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. Erythema multiforme (EM), Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. The approach to treatment should include discontinuation of any potentially causative medications and a search for any underlying malignancy. A population-based study with particular reference to reactions caused by drugs among outpatients. Do this 2 to 3 times a week. 8600 Rockville Pike Paraneoplastic pemphigus is associated with neoplasms, most commonly of lymphoid tissue, but also Waldenstrms macroglobulinemia, sarcomas, thymomas and Castlemans disease. J Am Acad Dermatol. Bullous dermatoses can be debilitating and possibly fatal. PMC 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]. 2015;56(4):298302. . In some studies, the nose and paranasal area are spared. 2012;12(4):37682. 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. Chung W-H, et al. Efficacy of plasmapheresis for the treatment of severe toxic epidermal necrolysis: is cytokine expression analysis useful in predicting its therapeutic efficacy? Minerva Stomatol. This is due to a reaction to certain medicines, a pre-existing skin condition, and sometimes cancer. 7 DRUG INTERACTIONS 7.1 PDE-5-Inhibitors and sGC-Stimulators 7.2 Ergotamine 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.2 Lactation 8.4 Pediatric Use 8.5 Geriatric Use 10 OVERDOSAGE 10.1 Signs and Symptoms, Methemoglobinemia 10.2 Treatment of Overdosage 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12. . Locharernkul C, et al. 2. Drug rashes are the body's reaction to a certain medicine. 2013;168(3):53949. It is challenging to diagnose this syndrome due to the variety . HLA-B* 5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. 2000;115(2):14953. 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. 2012;13(1):4954. Kirchhof MG, et al. Carbamazepine and phenytoin induced StevensJohnson syndrome is associated with HLA-B* 1502 allele in Thai population. 2008;53(1):28. Carrozzo M, Togliatto M, Gandolfo S. Erythema multiforme. N Engl J Med. Role of nanocrystalline silver dressings in the management of toxic epidermal necrolysis (TEN) and TEN/StevensJohnson syndrome overlap. The management of toxic epidermal necrolysis. The clinical course of patients with malignancies depends on the type of malignancy and the response to appropriate therapy. Article 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]. Corticosteroids could also reduce the amount of keratinocytes apoptosis and the activation of caspases [105]. (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 . The EuroSCAR-study. 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. 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]. 1996;44(2):1646. Br J Dermatol. Shiga S, Cartotto R. What are the fluid requirements in toxic epidermal necrolysis? Usually the amount of calories is 15002000kcal/day and the velocity of infusion is gradually increased based on patients tolerability [92]. Considered variables in SCORTEN are shown in Table2. Fitzpatricks dermatology in general medicine. The balance of fluids and electrolytes should be closely monitored, since dehydration or hypervolemia can be problems. Grieb G, et al. Strom BL, et al. 2023 BioMed Central Ltd unless otherwise stated. Exanthematous drug eruptions. Autologous transplantation of mesenchymal umbilical cord cells seems also to be highly efficacious [102]. Furosemide or ethacrynic acid may be required to maintain an adequate urinary output [90]. 2008;34(1):636. It is also extremely important to obtain within the first 24h cultural samples from skin together with blood, urine, nasal, pharyngeal and bronchus cultures. 2013;57(4):58396. Moreover, transpiration and thermoregulation are greatly impaired with an elevated loss of fluids, proteins and electrolytes through the damaged skin and mucosae. b. Atopic dermatitis. 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. AR 40-501 14 June 2017 33 e. Dermatitis herpetiformis. 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. 2012;27(4):21520. 1991;127(6):8318. 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]. Clin Exp Dermatol. Szary syndrome, the leukemic variant of mycosis fungoides, is also associated with exfoliative dermatitis. Some anti-seizure medicines have also been known to cause exfoliative dermatitis. 