1996;35(4):2346. Paradisi A, et al. 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. Exfoliative dermatitis is characterized by generalized erythema with scaling or desquamation affecting at least 90% of the body surface area. Wikizero - Basal-cell carcinoma HLA-A* 3101 and carbamazepine-induced hypersensitivity reactions in Europeans. 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]. Overall, T cells are the central player of these immune-mediated drug reactions. Springer Nature. Abstract Acute interstitial nephritis associated with hepatitis, exfoliative dermatitis, fever and eosinophilia is uncommon. Stern RS. Lin YT, et al. 5% silver nitrate compresses have antiseptic properties. The velocity of infusion should be regulated according to patients arterial pressure with the aim of 30mL/h urinary output (1mL/kg/h in case of a child). 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]. Four main pathways have been found to play important roles in the pathogenesis of keratinocyte death: (1) Fas-FasL interaction, (2) Perforin/granzyme B pathway, (3) Granulysin and (4) Tumor necrosis factor (TNF-) [26]. Recently, a meta-analysis based on 6 retrospective studies evaluating the role of corticosteroids alone or together with IVIG has been published [107]. Cancer Diagnosis & Prognosis 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]. The prognosis of cases associated with malignancy typically depends on the outcome of the underlying malignancy. 2. The long-term prognosis is good in patients with drug-induced disease, although the course tends to be remitting and relapsing in idiopathic cases. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis. New York: McGraw-Hill; 2003. p. 54357. 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. 2000;115(2):14953. Exp Dermatol. A heterogeneous pathologic phenotype. The overall mortality rate is roughly 30%, ranging from 10% for SJS to more than 30% for TEN, with the survival rate worsening until 1year after disease onset [9, 1821]. 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. A promising and complementary in vitro tool has been used by Polak ME et al. Anti-tubercular therapy (ATT) induced exfoliative dermatitis-A case 2011;50(2):2214. 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]. 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. (in Chinese) . Heat loss is another major concern that accompanies a defective skin barrier in patients with exfoliative dermatitis. CAS Incidence and drug etiology in France, 1981-1985. Gynecologist consultation is required for avoiding the appearance of vaginal phimosis or sinechias. Pfizer Receives Positive FDA Advisory Committee Votes Supporting 2002;118(4):72833. 2013;168(3):53949. Wetter DA, Davis MD. 2004;59(8):80920. Clinical, etiologic, and histopathologic features of StevensJohnson syndrome during an 8-year period at Mayo Clinic. -, Schwartz RA, McDonough PH, Lee BW. Drug-induced hypersensitivity syndrome (DiHS) or drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe adverse drug-induced reaction characterized by various symptoms: skin rash, fever, lymph node enlargement and internal organ involvement, which starts within 2 weeks to 3 months after drug initiation. Atypical target lesions manifest as raised, edematous, palpable lesions with only two zones of color change and/or an extensive exanthema with a poorly defined border darker in the center(Fig. 2007;56(5 Suppl):S1189. Epilepsia. 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]. J Immunol. 2008;53(1):28. Theoretically, any drug may cause exfoliative dermatitis. Fitzpatricks dermatology in general medicine. Perforin/granzyme B pathway: Nassif and colleagues have proposed a role for perforin/grazyme B in keratinocyte death [37]. Patients can be extremely suffering because of the pain induced by skin and mucosal detachment. Gonzalez-Delgado P, et al. Wolkenstein P, et al. Roujeau JC, Stern RS. Utility of the lymphocyte transformation test in the diagnosis of drug sensitivity: dependence on its timing and the type of drug eruption. The SJS histology is characterized by a poor dermal inflammatory cell infiltrate and full thickness necrosis of epidermis [20, 49]. A useful sign for differential diagnosis is the absence of mucosal involvement, except for conjunctiva. 