The most common causes of exfoliative dermatitis are preexisting dermatoses, drug reactions, malignancies and other miscellaneous or idiopathic disorders. A marked increase in serum soluble Fas ligand in drug-induced hypersensitivity syndrome. PubMedGoogle Scholar. During the acute reaction, diagnosis of ED is mainly based on clinical parameters. 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. Severe adverse cutaneous reactions to drugs. (in Chinese) . . Acute processes usually favor large scales, whereas chronic processes produce smaller ones. Initial symptoms could be aspecific, as fever, stinging eyes and discomfort upon swallowing, occurring few days before the onset of mucocutaneous involvement. Paraneoplastic pemphigus is associated with neoplasms, most commonly of lymphoid tissue, but also Waldenstrms macroglobulinemia, sarcomas, thymomas and Castlemans disease. National Library of Medicine 2013;168(3):53949. The .gov means its official. A catabolic state thus ensues, which is often responsible for significant weight loss. CAS The time interval between the appearance of exfoliative dermatitis and the appearance of cutaneous T-cell lymphoma lesions can vary from months to years or even decades. 2013;27(5):65961. Kreft B, et al. Int J Dermatol. Shiga S, Cartotto R. What are the fluid requirements in toxic epidermal necrolysis? View ABRIGO_Worksheet #8 Drug Study_Endocrine System.pdf from NCM 06 at Southern Luzon State University (multiple campuses). 2014;71(1):1956. A multidisciplinary team is fundamental in the therapeutic management of patients affected by exfoliative DHR. 1997;22(3):1467. ), Phenolphthalein (Agoral, Alophen, Modane), Rifampin (Rifadin, Rimactane; also in Rifamate), Trimethoprim (Trimpex; also in Bactrim, Septra). 2006;34(2):768. [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] Common acute symptoms include abdominal pain or cramps, nausea, vomiting, and diarrhea, jaundice, skin rash and eyes dryness and therefore could mimic the prodromal and early phase of ED. 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. 2013;69(4):37583. Eur J Clin Microbiol Infect Dis. The lymphocyte transformation test in the diagnosis of drug hypersensitivity. 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;29(3):51735. Int J Dermatol. Takahashi R, et al. Since the earliest descriptions of exfoliative dermatitis, medications have been known to be important causative agents. Arch Dermatol. Antiviral therapy. Verma R, Vasudevan B, Pragasam V. Severe cutaneous adverse drug reactions. Check the full list of possible causes and conditions now! 1984;101(1):4850. Nassif A, et al. 2023 Jan 30;11(2):346. doi: 10.3390/microorganisms11020346. Toxic epidermal necrolysis: Part II Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. Br J Dermatol. Half-life of the drug is approximately 54 h. Modification of nitisinone in liver and renal dysfunction is yet to be studied. Theoretically, any drug can trigger a reaction, but the medications most associated with this disorder are: Allopurinol; Antiepileptic medications; Barbiturates exfoliative conditions. 2011;3(1):e2011004. Prevalence is low, with mortality of roughly 512.5% for SJS and 50% for TEN [1, 2]. 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. Erythema multiforme and toxic epidermal necrolysis. 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. Google Scholar. Therefore, the clinician should always consider drugs as a possible cause. 2015;56(4):298302. Clinical features; Delayed type hypersensitivity; Drug hypersensitivity; Erythema multiforme; Exfoliative dermatitis; Lyells syndrome; Pathogenesis; StevensJohnson syndrome; Therapy; Toxic epidermal necrolysis. Paulmann M, Mockenhaupt M. Severe drug-induced skin reactions: clinical features, diagnosis, etiology, and therapy. A population-based study of StevensJohnson syndrome. 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]. PubMed 2011;50(2):2214. [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. Nature. (scFv) (directed against Dsg1/3) or AK23 (directed against Dsg3) with (as a control) or without exfoliative toxin A (ETA). 1991;127(6):83942. 2005;102(11):41349. Exp Dermatol. The diagnosis of GVDH requires histological confirmation [87]. Rifampin, paracetamol, metronidazole, paclitaxel, erythromycin, and ibuprofen have all been reported to cause bullous FDE. In approximately 25% of people, there is no identifiable cause. 1999;48(5):21726. (2.4, 5.6) Embryo-fetal Toxicity: Can cause fetal harm. Fritsch PO. The drug level peaks after 1- 4 h in plasma after ingestion with 95% protein binding. Clin Mol Allergy 14, 9 (2016). Fritsch PO. Hepatobiliary: jaundice, hepatitis, including . 2013;69(2):173174. Proc Natl Acad Sci USA. The Nikolskys sign is not specific for SJS/TEN, in fact it is present also in auto-immune blistering diseases like pemphigus vulgaris. Curr Opin Allergy Clin Immunol. 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 . 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. 