CAS Huang YC, Li YC, Chen TJ. 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. Several authors report the incidence of hospitalization for EM ranging from 0.46 cases per million people per year of northern Europe [11] to almost 40 cases per million people per year of United States [12]. 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 In acute phase it is crucial to assess the culprit agent, in particular when the patient was assuming several drugs at time of DHR. Huff JC, Weston WL, Tonnesen MG. Erythema multiforme: a critical review of characteristics, diagnostic criteria, and causes. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. government site. and transmitted securely. It is challenging to diagnose this syndrome due to the variety . 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. Br J Dermatol. 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. Ozeki T, et al. The clinical course of patients with malignancies depends on the type of malignancy and the response to appropriate therapy. Systemic and potentially life-threatening complications include fluid and electrolyte imbalance, thermoregulatory disturbance, fever, tachycardia, high-output failure, hypoalbuminemia, and septicemia. [3] The causes and their frequencies are as follows: Idiopathic - 30% Drug allergy - 28% Seborrheic dermatitis - 2% Contact dermatitis - 3% Atopic dermatitis - 10% Lymphoma and leukemia - 14% Psoriasis - 8% Treatment [ edit] ), Phenolphthalein (Agoral, Alophen, Modane), Rifampin (Rifadin, Rimactane; also in Rifamate), Trimethoprim (Trimpex; also in Bactrim, Septra). Descamps V, Ranger-Rogez S. DRESS syndrome. 2013;69(4):37583. Med., 1976, 6, pp. Article Mayo Clin Proc. 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. 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. 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). Exfoliative dermatitis is characterized by generalized erythema with scaling or desquamation affecting at least 90% of the body surface area. 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. Bullous FDE. Ibuprofen Zentiva can be prescribed with OTC Recipe - self-medication. Immune-histopathological features allow to distinguish generalized bullous drug eruption from SJS/TEN [36]. Antiviral therapy. The action of antithyroid drugs may be delayed in amiodarone-induced thyrotoxicosis because of substantial quantities of preformed thyroid hormones stored in the gland. The authors concluded for a potential beneficial effect of Cys A and a possible improvement in survival compared to IVIG. 2010;31(1):1004. Other cases are ultimately classifiable as another dermatosis. J Allergy Clin Immunol. Roujeau JC, Stern RS. Szary syndrome, the leukemic variant of mycosis fungoides, is also associated with exfoliative dermatitis. Sequelae of exfoliative dermatitis are not widely reported. 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. Increased level of retinoid acid could be responsible for keratinocytes apoptosis [99]. 2013;57(4):58396. Mortality rate of patients with TEN has shown to be directly correlated to SCORTEN. Schwartz RA, McDonough PH, Lee BW. Drug-induced erythroderma invariably recovers completely with prompt initial management and removal of the offending drug. PubMedGoogle Scholar. Sekula P, et al. Recurrent erythema multiforme: clinical characteristics, etiologic associations, and treatment in a series of 48 patients at Mayo Clinic, 2000 to 2007. Article 1996;44(2):1646. Federal government websites often end in .gov or .mil. Nassif A, et al. Google Scholar. Plasmapheresis. TEN is characterized by full-thickness epidermal necrosis with an evident epidermal detachment and sloughing caused by necrosis of keratinocytes following apoptosis [49, 52]. 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. Grosber M, et al. Erythema multiforme and latent herpes simplex infection. Here we provide a systematic review of frequency, risk factors, molecular and cellular mechanisms of reactions, clinical features, diagnostic work-up and therapy approaches to drug induced ED. . 00 Comments Please sign inor registerto post comments. MRY, MGS, EN and GC designed the study, selected scientifically relevant information, wrote and revised the manuscript. The applications of topical cyclosporine and autologous serum have also been showed to be useful in refractory cases [103]. 2018 Jan 28;2018:9095275. doi: 10.1155/2018/9095275. J Am Acad Dermatol. 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]. Pharmacogenomics J. 