2014;71(1):1956. CAS Drug induced exfoliative dermatitis - yxw_88 - | The former is usually a recurring, localized eruption of the skin characterized by pathognomonic target or iris lesions, with minimal or no mucosal involvement (Fig. If necessary, it can be repeated every 68h. NSAIDs should be avoided as they can induce ED as well. 2009;145(2):15762. [Stevens-Johnson Syndrom and Toxic Epidermal Necrolysis--based on literature]. The action of antithyroid drugs may be delayed in amiodarone-induced thyrotoxicosis because of substantial quantities of preformed thyroid hormones stored in the gland. In EMM their efficacyis demonstrated in controlling the evolution of the disease [106]. 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. Topical treatment. Am J Dermatopathol. Schneck J, et al. Fritsch PO. 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 . Clinical Considerations for Treatment and Prophylaxis of Mpox Infection Acute and chronic leukemia may also cause exfoliative dermatitis. Sokumbi O, Wetter DA. It is necessary to obtain as soon as possible a central venous access and to start a continuous monitoring of vital signs. Paradisi et al. Fluid balance is a main focus. Cutaneous drug eruptions are one of the most common types of adverse reaction to medications, with an overall incidence of 23% in hospitalized patients [1]. Erythroderma See more images of erythroderma. 1). Exfoliative dermatitis has been reported in association with hepatitis, acquired immunodeficiency syndrome, congenital immunodeficiency syndrome (Omenn's syndrome) and graft-versus-host disease.2,1517, In reviews of erythroderma, a significant percentage of patients (about 25 percent) do not receive a specific etiologic diagnosis. 2012;2012:915314. Clinical classification of cases of toxic epidermal necrolysis, StevensJohnson syndrome, and erythema multiforme. Toxic epidermal necrolysis: review of pathogenesis and management. N Engl J Med. 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. It is not completely clear whether EM and SJS are separate clinical entities or if they represent two different expressions of a single disease process. Dermatitis - Diagnosis and treatment - Mayo Clinic StevensJohnson syndrome and toxic epidermal necrolysis: a review of the literature. It recommended to used G-CSF in patients with febrile neutropenia [94, 95]. Department of Allergy and Clinical Immunology, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy, Mona-Rita Yacoub,Maria Grazia Sabbadini&Giselda Colombo, Vita-Salute San Raffaele University, Milan, Italy, Mona-Rita Yacoub,Alvise Berti,Corrado Campochiaro,Enrico Tombetti,Giuseppe Alvise Ramirez,Maria Grazia Sabbadini&Giselda Colombo, Section of Allergy and Clinical Immunology, Dept. 1997;19(2):12732. 2010;37(10):9046. Drug induced interstitial nephritis, hepatitis and exfoliative dermatitis A severity-of-Illness score for toxic epidermal necrolysis (SCORTEN) has been proposed and validated to predict the risk of death at admission [81]. PubMed 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. Ther Apher Dial. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Orton PW, et al. Nayak S, Acharjya B. 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. Huang YC, Li YC, Chen TJ. 2008;58(1):3340. Gout and its comorbidities: implications for therapy. Arch Dermatol. Drug-induced Exfoliative Dermatitis & Eosinophils Increased Symptom Checker: Possible causes include Exfoliative Dermatitis. In patients with this disorder, the mitotic rate and the absolute number of germinative skin cells are higher than normal. Usually the amount of calories is 15002000kcal/day and the velocity of infusion is gradually increased based on patients tolerability [92]. Etanercept therapy for toxic epidermal necrolysis. In SJS and TEN mucosal erosions on the lips, oral cavity, upper airways, conjunctiva, genital tract or ocular level are frequent [60, 6870]. Rheumatology (Oxford). J Am Acad Dermatol. It could also be useful to use artificial tears and lubricating antiseptic gels. Moreover, transpiration and thermoregulation are greatly impaired with an elevated loss of fluids, proteins and electrolytes through the damaged skin and mucosae. Paraneoplastic pemphigus is associated with neoplasms, most commonly of lymphoid tissue, but also Waldenstrms macroglobulinemia, sarcomas, thymomas and Castlemans disease. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. ), Phenolphthalein (Agoral, Alophen, Modane), Rifampin (Rifadin, Rimactane; also in Rifamate), Trimethoprim (Trimpex; also in Bactrim, Septra). Exfoliative Dermatitis | AAFP 2001;108(5):83946. 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. 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: a review of epidemiology, pathogenesis, clinical features, and treatment. 2018 Feb;54(1):147-176. doi: 10.1007/s12016-017-8654-z. Arch Dermatol. Ethambutol Induced Exfoliative Dermatitis. J Pharm Health Care Sci. 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 Bullous dermatoses can be debilitating and possibly fatal. SCITECH - Orphan Drug Nitisinone in Dermatology - Journal of Manganaro AM. Panitumumab Induced Forearm Panniculitis in Two Women With Metastatic Pehr K. The EuroSCAR study: cannot agree with the conclusions. 1995;5(4):2558. Erythema multiforme and toxic epidermal necrolysis. Br J Dermatol. Generalized bullous fixed drug eruption is distinct from StevensJohnson syndrome/toxic epidermal necrolysis by immunohistopathological features. 2008;53(1):28. Hum Mol Genet. Google Scholar. However, patchy, diffuse areas of postinflammatory hyperpigmentation and hypopigmentation may occur, especially in patients with darker skin.1,4 One case of posterythrodermic generalized vitiligo beginning six weeks after the onset of exfoliative dermatitis has been reported.29,30 Residual eruptive nevi and keloid formation are rare sequelae. Systemic and potentially life-threatening complications include fluid and electrolyte imbalance, thermoregulatory disturbance, fever, tachycardia, high-output failure, hypoalbuminemia, and septicemia. Oliveira L, Zucoloto S. Erythema multiforme minor: a revision. Schopf E, et al. GULIZ KARAKAYLI, M.D., GRANT BECKHAM, M.D., IDA ORENGO, M.D., AND TED ROSEN, M.D. 2009;182(12):80719. Su SC, Hung SI, Fan WL, Dao RL, Chung WH. 2008;159(4):9814. Bullous FDE. Fournier S, et al. During the acute reaction, diagnosis of ED is mainly based on clinical parameters. On the other hand, it has been demonstrated that genetic predisposition may increase the risk for sulphonamide-induced [24] and carbamazepine-induced TEN and SJS [25]. Exfoliative dermatitis is a disease process in which most, and sometimes all, of the skin is involved in erythematous inflammation resulting in massive scaling.1 A variety of diseases and other exogenous factors may cause exfoliative dermatitis. Curr Probl Dermatol. Ramirez GA, Yacoub MR, Ripa M, Mannina D, Cariddi A, Saporiti N, Ciceri F, Castagna A, Colombo G, Dagna L. Biomed Res Int. Wolkenstein P, et al. Infectious agents are the major cause of EM, in around 90% of cases, especially for EM minor and in children. Ann Burns Fire. 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]. Von Hebra first described erythroderma (exfoliative dermatitis) in 1868. Exfoliative dermatitis is a rare inflammatory skin condition that is characterized by desquamation and erythema involving more than 90% of the body surface area. PubMed All non-indispensable drugs have to be stopped because they could alter the metabolism of the culprit agent. Some anti-seizure medicines have also been known to cause exfoliative dermatitis. For SJS/TEN, corticosteroids are the cornerstone of treatment albeit efficacy remains unclear. 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. 2010;88(1):608. The Nikolskys sign is not specific for SJS/TEN, in fact it is present also in auto-immune blistering diseases like pemphigus vulgaris. Tohyama M, et al. TNF- has a dual role: interacts with TNF-R1 activating Fas pathway and activates NF-B leading to cell survival. Article In fact, it was demonstrated that the specificity of the TCR is a required condition for the self-reaction to occur. In patients with SJS/TEN increased serum levels of retinoid acid have been found. Also a vesical catheter should be placed to avoid urethral synechiae and to have a precise fluid balance. Iv bolus of steroid (dexamethasone 100300mg/day or methylprednisolone 2501000mg/day) for 3 consecutive days with a gradual taper steroid therapy is sometimes advised. 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. A slow acetylator genotype is a risk factor for sulphonamide-induced toxic epidermal necrolysis and StevensJohnson syndrome. 2012;66(6):e22936. Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED.