PubMed An official website of the United States government. Lin YT, et al. Br J Clin Pharmacol. Google Scholar. A drug eruption may start as a rash but eventually progress to more generalized exfoliative dermatitis. Exfoliative Dermatitis - StatPearls - NCBI Bookshelf Int J Mol Sci. Skin and appendages: acne, bruising, erythema multiforme, exfoliative dermatitis, pruritus ani, rash, skin ulceration, Stevens . SJS and TEN are two overlapping syndromes resembling severe burn lesions and characterized by skin detachment. 2013;168(3):55562. EM usually occurs in young adults of 2040years of age [13], with women affected more frequently than men (1.5:1.0) [14]. J Allergy Clin Immunol. Pathogenicity and Virulence of Staphylococcus Aureus | PDF This compressed maturation process results in an overall greater loss of epidermal material, which is manifested clinically as severe scaling and shedding. 00 Comments Please sign inor registerto post comments. J Burn Care Res. Most common used drugs are: morphine, fentanyl, propofol and midazolam. Ann Allergy Asthma Immunol. J Am Acad Dermatol. Br J Dermatol. In SJS, SJS/TEN and TEN the efficacy of corticosteroids is far from being demonstrated. 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. Chang CC, et al. Oral hygiene with antiseptic and painkiller mouthwash (chlorhexidine+lidocaine+aluminum hydroxide) together with aerosol therapy with saline and bronchodilators can reduce upper airways symptoms. A useful sign for differential diagnosis is the absence of mucosal involvement, except for conjunctiva. Rarely, Mycoplasma pneumoniae, dengue virus, cytomegalovirus, and contrast media may be the causative agent of SJS and TEN [22, 6567]. 19 Key critical interactions are discussed below for each mpox antiviral. Drug-induced Exfoliative Dermatitis & Eosinophils Increased: Causes Smith SD, et al. Chemicals and Drugs 61. The long-term prognosis is good in patients with drug-induced disease, although the course tends to be remitting and relapsing in idiopathic cases. Supportive and specific care includes both local and systemic measures, as represented in Fig. In acute phase it is crucial to assess the culprit agent, in particular when the patient was assuming several drugs at time of DHR. Toxic epidermal necrolysis treated with cyclosporin and granulocyte colony stimulating factor. 1998;282(5388):4903. Also, physicians should be vigilant about possible secondary infection, whether cutaneous, pulmonary or systemic. Paraneoplastic pemphigus is associated with neoplasms, most commonly of lymphoid tissue, but also Waldenstrms macroglobulinemia, sarcomas, thymomas and Castlemans disease. Panitumumab Induced Forearm Panniculitis in Two Women With Metastatic Background: Panitumumab is an EGFR inhibitor used for the treatment of metastatic colorectal cancer (mCRC), even if its use is related to skin toxicity. 2013;168(3):53949. 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/. Am J Clin Dermatol. The Nikolskys sign is not specific for SJS/TEN, in fact it is present also in auto-immune blistering diseases like pemphigus vulgaris. 2011;71(5):67283. Fitzpatricks dermatology in general medicine. Nutr Clin Pract. It has a wide spectrum of severity, and it is divided in minor and major (EMM). Aminoglutethimide: Aminoglutethimide may lead to a loss of corticosteroid-induced adrenal suppression. Morel E, et al. The most notable member of this group is mycosis fungoides. Two Cases in Adult Patients. TEN is also known as Lyell syndrome, since it was first described by Alan Lyell in 1956 [2, 60]. 2013;27(3):35664. 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. Privacy Do this 2 to 3 times a week. Article 2014;70(3):53948. Cutaneous graft-versus-host diseaseclinical considerations and management. Bookshelf (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 . Please enable it to take advantage of the complete set of features! 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]. New York: McGraw-Hill; 2003. pp. [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. 2000;22(5):4137. Herpes simplex virus (HSV) 1 and 2 are the main triggers in young adults (>80% of cases), followed by Epstein-Barr virus (EBV), and Mycoplasma pneumonia [5558]. . 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]. Tohyama M, et al. Incidence of hypersensitivity skin reactions. Medical search. Frequent Options include use of PUVA light therapy, total-body electron beam irradiation, topical nitrogen mustard, systemic chemotherapy and extracorporeal photopheresis. Analysis for circulating Szary cells may be helpful, but only if the cells are identified in unequivocally large numbers. Toxic epidermal necrolysis and StevensJohnson syndrome. Histopathological and epidemiological characteristics of patients with erythema exudativum multiforme major, StevensJohnson syndrome and toxic epidermal necrolysis. 