the category of NSAID analgesics and specifically derivatives of propionic acid. Retrospective review of StevensJohnson syndrome/toxic epidermal necrolysis treatment comparing intravenous immunoglobulin with cyclosporine. Federal government websites often end in .gov or .mil. 1984;101(1):4850. Nutritional support. Drug eruptions that initially present as morbilliform, lichenoid or urticarial rashes may progress to generalized exfoliative dermatitis. ), Phenolphthalein (Agoral, Alophen, Modane), Rifampin (Rifadin, Rimactane; also in Rifamate), Trimethoprim (Trimpex; also in Bactrim, Septra). Erythema multiforme to amoxicillin with concurrent infection by Epstein-Barr virus. Mild to severe alopecia and transient or permanent nail dystrophy also may be encountered. In conclusion we suggest that therapy with cyclosporine is valuable option with a dosage of 35mg/kg oral or iv for 7days. Sekula P, et al. It has a wide spectrum of severity, and it is divided in minor and major (EMM). New York: McGraw-Hill; 2003. pp. Google Scholar. 2012;97:14966. Br J Dermatol. doi: 10.4103/0019-5154.39732. Role of nanocrystalline silver dressings in the management of toxic epidermal necrolysis (TEN) and TEN/StevensJohnson syndrome overlap. Hospitalization is usually necessary for initial evaluation and treatment. Del Pozzo-Magana BR, 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 . J Am Acad Dermatol. 2002;65(9):186170. Main discriminating factors between EMM, SJS, SJS-TEN, TEN and SSSS is summarized in Table3 [84]. Paquet P, et al. PMC ACE inhibitor-induced cough should be considered in the differential diagnosis of cough. An extremely rare mucocutaneous adverse reaction following COVID-19 vaccination: Toxic epidermal necrolysis. loss of taste Derm: stevens-johnson syndrome, toxic epidermal necrolysis, rash, exfoliative dermatitis, hair . A classic example of an idiosyncratic reaction is drug-induced . In patients with this disorder, the mitotic rate and the absolute number of germinative skin cells are higher than normal. 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. A review of DRESS-associated myocarditis. . 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. . 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 . Archivio Istituzionale della Ricerca Unimi, Nayak S, Acharjya B. Etanercept: monoclonal antibody against the TNF- receptor. Am Fam Physician. Apoptosis as a mechanism of keratinocyte death in toxic epidermal necrolysis. Samim F, et al. . Joint Bone Spine. Roujeau JC, Stern RS. [113] retrospectively compared mortality in 64 patients with ED treated either with iv or oral Cys A (35mg/kg) or IVIG (25g/Kg). Although the etiology is often unknown, exfoliative dermatitis may be the result of a drug reaction or an underlying malignancy. The induction dosage in EMM is usually 1mg/kg/day that should be maintained until a complete control of the skin is obtained. 2008;23(5):54750. J Allergy Clin Immunol. Recombinant granulocyte colony-stimulating factor in the management of toxic epidermal necrolysis. Takahashi R, et al. Although the etiology is. 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]. Kirchhof MG et al. Severe adverse cutaneous reactions to drugs. A multicentre study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions. They found that the inhibition of these molecules could attenuate the cytotoxic effect of lymphocytes toward keratinocytes. Exfoliative dermatitis is a rare inflammatory skin condition that is characterized by desquamation and erythema involving more than 90% of the body surface area. Kano Y, et al. PubMed [Stevens-Johnson Syndrom and Toxic Epidermal Necrolysis--based on literature]. 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. 2010;62(1):4553. Contact dermatitis from topical antihistamine . 2013;57(4):58396. For these reasons, patients should be admitted to intensive burn care units or in semi-intensive care units where they may have access to sterile rooms and to dedicated medical personnel [49, 88]. Allergy. Orphanet J Rare Dis. A marked increase in serum soluble Fas ligand in drug-induced hypersensitivity syndrome. Interstitial nephritis is common in DRESS syndrome, occurring roughly in 40% of cases, whereas pre-renal azotemia may occur in SJS and TEN. Rzany B, et al. Most common used drugs are: morphine, fentanyl, propofol and midazolam. Exanthematous drug eruptions. J. Albeit the lack of epidemiologic data regarding EM, its reported prevalence is less than 1% [710]. Initial symptoms could be aspecific, as fever, stinging eyes and discomfort upon swallowing, occurring few days before the onset of mucocutaneous involvement. Four cases are described, two of which were due to phenindione sensitivity. 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. Antibiotic therapy. 2009;182(12):80719. Histopathological and epidemiological characteristics of patients with erythema exudativum multiforme major, StevensJohnson syndrome and toxic epidermal necrolysis. Clipboard, Search History, and several other advanced features are temporarily unavailable. Indian J Dermatol. 1990;126(1):3742. Iv bolus of steroid (dexamethasone 100300mg/day or methylprednisolone 2501000mg/day) for 3 consecutive days with a gradual taper steroid therapy is sometimes advised. Article Epilepsia. J Am Acad Dermatol. Hypothermia can result in ventricular flutter, decreased heart rate and hypotension. Hematologic: anemia, including aplastic and hemolytic. 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 authors declare that they have no competing interests. The diagnosis of GVDH requires histological confirmation [87]. Topical treatment. 