2013;69(2):1734. Google Scholar. The applications of topical cyclosporine and autologous serum have also been showed to be useful in refractory cases [103]. Google Scholar. By using this website, you agree to our Fritsch PO. CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. 1996;44(2):1646. Copyright 1999 by the American Academy of Family Physicians. T and NK lymphocytes can produce FasL that eventually binds to target cells. Joint Bone Spine. Continue Reading. Medication use and the risk of StevensJohnson syndrome or toxic epidermal necrolysis. Medical genetics: a marker for StevensJohnson syndrome. A heterogeneous pathologic phenotype. Contact Dermatitis. Hospitalization is usually necessary for initial evaluation and treatment. Int J Mol Sci. Initial symptoms could be aspecific, as fever, stinging eyes and discomfort upon swallowing, occurring few days before the onset of mucocutaneous involvement. 2013;168(3):55562. The most notable member of this group is mycosis fungoides. Temporary tracheostomy may be necessary in case of extended mucosal damage. Correspondence to Before Case Report Erythema multiforme StevensJohnson syndrome and toxic epidermal necrolysis. 2004;59(8):80920. Br J Dermatol. 2015;56(4):298302. 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]. . Part of N.Z. A population-based study with particular reference to reactions caused by drugs among outpatients. The timing of the rash can also vary. Cyclosporine A (Cys A): Cys A works through the inhibition of calcineurin, that is fundamental for cytotoxic T lymphocytes activation. Erythema multiforme (EM), StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. 2011;71(5):67283. Generalized. The SCORTEN scale is based on a minimal set of parameters as described in the following table. In patients with this disorder, the mitotic rate and the absolute number of germinative skin cells are higher than normal. Drug eruptions that initially present as morbilliform, lichenoid or urticarial rashes may progress to generalized exfoliative dermatitis. Sekula P, et al. [113] retrospectively compared mortality in 64 patients with ED treated either with iv or oral Cys A (35mg/kg) or IVIG (25g/Kg). 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/. 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 approximately 25% of people, there is no identifiable cause. For the prevention of deep venous thrombosis; usually low molecular weight heparin at prophylactic dose are used. Barbaud A, et al. These studies have confirmed an association between carbamazepine-induced SJS/TEN with HLA-B*1502 allele among Han Chinese [27], carbamazepine and HLA-A*3101 and HLA-B*1511 [16], phenytoin and HLA-B*1502 [28], allopurinol and HLA-B*5801 [29]. 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. See this image and copyright information in PMC. Roujeau JC, Stern RS. 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]. A classic example of an idiosyncratic reaction is drug-induced . 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. An extremely rare mucocutaneous adverse reaction following COVID-19 vaccination: Toxic epidermal necrolysis. Topical treatment. 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]. Ann Intern Med. Smith SD, et al. In some studies, the nose and paranasal area are spared. Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity. Skin testing and patch testing in non-IgE-mediated drug allergy. The taper of steroid therapy should be gradual [93]. More than moderate, unresponsive to treatment, and which interferes with the Soldier's perfor-mance of duty. 2011;128(6):126676. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Erythema multiforme to amoxicillin with concurrent infection by Epstein-Barr virus. The exact role of FasL in the pathogenesis of toxic epidermal necrolysis is still questionable especially because a correlation between serum FasL levels and disease severity has not been established and because its levels have been found to be increased also in drug-induced hypersensitivity syndrome and maculopapular eruption [36]. Article Nassif A, et al. Many people have had success using a dilute vinegar bath rather than a bleach bath. Hence, the apparent increase in cases of exfoliative dermatitis may be related to the introduction of many new drugs. Rheumatology (Oxford). Ann Pharmacother. 2005;136(3):20516. It was used with success in different case reports [114116]. EM usually occurs in young adults of 2040years of age [13], with women affected more frequently than men (1.5:1.0) [14]. 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). FOIA 1. 2011;38(3):23645. Erythema multiforme: a review of epidemiology, pathogenesis, clinical features, and treatment. -. J Immunol. Khalaf D, et al. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Mortality rate of patients with TEN has shown to be directly correlated to SCORTEN. 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. SJS/TEN syndrome is associated with severe blistering, mucocutaneous peeling, and multi-organ damage and could be life threatening. The most common of these are psoriasis, atopic dermatitis, seborrheic dermatitis, contact dermatitis and pityriasis rubra pilaris. Int J Dermatol. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough. It is important to protect the damaged skin with sterile fat dressing especially in the genital area. Article J Popul Ther Clin Pharmacol. Arch Dermatol. Still, treatment indication, choice and dosage remain unclear, and efficacy yet unproven. Mardani M, Mardani S, Asadi Kani Z, Hakamifard A. Dermatol Ther. Each of these physiologic disruptions is potentially life-threatening. 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 2009;29(3):51735. 2008;58(1):3340. The clinical course of patients with malignancies depends on the type of malignancy and the response to appropriate therapy. Exfoliative dermatitis is also a risk factor for epidemic spread of methicillin-resistant Staphylococcus aureus.6,20. CAS 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. 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 . Avoid rubbing and scratching. 2008;59(5):8989. Cite this article. Recurrent erythema multiforme in association with recurrent Mycoplasma pneumoniae infections. 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. 2007;56(5 Suppl):S1189. Plasmapheresis. 