2011;66(3):3607. Topical treatment. Detection of a herpes simplex viral antigen in skin lesions of erythema multiforme. Comprehensive survival analysis of a cohort of patients with StevensJohnson syndrome and toxic epidermal necrolysis. Their occurrence can be prevented by avoiding drug over-prescription and drug associations that interfere with the metabolism of the most frequent triggers [118]. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. 1990;126(1):437. Energy requirements of pediatric patients with StevensJohnson syndrome and toxic epidermal necrolysis. Oral hygiene with antiseptic and painkiller mouthwash (chlorhexidine+lidocaine+aluminum hydroxide) together with aerosol therapy with saline and bronchodilators can reduce upper airways symptoms. PTs have to be performed at least 6months after the recovery of the reaction, and show a variable sensitivity considering the implied drug, being higher for beta-lactam, glycopeptide antibiotics, carbamazepine, lamotrigine, proton pump inhibitors, tetrazepam, trimethoprimsulfametoxazole, pseudoephedrine and ramipril [7376]. Toxic epidermal necrolysis associated with severe cytomegalovirus infection in a patient on regular hemodialysis. Among drug related cases, the main triggering factors are sulfonamides, nonsteroidal anti-inflammatories (NSAIDs), penicillins, and anticonvulsants (Table1) [59]. 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]. In patients who develop complications (i.e., infection, fluid and electrolyte abnormalities, cardiac failure), the rate of mortality is often high. Bookshelf 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. 2004;59(8):80920. 2010;85(2):131138. 2014;71(2):27883. Garza A, Waldman AJ, Mamel J. Kreft B, et al. Hypothermia can result in ventricular flutter, decreased heart rate and hypotension. Etanercept therapy for toxic epidermal necrolysis. Nutritional support. All Rights Reserved. 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. Ann Pharmacother. Ther Apher Dial. Huang SH, et al. Patients with underlying skin disorders may respond much more slowly to therapy, but clearing almost always occurs eventually. Drug reactions are one of the most common causes of exfoliative dermatitis. AB, CC, ET, GAR, AN, EDL, PF performed a critical revision on the current literature about the described topic, wrote and revised the manuscript. 2011;20(5):103441. Possible involvement of CD14+CD16+monocyte lineage cells in the epidermal damage of StevensJohnson syndrome and toxic epidermal necrolysis. Aminoglutethimide: Aminoglutethimide may lead to a loss of corticosteroid-induced adrenal suppression. 2009;182(12):80719. [71] realized an algorhitm named ALDEN (algorithm of drug causality for epidermal necrolysis) which helps to establish a cause/effect relationship as probable or very probable in 70% of cases. Kirchhof MG et al. Hence, the apparent increase in cases of exfoliative dermatitis may be related to the introduction of many new drugs. Exfoliative dermatitis is characterized by generalized erythema with scaling or desquamation affecting at least 90% of the body surface area. Nassif A, et al. Recent advances in the genetics and immunology of StevensJohnson syndrome and toxic epidermal necrosis. In any case all authors concluded that the blockage of FasL prevents keratinocyte apoptosis [35]. Poor relevance of a lymphocyte proliferation assay in lamotrigine-induced StevensJohnson syndrome or toxic epidermal necrolysis. Half-life of the drug is approximately 54 h. Modification of nitisinone in liver and renal dysfunction is yet to be studied. Br J Dermatol. 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. 2013;69(2):187. 543557. [113] retrospectively compared mortality in 64 patients with ED treated either with iv or oral Cys A (35mg/kg) or IVIG (25g/Kg). 2011;38(3):23645. Plasmapheresis. J Burn Care Res. [80], which consists of the determination of IFN and IL4 by ELISpot (Enzyme-linked immunospot assay), allowing to increase the sensitivity of LTT during acute DHR (82 versus 50% if compared to LPA). Clinical features; Delayed type hypersensitivity; Drug hypersensitivity; Erythema multiforme; Exfoliative dermatitis; Lyells syndrome; Pathogenesis; StevensJohnson syndrome; Therapy; Toxic epidermal necrolysis. Bethesda, MD 20894, Web Policies Federal government websites often end in .gov or .mil. 