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]. In the hospital, special attention must be given to maintaining temperature control, replacing lost fluids and electrolytes, and preventing and treating infection. Acute and chronic leukemia may also cause exfoliative dermatitis. Incidence of toxic epidermal necrolysis and StevensJohnson Syndrome in an HIV cohort: an observational, retrospective case series study. Perforin/granzyme B pathway: Nassif and colleagues have proposed a role for perforin/grazyme B in keratinocyte death [37]. 2013;133(5):1197204. Khalaf D, et al. More recently, carcinomas of the fallopian tube,12 larynx13 and esophagus14 have been reported as causes of exfoliative dermatitis. Erythema multiforme StevensJohnson syndrome and toxic epidermal necrolysis. An official website of the United States government. In case of an oral mucositis that impairs nutrition, it is indicated to position a nasogastric tube. Polak ME, et al. J Clin Apher. 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]. Clinical clues of a drug-induced etiology include: Abrupt onset, previous morbilliform eruption, multiple, varied cutaneous morphologic lesions present together Extensive erythema is followed in 2-6 days by exfoliative scaling Pruritus can be severe, leading to scratching and lichenification in more chronic processes TEN is also known as Lyell syndrome, since it was first described by Alan Lyell in 1956 [2, 60]. Add 1 cup (about 236 milliliters) of vinegar to a bathtub filled with warm water. Google Scholar. The therapeutic approach of EMM, SJS, TEN depends on extension of skin, mucosal involvement and systemic patients conditions. Case Rep Dermatol. CAS Ko TM, et al. Autologous transplantation of mesenchymal umbilical cord cells seems also to be highly efficacious [102]. EMs mortality rate is not well reported. 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. Nayak S, Acharjya B. Harr T, French LE. Still, treatment indication, choice and dosage remain unclear, and efficacy yet unproven. 2000;22(5):4137. 2012;2012:915314. Am J Clin Dermatol. Analysis of StevensJohnson syndrome and toxic epidermal necrolysis using the Japanese Adverse Drug Event Report database. The strength of association with the development of SJS/TEN may vary among countries and historical periods, reflecting differences in ethnicities and prescription habits among the studied populations [6164]. 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. PubMed Central Affiliated tissues include skin, liver and bone marrow. 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. Wetter DA, Davis MD. Clin Exp Dermatol. Wetter DA, Camilleri MJ. 2008;53(1):28. Exfoliative dermatitis may happen as a complication of other skin issues. Epub 2022 Mar 9. 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. Loss of normal vasoconstrictive function in the dermis, decreased sensitivity to the shivering reflex and extra cooling that comes from evaporation of the fluids leaking out of the weeping skin lesions all result in thermoregulatory dysfunction that can cause hypothermia or hyperthermia.6 The basal metabolic rate also is increased in patients with exfoliative dermatitis. Allergol Int. HLA-A* 3101 and carbamazepine-induced hypersensitivity reactions in Europeans. EM usually occurs in young adults of 2040years of age [13], with women affected more frequently than men (1.5:1.0) [14]. 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. The epidermal-dermal junction shows changes, ranging from vacuolar alteration to subepidermal blisters [20]. Current Perspectives on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. Four cases are described, two of which were due to phenindione sensitivity. Chan HL, et al. 2003;21(1):195205. Yacoub, MR., Berti, A., Campochiaro, C. et al. It is also recommended to void larger vesicles with a syringe. Ozeki T, et al. Graft versus host disease (GVHD) Acute GVHD usually happens within the first 6months after a transplant. Am J Dermatopathol. They found that the inhibition of these molecules could attenuate the cytotoxic effect of lymphocytes toward keratinocytes. Article Cite this article. Clin Exp Allergy. c. Amyloidosis. Association between HLA-B* 1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Do this 2 to 3 times a week. See this image and copyright information in PMC. Google Scholar. In: Eisen AZ, Wolff K, editors. Severe Cutaneous Adverse Reactions: The Pharmacogenomics from Research to Clinical Implementation. and transmitted securely. It is a reaction pattern and cutaneous manifestation of a myriad of underlying ailments, including psoriasis and eczema, or a reaction to the consumption of . The scales may be small or large, superficial or deep. Tumor necrosis factor : TNF- seems also to play an important role in TEN [41]. Detection of a herpes simplex viral antigen in skin lesions of erythema multiforme. 2008;14(12):134350. Descamps V, Ranger-Rogez S. DRESS syndrome. . Retrospective review of StevensJohnson syndrome/toxic epidermal necrolysis treatment comparing intravenous immunoglobulin with cyclosporine. Next vol/issue Posadas SJ, 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. Poor relevance of a lymphocyte proliferation assay in lamotrigine-induced StevensJohnson syndrome or toxic epidermal necrolysis. Toxic epidermal necrolysis: effector cells are drug-specific cytotoxic T cells. The authors declare that they have no competing interests. 