drug induced exfoliative dermatitis

Google Scholar. Overall, incidence of SJS/TEN ranges from 2 to 7 cases per million person per year [9, 1820], with SJS the commonest [21]. 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 In SJS and TEN mucosal erosions on the lips, oral cavity, upper airways, conjunctiva, genital tract or ocular level are frequent [60, 6870]. They usually have fever, are dyspneic and cannot physiologically feed. Tohyama M, et al. In some studies, the nose and paranasal area are spared. Infliximab was used in cases refractory to high-dosage steroid therapy and/or IVIG. N Engl J Med. c. Amyloidosis. Del Pozzo-Magana BR, et al. In contrast with DRESS, eosinophilia and atypical lymphocytes are not described in patients with SJS or TEN. Gen Dent. HHS Vulnerability Disclosure, Help Med J Armed Forces India. Rheumatology (Oxford). Ardern-Jones MR, Friedmann PS. 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. Analysis of StevensJohnson syndrome and toxic epidermal necrolysis using the Japanese Adverse Drug Event Report database. 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]. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis. Bullous FDE. Paul C, et al. PubMed Moreover, transpiration and thermoregulation are greatly impaired with an elevated loss of fluids, proteins and electrolytes through the damaged skin and mucosae. Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED. Erythema multiforme to amoxicillin with concurrent infection by Epstein-Barr virus. 2014;71(2):27883. Drug induced exfoliative dermatitis: state of the art. 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. It should be used only in case of a documented positivity of cultural samples. See permissionsforcopyrightquestions and/or permission requests. Nayak S, Acharjya B. Fritsch PO. Carbamazepine and phenytoin induced StevensJohnson syndrome is associated with HLA-B* 1502 allele in Thai population. In more severe cases antiviral therapies should be given together with intravenous immunoglobulins [93]. Khalil I, et al. 2011;38(3):23645. Mucosal involvement could achieve almost 65% of patients [17]. Int Arch Allergy Immunol. 2011;3(1):e2011004. 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. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. Toxic epidermal necrolysis: effector cells are drug-specific cytotoxic T cells. 2016;2:14. In: Eisen AZ, Wolff K, editors. Kavitha Saravu. Roujeau JC, et al. 2012;13(1):4954. Clipboard, Search History, and several other advanced features are temporarily unavailable. PubMed Central 2013;52(1):3444. volume14, Articlenumber:9 (2016) exfoliative dermatitis. Curr Probl Dermatol. 2008;52(3):1519. . Cookies policy. Int J Mol Sci. 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. 1). Chang CC, et al. 2004;114(5):120915. Pemphigus vulgaris usually starts in the oral mucosa followed by blistering of the skin, which is often painful. Increased level of retinoid acid could be responsible for keratinocytes apoptosis [99]. Poor relevance of a lymphocyte proliferation assay in lamotrigine-induced StevensJohnson syndrome or toxic epidermal necrolysis. 5% silver nitrate compresses have antiseptic properties. The SJS histology is characterized by a poor dermal inflammatory cell infiltrate and full thickness necrosis of epidermis [20, 49]. Supportive and specific care includes both local and systemic measures, as represented in Fig. Exfoliative dermatitis is a rare inflammatory skin condition that is characterized by desquamation and erythema involving more than 90% of the body surface area. 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. Read this article to find out all its symptoms, causes and treatments. However, according to a consensus definition [54], EMM syndrome has been separated from SJS/TEN spectrum. 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. It is important to take into consideration the mechanism of action of the different drugs in the pathogenesis of ED [104]. 2019 Jan 6;59:463-486. doi: 10.1146/annurev-pharmtox-010818-021818. 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]. Abe J, et al. PubMed Article 2010;85(2):1318. Skin testing in delayed reactions to drugs. Please enable it to take advantage of the complete set of features! Szary syndrome, the leukemic variant of mycosis fungoides, is also associated with exfoliative dermatitis. Corticosteroids could also reduce the amount of keratinocytes apoptosis and the activation of caspases [105]. Indian J Dermatol. 2002;118(4):72833. Mayes T, et al. In patients who develop complications (i.e., infection, fluid and electrolyte abnormalities, cardiac failure), the rate of mortality is often high. Eur J Clin Microbiol Infect Dis. 