-. 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. Curr Opin Allergy Clin Immunol. Erythroderma is the term used to describe intense and usually widespread reddening of the skin due to inflammatory skin disease. Clinical practice. It is not recommended to use prophylactic antibiotic therapy. J Am Acad Dermatol. Fitzpatricks dermatology in general medicine. Antitumour necrosis factor-alpha antibodies (infliximab) in the treatment of a patient with toxic epidermal necrolysis. Fritsch PO. J Invest Dermatol. 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. Skin testing and patch testing in non-IgE-mediated drug allergy. Ozeki T, et al. 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. Allergol Immunopathol (Madr). In fact, it was demonstrated that the specificity of the TCR is a required condition for the self-reaction to occur. This has been called the nose sign.18, Once the erythema is well established, scaling inevitably follows (Figure 1). Infliximab: chimeric IgG monoclonal anti-TNF- antibody. Jarrett P, et al. Nassif A, et al. Posadas SJ, et al. Heat loss is another major concern that accompanies a defective skin barrier in patients with exfoliative dermatitis. Barbaud A. Shiga S, Cartotto R. What are the fluid requirements in toxic epidermal necrolysis? Some of these patients undergo spontaneous resolution. Von Hebra first described erythroderma (exfoliative dermatitis) in 1868. In addition to all these mechanisms, alarmins, endogenous molecules released after cell damage, were found to be transiently increased in SJS/TEN patients, perhaps amplifying the immune response, including -defensin, S100A and HMGB1 [47]. 1996;135(1):611. 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). TEN is characterized by full-thickness epidermal necrosis with an evident epidermal detachment and sloughing caused by necrosis of keratinocytes following apoptosis [49, 52]. Although the etiology is. Grieb G, et al. Etanercept therapy for toxic epidermal necrolysis. 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. Stamp LK, Chapman PT. 2013;69(4):37583. It can lead to pain, appear on large parts of the body and may require hospitalization. TEN is also known as Lyell syndrome, since it was first described by Alan Lyell in 1956 [2, 60]. Br J Dermatol. The most common causes of death in patients with exfoliative dermatitis are pneumonia, septicemia and heart failure. A marked increase in serum soluble Fas ligand in drug-induced hypersensitivity syndrome. Analysis of StevensJohnson syndrome and toxic epidermal necrolysis using the Japanese Adverse Drug Event Report database. 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]. For the calculation, available values on vital and laboratory parameters within the first 3days after admission to the first hospital are considered when the reaction started outside the hospital (community patients) or at the date of hospitalization for in-hospital patients. 2013;168(3):55562. Recurrence occurs in around one-third of cases [15] and there is a genetic predisposition for certain Asian groups [16]. 2013;27(5):65961. Annu Rev Pharmacol Toxicol. Sequelae of exfoliative dermatitis are not widely reported. doi: 10.4065/mcp.2009.0379. Epilepsia. Dermatologic disorders occasionally present as exfoliative dermatitis. 2008;34(1):636. A catabolic state thus ensues, which is often responsible for significant weight loss. A case of anti-BP230 antibody-positive dyshidrosiform bullous pemphigoid secondary to dipeptidyl peptidase-4 inhibitor in a 65-year-old Filipino female 2006;34(2):768. 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. Not responsive to therapy. Patients with underlying skin disorders may respond much more slowly to therapy, but clearing almost always occurs eventually. Since cutaneous function as a multiprotective barrier is so disrupted in exfoliative dermatitis, the body loses heat, water, protein and electrolytes, and renders itself much more vulnerable to infection. 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). Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Mawson AR, Eriator I, Karre S. StevensJohnson syndrome and toxic epidermal necrolysis (SJS/TEN): could retinoids play a causative role? Energy requirements of pediatric patients with StevensJohnson syndrome and toxic epidermal necrolysis. 2015;49(3):33542. In more severe cases antiviral therapies should be given together with intravenous immunoglobulins [93]. The SJS histology is characterized by a poor dermal inflammatory cell infiltrate and full thickness necrosis of epidermis [20, 49]. 