2. J Am Acad Dermatol. ADRJ,2015,17(6):464-465. These molecules may play a role in amplifying the immune response and in increasing the release of other toxic metabolites from inflammatory cells [48]. Previous vol/issue. One of the most common malignancies associated with exfoliative dermatitis is cutaneous T-cell lymphoma, which may not manifest for months or even years after the onset of the skin condition. 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. EMs mortality rate is not well reported. 2019 Jan 6;59:463-486. doi: 10.1146/annurev-pharmtox-010818-021818. 2012;366(26):2492501. Open trial of ciclosporin treatment for StevensJohnson syndrome and toxic epidermal necrolysis. Med., 1976, 6, pp. In conclusion we suggest that therapy with cyclosporine is valuable option with a dosage of 35mg/kg oral or iv for 7days. Annu Rev Pharmacol Toxicol. 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 . Cho YT, et al. 2023 Jan 30;11(2):346. doi: 10.3390/microorganisms11020346. Sequelae of exfoliative dermatitis are not widely reported. [16] Drug-induced Liver Disease Study Group,Chinese Society of Hepatology,Chinese Medical Association. 1994;331(19):127285. Apoptosis as a mechanism of keratinocyte death in toxic epidermal necrolysis. Abe J, et al. The https:// ensures that you are connecting to the Von Hebra first described erythroderma (exfoliative dermatitis) in 1868. [81]. 2012;97:14966. Antipyretic therapy. 1996;134(4):7104. Jarrett P, et al. Indian J Dermatol. Skin and appendages: acne, bruising, erythema multiforme, exfoliative dermatitis, pruritus ani, rash, skin ulceration, Stevens . 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. A useful sign for differential diagnosis is the absence of mucosal involvement, except for conjunctiva. Generalized exfoliative dermatitis, or erythroderma, is a severe inflammation of the entire skin surface. J Am Acad Dermatol. Acute interstitial nephritis associated with hepatitis, exfoliative dermatitis, fever and eosinophilia is uncommon. EM is a self-limited skin condition mainly associated with infections and drugs [53, 54]. . It should be used only in case of a documented positivity of cultural samples. HHS Vulnerability Disclosure, Help 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. In an open trial on cyclosporine in 29 patients with TEN, the use of Cys A for at least 10days led to a rapid improvement without infective complications [112]. Erythema multiforme (EM), StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Goulden V, Goodfield MJ. 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. 2009;182(12):80719. 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). SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. Also, physicians should be vigilant about possible secondary infection, whether cutaneous, pulmonary or systemic. -. Fritsch PO. A case of anti-BP230 antibody-positive dyshidrosiform bullous pemphigoid secondary to dipeptidyl peptidase-4 inhibitor in a 65-year-old Filipino female Federal government websites often end in .gov or .mil. Roujeau JC, et al. In SJS and TEN mucosal erosions on the lips, oral cavity, upper airways, conjunctiva, genital tract or ocular level are frequent [60, 6870]. Its also characterized by a cell-poor infiltrate, where macrophages and dendrocytes with a strong TNF- immunoreactivity predominate [6, 50]. Mediterr J Hematol Infect Dis. Systemic and potentially life-threatening complications include fluid and electrolyte imbalance, thermoregulatory disturbance, fever, tachycardia, high-output failure, hypoalbuminemia, and septicemia. Pemphigus vulgaris usually starts in the oral mucosa followed by blistering of the skin, which is often painful. 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. J Am Acad Dermatol. Huff JC. 2013;168(3):53949. Fournier S, et al. New York: McGraw-Hill; 2003. p. 585600. Antitumour necrosis factor-alpha antibodies (infliximab) in the treatment of a patient with toxic epidermal necrolysis. 2008;34(1):636. 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. Chang CC, et al. Clin Exp Allergy. Oral hygiene with antiseptic and painkiller mouthwash (chlorhexidine+lidocaine+aluminum hydroxide) together with aerosol therapy with saline and bronchodilators can reduce upper airways symptoms. 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]. Role of nanocrystalline silver dressings in the management of toxic epidermal necrolysis (TEN) and TEN/StevensJohnson syndrome overlap. 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]. Orphanet J Rare Dis. Anticoagulation therapy. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Intravenous administration is recommended. Unlike EMM, SJS and TEN are mainly related to medication use. A catabolic state thus ensues, which is often responsible for significant weight loss. 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. Bastuji-Garin S, et al. 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]. 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. 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. Synthetic bilaminar membranes with silver nitrate have also a role in skin repairing and avoid protein loss through the damaged skin [100, 101]. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED. 543557. 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. 2010;2(3):18994. A severity-of-Illness score for toxic epidermal necrolysis (SCORTEN) has been proposed and validated to predict the risk of death at admission [81]. J Am Acad Dermatol. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Erythema multiforme (EM), Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Epidemiological studies on EM, SJS and TEN syndromes report different results, probably related to several biases, such as ethnical differences, diagnostic criteria and drug consumption patterns in different socio-economic systems. 2023 BioMed Central Ltd unless otherwise stated. Therefore, the clinician should always consider drugs as a possible cause. Prevalence is low, with mortality of roughly 512.5% for SJS and 50% for TEN [1, 2]. 2013;133(5):1197204. The epidermal-dermal junction shows changes, ranging from vacuolar alteration to subepidermal blisters [20]. Hum Mol Genet. Also a vesical catheter should be placed to avoid urethral synechiae and to have a precise fluid balance. 8600 Rockville Pike Corticosteroids could also reduce the amount of keratinocytes apoptosis and the activation of caspases [105]. The most commonly used steroids were methylprednisolone, prednisolone and dexamethasone. Fritsch PO. Barbaud A. Clin Exp Dermatol. 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. 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.