Pharmacology and therapeutics Blackwell Oxford, International IJD © 0011-9059 46 2007 The UK Publishing, International Journal of Ltd. Dermatology Society of Dermatology
Practical guidelines for the management of toxic epidermal necrolysis and Stevens–Johnson syndrome ManagementRamos-Caro, Fromowitz, PHARMACOLOGY of TEN and and THERAPEUTICS and SJS Flowers
Jeffrey S. Fromowitz, MD, Francisco A. Ramos-Caro, MD, and Franklin P. Flowers, MD
From the Department of Medicine, Division of Dermatology and Cutaneous Surgery, University of Florida College of Medicine, and Dermatology and Cutaneous Surgery Section, Malcolm Randall Veterans Administration Medical Center, Gainesville, Florida
Abstract Toxic epidermal necrolysis and Stevens–Johnson syndrome are acute life-threatening dermatoses characterized by extensive sloughing and mucositis. At the University of Florida, we use practical guidelines for the management of these gravely ill patients. These can be of help to other practitioners.
Correspondence Francisco A. Ramos-Caro, MD Division of Dermatology and Cutaneous Surgery University of Florida College of Medicine PO Box 100277 Gainesville, FL 32610-0277 E-mail: Ramosfa@medicine.ufl.edu
Introduction Toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS) are acute life-threatening dermatoses characterized by extensive epidermal sloughing and mucositis. This sloughing and mucositis result from extensive keratinocyte apoptosis. The increased morbidity and mortality associated with these conditions require rapid diagnosis and initiation of treatment. In 1991, our group at the University of Florida published a review on TEN which included our management approach at the time.1 Over the years, our residents have used it when they approach these gravely ill patients. We have updated these guidelines for the residents at our institution to reflect current advances, such as the use of intravenous immunoglobulins (IVIGs).2–4 It is our hope that these guidelines (Table 1) will serve to assist other physicians at other institutions. Discussion
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TEN and SJS are characterized by extensive keratinocyte apoptosis that is, at least in part, mediated by the interaction of the fas receptor and fas ligand.2,5 Both laboratory investigation and human studies have shown that IVIG blocks fas ligand binding to the fas receptor, and interferes with the downstream signaling responsible for programmed cell death.2 International Journal of Dermatology 2007, 46, 1092–1094
We manage both TEN and SJS in a similar fashion as, from a practical standpoint, they both behave similarly and both carry significant morbidity and mortality. Our choice of IVIG over other immunosuppressive agents is supported by two recent papers.2,4 IVIG is prepared from pooled plasma, and contains many variable immune antibodies that interfere with the apoptotic pathway by blocking the binding of the fas ligand and receptor.2 If fas ligand and receptor binding has occurred prior to giving IVIG, downstream signaling continues unperturbed and programmed cell death follows. This emphasizes the importance of rapid disease recognition and treatment within 48–72 h from the start of bulla formation; however, we use IVIG in patients outside this window if new lesions continue to develop. We view this clinical observation as indirect evidence of continued fas to fas ligand binding, and these patients may still respond to IVIG. The dosage and infusion time recommended originate from the work of the TEN-IVIG Study Group.2 We use sucrose-depleted IVIG to minimize the risks of renal failure. The use of IVIG in patients with immunoglobulin A (IgA) deficiency is contraindicated because of increased risks of anaphylaxis. Postponing treatment with IVIG whilst awaiting the results of IgA levels may not always be practical because of the different laboratory turnaround times at each institution. In this case, the decision to treat with IVIG may be based on a thorough history, specifically querying the patient with regard to problems with recurrent sinopulmonary and gastrointestinal infections.6 © 2007 The International Society of Dermatology