2009;145(2):15762. 2016;2:14. The drug level peaks after 1- 4 h in plasma after ingestion with 95% protein binding. 2003;21(1):195205. These highlights do not include all the information needed to use Erythema multiforme and toxic epidermal necrolysis: a comparative study. Schwartz RA et al. Takahashi R, et al. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. Wikizero - Basal-cell carcinoma An increased metabolism is typical of patients with extended disepithelizated areas. Intravenous administration is recommended. Since cutaneous function as a multiprotective barrier is so disrupted in exfoliative dermatitis, the body loses heat, water, protein and electrolytes, and renders itself much more vulnerable to infection. 2010;62(1):4553. 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. Kamaliah MD, et al. Mortality rate of patients with TEN has shown to be directly correlated to SCORTEN, as shown in Fig. A switch to oral therapy can be performed once the mucosal conditions improve. Exfoliative Dermatitis as a Para-neoplastic Syndrome of Prostate 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. California Privacy Statement, Recent advances in the genetics and immunology of StevensJohnson syndrome and toxic epidermal necrosis. PMC 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]. Roujeau JC, Stern RS. . PubMed Drug-induced LPP. Samim F, et al. Etanercept therapy for toxic epidermal necrolysis. It should be used only in case of a documented positivity of cultural samples. Google Scholar. Kirchhof MG, et al. J Am Acad Dermatol. Download. Half-life of the drug is approximately 54 h. Modification of nitisinone in liver and renal dysfunction is yet to be studied. 2010;5:39. 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]. Moreover, transpiration and thermoregulation are greatly impaired with an elevated loss of fluids, proteins and electrolytes through the damaged skin and mucosae. 2010;31(1):1004. Trialon | 40 mg/ml | Injection | ../.. Paquet P, Pierard GE, Quatresooz P. Novel treatments for drug-induced toxic epidermal necrolysis (Lyells syndrome). J Immunol. 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. Google Scholar. The https:// ensures that you are connecting to the 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. Polak ME, et al. 2023 BioMed Central Ltd unless otherwise stated. Google Scholar. 2022 May;35(5):e15416. Detection of a herpes simplex viral antigen in skin lesions of erythema multiforme. 2014;71(1):1956. Therefore, the clinician should always consider drugs as a possible cause. Sekula P, et al. Drug-induced exfoliative dermatitis is usually short-lived once the inciting medication is withdrawn and appropriate therapy is administered. Epub 2022 Mar 9. Science. Allergic rhinitis and atopic dermatitis. Medical search. Web 1996;135(1):611. Br J Dermatol. Talk to our Chatbot to narrow down your search. 2008;34(1):636. The epidermal-dermal junction shows changes, ranging from vacuolar alteration to subepidermal blisters [20]. 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]. Archivio Istituzionale della Ricerca Unimi, Nayak S, Acharjya B. 2008;12(5):3559. 49th Annual Meeting of the Arbeitsgemeinschaft Dermatologische It is challenging to diagnose this syndrome due to the variety . Frequently reported adverse events of rebamipide compared to other drugs for peptic ulcer and gastroesophageal reflux disease. Erythema multiforme (EM), StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. A rare case of toxic epidermal necrolysis with unexpected Fever resulting from dengue virus. Exfoliative Dermatitis | AAFP Captopril and Hydrochlorothiazide Tablet Prescribing Information PubMed Case Report AQUACEL Ag in the treatment of toxic epidermal necrolysis (TEN). In most severe cases the suggested dosage is iv 11.5mg/kg/day. Paulmann M, Mockenhaupt M. Severe drug-induced skin reactions: clinical features, diagnosis, etiology, and therapy. Drug-Induced Kidney Injury & Exfoliative Dermatitis: Causes & Reasons Paradisi et al. If there is a high suspicion of infection without a documented source of infection, broad range empiric therapy should be started. 2008;23(5):54750. Acute processes usually favor large scales, whereas chronic processes produce smaller ones. 2012;12(4):37682. 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). The timing of the rash can also vary. Correspondence to 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. Temporary tracheostomy may be necessary in case of extended mucosal damage. Skin testing in delayed reactions to drugs. Li X, et al. Skin testing and patch testing in non-IgE-mediated drug allergy. 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]. 