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. 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]. volume14, Articlenumber:9 (2016) Grosber M, et al. Article 2. -. Morel E, et al. It is important to protect the damaged skin with sterile fat dressing especially in the genital area. J Dtsch Dermatol Ges. Heat loss is another major concern that accompanies a defective skin barrier in patients with exfoliative dermatitis. Clipboard, Search History, and several other advanced features are temporarily unavailable. Erythema multiforme and toxic epidermal necrolysis. Schwartz RA, McDonough PH, Lee BW. Because a certain degree of cross-reactivity between the various aromatic anti-epileptic drugs exists, some HLAs have been found to be related to SJS/TEN with two drugs, as the case of HLA-B*1502 with both phenytoin and oxcarbazepine [32]. Robyn A. McMenamin, L M. Davies and P. W. Craswell, Aust. (2.4, 5.6) Embryo-fetal Toxicity: Can cause fetal harm. Adverse cutaneous drug reaction. Disasters. Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity. Goulden V, Goodfield MJ. PubMed This compressed maturation process results in an overall greater loss of epidermal material, which is manifested clinically as severe scaling and shedding. In more severe cases antiviral therapies should be given together with intravenous immunoglobulins [93]. Google Scholar. 2008;49(12):208791. Bickle K, Roark TR, Hsu S. Autoimmune bullous dermatoses: a review. In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of NSAID therapy. 2010;2(3):18994. Allergy. Combination of infliximab and high-dose intravenous immunoglobulin for toxic epidermal necrolysis: successful treatment of an elderly patient. HLA DQB1* 0301 allele is involved in the susceptibility to erythema multiforme. Mortality rate of patients with TEN has shown to be directly correlated to SCORTEN, as shown in Fig. Erythroderma (literally, "red skin"), also sometimes called exfoliative dermatitis, is a severe and potentially life-threatening condition that presents with diffuse erythema and scaling involving all or most of the skin surface area (90 percent, in the most common definition). Bastuji-Garin S, et al. 2015;49(3):33542. [49] confirmed these results and even suggested that higher dosage regimen with 2.74g/kg seem to be more effective in survival outcome. In case of an oral mucositis that impairs nutrition, it is indicated to position a nasogastric tube. CAS A catabolic state thus ensues, which is often responsible for significant weight loss. 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]. Ann Burns Fire. Med Sci Monit. Soak for 5 to 10 minutes and rinse off before patting dry. Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal necrolysis. The syndrome has been described previously in association with phenindione administration, leptospirosis and heavy metal poisoning. 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. Ko TM, et al. 2016 Nov 15;17(11):1890. doi: 10.3390/ijms17111890. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Focus on the Pathophysiological and Diagnostic Role of Viruses. Granulysin as a marker for early diagnosis of the StevensJohnson syndrome. HLA-A* 3101 and carbamazepine-induced hypersensitivity reactions in Europeans. Erythroderma is the term used to describe intense and usually widespread reddening of the skin due to inflammatory skin disease. Exfoliative dermatitis, also known as erythroderma, is an uncommon but serious skin disorder that family physicians must be able to recognize and treat appropriately. Iv bolus of steroid (dexamethasone 100300mg/day or methylprednisolone 2501000mg/day) for 3 consecutive days with a gradual taper steroid therapy is sometimes advised. Moreover, the time necessary for cells to mature and travel through the epidermis is decreased. EMM is a clinically severe, potentially life-threatening, extensive sloughing of epidermis, generally involving mucosal tissue. Exfoliative Dermatitis is a serious skin cell disorder that requires early diagnosis and treatment. Semin Dermatol. Reticuloendothelial neoplasms, as well as internal visceral malignancies, can produce erythroderma, with the former being the more predominant cause. Ann Allergy Asthma Immunol. Roujeau JC, et al. 5% silver nitrate compresses have antiseptic properties. Tohyama M, et al. Genotyping is recommended in specific high-risk ethnic groups (e.g. ADRJ,2015,17(6):464-465. More than moderate, unresponsive to treatment, and which interferes with the Soldier's perfor-mance of duty. Open trial of ciclosporin treatment for StevensJohnson syndrome and toxic epidermal necrolysis. 