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. Allergy. Wetter DA, Davis MD. PubMed Viard I, et al. Contact dermatitis from topical antihistamine . A marked increase in serum soluble Fas ligand in drug-induced hypersensitivity syndrome. Accurate eye cleaning with saline solution is fundamental for the prevention of synechiae and for reducing corneal damage. Overall, T cells are the central player of these immune-mediated drug reactions. Dent Clin North Am. loss of taste Derm: stevens-johnson syndrome, toxic epidermal necrolysis, rash, exfoliative dermatitis, hair . 2012;12(4):37682. Google Scholar. It might be. 2008;58(1):3340. These levels could reflect the interaction between culprit drugs and aldehyde dehydrogenase that is the enzyme which metabolizes retinoid acid. Descamps V, Ranger-Rogez S. DRESS syndrome. Systemic derangements may occur with exfoliative. Gastrointestinal: pancreatitis, glossitis, dyspepsia. Curr Allergy Asthma Rep. 2014;14(6):442. It could also be useful to use artificial tears and lubricating antiseptic gels. Schwartz RA, McDonough PH, Lee BW. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Pehr K. The EuroSCAR study: cannot agree with the conclusions. J Immunol. Dermatol Clin. 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. J Invest Dermatol. Abe R. Toxic epidermal necrolysis and StevensJohnson syndrome: soluble Fas ligand involvement in the pathomechanisms of these diseases. Theoretically, any drug can trigger a reaction, but the medications most associated with this disorder are: Allopurinol; Antiepileptic medications; Barbiturates Abe J, et al. f. Privacy The approach to treatment should include discontinuation of any potentially causative medications and a search for any underlying malignancy. 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]. Fitzpatricks dermatology in general medicine. Trigger is an exotoxin released by Staphylococcus aureus [83]. By using this website, you agree to our The .gov means its official. Fritsch PO. The dermis shows an inflammatory infiltrate characterized by a high-density lichenoid infiltrate rich in T cells (CD4+ more than CD8+) with macrophages, few neutrophils and occasional eosinophils; the latter especially seen in cases of DHR [5, 50]. 19 Key critical interactions are discussed below for each mpox antiviral. J Am Acad Dermatol. HLA-B* 5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Generalized bullous fixed drug eruption is distinct from StevensJohnson syndrome/toxic epidermal necrolysis by immunohistopathological features. Defective regulatory T cells in patients with severe drug eruptions: timing of the dysfunction is associated with the pathological phenotype and outcome. Fernando SL. EM is a self-limited skin condition mainly associated with infections and drugs [53, 54]. J Allergy Clin Immunol. Because a certain degree of cross-reactivity between the various aromatic anti-epileptic drugs exists, some HLAs have been found to be related to SJS/TEN with two drugs, as the case of HLA-B*1502 with both phenytoin and oxcarbazepine [32]. 1991;127(6):8318. [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] 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. The most common causes of exfoliative dermatitis are best remembered by the mnemonic device ID-SCALP. Contact Dermatitis. Google Scholar. 2013;69(4):37583. Tang YH, et al. 2008;59(5):8989. Clin Exp Allergy. 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]. 2015;56(4):298302. 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]. 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. . Ann Intern Med. Kostal M, et al. The type of rash that happens depends on the medicine causing it and your response. The authors declare that they have no competing interests. Theoretically, any drug may cause exfoliative dermatitis. J Am Acad Dermatol. The applications of topical cyclosporine and autologous serum have also been showed to be useful in refractory cases [103]. Patients must be cleaned in the affected areas until epithelization starts. Soak for 5 to 10 minutes and rinse off before patting dry. Exposure to anticonvulsivants (phenytoin, phenobarbital, lamotrigine), non-nucleoside reverse transcriptase inhibitors (nevirapine), cotrimoxazole and other sulfa drugs (sulfasalazine), allopurinol and oxicam NSAIDs [2] confers a higher risk of developing SJS/TEN. Accessibility In: Eisen AZ, Wolff K, editors. The incidence of erythema multiforme, StevensJohnson syndrome, and toxic epidermal necrolysis. Sokumbi O, Wetter DA. J Invest Dermatol. StevensJohnson syndrome and toxic epidermal necrolysis: the Food and Drug Administration adverse event reporting system, 2004-2013. Manage cookies/Do not sell my data we use in the preference centre. 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). It characteristically demonstrates diffuse erythema and scaling of greater than 90% of the body surface area. Huang YC, Li YC, Chen TJ. Ann Intern Med. Mockenhaupt M, et al. Patients should be educated to avoid any causative drugs. Medicines have been linked to every type of rash, ranging from mild to life-threatening. 2015;21:13343. 