2003 Oct 25;147(43):2089-94. The most common causes of exfoliative dermatitis are best remembered by the mnemonic device ID-SCALP. Roujeau JC, et al. Clinical features; Delayed type hypersensitivity; Drug hypersensitivity; Erythema multiforme; Exfoliative dermatitis; Lyells syndrome; Pathogenesis; StevensJohnson syndrome; Therapy; Toxic epidermal necrolysis. Palynziq PEGVALIASE 20 mg/mL BioMarin Pharmaceutical Inc. N Engl J Med. It is a clinical manifestation and usually associated with various underlying cutaneous disorders, drug induced reactions and malignancies. In conclusion, therapy wth IVIG should be started within the first 5days and an high-dosage regimen should be preferred (2.54g/kg for adults and 0.251.5g/kg in children divided in 35days). In more severe cases corneal protective lens can be used. Federal government websites often end in .gov or .mil. EMM is characterizes by target lesions, circular lesions of 1-2cm of diameter, that are defined as typical or atypical that tends to blister. 2004;114(5):120915. Drug induced exfoliative dermatitis: State of the art - ResearchGate Antipyretic therapy. Guidelines for the management of drug-induced liver injury[J]. In case of a respiratory failure, oxygen should be administrated and a NIMV may be required. Rare dermatological side effects such as alopecia, exfoliative dermatitis, xeroderma, pruritus have been reported. 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. Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity. Google Scholar. FOIA Even though there is not a significant increase in the number of T cells infiltrating the skin of TEN patients, it was found that their role is crucial, even more than HLAs types. Exfoliative Dermatitis to Anti Tubercular Drugs - Academia.edu 2014;81(1):1521. 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]. Erythroderma is the term used to describe intense and usually widespread reddening of the skin due to inflammatory skin disease. Copyright 2023 American Academy of Family Physicians. Dent Clin North Am. 2004;59(8):80920. Drug induced exfoliative dermatitis - yxw_88 - | It is advised against the use of silver sulfadiazine because sulphonamide can be culprit agents. Antitumour necrosis factor-alpha antibodies (infliximab) in the treatment of a patient with toxic epidermal necrolysis. The clinical course of patients with malignancies depends on the type of malignancy and the response to appropriate therapy. Clinical practice. Exfoliative Dermatitis: Symptoms, Diagnosis & Treatments - Healthline Pathophysiology DIP. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Their occurrence can be prevented by avoiding drug over-prescription and drug associations that interfere with the metabolism of the most frequent triggers [118]. Am Fam Physician. . Kreft B, et al. 1993;129(1):926. 1992;11(3):20710. Patients must be cleaned in the affected areas until epithelization starts. Nature. Ther Apher Dial. Kostal M, et al. Toxic epidermal necrolysis: effector cells are drug-specific cytotoxic T cells. 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]. Arch Dermatol. 2010;125(3):70310. Applications of Immunopharmacogenomics: Predicting, Preventing, and Understanding Immune-Mediated Adverse Drug Reactions. PubMed Shiga S, Cartotto R. What are the fluid requirements in toxic epidermal necrolysis? 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. J Am Acad Dermatol. Exfoliative dermatitis is also a risk factor for epidemic spread of methicillin-resistant Staphylococcus aureus.6,20. Considered variables in SCORTEN are shown in Table2. 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]. N Engl J Med. 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. 2009;182(12):80719. Increased level of retinoid acid could be responsible for keratinocytes apoptosis [99]. official website and that any information you provide is encrypted Once ED has occurred, it has to be managed in the adequate setting with a multidisciplinary approach, and every effort has to be made to identify and avoid the trigger and to prevent infectious and non-infectious complications. Genome-wide association study identifies HLA-A* 3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population. The applications of topical cyclosporine and autologous serum have also been showed to be useful in refractory cases [103]. CAS In contrast with DRESS, eosinophilia and atypical lymphocytes are not described in patients with SJS or TEN. Linear IgA dermatosis most commonly presents in patients older than 30years. Hypervolemia can also occur in patients with exfoliative dermatitis, contributing to the likelihood of cardiac failure.2124, In most patients with erythroderma, skin biopsies show nonspecific histopathologic features, such as hyperkeratosis, parakeratosis, acanthosis and a chronic perivascular inflammatory infiltrate, with or without eosinophils. 