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. Adverse cutaneous drug reaction. doi: 10.1111/dth.15416. Still, treatment indication, choice and dosage remain unclear, and efficacy yet unproven. Huff JC. Therefore, the clinician should always consider drugs as a possible cause. Paul C, et al. Clin Mol Allergy 14, 9 (2016). 1997;19(2):12732. 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. 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. J Allergy Clin Immunol. Bastuji-Garin S, et al. Clinical, etiologic, and histopathologic features of StevensJohnson syndrome during an 8-year period at Mayo Clinic. Pichler WJ, Tilch J. 2005;102(11):41349. 2011;50(2):2214. A switch to oral therapy can be performed once the mucosal conditions improve. Immune-histopathological features allow to distinguish generalized bullous drug eruption from SJS/TEN [36]. Genome-scale investigation of drug-induced termination codon-readthrough in a model system of epidermolysis bullosa . Huff JC, Weston WL, Tonnesen MG. Erythema multiforme: a critical review of characteristics, diagnostic criteria, and causes. Increased peripheral blood flow can result in high-output cardiac failure. Continue Reading. Google Scholar. 2010;2(3):18994. b. Atopic dermatitis. J Am Acad Dermatol. 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. SSSS is characterized by periorificial face scabs, de-epithelialization of friction zones and conspicuous desquamation after initial erythroderma. Morel E, et al. The erythrodermic form of mycosis fungoides and the Szary syndrome may also be difficult to distinguish from benign erythroderma. Check the full list of possible causes and conditions now! J Burn Care Res. 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. 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]. 1995;333(24):16007. (2.4, 5.6) Embryo-fetal Toxicity: Can cause fetal harm. Valeyrie-Allanore L, et al. Exfoliative dermatitis, also known as erythroderma, is an uncommon but serious skin disorder that family physicians must be able to recognize and treat appropriately. Abstract Acute interstitial nephritis associated with hepatitis, exfoliative dermatitis, fever and eosinophilia is uncommon. loss of taste Derm: stevens-johnson syndrome, toxic epidermal necrolysis, rash, exfoliative dermatitis, hair . Bethesda, MD 20894, Web Policies [113] retrospectively compared mortality in 64 patients with ED treated either with iv or oral Cys A (35mg/kg) or IVIG (25g/Kg). EM is a self-limited skin condition mainly associated with infections and drugs [53, 54]. 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 . 2010;62(1):4553. Posadas SJ, et al. Hypothermia can result in ventricular flutter, decreased heart rate and hypotension. Toxic epidermal necrolysis (Lyell syndrome). T and NK lymphocytes can produce FasL that eventually binds to target cells. J Popul Ther Clin Pharmacol. 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. 2019 Jan 6;59:463-486. doi: 10.1146/annurev-pharmtox-010818-021818. Medication use and the risk of StevensJohnson syndrome or toxic epidermal necrolysis. Drug-induced erythroderma invariably recovers completely with prompt initial management and removal of the offending drug. J Am Acad Dermatol. 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. 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 Karnes JH, Miller MA, White KD, Konvinse KC, Pavlos RK, Redwood AJ, Peter JG, Lehloenya R, Mallal SA, Phillips EJ. Toxic epidermal necrolysis associated with severe cytomegalovirus infection in a patient on regular hemodialysis. Google Scholar. Four cases are described, two of which were due to phenindione sensitivity. 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 J Invest Dermatol. 1996;134(4):7104. The Nikolskys sign is not specific for SJS/TEN, in fact it is present also in auto-immune blistering diseases like pemphigus vulgaris. 1991;127(6):8318. 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]. [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. A useful sign for differential diagnosis is the absence of mucosal involvement, except for conjunctiva. A population-based study with particular reference to reactions caused by drugs among outpatients. In spared areas it is necessary to avoid skin detachment. Other cases are ultimately classifiable as another dermatosis. 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. Etoricoxib-induced toxic epidermal necrolysis: successful treatment with infliximab. TNF- has a dual role: interacts with TNF-R1 activating Fas pathway and activates NF-B leading to cell survival. Granulysin as a marker for early diagnosis of the StevensJohnson syndrome. Gastric protection. Paradisi A, et al. 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. Mayo Clin Proc. Incidence and antecedent drug exposures. 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. 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. 