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. Cite this article. Mayes T, et al. Eosinophils from Physiology to Disease: A Comprehensive Review. J Dermatol Sci. In EMM lesions typically begin on the extremities and sometimes spread to the trunk. Gout and its comorbidities: implications for therapy. This has been called the nose sign.18, Once the erythema is well established, scaling inevitably follows (Figure 1). J Am Acad Dermatol. CAS Med., 1976, 6, 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. Case Report Toxic epidermal necrolysis: review of pathogenesis and management. AB, CC, ET, GAR, AN, EDL, PF performed a critical revision on the current literature about the described topic, wrote and revised the manuscript. 2005;102(11):41349. Fritsch PO. Disasters. 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]. CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. Descamps V, Ranger-Rogez S. DRESS syndrome. Fitzpatricks dermatology in general medicine. 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]. J Clin Apher. 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]. 2003;21(1):195205. Arch Dermatol. Recently, a meta-analysis based on 6 retrospective studies evaluating the role of corticosteroids alone or together with IVIG has been published [107]. In case of an oral mucositis that impairs nutrition, it is indicated to position a nasogastric tube. This site needs JavaScript to work properly. Arch Dermatol. Defective regulatory T cells in patients with severe drug eruptions: timing of the dysfunction is associated with the pathological phenotype and outcome. 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. In contrast with DRESS, eosinophilia and atypical lymphocytes are not described in patients with SJS or TEN. government site. 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 . Systemic and potentially life-threatening complications include fluid and electrolyte imbalance, thermoregulatory disturbance, fever, tachycardia, high-output failure, hypoalbuminemia, and septicemia. 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. 2012;166(2):32230. Napoli B, et al. Google Scholar. The .gov means its official. 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. Both DRESS and SJS may have increased liver enzymes and hepatitis, but they occur in only 10% of cases of SJS compared to 80% of DRESS. Am J Dermatopathol. HHS Vulnerability Disclosure, Help [Erythema multiforme vs. Stevens-Johnson syndrome and toxic epidermal necrolysis: an important diagnostic distinction]. 1). Valeyrie-Allanore L, et al. 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. EDs are serious and potentially fatal conditions. 2010;37(10):9046. Mockenhaupt M, et al. N.Z. Moreover, after granulysin depletion, they observed an increase in cell viability. Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis. As written before, Sassolas B. et al. 2012;167(2):42432. Ann Allergy Asthma Immunol. Patients must be cleaned in the affected areas until epithelization starts. Dermatol Clin. 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. 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. Incidence and drug etiology in France, 1981-1985. Indian J Dermatol. Paraneoplastic pemphigus is associated with neoplasms, most commonly of lymphoid tissue, but also Waldenstrms macroglobulinemia, sarcomas, thymomas and Castlemans disease. Analysis of StevensJohnson syndrome and toxic epidermal necrolysis using the Japanese Adverse Drug Event Report database. This is particularly true for patients with many comorbidities and poli-drug therapy, where it is advisable to monitor liver and kidney toxicity and to avoid Vitamin A excess [99]. Given the different histopathological features of the EM, SJS and TEN, we decided to discuss them separately. Clin Exp Allergy. A severity-of-Illness score for toxic epidermal necrolysis (SCORTEN) has been proposed and validated to predict the risk of death at admission [81]. A serious cutaneous adverse drug reaction namely exfoliative dermatitis (erythroderma) is associated with isoniazid use . Toxic epidermal necrolysis associated with severe cytomegalovirus infection in a patient on regular hemodialysis. Clinical practice. EMs mortality rate is not well reported. 2003 Oct 25;147(43):2089-94. Nature. Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Oliveira L, Zucoloto S. Erythema multiforme minor: a revision. 2008;58(1):3340. Although the final result of this dual interaction is still under investigation, it seems that the combination of TNF-, IFN- (also present in TEN patients) and the activation of other death receptors such as TWEAK can lead to apoptosis of keratinocytes [44]. TNF- has a dual role: interacts with TNF-R1 activating Fas pathway and activates NF-B leading to cell survival. Tang YH, et al. 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). 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. The epidermal-dermal junction shows changes, ranging from vacuolar alteration to subepidermal blisters [20]. . For SJS/TEN, corticosteroids are the cornerstone of treatment albeit efficacy remains unclear. 1998;282(5388):4903. Erythema multiforme: a review of epidemiology, pathogenesis, clinical features, and treatment. Ramirez GA, Yacoub MR, Ripa M, Mannina D, Cariddi A, Saporiti N, Ciceri F, Castagna A, Colombo G, Dagna L. Biomed Res Int. Hence, the apparent increase in cases of exfoliative dermatitis may be related to the introduction of many new drugs. Theoretically, any drug may cause exfoliative dermatitis. In fact, it was demonstrated that the specificity of the TCR is a required condition for the self-reaction to occur. Unlike EMM, SJS and TEN are mainly related to medication use. 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.