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 . Open trial of ciclosporin treatment for StevensJohnson syndrome and toxic epidermal necrolysis. Am J Infect Dis. Napoli B, et al. 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 Recurrent erythema multiforme: clinical characteristics, etiologic associations, and treatment in a series of 48 patients at Mayo Clinic, 2000 to 2007. Prevalence is low, with mortality of roughly 512.5% for SJS and 50% for TEN [1, 2]. Hypersensitivity, Delayed Drug Hypersensitivity Radiodermatitis Drug Eruptions Skin Diseases Hypersensitivity Hand-Foot Syndrome Hypersensitivity, Immediate Dermatitis, Contact Erythema Foot Dermatoses Hand Dermatoses Skin Neoplasms Dermatitis, Allergic Contact Alveolitis, Extrinsic Allergic Acneiform Eruptions Dentin Sensitivity Dermatitis Exanthematous drug eruptions. J Am Acad Dermatol. Each of these physiologic disruptions is potentially life-threatening. 2002;109(1):15561. Typical target lesions consist of three components: a dusky central area or blister, a dark red inflammatory zone surrounded by a pale ring of edema, and an erythematous halo on the periphery. ADRJ,2015,17(6):464-465. The relative risk of leukemia inducing erythroderma is highly variable, ranging from 11 to 50 percent.11, Internal (visceral) malignancies cause about 1 percent of all cases of exfoliative dermatitis.11 Frequently, erythroderma is the presenting sign of the malignancy. J Am Acad Dermatol. Hypothermia can result in ventricular flutter, decreased heart rate and hypotension. 2011;18:e12133. In ED increased levels of FasL have been detected in patients sera [33]. De Araujo E, et al. J Invest Dermatol. 2013;57(4):58396. Mucosal involvement could achieve almost 65% of patients [17]. Ann Intern Med. -. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Etanercept: monoclonal antibody against the TNF- receptor. In: Eisen AZ, Wolff K, editors. Khalil I, et al. In more severe cases continuous iv therapy can be necessary. 1995;333(24):16007. It is a clinical manifestation and usually associated with various underlying cutaneous disorders, drug induced reactions and malignancies. Terms and Conditions, 2000;115(2):14953. Nutritional support. 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. Toxic epidermal necrolysis: Part I Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. Ardern-Jones MR, Friedmann PS. 2008;14(12):134350. 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]. 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. Szary syndrome, the leukemic variant of mycosis fungoides, is also associated with exfoliative dermatitis. It characteristically demonstrates diffuse erythema and scaling of greater than 90% of the body surface area. 2009;151(7):5145. A recent review [111] on 33 pediatric cases of TEN and 6 cases of SJS/TEN overlap showed that therapy with IVIG with a dosage of 0.251.5g/kg for 5days resulted in 0% mortality rate and faster epithelization. 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. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis. ), Phenolphthalein (Agoral, Alophen, Modane), Rifampin (Rifadin, Rimactane; also in Rifamate), Trimethoprim (Trimpex; also in Bactrim, Septra). Allergy. Medical genetics: a marker for StevensJohnson syndrome. National Library of Medicine A marker for StevensJohnson syndrome: ethnicity matters. It is recommended to use 1.5mg/kg hydrocortisone. Gastric protection. 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. Barbaud A. J. Clin Pharmacol Ther. doi: 10.4065/mcp.2009.0379. For the prevention of deep venous thrombosis; usually low molecular weight heparin at prophylactic dose are used. This content is owned by the AAFP. 2015;56(4):298302. 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. Strom BL, et al. Schwartz RA, McDonough PH, Lee BW. In more severe cases antiviral therapies should be given together with intravenous immunoglobulins [93]. A systematic review of treatment of drug-induced StevensJohnson syndrome and toxic epidermal necrolysis in children. Tohyama M, Hashimoto K. Immunological mechanisms of epidermal damage in toxic epidermal necrolysis. 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). 2012;27(4):21520. Copyright 1999 by the American Academy of Family Physicians. Fitzpatricks dermatology in general medicine. In approximately 25% of people, there is no identifiable cause. 2013;133(5):1197204. 1 Fernando SL. 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]. Erythema multiforme (EM), StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Journal of Pharmaceutical Research and health Care. Also a vesical catheter should be placed to avoid urethral synechiae and to have a precise fluid balance. Case Rep Dermatol. Arch Dermatol. Indian J Dermatol. 2013;69(2):173174. Epilepsia. A multidisciplinary team is fundamental in the therapeutic management of patients affected by exfoliative DHR.