2013;168(3):53949. Four cases are described, two of which were due to phenindione sensitivity. In case of a respiratory failure, oxygen should be administrated and a NIMV may be required. PubMed Add 1 cup (about 236 milliliters) of vinegar to a bathtub filled with warm water. 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]. Even though exfoliative dermatitis is a complex disorder involving many factors, the underlying disease is usually the key determinant of the course and prognosis. Strom BL, et al. Nature. Adverse cutaneous drug reaction. J Am Acad Dermatol. Death ligand TRAIL, secreted by CD1a+and CD14+cells in blister fluids, is involved in killing keratinocytes in toxic epidermal necrolysis. Current Perspectives on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. Autologous transplantation of mesenchymal umbilical cord cells seems also to be highly efficacious [102]. Ophthalmologic consultations must be repeated at fixed intervals to avoid the appearance of conjunctival irreversible complications such as chronic conjunctivitis with squamous metaplasia, trichiasis, symblepharon, punctate keratitis and sicca syndrome. . During the acute reaction, diagnosis of ED is mainly based on clinical parameters. [Stevens-Johnson Syndrom and Toxic Epidermal Necrolysis--based on literature]. National Library of Medicine The https:// ensures that you are connecting to the The most common of these are psoriasis, atopic dermatitis, seborrheic dermatitis, contact dermatitis and pityriasis rubra pilaris. Antibiotics: amoxicillin, ampicillin, ciprofloxacin, demeclocycline , doxycycline , minocycline, nalidixic acid, nitrofurantoin, norfloxacin, penicillin , rifampicin, streptomycin, tetracycline , tobramycin, trimethoprim, trimethoprim + sulphamethoxazole, vancomycin Anticonvulsants : barbiturates, carbamazepine Am J Infect Dis. J Allergy Clin Immunol. Clinical features; Delayed type hypersensitivity; Drug hypersensitivity; Erythema multiforme; Exfoliative dermatitis; Lyells syndrome; Pathogenesis; StevensJohnson syndrome; Therapy; Toxic epidermal necrolysis. The management of toxic epidermal necrolysis. It should be considered only once the patient is stable and if the skin damage is still ongoing and doesnt respond to other conventional therapies (corticosteroids or IVIG). (sometimes fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, bullous dermatitis, drug rash with eosinophilia and systemic symptoms (DRESS . J Am Acad Dermatol. Epub 2018 Aug 22. Terms and Conditions, 1997;22(3):1467. 2000;22(5):4137. Clinical, etiologic, and histopathologic features of StevensJohnson syndrome during an 8-year period at Mayo Clinic. Analysis for circulating Szary cells may be helpful, but only if the cells are identified in unequivocally large numbers. Effects of treatments on the mortality of StevensJohnson syndrome and toxic epidermal necrolysis: a retrospective study on patients included in the prospective EuroSCAR Study. Reticuloendothelial neoplasms, as well as internal visceral malignancies, can produce erythroderma, with the former being the more predominant cause. In most severe cases the suggested dosage is iv 11.5mg/kg/day. PTs have to be performed at least 6months after the recovery of the reaction, and show a variable sensitivity considering the implied drug, being higher for beta-lactam, glycopeptide antibiotics, carbamazepine, lamotrigine, proton pump inhibitors, tetrazepam, trimethoprimsulfametoxazole, pseudoephedrine and ramipril [7376]. . 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). Careers. . A switch to oral therapy can be performed once the mucosal conditions improve. Acute processes usually favor large scales, whereas chronic processes produce smaller ones. Pichler WJ, Tilch J. Albeit the lack of epidemiologic data regarding EM, its reported prevalence is less than 1% [710]. Exfoliative dermatitis may happen as a complication of other skin issues. Br J Dermatol. 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]. 2009;145(2):15762. Growth-factors (G-CSF). 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. Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involv ing skin and usually occurring from days to several weeks after drug exposure. All non-indispensable drugs have to be stopped because they could alter the metabolism of the culprit agent. Mayo Clin Proc. Int J Dermatol. Other cases are ultimately classifiable as another dermatosis. HLA DQB1* 0301 allele is involved in the susceptibility to erythema multiforme. CAS Avoid rubbing and scratching. Genotyping is recommended in specific high-risk ethnic groups (e.g. Tumor necrosis factor : TNF- seems also to play an important role in TEN [41]. The site is secure. Keywords: Article 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. De Araujo E, 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 exposure. Chung WH, Hung SI. PubMed Central Erythema multiforme and latent herpes simplex infection. Studies indicate that mycosis fungoides may cause 25 to 40 percent of all cases of malignancy-related erythroderma.6,7 The erythroderma may arise as a progression from a previous cutaneous T-cell lymphoma lesion or appear simultaneously with the cutaneous T-cell lymphoma, or it may precede the appearance of the cutaneous T-cell lymphoma lesion. 