1983;8(6):76375. In the hospital, special attention must be given to maintaining temperature control, replacing lost fluids and electrolytes, and preventing and treating infection. Lonjou C, et al. Since the earliest descriptions of exfoliative dermatitis, medications have been known to be important causative agents. 1996;134(4):7104. 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 Tumor necrosis factor : TNF- seems also to play an important role in TEN [41]. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Although the etiology is often unknown, exfoliative dermatitis may be the result of a drug reaction or an underlying malignancy. Oral manifestations of erythema multiforme. Wetter DA, Davis MD. This site needs JavaScript to work properly. 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. Roujeau JC, et al. As written before, Sassolas B. et al. J Am Acad Dermatol. The exfoliative process also may involve the scalp, with 25 percent of patients developing alopecia.4 Nails can often become dystrophic, particularly in patients with preexisting psoriasis.4,6, The most frequently noted symptoms in patients with exfoliative dermatitis include malaise, pruritis and a chilly sensation. 00 Comments Please sign inor registerto post comments. Mona-Rita Yacoub. When less than 10% of the body surface area (BSA) is involved, it is defined SJS, when between 10 and 30% of BSA it is defined overlapping SJS/TEN, when more than 30% of BSA, TEN [2] (Additional file 1: Figure S1, Additional file 2: Figure S2). The induction dosage in EMM is usually 1mg/kg/day that should be maintained until a complete control of the skin is obtained. TEN is characterized by full-thickness epidermal necrosis with an evident epidermal detachment and sloughing caused by necrosis of keratinocytes following apoptosis [49, 52]. Australas J Dermatol. Recurrence occurs in around one-third of cases [15] and there is a genetic predisposition for certain Asian groups [16]. Wetter DA, Camilleri MJ. Br J Dermatol. . Anticoagulation therapy. Case Rep Dermatol Med. Curr Allergy Asthma Rep. 2014;14(6):442. Expression of alpha-defensin 1-3 in T cells from severe cutaneous drug-induced hypersensitivity reactions. Genome-wide association study identifies HLA-A* 3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population. In more severe cases corneal protective lens can be used. The fluid of blisters from TEN patients was found to be rich in TNF-, produced by monocytes/macrophages present in the epidermis [42], especially the subpopulation expressing CD16, known to produce higher levels of inflammatory cytokines [43]. Fritsch PO. A correlation between increased levels of perforin/granzyme B and the severity of TEN was also described [38]. sharing sensitive information, make sure youre on a federal Bastuji-Garin S, et al. 2008;12(5):3559. f. Hung S-I, et al. Gonzalez-Delgado P, et al. Utility of the lymphocyte transformation test in the diagnosis of drug sensitivity: dependence on its timing and the type of drug eruption. PubMed In acute phase it is crucial to assess the culprit agent, in particular when the patient was assuming several drugs at time of DHR. 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. Its also characterized by a cell-poor infiltrate, where macrophages and dendrocytes with a strong TNF- immunoreactivity predominate [6, 50]. Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis. The erythrodermic form of mycosis fungoides and the Szary syndrome may also be difficult to distinguish from benign erythroderma. Toxic epidermal necrolysis (Lyell syndrome). Generalized exfoliative dermatitis, or erythroderma, is a severe inflammation of the entire skin surface. Current Perspectives on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. 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. Paquet P, Pierard GE. Careers. Am J Infect Dis. Recombinant granulocyte colony-stimulating factor in the management of toxic epidermal necrolysis. Download. 