Pemphigus Vulgaris: An Evidence-Based Treatment Update
- 1.4k Downloads
While a variety of intervention options have been described for pemphigus vulgaris, the optimal treatment strategy has not been established.
The objective of this systematic review is to assess the literature on the efficacy and safety of interventions for the treatment of pemphigus vulgaris.
Five electronic databases were searched, including The Cochrane Skin Group’s Specialized Register, The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE and Latin American and Caribbean Health science Information database (LILACS). Five trial registers as well as reference lists of included RCTs were also searched.
Study Eligibility Criteria
Any published randomised controlled trial (RCT) on intervention for pemphigus vulgaris was included, provided the diagnosis of pemphigus vulgaris was confirmed with appropriate clinical features, histopathology and immunofluorescence studies. Studies which included forms of pemphigus other than pemphigus vulgaris were excluded.
Altogether 18 RCTs were identified including 16 distinct interventions.
Study Appraisal and Synthesis Methods
Included studies were assessed for patient selection, methods of randomisation, blinding, follow-up and selective reporting.
Current evidence is incomplete and inconclusive. The interventions which appear promising, but will require further evaluation include adjuvant mycophenolate mofetil (MMF), azathioprine, intravenous immunoglobulins (IVIG), sulfasalazine and pentoxifylline, infliximab, epidermal growth factor and pimecrolimus. Interventions with inconclusive evidence include high (120–180 mg) versus low (45–60 mg) prednisone dosage, pulsed dexamethasone, cyclophosphamide, dexamethasone–cyclophosphamide pulse therapy (DCP), cyclosporine, dapsone, etanercept, acyclovir and tacrolimus.
Our review is limited by the small number of high-quality RCTs and variety of outcome measures, precluding the performing of a meta-analysis.
Conclusions and Implications of Key Findings
The optimal treatment strategy for pemphigus vulgaris remains unclear. Higher quality RCTs are required in the future to re-evaluate many interventions and to explore other unstudied interventions.
KeywordsPemphigus Pimecrolimus Report Outcome Measure Cyclophosphamide Pulse Therapy Cumulative Steroid Dose
No funding has been received for the completion of this systematic review. Both authors of the paper (Cathy Y. Zhao and Dedee F. Murrell) are investigators of a Roche-sponsored trial of rituximab and a GlaxoSmithKline-sponsored trial of ofatumumab.
- 2.Martin LK, Agero ALC, Werth V, Villanueva E, Segall J, Murrell DF. Interventions for pemphigus vulgaris and pemphigus foliaceus. Cochrane Database Syst Rev. 2009;(1):CD006263.Google Scholar
- 10.Chams-Davatchi C, Mortazavizadeh A, Daneshpazhooh M, Davatchi F, Balighi K, Esmaili N, et al. Randomized double blind trial of prednisolone and azathioprine, vs. prednisolone and placebo, in the treatment of pemphigus vulgaris. J Eur Acad Dermatol Venereol JEADV. 2013;27(10):1285–92. doi: 10.1111/j.1468-3083.2012.04717.x.Google Scholar
- 12.Rahbar Z, Daneshpazhooh M, Mirshams-Shahshahani M, Esmaili N, Heidari K, Aghazadeh N, et al. Pemphigus disease activity measurements: pemphigus disease area index, autoimmune bullous skin disorder intensity score, and pemphigus vulgaris activity score. JAMA Dermatol. 2014;150(3):266–72. doi: 10.1001/jamadermatol.2013.8175.CrossRefPubMedGoogle Scholar
- 17.Parmar NV, Kanwar AJ, Minz RW, Parsad D, Vinay K, Tsuruta D, et al. Assessment of the therapeutic benefit of dexamethasone cyclophosphamide pulse versus only oral cyclophosphamide in phase II of the dexamethasone cyclophosphamide pulse therapy: a preliminary prospective randomized controlled study. Indian J Dermatol Venereol Leprol. 2013;79(1):70–6.CrossRefPubMedGoogle Scholar
- 20.El-Darouti M, Marzouk S, Abdel Hay R, El-Tawdy A, Fawzy M, Leheta T, et al. The use of sulfasalazine and pentoxifylline (low-cost antitumour necrosis factor drugs) as adjuvant therapy for the treatment of pemphigus vulgaris: a comparative study. Br J Dermatol. 2009;161(2):313–9. doi: 10.1111/j.1365-2133.2009.09208.x.CrossRefPubMedGoogle Scholar
- 26.Tabrizi MN, Chams-Davatchi C, Esmaeeli N, Noormohammadpoor P, Safar F, Etemadzadeh H, et al. Accelerating effects of epidermal growth factor on skin lesions of pemphigus vulgaris: a double-blind, randomized, controlled trial. J Eur Acad Dermatol Venereol JEADV. 2007;21(1):79–84. doi: 10.1111/j.1468-3083.2006.01873.x.CrossRefGoogle Scholar
- 27.Nazemi-Tabrizi MJ, Hatami P, Ghiasi M, Daneshpazhooh M, Chams-Davatchi C. Randomized trial of tacrolimus 0.1 % ointment versus triamcinolone acetonide 0.1 % paste in the treatment of oral pemphigus vulgaris. Iran J Dermatol. 2012;15(60):42–6.Google Scholar
- 28.Iraji F, Asilian A, Siadat AH. Pimecrolimus 1 % cream in the treatment of cutaneous lesions of pemphigus vulgaris: a double-blind, placebo-controlled clinical trial. J Drugs Dermatol JDD. 2010;9(6):684–6.Google Scholar
- 29.Tjokrowidjaja A, Daniel BS, Frew JW, Sebaratnam DF, Hanna AM, Chee S, et al. The development and validation of the treatment of autoimmune bullous disease quality of life questionnaire, a tool to measure the quality of life impacts of treatments used in patients with autoimmune blistering disease. Br J Dermatol. 2013;169(5):1000–6. doi: 10.1111/bjd.12623.CrossRefPubMedGoogle Scholar
- 35.Kanwar AJ, Vinay K, Sawatkar GU, Dogra S, Minz RW, Shear NH, et al. Clinical and immunological outcomes of high- and low-dose rituximab treatments in patients with pemphigus: a randomized, comparative, observer-blinded study. Br J Dermatol. 2014;170(6):1341–9. doi: 10.1111/bjd.12972.CrossRefPubMedGoogle Scholar
- 36.Amber KT, Hertl M. An assessment of treatment history and its association with clinical outcomes and relapse in 155 pemphigus patients with response to a single cycle of rituximab. J Eur Acad Dermatol Venereol JEADV. 2014. doi: 10.1111/jdv.12678.
- 37.Ahmed AR, Shetty S. A comprehensive analysis of treatment outcomes in patients with pemphigus vulgaris treated with rituximab. Autoimmun Rev. 2014. doi: 10.1016/j.autrev.2014.12.002.