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. HLA-A* 3101 and carbamazepine-induced hypersensitivity reactions in Europeans. Role of nanocrystalline silver dressings in the management of toxic epidermal necrolysis (TEN) and TEN/StevensJohnson syndrome overlap. Exfoliative dermatitis is also a risk factor for epidemic spread of methicillin-resistant Staphylococcus aureus.6,20. Erythema multiforme (EM), StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Skin testing in delayed reactions to drugs. 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). Please enable it to take advantage of the complete set of features! In SJS, SJS/TEN and TEN the efficacy of corticosteroids is far from being demonstrated. 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]. Google Scholar. Contact dermatitis from topical antihistamine . Abe J, et al. . PubMed Painkiller therapy. In patients with this disorder, the mitotic rate and the absolute number of germinative skin cells are higher than normal. 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. Ardern-Jones MR, Friedmann PS. In the 5 studies that concluded negatively for IVIG, the dosage was below 0.4g/kg/day and treatment was maintained for less than 5days. Arch Dermatol. 1996;135(1):611. 2008;159(4):9814. 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. 2004;59(8):80920. 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. Google Scholar. Blood counts and bone marrow studies may reveal an underlying leukemia. Roujeau JC, et al. HLA-B1502, HLA-B5701, HLA-B5801 and carbamazepine, abacavir, and allopurinol, respectively). 2012;13(1):4954. Erythroderma See more images of erythroderma. CAS Fritsch PO. 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. The syndrome has been described previously in association with phenindione administration, leptospirosis and heavy metal poisoning. Some of these patients undergo spontaneous resolution. 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. J Popul Ther Clin Pharmacol. N Engl J Med. Vasoactive amines may be necessary in case of shock. c. Amyloidosis. In the hospital, special attention must be given to maintaining temperature control, replacing lost fluids and electrolytes, and preventing and treating infection. In recent years, clinicians have come to believe that this condition is secondary to a complicated interaction of cytokines and cellular adhesion molecules. 2010 Oct;35(7):723-8. doi: 10.1111/j.1365-2230.2009.03718.x. 2022 May;35(5):e15416. Allergy. An epidemiologic study from West Germany. 2012;66(3):1906. ADRJ,2015,17(6):464-465. 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). Loss of normal vasoconstrictive function in the dermis, decreased sensitivity to the shivering reflex and extra cooling that comes from evaporation of the fluids leaking out of the weeping skin lesions all result in thermoregulatory dysfunction that can cause hypothermia or hyperthermia.6 The basal metabolic rate also is increased in patients with exfoliative dermatitis. The long-term prognosis is good in patients with drug-induced disease, although the course tends to be remitting and relapsing in idiopathic cases. Exfoliative dermatitis, also known as erythroderma, is an uncommon but serious skin disorder that family physicians must be able to recognize and treat appropriately. Pemphigus vulgaris, paraneoplastic pemphigus, bullous pemphigoid and linear IgA dermatosis have to be considered. 2016 Nov 15;17(11):1890. doi: 10.3390/ijms17111890. In case of an oral mucositis that impairs nutrition, it is indicated to position a nasogastric tube. (sometimes fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, bullous dermatitis, drug rash with eosinophilia and systemic symptoms (DRESS . 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]. Unauthorized use of these marks is strictly prohibited. Exfoliative Dermatitis is a serious skin cell disorder that requires early diagnosis and treatment. During the acute reaction, diagnosis of ED is mainly based on clinical parameters. . Br J Dermatol. J Eur Acad Dermatol Venereol. A useful sign for differential diagnosis is the absence of mucosal involvement, except for conjunctiva. Paraneoplastic pemphigus is associated with neoplasms, most commonly of lymphoid tissue, but also Waldenstrms macroglobulinemia, sarcomas, thymomas and Castlemans disease. See permissionsforcopyrightquestions and/or permission requests. All non-indispensable drugs have to be stopped because they could alter the metabolism of the culprit agent. Nutritional support. The site is secure. The average age at onset is 55 years, although exfoliative dermatitis may occur at any time.2, Exfoliative dermatitis is the result of a dramatic increase in the epidermal turnover rate. Acute and chronic leukemia may also cause exfoliative dermatitis. Yacoub, MR., Berti, A., Campochiaro, C. et al. Toxic epidermal necrolysis and StevensJohnson syndrome. 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]. Moreover Mawson A and colleagues hypothesized that the efficacy of plasmapheresis is able to reduce serum level of vitamin A. Unfortunately, the clinical picture does not contribute to an understanding of the underlying cause. It can lead to pain, appear on large parts of the body and may require hospitalization. 1991;127(6):8318. Kirchhof MG, et al. A systematic review of treatment of drug-induced StevensJohnson syndrome and toxic epidermal necrolysis in children. California Privacy Statement, If necessary, it can be repeated every 68h. NSAIDs should be avoided as they can induce ED as well. A multidisciplinary team is fundamental in the therapeutic management of patients affected by exfoliative DHR. Each of these physiologic disruptions is potentially life-threatening. It is also recommended to void larger vesicles with a syringe. 2010;2(3):18994. Fritsch PO. This is due to a reaction to certain medicines, a pre-existing skin condition, and sometimes cancer. . For the prevention of deep venous thrombosis; usually low molecular weight heparin at prophylactic dose are used. J Clin Apher. Gueudry J, et al. Overall, T cells are the central player of these immune-mediated drug reactions. In most severe cases the suggested dosage is iv 11.5mg/kg/day. Advise of potential risk to a fetus and use of effective contraception. Pemphigus vulgaris usually starts in the oral mucosa followed by blistering of the skin, which is often painful. 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). In approximately 25% of people, there is no identifiable cause. Karnes JH, Miller MA, White KD, Konvinse KC, Pavlos RK, Redwood AJ, Peter JG, Lehloenya R, Mallal SA, Phillips EJ. In any case all authors concluded that the blockage of FasL prevents keratinocyte apoptosis [35]. Br J Dermatol. 1993;129(1):926. CAS Usually, but not always, the palms of the hands, the soles of the feet and the mucous membranes are spared. Download Free PDF. Scientific evidences suggest a role for HLAs and drug-induced SJS/TEN, although some racial differences have been found that can be due to variation of frequencies of these alleles and to the presence of other susceptibility genes [26]. Background: Panitumumab is an EGFR inhibitor used for the treatment of metastatic colorectal cancer (mCRC), even if its use is related to skin toxicity. Man CB, et al. 1992;11(3):20710. 2014;71(2):27883. The epidermal-dermal junction shows changes, ranging from vacuolar alteration to subepidermal blisters [20]. Exfoliative dermatitis (ED) is defined as diffuse erythema and scaling of the skin involving more than 90% of the total body skin surface area. 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 Possible involvement of CD14+CD16+monocyte lineage cells in the epidermal damage of StevensJohnson syndrome and toxic epidermal necrolysis. Schopf E, et al. 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]. Nat Med. 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]. Jarrett P, et al. Abe J, et al. The prognosis of cases associated with malignancy typically depends on the outcome of the underlying malignancy. 2005;136(3):20516. Manage cookies/Do not sell my data we use in the preference centre. Epub 2018 Aug 22. 585600. Arch Dermatol. Paquet P, Pierard GE, Quatresooz P. Novel treatments for drug-induced toxic epidermal necrolysis (Lyells syndrome). 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. Curr Allergy Asthma Rep. 2014;14(6):442. Bullous dermatoses can be debilitating and possibly fatal. 1995;333(24):16007. Association of HLA-B*1502 allele with carbamazepine-induced toxic epidermal necrolysis and StevensJohnson syndrome in the multi-ethnic Malaysian population. Bastuji-Garin S, et al. 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. Rabelink NM, Brakman M, Maartense E, Bril H, Bakker-Wensveen CA, Bavinck JN. Autologous transplantation of mesenchymal umbilical cord cells seems also to be highly efficacious [102]. When it precedes cutaneous T-cell lymphoma lesions, exfoliative dermatitis becomes the presenting sign of the underlying malignancy. PubMed Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. It is a reaction pattern and cutaneous manifestation of a myriad of underlying ailments, including psoriasis and eczema, or a reaction to the consumption of . 2000;115(2):14953. 2006;19(4):18891. Am J Infect Dis. The scales may be small or large, superficial or deep. 2011;38(3):23645. CAS Ann Burns Fire. Law EH, Leung M. Corticosteroids in StevensJohnson Syndrome/toxic epidermal necrolysis: current evidence and implications for future research. Erythema multiforme: a review of epidemiology, pathogenesis, clinical features, and treatment.

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