2005;94(4):41923. 2010 Oct;35(7):723-8. doi: 10.1111/j.1365-2230.2009.03718.x. Mayes T, et al. CAS Descamps V, Ranger-Rogez S. DRESS syndrome. Mayo Clin Proc. The timing of the rash can also vary. 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]. Toxic epidermal necrolysis: Part I Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad Dermatol. Options include use of PUVA light therapy, total-body electron beam irradiation, topical nitrogen mustard, systemic chemotherapy and extracorporeal photopheresis. Patient must be placed in an antidecubitus fluidized bed and room temperature must be kept at 3032C in order to slow catabolism and reduce the loss of calories through the skin [89]. A slow acetylator genotype is a risk factor for sulphonamide-induced toxic epidermal necrolysis and StevensJohnson syndrome. Int J Mol Sci. IBUPROFENE ZENTIVA is indicated for the symptomatic treatment of headaches, migraines, dental pain, back pain, dysmenorrhea, muscle pain, neuralgia . erythroderma, exfoliative dermatitis, and fixed drug reactions) 4, 5 and . Volume 8, Issue 1 Pages 1-90 (August 1994). Prevalence is low, with mortality of roughly 512.5% for SJS and 50% for TEN [1, 2]. It is necessary to obtain as soon as possible a central venous access and to start a continuous monitoring of vital signs. Exfoliative dermatitis is a rare inflammatory skin condition that is characterized by desquamation and erythema involving more than 90% of the body surface area. As described in Table3, major differential diagnosis of EM and SJS/TEN are (1) staphylococcal scalded skin syndrome (SSSS), (2) autoimmune blistering diseases and disseminated fixed bullous drug eruption, (3) others severe delayed DHR [6, 70, 82] (4) Graft versus host disease. 2013;69(2):173174. Br J Dermatol. J Am Acad Dermatol. The enhanced activation of CD8 T cells seems also to be influenced by the impaired function of CD4+CD25+FoxP3+Treg cells found in the peripheral blood of TEN patients in the acute phase [46]. Defective regulatory T cells in patients with severe drug eruptions: timing of the dysfunction is associated with the pathological phenotype and outcome. 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. 2010;88(1):608. Add 1 cup (about 236 milliliters) of vinegar to a bathtub filled with warm water. The most common of these are psoriasis, atopic dermatitis, seborrheic dermatitis, contact dermatitis and pityriasis rubra pilaris. Erythema multiforme and latent herpes simplex infection. HHS Vulnerability Disclosure, Help Disclaimer. Gastrointestinal: pancreatitis, glossitis, dyspepsia. Incidence and drug etiology in France, 1981-1985. All authors read and approved the final manuscript. 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. Trautmann A, et al. Skin and appendages: acne, bruising, erythema multiforme, exfoliative dermatitis, pruritus ani, rash, skin ulceration, Stevens . J Eur Acad Dermatol Venereol. PubMed Central Erythema multiforme (EM), StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Fritsch PO. 2006;34(2):768. Association between HLA-B* 1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Br J Dermatol. A multidisciplinary team is fundamental in the therapeutic management of patients affected by exfoliative DHR. J Allergy Clin Immunol. SJS/TEN syndrome is associated with severe blistering, mucocutaneous peeling, and multi-organ damage and could be life threatening. In patients with this disorder, the mitotic rate and the absolute number of germinative skin cells are higher than normal. Painkiller therapy. J Popul Ther Clin Pharmacol. Med., 1976, 6, pp. Perforin/granzyme B pathway: Nassif and colleagues have proposed a role for perforin/grazyme B in keratinocyte death [37]. and transmitted securely. PubMed Central Narita YM, et al. https://doi.org/10.1186/s12948-016-0045-0, DOI: https://doi.org/10.1186/s12948-016-0045-0. 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. 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. Systemic derangements may occur with exfoliative. The dermo-epidermal junction and epidermis are infiltrated mostly by CD8+ T lymphocytes whereas dermal infiltrate, mainly made from CD4+ T lymphocytes, is superficial and mostly perivascular [20, 51].

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