Recent advances in the genetics and immunology of StevensJohnson syndrome and toxic epidermal necrosis. 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. J Invest Dermatol. CAS It is important to take into consideration the mechanism of action of the different drugs in the pathogenesis of ED [104]. The site is secure. Erythema multiforme. 22 Abacavir-induced hypersensitivity syndrome is strongly associated with HLA-B*5701 during treatment . 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. 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). 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]. 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. 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. Grieb G, et al. [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. In EMM lesions typically begin on the extremities and sometimes spread to the trunk. asiatic) before starting therapies with possible triggers (e.g. Science. Hung S-I, et al. Blood counts and bone marrow studies may reveal an underlying leukemia. 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. 2008;14(12):134350. Topical treatment. Rabelink NM, Brakman M, Maartense E, Bril H, Bakker-Wensveen CA, Bavinck JN. 2011;20(5):103441. Although the etiology is. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti-PD-1/PD-L1 treatments. J Dtsch Dermatol Ges. McCormack M, et al. 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]. PubMed A slow acetylator genotype is a risk factor for sulphonamide-induced toxic epidermal necrolysis and StevensJohnson syndrome. 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. In: Eisen AZ, Wolff K, editors. 2018 Feb;54(1):147-176. doi: 10.1007/s12016-017-8654-z. Gastrointest Endosc. 2010;85(2):131138. 1991;127(6):83942. Analysis of StevensJohnson syndrome and toxic epidermal necrolysis using the Japanese Adverse Drug Event Report database. Mardani M, Mardani S, Asadi Kani Z, Hakamifard A. Dermatol Ther. Ibuprofen Zentiva is a drug based on the active ingredient ibuprofen (DC.IT) (FU), belonging to the category of NSAID analgesics and specifically derivatives of propionic acid. Wetter DA, Camilleri MJ. 1993;129(1):926. 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. A central role in the pathogenesis of ED is played by CD8+ lymphocytes and NK cells. Huff JC, Weston WL, Tonnesen MG. Erythema multiforme: a critical review of characteristics, diagnostic criteria, and causes. Tang YH, et al. 1). Erythroderma is the term used to describe intense and usually widespread reddening of the skin due to inflammatory skin disease. In: Eisen AZ, Wolff K, editors. A marked increase in serum soluble Fas ligand in drug-induced hypersensitivity syndrome. Exfoliative dermatitis is a rare inflammatory skin condition that is characterized by desquamation and erythema involving more than 90% of the body surface area. J Invest Dermatol. 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. Painkiller therapy. Gastric protection. EMM is a clinically severe, potentially life-threatening, extensive sloughing of epidermis, generally involving mucosal tissue. Antiviral therapy. 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]. New York: McGraw-Hill; 2003. p. 585600. Viard I, et al. 2005;136(3):20516. Ozeki T, et al. Possible involvement of CD14+CD16+monocyte lineage cells in the epidermal damage of StevensJohnson syndrome and toxic epidermal necrolysis. 3. Pharmacogenet Genom. Fritsch PO. A promising and complementary in vitro tool has been used by Polak ME et al. 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. Risk factors for the development of ocular complications of StevensJohnson syndrome and toxic epidermal necrolysis. 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. Given the different histopathological features of the EM, SJS and TEN, we decided to discuss them separately. 1992;11(3):20710. Recurrent erythema multiforme: clinical characteristics, etiologic associations, and treatment in a series of 48 patients at Mayo Clinic, 2000 to 2007. Diagnosis in a routine setting is based on patch test (PT) while skin test (prick and intradermal tests) with a delayed reading are contraindicated in these patients [72]. Targeting keratinocyte apoptosis in the treatment of atopic dermatitis and allergic contact dermatitis. Synthetic bilaminar membranes with silver nitrate have also a role in skin repairing and avoid protein loss through the damaged skin [100, 101]. 2012;27(4):21520. An increased metabolism is typical of patients with extended disepithelizated areas. StevensJohnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. PubMed Central Gastrointestinal: pancreatitis, glossitis, dyspepsia. 2016 Nov 15;17(11):1890. doi: 10.3390/ijms17111890. The diagnosis of GVDH requires histological confirmation [87]. Defective regulatory T cells in patients with severe drug eruptions: timing of the dysfunction is associated with the pathological phenotype and outcome. Schwartz RA et al. Ann Allergy Asthma Immunol. Clin Exp Allergy. Chan HL, et al. The exfoliative process also may involve the scalp, with 25 percent of patients developing alopecia.4 Nails can often become dystrophic, particularly in patients with preexisting psoriasis.4,6, The most frequently noted symptoms in patients with exfoliative dermatitis include malaise, pruritis and a chilly sensation. Toxic epidermal necrolysis and StevensJohnson syndrome. 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]. PubMed In some studies, the nose and paranasal area are spared. A switch to oral therapy can be performed once the mucosal conditions improve. 2012;66(3):1906. The authors wish to thank Dr. Gary White for the picture of EM showed in Fig. 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. 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]. Skin testing and patch testing in non-IgE-mediated drug allergy. Chemicals and Drugs 61. Recombinant granulocyte colony-stimulating factor in the management of toxic epidermal necrolysis. 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. Clipboard, Search History, and several other advanced features are temporarily unavailable. doi: 10.4065/mcp.2009.0379. 2008;53(1):28. volume14, Articlenumber:9 (2016) J Am Acad Dermatol. Dermatologic disorders occasionally present as exfoliative dermatitis. J Am Acad Dermatol. 2000;115(2):14953. ALDEN has shown a good accuracy to assess drug causality compared to data obtained by pharmacovigilance method and casecontrol results of the EuroSCAR casecontrol analysis for drugs associated with TEN. Acute and chronic leukemia may also cause exfoliative dermatitis. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough. 2014;81(1):1521. J Am Acad Dermatol. Apoptosis-inducing factors and lymphocyte-mediated cytotoxicity have been deeply investigated in ED. 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. If it is exfoliative dermatitis that's drug induced, it's easy to treat . 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. Immune-histopathological features allow to distinguish generalized bullous drug eruption from SJS/TEN [36]. 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 . Drug induced exfoliative dermatitis: state of the art. Copyright 1999 by the American Academy of Family Physicians. Systemic corticosteroids: These are the most common used drugs because of their known anti-inflammatory and immunosuppressive effect through the inhibition of activated cytotoxic T-cells and the production of cytokines. 2011;71(5):67283. Fitzpatricks dermatology in general medicine. Chung W-H, et al. EMs mortality rate is not well reported. Gynecologist consultation is required for avoiding the appearance of vaginal phimosis or sinechias. In spared areas it is necessary to avoid skin detachment. 2013;69(2):1734. Clinical, etiologic, and histopathologic features of StevensJohnson syndrome during an 8-year period at Mayo Clinic. Wu PA, Cowen EW. Contact Dermatitis. . Del Pozzo-Magana BR, et al. Harr T, French LE. Antitumour necrosis factor-alpha antibodies (infliximab) in the treatment of a patient with toxic epidermal necrolysis. Arch Dermatol. [Stevens-Johnson Syndrom and Toxic Epidermal Necrolysis--based on literature]. Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED. Ann Intern Med. PubMed Central Allergy. Overall, T cells are the central player of these immune-mediated drug reactions. Not responsive to therapy. 00 Comments Please sign inor registerto post comments. Schopf E, et al. Vasoactive amines may be necessary in case of shock. 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]. Gen Dent. Some anti-seizure medicines have also been known to cause exfoliative dermatitis. A serious cutaneous adverse drug reaction namely exfoliative dermatitis (erythroderma) is associated with isoniazid use . 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. Carrozzo M, Togliatto M, Gandolfo S. Erythema multiforme. All the linen must be sterile. Su SC, Hung SI, Fan WL, Dao RL, Chung WH. The cutaneous T-cell lymphomas are the lymphomas most commonly associated with exfoliative dermatitis. 2010;88(1):608. Add 1 cup (about 236 milliliters) of vinegar to a bathtub filled with warm water. Nat Med. Ardern-Jones MR, Friedmann PS. The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Cho YT, et al. Med., 1976, 6, pp. Hepatobiliary: jaundice, hepatitis, including . 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. A drug eruption may start as a rash but eventually progress to more generalized exfoliative dermatitis. Kreft B, et al. Arch Dermatol. 1995;333(24):16007. Exfoliative dermatitis, also known as erythroderma, is an uncommon but serious skin disorder that family physicians must be able to recognize and treat appropriately. Accessibility Pharmacogenomics J. 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. However, according to a consensus definition [54], EMM syndrome has been separated from SJS/TEN spectrum. Open trial of ciclosporin treatment for StevensJohnson syndrome and toxic epidermal necrolysis. Genome-scale investigation of drug-induced termination codon-readthrough in a model system of epidermolysis bullosa . Toxic epidermal necrolysis associated with severe cytomegalovirus infection in a patient on regular hemodialysis. Chung WH, et al. Erythema multiforme StevensJohnson syndrome and toxic epidermal necrolysis. In patients with SJS/TEN increased serum levels of retinoid acid have been found. 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]. Drug-induced Exfoliative Dermatitis & Eosinophils Increased Symptom Checker: Possible causes include Exfoliative Dermatitis. Association between HLA-B* 1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Jarrett P, et al. 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. Ann Pharmacother. Furosemide or ethacrynic acid may be required to maintain an adequate urinary output [90]. Epub 2022 Mar 9. Kamaliah MD, et al. This content is owned by the AAFP. Pehr K. The EuroSCAR study: cannot agree with the conclusions. Br J Dermatol. As described in Table3, major differential diagnosis of EM and SJS/TEN are (1) staphylococcal scalded skin syndrome (SSSS), (2) autoimmune blistering diseases and disseminated fixed bullous drug eruption, (3) others severe delayed DHR [6, 70, 82] (4) Graft versus host disease. Oliveira L, Zucoloto S. Erythema multiforme minor: a revision. In EM a lymphocytic infiltrate (CD8+ and macrophages), associated with vacuolar changes and dyskeratosis of basal keratinocytes, is found along the dermo-epidermal junction, while there is a moderate lymphocytic infiltrate around the superficial vascular plexus [20]. Fitzpatricks dermatology in general medicine. 2009;29(3):51735. It is also extremely important to obtain within the first 24h cultural samples from skin together with blood, urine, nasal, pharyngeal and bronchus cultures. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. ), Phenolphthalein (Agoral, Alophen, Modane), Rifampin (Rifadin, Rimactane; also in Rifamate), Trimethoprim (Trimpex; also in Bactrim, Septra). https://doi.org/10.1186/s12948-016-0045-0, DOI: https://doi.org/10.1186/s12948-016-0045-0. Toxic epidermal necrolysis: review of pathogenesis and management. Bourgeois GP, et al. Rifampin, paracetamol, metronidazole, paclitaxel, erythromycin, and ibuprofen have all been reported to cause bullous FDE. Fournier S, et al. 1990;126(1):3742. Many people have had success using a dilute vinegar bath rather than a bleach bath. PubMed 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. New York: McGraw-Hill; 2003. p. 54357. 2018 Jan 28;2018:9095275. doi: 10.1155/2018/9095275. 2010;85(2):1318. Arch Dermatol. Paraneoplastic pemphigus is associated with neoplasms, most commonly of lymphoid tissue, but also Waldenstrms macroglobulinemia, sarcomas, thymomas and Castlemans disease. Allergy. After 24 hours, split formation was evident in hematoxylin and eosin-stained sections of HOSCs treated . Staphylococcal Scalded Skin Syndrome: criteria for Differential Diagnosis from Lyells Syndrome. 2012;43:10115. Mortality rate of patients with TEN has shown to be directly correlated to SCORTEN. 2013;27(5):65961. Continue Reading. (See paras 3 - 42 and 3- 43.) 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. Nassif A, et al. It might be. In the acute phase, before determination of the etiology, treatment consists of measures to soothe the inflamed skin. Epub 2018 Aug 22. . Initial symptoms could be aspecific, as fever, stinging eyes and discomfort upon swallowing, occurring few days before the onset of mucocutaneous involvement. 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]. During the acute reaction, diagnosis of ED is mainly based on clinical parameters. Int J Dermatol. These levels could reflect the interaction between culprit drugs and aldehyde dehydrogenase that is the enzyme which metabolizes retinoid acid. Erythema multiforme: a review of epidemiology, pathogenesis, clinical features, and treatment. Infliximab: chimeric IgG monoclonal anti-TNF- antibody. Abe R, et al. Am J Infect Dis. Provided by the Springer Nature SharedIt content-sharing initiative. Background: Panitumumab is an EGFR inhibitor used for the treatment of metastatic colorectal cancer (mCRC), even if its use is related to skin toxicity. Usually the amount of calories is 15002000kcal/day and the velocity of infusion is gradually increased based on patients tolerability [92]. d. Cysts and tumors. [71] realized an algorhitm named ALDEN (algorithm of drug causality for epidermal necrolysis) which helps to establish a cause/effect relationship as probable or very probable in 70% of cases. 1994;331(19):127285. Advise of potential risk to a fetus and use of effective contraception. The management of toxic epidermal necrolysis. A rare case of toxic epidermal necrolysis with unexpected Fever resulting from dengue virus. 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. 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). Previous vol/issue. Google Scholar. 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. 2002;118(4):72833. SJS and TEN are two overlapping syndromes resembling severe burn lesions and characterized by skin detachment. eCollection 2018. Bullous dermatoses can be debilitating and possibly fatal. . Albeit the lack of epidemiologic data regarding EM, its reported prevalence is less than 1% [710]. Drugs such as paracetamol, other non-oxicam NSAIDs and furosemide, bringing a relatively low risk of SJS/TEN a priori, are also highly prevalent as putative culprit agents in large SJS/TEN registries, due to their widespread use in the general population [63, 64] (Table1). 2008;52(3):1519. Cyclosporine A (Cys A): Cys A works through the inhibition of calcineurin, that is fundamental for cytotoxic T lymphocytes activation. Mayo Clin Proc. Generalized bullous fixed drug eruption is distinct from StevensJohnson syndrome/toxic epidermal necrolysis by immunohistopathological features. The balance of fluids and electrolytes should be closely monitored, since dehydration or hypervolemia can be problems. Patients who have exfoliative dermatitis of unknown cause tend to have an unpredictable course, usually replete with multiple remissions and exacerbations.4. f. The most common causes of death in patients with exfoliative dermatitis are pneumonia, septicemia and heart failure. The epidermal-dermal junction shows changes, ranging from vacuolar alteration to subepidermal blisters [20]. Also, physicians should be vigilant about possible secondary infection, whether cutaneous, pulmonary or systemic. Half-life of the drug is approximately 54 h. Modification of nitisinone in liver and renal dysfunction is yet to be studied. N Engl J Med. Adverse cutaneous drug reaction. N Engl J Med. Allergol Immunopathol (Madr). Immunol Allergy Clin North Am. Medical genetics: a marker for StevensJohnson syndrome. 2015;13(7):62545. 2000;22(5):4137. Australas J Dermatol. 1996;135(1):611. Cite this article. Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED. Clinical practice. 2003 Oct 25;147(43):2089-94. 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. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Abe J, et al. Google Scholar. 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]. Exfoliative dermatitis is a dangerous form of CADR which needs immediate withdrawl of all the four drugs. Next vol/issue All authors read and approved the final manuscript. 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. In contrast with DRESS, eosinophilia and atypical lymphocytes are not described in patients with SJS or TEN. 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. Other cases are ultimately classifiable as another dermatosis. A heterogeneous pathologic phenotype. 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]. Main discriminating factors between EMM, SJS, SJS-TEN, TEN and SSSS is summarized in Table3 [84]. New York: McGraw-Hill; 2003. pp. . Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Guidelines for the management of drug-induced liver injury[J]. Orphanet J Rare Dis. 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.
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