1998;282(5388):4903. Synthetic bilaminar membranes with silver nitrate have also a role in skin repairing and avoid protein loss through the damaged skin [100, 101]. 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. Also, physicians should be vigilant about possible secondary infection, whether cutaneous, pulmonary or systemic. In conclusion we suggest that therapy with cyclosporine is valuable option with a dosage of 35mg/kg oral or iv for 7days. In particular, drug induced exfoliative dermatitis (ED) are a group of rare and more severe drug hypersensitivity reactions (DHR) involving skin and mucous membranes and usually occurring from days to several weeks after drug exposure [2]. Huff JC, Weston WL, Tonnesen MG. Erythema multiforme: a critical review of characteristics, diagnostic criteria, and causes. HHS Vulnerability Disclosure, Help Ayangco L, Rogers RS 3rd. PMC Barbaud A. Kaffenberger BH, Rosenbach M. Toxic epidermal necrolysis and early transfer to a regional burn unit: is it time to reevaluate what we teach? 2018 Jan 28;2018:9095275. doi: 10.1155/2018/9095275. Genome-wide association study identifies HLA-A* 3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population. Most common used drugs are: morphine, fentanyl, propofol and midazolam. 2011;66(3):3607. 1. 2014;81(1):1521. 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. Mediterr J Hematol Infect Dis. A recent review [111] on 33 pediatric cases of TEN and 6 cases of SJS/TEN overlap showed that therapy with IVIG with a dosage of 0.251.5g/kg for 5days resulted in 0% mortality rate and faster epithelization. See permissionsforcopyrightquestions and/or permission requests. These include a cutaneous reaction to other drugs, exacerbation of a previously existing condition, infection, metastatic tumor involvement, a paraneoplastic phenomenon, graft-versus-host disease, or a nutritional disorder. Exfoliative dermatitis is a rare inflammatory skin condition that is characterized by desquamation and erythema involving more than 90% of the body surface area. Wolkenstein P, et al. Mawson AR, Eriator I, Karre S. StevensJohnson syndrome and toxic epidermal necrolysis (SJS/TEN): could retinoids play a causative role? Options include use of PUVA light therapy, total-body electron beam irradiation, topical nitrogen mustard, systemic chemotherapy and extracorporeal photopheresis. Staphylococcal Scalded Skin Syndrome: criteria for Differential Diagnosis from Lyells Syndrome. J Allergy Clin Immunol. Kirchhof MG, et al. Bullous pemphigoid is characterized by large, tense bullae, but may begin as an urticarial eruption. Ramirez GA, Yacoub MR, Ripa M, Mannina D, Cariddi A, Saporiti N, Ciceri F, Castagna A, Colombo G, Dagna L. Biomed Res Int. Pregnancy . Smith SD, et al. Given the different histopathological features of the EM, SJS and TEN, we decided to discuss them separately. 1991;127(6):8318. Fluid balance is a main focus. Toxic epidermal necrolysis associated with Mycoplasma pneumoniae infection. Adverse cutaneous drug reaction. J Allergy Clin Immunol. J Am Acad Dermatol. Oliveira L, Zucoloto S. Erythema multiforme minor: a revision. Barbaud A. It is necessary to obtain as soon as possible a central venous access and to start a continuous monitoring of vital signs. 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]. In case of a respiratory failure, oxygen should be administrated and a NIMV may be required. 2023 BioMed Central Ltd unless otherwise stated. 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]. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Trautmann A, et al. Gastrointestinal: pancreatitis, glossitis, dyspepsia. 1995;333(24):16007. 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]. Overall, T cells are the central player of these immune-mediated drug reactions. Etanercept: monoclonal antibody against the TNF- receptor. 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]. In: Eisen AZ, Wolff K, editors. SJS and TEN are two overlapping syndromes resembling severe burn lesions and characterized by skin detachment. Drug-induced LPP. 2012;66(6):9951003. 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. 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. 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. Continue Reading. . 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 Law EH, Leung M. Corticosteroids in StevensJohnson Syndrome/toxic epidermal necrolysis: current evidence and implications for future research. Ann Intern Med. Erythema multiforme (EM), StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Burns. Applications of Immunopharmacogenomics: Predicting, Preventing, and Understanding Immune-Mediated Adverse Drug Reactions. Check the full list of possible causes and conditions now! Careers. This site needs JavaScript to work properly. Huang SH, et al. In more severe cases corneal protective lens can be used.