2014;71(5):9417. Gout and its comorbidities: implications for therapy. Disasters. Medical genetics: a marker for StevensJohnson syndrome. 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). 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. It might be. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. Clin Mol Allergy 14, 9 (2016). 2011;66(3):3607. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. Interstitial nephritis is common in DRESS syndrome, occurring roughly in 40% of cases, whereas pre-renal azotemia may occur in SJS and TEN. 2016;2:14. In HIV patients, the risk of SJS and TEN have been reported to be thousand-fold higher, roughly 1 per 1000 per year [19]. 1994;331(19):127285. However, according to a consensus definition [54], EMM syndrome has been separated from SJS/TEN spectrum. . 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. Descamps V, Ranger-Rogez S. DRESS syndrome. Toxic epidermal necrolysis associated with severe cytomegalovirus infection in a patient on regular hemodialysis. erythroderma, exfoliative dermatitis, and fixed drug reactions) 4, 5 and . Wu PA, Cowen EW. A drug eruption may start as a rash but eventually progress to more generalized exfoliative dermatitis. Role of nanocrystalline silver dressings in the management of toxic epidermal necrolysis (TEN) and TEN/StevensJohnson syndrome overlap. CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. 1995;14(6):5589. Even though exfoliative dermatitis is a complex disorder involving many factors, the underlying disease is usually the key determinant of the course and prognosis. Gastric protection. Arch Dermatol. A correlation between increased levels of perforin/granzyme B and the severity of TEN was also described [38]. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Each of these physiologic disruptions is potentially life-threatening. Rheumatology (Oxford). Mockenhaupt M, et al. J Am Acad Dermatol. Int Arch Allergy Immunol. Chang CC, et al. Careers. In SJS and TEN mucosal erosions on the lips, oral cavity, upper airways, conjunctiva, genital tract or ocular level are frequent [60, 6870]. J Immunol. Barbaud A, et al. Theoretically, any drug can trigger a reaction, but the medications most associated with this disorder are: Allopurinol; Antiepileptic medications; Barbiturates J Eur Acad Dermatol Venereol. 2023 Jan 30;11(2):346. doi: 10.3390/microorganisms11020346. Exfoliative dermatitis is a dangerous form of CADR which needs immediate withdrawl of all the four drugs. Applications of Immunopharmacogenomics: Predicting, Preventing, and Understanding Immune-Mediated Adverse Drug Reactions. The authors wish to thank Dr. Gary White for the picture of EM showed in Fig. J Am Acad Dermatol. 1996;44(2):1646. Anticoagulation therapy. 2008;4(4):22431. Association between HLA-B* 1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. The most commonly used steroids were methylprednisolone, prednisolone and dexamethasone. Talk to our Chatbot to narrow down your search. 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 . J Am Acad Dermatol. In any case all authors concluded that the blockage of FasL prevents keratinocyte apoptosis [35]. Ned Tijdschr Geneeskd. Proc Natl Acad Sci USA. Polak ME, et al. No uniformity of opinion exists concerning the best treatment for cutaneous T-cell lymphoma. AB, CC, ET, GAR, AN, EDL, PF performed a critical revision on the current literature about the described topic, wrote and revised the manuscript. Targeting keratinocyte apoptosis in the treatment of atopic dermatitis and allergic contact dermatitis. 1983;8(6):76375. To avoid the appearance of gastric stress ulcer it is recommended to start a therapy with intravenous proton pump inhibitors. Prevalence is low, with mortality of roughly 512.5% for SJS and 50% for TEN [1, 2]. In this study, 965 patients were reviewed. ), Phenolphthalein (Agoral, Alophen, Modane), Rifampin (Rifadin, Rimactane; also in Rifamate), Trimethoprim (Trimpex; also in Bactrim, Septra). A useful sign for differential diagnosis is the absence of mucosal involvement, except for conjunctiva. 