inflammation. They inhibit T-cell mediated inflammation at least in part by increasing the number of Treg cells. The authors suggest that vitamin D, presumably via 1,25(OH) 2 D, induces this gene, although it is equally plau- sible that the response to vitamin D is indirect. Regardless, this would be a novel action of vitamin D and could contribute both to the inhibition of inflammation and tumor formation by vitamin D. Although this study focused on the ability of pharmacologic doses of vitamin D to suppress the inflam- mation caused by UVR, the results may suggest a potential for vitamin D to suppress tumor formation, although the administration of 200,000 IU vitamin D for an extended period cannot be recommended. ORCID Daniel D. Bikle: http://orcid.org/0000-0002-1040- 475X CONFLICT OF INTEREST The authors state no conflict of interest. REFERENCES Amer M, Qayyum R. Relation between serum 25- hydroxyvitamin D and C-reactive protein in asymptomatic adults (from the continuous Na- tional Health and Nutrition Examination Survey 2001 to 2006). The American Journal of Car- diology 2012;109:226e30. Bellia A, Garcovich C, D’Adamo M, Lombardo M, Tesauro M, Donadel G, et al. Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects. Intern Emerg Med 2013;8:33e40. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chemistry & Biology 2014;21:319e29. Bikle DD. Vitamin D receptor, a tumor suppressor in skin. Can J Physiol Pharmacol 2015;93: 349e54. Bikle DD, Nemanic MK, Gee E, Elias P. 1,25- Dihydroxyvitamin D3 production by human keratinocytes. Kinetics and regulation. The Journal of Clinical Investigation 1986;78: 557e66. Bikle DD, Pillai S, Gee E, Hincenbergs M. Tumor necrosis factor-alpha regulation of 1,25- dihydroxyvitamin D production by human ker- atinocytes. Endocrinology 1991;129:33e8. Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocrine Reviews 2008;29:726e76. Cannell JJ, Grant WB, Holick MF. Vitamin D and inflammation. Dermato-endocrinology 2014;6: e983401. Feldmeyer L, Keller M, Niklaus G, Hohl D, Werner S, Beer HD. The inflammasome medi- ates UVB-induced activation and secretion of interleukin-1beta by keratinocytes. Curr Biol 2007;17:1140e5. Feng X, Lv C, Wang F, Gan K, Zhang M, Tan W. Modulatory effect of 1,25-dihydroxyvitamin D 3 on IL1 beta - induced RANKL, OPG, TNF alpha, and IL-6 expression in human rheuma- toid synoviocyte MH7A. Clin Dev Immunol 2013:160123. Korf H, Wenes M, Stijlemans B, Takiishi T, Robert S, Miani M, et al. 1,25-Dihydroxyvitamin D3 cur- tails the inflammatory and T cell stimulatory capacity of macrophages through an IL-10- dependent mechanism. Immunobiology 2012;217:1292e300. Kwak Y, Kim HE, Park SG. Insights into myeloid- derived suppressor cells in inflammatory dis- eases. Arch Immunol Ther Exp (Warsz) 2015;63:269e85. Matsuoka LY, Wortsman J, Haddad JG, Hollis BW. In vivo threshold for cutaneous synthesis of vitamin D3. The Journal of Laboratory and Clinical Medicine 1989;114:301e5. Muthusamy V, Piva TJ. The UV response of the skin: a review of the MAPK, NFkappaB and TNFalpha signal transduction pathways. Archives of Dermatological Research 2009;302:5e17. Nasti TH, Timares L. Inflammasome activation of IL-1 family mediators in response to cutaneous photodamage. Photochemistry and Photobi- ology 2012;88:1111e25. Scott JF, Das LM, Ahsanuddin S, Qiu Y, Binko AM, Traylor ZP, et al. Oral vitamin D rapidly attenuates inflammation from sunburn: an interventional study. J Invest Dermatol 2017;137:2078e86. See related article on pg 2092 New Evidence Supporting Cyclosporine Efficacy in Epidermal Necrolysis Jean-Claude Roujeau 1 , Maja Mockenhaupt 2 , Jean-Claude Guillaume 3 and Jean Revuz 4 Sixty years after its original description by Sir Alan Lyell, epidermal necrolysis (from Stevens-Johnson syndrome to toxic epidermal necrolysis) seems finally amenable to a specific treatment in addition to essential symptomatic measures in specialized settings. A recently published systematic review and an article by Gonzales-Herrada et al. strongly suggest that cyclosporine is effective in reducing the risk of death. Journal of Investigative Dermatology (2017) 137, 2047e2049. doi:10.1016/j.jid.2017.07.828 Epidermal necrolysis (EN), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and overlapping forms, is a rare but very severe cuta- neous adverse reaction most often due to medications. In a European pro- spective cohort, the overall mortality for all subgroups considered together was 22% at 6 weeks and 34% at 1 year (Sekula et al., 2013). Over decades, many small studies reported the empiric use of high-dose corticosteroids, cyclophosphamide, plasma exchanges, and anti-tumor ne- crosis factor-a monoclonal antibodies as specific measures that halted the progression of lesions. More recent studies recommended high doses of intravenous immunoglobulins (IVIg). Each of these interventions was sup- ported by the enthusiasm of their pro- motors and in some cases their funders, but subsequent critical reviews and/or meta-analyses did not confirm efficacy. Treatment recommendations for EN issued by burn units in the United States, the Health Minister in France, and the British Association of Dermatologists (Creamer et al., 2016) were that no etio- logic treatment was efficacious and that supportive measures in burn units or other specialized departments (in Europe including departments of dermatology and intensive care units) were the best 1 University Paris-Est, Cre´teil, France; 2 Universita¨tsklinikum/Medical Center and Faculty of Medicine, University of Freiburg, Germany; 3 La Rochelle, France (retired); and 4 Paris, France (retired) Correspondence: 139 Ave Jean Jaure`s 92290 Chatenay-Malabry, France. E-mail: jean- claude.roujeau@wanadoo.fr ª 2017 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. COMMENTARY www.jidonline.org 2047