1996;44(2):1646. 2023 BioMed Central Ltd unless otherwise stated. 2010;5:39. 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. Joint Bone Spine. 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. A correlation between increased levels of perforin/granzyme B and the severity of TEN was also described [38]. This has been called the nose sign.18, Once the erythema is well established, scaling inevitably follows (Figure 1). Napoli B, et al. AB, CC, ET, GAR, AN, EDL, PF performed a critical revision on the current literature about the described topic, wrote and revised the manuscript. Energy requirements of pediatric patients with StevensJohnson syndrome and toxic epidermal necrolysis. Gynecologist consultation is required for avoiding the appearance of vaginal phimosis or sinechias. The Nikolskys sign is not specific for SJS/TEN, in fact it is present also in auto-immune blistering diseases like pemphigus vulgaris. It has a wide spectrum of severity, and it is divided in minor and major (EMM). 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, StevensJohnson syndrome and toxic epidermal necrolysis in northeastern Malaysia. Risk factors for the development of ocular complications of StevensJohnson syndrome and toxic epidermal necrolysis. Toxic epidermal necrolysis (Lyell syndrome). Some of these patients undergo spontaneous resolution. J Am Acad Dermatol. CAS Hung S-I, et al. Chung W-H, et al. 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. 2015;64(3):2779. In spared areas it is necessary to avoid skin detachment. Clinicians using antivirals for mpox should be alert for drug-drug interactions with any antiretrovirals used to prevent 16, 17 or treat 18 HIV infection as well as with any other medications used to prevent or treat HIV-related opportunistic infections. 2003;21(1):195205. In general, they occur more frequently in women, with a male to female ratio of 0.6 [22]. Many people have had success using a dilute vinegar bath rather than a bleach bath. The EuroSCAR-study. If there is a high suspicion of infection without a documented source of infection, broad range empiric therapy should be started. J Eur Acad Dermatol Venereol. 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. Huang SH, et al. Arch Dermatol. 2, and described below. 2015;49(3):33542. Article erythroderma, exfoliative dermatitis, and fixed drug reactions) 4, 5 and . 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 StevensJohnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. A systematic review of treatment of drug-induced StevensJohnson syndrome and toxic epidermal necrolysis in children. The erythrodermic form of mycosis fungoides and the Szary syndrome may also be difficult to distinguish from benign erythroderma. Guidelines for the management of drug-induced liver injury[J]. A multidisciplinary team is fundamental in the therapeutic management of patients affected by exfoliative DHR. These measures include bed rest, lukewarm soaks or baths, bland emollients and oral antihistamines.2527, In patients with chronic idiopathic erythroderma, emollients and topical steroids may be effective. Generalized exfoliative dermatitis, or erythroderma, is a severe inflammation of the entire skin surface. IBUPROFENE ZENTIVA is indicated for the symptomatic treatment of headaches, migraines, dental pain, back pain, dysmenorrhea, muscle pain, neuralgia . Exfoliative dermatitis, also known as erythroderma, is an uncommon but serious skin disorder that family physicians must be able to recognize and treat appropriately. 2009;151(7):5145. 2008;4(4):22431. -, Schwartz RA, McDonough PH, Lee BW. 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]. Incidence of toxic epidermal necrolysis and StevensJohnson Syndrome in an HIV cohort: an observational, retrospective case series study. Ramirez GA, Yacoub MR, Ripa M, Mannina D, Cariddi A, Saporiti N, Ciceri F, Castagna A, Colombo G, Dagna L. Biomed Res Int. In conclusion we suggest that therapy with cyclosporine is valuable option with a dosage of 35mg/kg oral or iv for 7days. New York: McGraw-Hill; 2003. pp. [80], which consists of the determination of IFN and IL4 by ELISpot (Enzyme-linked immunospot assay), allowing to increase the sensitivity of LTT during acute DHR (82 versus 50% if compared to LPA). Among the anti-tubercular drugs exfoliative dermatitis is reported with rifampicin, isoniazid, ethambutol, pyrazinamide, streptomycin, PAS either singly or in combination of two drugs in some cases. Ann Pharmacother. PubMed It is important to protect the damaged skin with sterile fat dressing especially in the genital area.