2012;167(2):42432. Systemic and potentially life-threatening complications include fluid and electrolyte imbalance, thermoregulatory disturbance, fever, tachycardia, high-output failure, hypoalbuminemia, and septicemia. ADRJ,2015,17(6):464-465. Wetter DA, Camilleri MJ. 2018 Feb;54(1):147-176. doi: 10.1007/s12016-017-8654-z. J Invest Dermatol. These levels could reflect the interaction between culprit drugs and aldehyde dehydrogenase that is the enzyme which metabolizes retinoid acid. Erythema multiforme StevensJohnson syndrome and toxic epidermal necrolysis. Curr Allergy Asthma Rep. 2014;14(6):442. A serious cutaneous adverse drug reaction namely exfoliative dermatitis (erythroderma) is associated with isoniazid use . Abe R. Toxic epidermal necrolysis and StevensJohnson syndrome: soluble Fas ligand involvement in the pathomechanisms of these diseases. Strom BL, et al. Linear IgA dermatosis most commonly presents in patients older than 30years. The most notable member of this group is mycosis fungoides. Provided by the Springer Nature SharedIt content-sharing initiative. 1991;127(6):8318. Oral hygiene with antiseptic and painkiller mouthwash (chlorhexidine+lidocaine+aluminum hydroxide) together with aerosol therapy with saline and bronchodilators can reduce upper airways symptoms. Huff JC. J Dermatol. 1991;97(4):697700. Graft versus host disease (GVHD) Acute GVHD usually happens within the first 6months after a transplant. Some anti-seizure medicines have also been known to cause exfoliative dermatitis. HLA-A* 3101 and carbamazepine-induced hypersensitivity reactions in Europeans. J Am Acad Dermatol. Kirchhof MG et al. A multicentre study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Google Scholar. Malignancies are a major cause of exfoliative dermatitis. Moreover, transpiration and thermoregulation are greatly impaired with an elevated loss of fluids, proteins and electrolytes through the damaged skin and mucosae. Many people have had success using a dilute vinegar bath rather than a bleach bath. The type of rash that happens depends on the medicine causing it and your response. Br J Dermatol. Part of 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 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. Check the full list of possible causes and conditions now! 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. This content is owned by the AAFP. Patients present an acute high-grade of skin and mucosal insufficiency that obviously leads to great impairment in the defenses against bacteria that normally live on the skin, increasing the high risk of systemic infections. Eosinophils from Physiology to Disease: A Comprehensive Review. 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]. -. AR 40-501 14 June 2017 33 e. Dermatitis herpetiformis. Death ligand TRAIL, secreted by CD1a+and CD14+cells in blister fluids, is involved in killing keratinocytes in toxic epidermal necrolysis. Exanthematous drug eruptions. 1990;126(1):437. Su SC, Hung SI, Fan WL, Dao RL, Chung WH. Also, physicians should be vigilant about possible secondary infection, whether cutaneous, pulmonary or systemic. Epilepsia. The https:// ensures that you are connecting to the Int J Dermatol. Adverse cutaneous drug reaction. 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. Moreover Mawson A and colleagues hypothesized that the efficacy of plasmapheresis is able to reduce serum level of vitamin A. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Focus on the Pathophysiological and Diagnostic Role of Viruses. Abe J, et al. Karnes JH, Miller MA, White KD, Konvinse KC, Pavlos RK, Redwood AJ, Peter JG, Lehloenya R, Mallal SA, Phillips EJ. Toxic epidermal necrolysis associated with Mycoplasma pneumoniae infection. Efficacy of plasmapheresis for the treatment of severe toxic epidermal necrolysis: is cytokine expression analysis useful in predicting its therapeutic efficacy? 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]. PMC (adult rickets), anticonvulsant-induced rickets and osteomalacia, osteoporosis, renal osteodystrophy . 2011;20(5):103441. Br J Dermatol. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Detection of a herpes simplex viral antigen in skin lesions of erythema multiforme. Wolkenstein P, et al. 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]. c. Amyloidosis. Rifampin, paracetamol, metronidazole, paclitaxel, erythromycin, and ibuprofen have all been reported to cause bullous FDE. Blood counts and bone marrow studies may reveal an underlying leukemia. Analysis for circulating Szary cells may be helpful, but only if the cells are identified in unequivocally large numbers. All the linen must be sterile. The induction dosage in EMM is usually 1mg/kg/day that should be maintained until a complete control of the skin is obtained. 12 out of 17 studies concluded for a positive role of IVIG in ED. It has a wide spectrum of severity, and it is divided in minor and major (EMM). 