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. Smith SD, et al. 2015;56(4):298302. Erythema multiforme (photo reproduced with permission of Gary White, MD): typical target lesions (white arrows) together with atypical two-zoned lesions (black arrows). Exfoliative dermatitis may happen as a complication of other skin issues. Cutaneous graft-versus-host diseaseclinical considerations and management. Theoretically, any drug may cause exfoliative dermatitis. The lesions consist of pruritic, annular papules, vesicles, and bullae that are found in groups, clinically it is similar to dermatitis herpetiformis, without a gluten-sensitive enteropathy [85]. Hydration and hemodynamic balance. TEN is characterized by full-thickness epidermal necrosis with an evident epidermal detachment and sloughing caused by necrosis of keratinocytes following apoptosis [49, 52]. The diagnosis of GVDH requires histological confirmation [87]. Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal necrolysis. Tang YH, et al. Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involving skin and usually occurring from days to several weeks after drug. Br J Dermatol. Erythema multiforme StevensJohnson syndrome and toxic epidermal necrolysis. Other dermatoses associated with erythroderma are listed in Table 1.2,3,68. 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. Contact Dermatitis. Ozeki T, et al. Skin manifestations of drug allergy. 2000;22(5):4137. volume14, Articlenumber:9 (2016) The lymphocyte transformation test in the diagnosis of drug hypersensitivity. 2015;49(3):33542. J Allergy Clin Immunol. Paraneoplastic pemphigus is associated with neoplasms, most commonly of lymphoid tissue, but also Waldenstrms macroglobulinemia, sarcomas, thymomas and Castlemans disease. Increased level of retinoid acid could be responsible for keratinocytes apoptosis [99]. Int J Dermatol. 1). 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]. Cite this article. Pathophysiology DIP. A severity-of-Illness score for toxic epidermal necrolysis (SCORTEN) has been proposed and validated to predict the risk of death at admission [81]. 2. J Immunol. Ann Burns Fire. Recurrence occurs in around one-third of cases [15] and there is a genetic predisposition for certain Asian groups [16]. 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]. Arch Dermatol. These patches tend to spread until, after a matter of days or weeks, most of the skin surface is covered with an erythematous, pruritic eruption. Systemic and potentially life-threatening complications include fluid and electrolyte imbalance, thermoregulatory disturbance, fever, tachycardia, high-output failure, hypoalbuminemia, and septicemia. The action of antithyroid drugs may be delayed in amiodarone-induced thyrotoxicosis because of substantial quantities of preformed thyroid hormones stored in the gland. 583-587. PubMed Central 2013;168(3):53949. Roujeau JC, et al. 2006;6(4):2658. Recently, a meta-analysis based on 6 retrospective studies evaluating the role of corticosteroids alone or together with IVIG has been published [107]. Careers. Harr T, French LE. government site. Even patients with clear histories of preexisting dermatoses tend to have biopsies that are not diagnostic when they present with erythroderma.2, Laboratory evaluation of patients with erythroderma is generally not very helpful in determining a specific diagnosis. 1998;37(7):5203. Epilepsia. Acute processes usually favor large scales, whereas chronic processes produce smaller ones. Verma R, Vasudevan B, Pragasam V. Severe cutaneous adverse drug reactions. Downey A, et al. Int J Dermatol. Tohyama M, Hashimoto K. Immunological mechanisms of epidermal damage in toxic epidermal necrolysis. Toxic epidermal necrolysis: Part I Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. 2012;53(3):16571. Clin Exp Dermatol. An official website of the United States government. The SJS histology is characterized by a poor dermal inflammatory cell infiltrate and full thickness necrosis of epidermis [20, 49]. A central role in the pathogenesis of ED is played by CD8+ lymphocytes and NK cells. Man CB, et al. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Severe adverse cutaneous reactions to drugs. Clipboard, Search History, and several other advanced features are temporarily unavailable. 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. Erythema multiforme: a review of epidemiology, pathogenesis, clinical features, and treatment. It is a clinical manifestation and usually associated with various underlying cutaneous disorders, drug induced reactions and malignancies. J Dtsch Dermatol Ges. Open trial of ciclosporin treatment for StevensJohnson syndrome and toxic epidermal necrolysis. 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 . Science. The approach to treatment should include discontinuation of any potentially causative medications and a search for any underlying malignancy. 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. Oliveira L, Zucoloto S. Erythema multiforme minor: a revision. In the hospital, special attention must be given to maintaining temperature control, replacing lost fluids and electrolytes, and preventing and treating infection. f. Napoli B, et al. 2012;66(3):1906. Patients should be educated to avoid any causative drugs. If there is a high suspicion of infection without a documented source of infection, broad range empiric therapy should be started.
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