PracticeUpdate Dermatology February 2019

EXPERT OPINION 26

Tetracycline, Nicotinamide, and Lesionally Administered Clobetasol as a Therapeutic Option to Prednisone in Patients With Bullous Pemphigoid By Misha A. Rosenbach MD

W e are living in an exciting era for therapeutics in dermatology in general, and in the treatment of blistering diseases in particular. The past year brought formal recognition of the impact of rituximab on pemphigus vulgaris (PV), 1 with the FDA approving it as first-line treatment for PV in June of 2018. There have also been a number of other treat- ment trials for bullous pemphigoid (BP) of which readers should be aware. One is the BLISTER trial, demonstrating noninferiority of doxycycline compared with oral pred- nisone in managing bullous pemphigoid. 2 Another study is the series highlighted here, a 3-year retrospective review from a single institution in Warsaw of 106 patients treated with tetracycline 1.5 g/day, nico- tinamide 1.2 g/day, and clobetasol 0.05% cream in 59 patients, compared with 47 patients who received prednisone 0.5 mg/kg/day. 3 Both groups displayed sim- ilar results overall in terms of disease response. As a nonblinded study, it is hard to know what to make of the observation of improved survival in the group that did not receive prednisone (one can imagine that more severely affected patients may have required prednisone, for instance), as the prednisone-treated group had higher baseline rates of severe comorbidities (dia- betes, stroke, coronary artery disease). The more important outcome in my mind is highlighting that there are anti-inflamma- tory, immunomodulatory treatments for BP, which can impact the disease course and which may be particularly useful in patients with a contraindication to traditional immu- nosuppressive therapy. These new data are helpful, broadening the array of treatment options that dermatolo- gists have in our toolboxes for managing these diseases. This may be extra impor- tant, given there is growing recognition that due to emerging classes of drugs that can induce BP. " " Another reason these treatments may be important to keep in mind is that our population of patients with BP may expand in the near future,

BP may be underdiagnosed as a cause of pruritus, particularly in the elderly, who may suffer from “prebullous” or “nonbullous” BP. 4 Another reason these treatments may be important to keep in mind is that our popu- lation of patients with BP may expand in the near future, due to emerging classes of drugs that can induce BP. Dermatologists should be aware of some additional new data about bullous disorders – in particular, reports highlighting drug-induced cases of BP. The checkpoint inhibitors work via unleashing the immune system to fight cancer, and they can induce autoimmune diseases, including BP. 5 DPP-4 agents are a class of drugs used to manage diabetes, and they have demon- strated the potential to induce BP as well. 6 In treating patients with BP, dermatologists should consider not only what new ther- apeutic options exist, but also consider repurposing traditional treatment options, utilizing anti-inflammatory agents, using aggressive topical therapy, 7 and investigat- ing for the potential of drug-induced cases. References 1. Joly P, Maho-Vaillant M, Prost-Squarcioni C, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective multicenter, parallel-group, open-label randomized trial. Lancet 2017;389(10083):2031-2040. 2. Williams HC, Wojnarowska F, Kirtschig G, et al. Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomized controlled trial. Lancet 2017;389(10079):1630-1638. 3. Kalinska-Bienias A, Kowalczyk E, Jagielski P, et al. Tetracycline, nicotinamide, and lesionally administered clobetasol as a therapeutic option to prednisone in patients with Bullous Pemphigoid: A comparative, retrospective analysis of 106 patients with long-term follow-up. Int J Dermatol 2018 Oct 22;[EPub Ahead of Print] 4. Lamberts A, Meijer JM, Jonkman MF. Nonbullous pemphigoid: a systematic review. J Am Acad Dermatol 2018;78(5):989-995. 5. Mochel MC, MingME, Imadojemu S, et al. Cutaneous autoimmune effects in the setting of therapeutic immune checkpoint inhibition for metastatic melanoma. J Cutan Pathol 2016;43(9):787-791. 6. Kridin K, Bergman R. Association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors in patients with diabetes: estimating the risk of the new agents and characterizing the patients. JAMA Dermatol 2018;154(10):1152-1158. 7. Joly P, Roujeau JC, Benichou J, et al. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid. N Engl J Med 2002;346(5):321-327. www.practiceupdate.com/c/75309

Dr. Rosenbach is Assistant Professor of

Dermatology at Hospital of the University of Pennsylvania in Philadelphia, Pennsylvania.

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