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]. Adapted from Ref. 2010;5:39. As written before, Sassolas B. et al. Usually, but not always, the palms of the hands, the soles of the feet and the mucous membranes are spared. loss of taste Derm: stevens-johnson syndrome, toxic epidermal necrolysis, rash, exfoliative dermatitis, hair . . Before Granulysin is a key mediator for disseminated keratinocyte death in StevensJohnson syndrome and toxic epidermal necrolysis. Pemphigus vulgaris usually starts in the oral mucosa followed by blistering of the skin, which is often painful. Please enable it to take advantage of the complete set of features! 2019 Jan 6;59:463-486. doi: 10.1146/annurev-pharmtox-010818-021818. Sassolas B, et al. Int J Dermatol. Recent advances in the genetics and immunology of StevensJohnson syndrome and toxic epidermal necrosis. Antiviral therapy. 2013;27(3):35664. 2015;21:13343. Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED. The most common causes of exfoliative dermatitis are best remembered by the mnemonic device ID-SCALP. Ther Apher Dial. J Am Acad Dermatol. An increased metabolism is typical of patients with extended disepithelizated areas. 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. The Nikolskys sign is not specific for SJS/TEN, in fact it is present also in auto-immune blistering diseases like pemphigus vulgaris. 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. Manage cookies/Do not sell my data we use in the preference centre. Br J Dermatol. Hematologic: anemia, including aplastic and hemolytic. Dermatol Clin. Wetter DA, Davis MD. Antibiotic therapy. 2004;114(5):120915. 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. Unfortunately, the clinical picture does not contribute to an understanding of the underlying cause. J Am Acad Dermatol. Paradisi et al. Read this article to find out all its symptoms, causes and treatments. PubMed Erythroderma is a rare but severe Adverse Drug Reaction (ADR) of phenytoin. government site. 2016 Nov 15;17(11):1890. doi: 10.3390/ijms17111890. 2011;128(6):126676. Patch testing in severe cutaneous adverse drug reactions, including StevensJohnson syndrome and toxic epidermal necrolysis. It is necessary to obtain as soon as possible a central venous access and to start a continuous monitoring of vital signs. 2013;69(2):1734. Man CB, et al. Drugs that have been implicated in the causation of LPP include captopril, cinnarizine, ramipril, simvastatin, PUVA, and antituberculous medications. The epidermal-dermal junction shows changes, ranging from vacuolar alteration to subepidermal blisters [20]. Pharmacogenet Genom. Overall, T cells are the central player of these immune-mediated drug reactions. In recent years, clinicians have come to believe that this condition is secondary to a complicated interaction of cytokines and cellular adhesion molecules. In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of therapy, but can occur at any time during treatment with diclofenac. Harr T, French LE. Contact Dermatitis. In patients with SJS/TEN increased serum levels of retinoid acid have been found. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. 2012;43:10115. Fluid balance is a main focus. Nutritional support. New York: McGraw-Hill; 2003. pp. Cutaneous graft-versus-host diseaseclinical considerations and management. Szary syndrome, the leukemic variant of mycosis fungoides, is also associated with exfoliative dermatitis. Roujeau JC, et al. 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. If it is exfoliative dermatitis that's drug induced, it's easy to treat . 1997;19(2):12732. Ann Burns Fire. 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. 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. Huang SH, et al. 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. 2, and described below. The therapeutic approach of EMM, SJS, TEN depends on extension of skin, mucosal involvement and systemic patients conditions. Exfoliative dermatitis (ED) is defined as diffuse erythema and scaling of the skin involving more than 90% of the total body skin surface area. (See paras 3 - 42 and 3- 43.) Nassif A, et al. 2009;182(12):80719. Journal of Pharmaceutical Research and health Care. 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 case of an oral mucositis that impairs nutrition, it is indicated to position a nasogastric tube. 2000;22(5):4137. Mediterr J Hematol Infect Dis. 2004;59(8):80920. The taper of steroid therapy should be gradual [93].