Dapsone and Sulfasalazine as Adjuvant Therapies in Pemphigus Vulgaris: A Systematic Review

Main Article Content

Kevin Nguyen
Thomas Norman
Dr. Scott Worswick

Keywords

Bullous disorders, Pemphigus, Pemphigus Vulgaris, Adjuvant therapy, Dermatology

Abstract

Background: Adjuvant treatments are often employed in pemphigus vulgaris (PV) to reduce dependence on corticosteroids. When first-line adjuvants are ineffective, considering alternative adjuvant therapies may be necessary. Dapsone and sulfasalazine represent two options.


Objective: To evaluate the use of dapsone and sulfasalazine in the treatment of PV. 


Methods: A PubMed search identified patients with PV treated with dapsone or sulfasalazine. We included all studies with ≥3 patients published in English between 1980 and December 2022. Clinical improvement was defined as disease control or complete remission (when adjuvant therapy was initiated in uncontrolled disease) and as a reduction of corticosteroids to ≤7.5 mg per day (when adjuvant therapy was initiated in controlled disease).  


Results: Eleven studies were identified representing 75 patients treated with dapsone and 66 patients treated with sulfasalazine. Six patients received dapsone monotherapy, and all had clinical improvement. Sixty-nine received adjuvant dapsone, leading to clinical improvement in 40 (58%). Fifty-seven patients received sulfasalazine as an adjuvant to intravenous corticosteroids, leading to clinical improvement in 49 (86%). The remaining 9 patients received sulfasalazine following rituximab, and all had clinical improvement.


Conclusions: Dapsone and sulfasalazine have evidence supporting their efficacy and can be considered when first-line adjuvant therapies are unsuccessful.

References

1. Amagai M. Pemphigus. In: Bolognia JL, Schaffer JV, Cerroni L,: eds. Dermatology. 4th ed. Elsevier. 2018:494-509.

2. Schmidt E, Kasperkiewicz M, Joly P.: Pemphigus. Lancet. 2019;394(10201):882-894.

3. Harman KE, Brown D, Exton LS, et al.: British Association of Dermatologists’ guidelines for the management of pemphigus vulgaris 2017. B Jr Dermatol. 2017;177(5):1170-1201.

4. Joly P, Horvath B, Patsatsi A, et al.: Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the European academy of dermatology and venereology (EADV). J Eur Acad Dermatol Venereol. 2020;34(9):1900-1913.

5. Sarnes E, Crofford L, Watson M, Dennis G, Kan H, Bass D.: Incidence and US costs of corticosteroid-associated adverse events: a systematic literature review. Clin Ther. 2011;33(10):1413-1432.
6. Joly P, Horvath B, Patsatsi A, et al. Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the European academy of dermatology and venereology (EADV). J Eur Acad Dermatol Venereol. 2020;34(9):1900-1913.

7. Almugairen N, Hospital V, Bedane C et al.: Assessment of the rate of long-term complete remission off therapy in patients with pemphigus treated with different regimens including medium- and high-dose corticosteroids. J Am Acad Dermatol. 2013;69(4):583-588.

8. A Herbst, JC Brystyn. Patterns of remission in pemphigus vulgaris.: J Am Acad Dermatol. 2000;42(3):422-427.

9. 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, muticentre, parallel-group, open-label randomised trial. Lancet. 2017;389(10083):2031-2040.

10. Ahmed AR, Shetty S.: A comprehensive analysis of treatment outcomes in patients with pemphigus vulgaris treated with rituximab. Autoimmun Rev. 2015;14(4):323-331.

11. Sukanjanapong S, Thongtan D, Kanokrungsee S, Suchonwanit P, Chanprapaph K.: A comparison of azathioprine and mycophenolate mofetil as adjuvant drugs in patients with pemphigus: a retrospective cohort study. Dermatol Ther (Heidelb). 2020;10(1):179-189.

12. Winkelmann RK, Roth HL.: Dermatitis herpetiformis with acantholysis or pemphigus with response to sulfonamides: report of two cases. Arch Dermatol. 1960;82:385-390.

13. Murrel DF, Dick S, Ahmed AR, et al.: Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J Am Acad Dermatol. 2008;58(6):1043-1046.

14. Pearson RW, O’Donoghue M, Kaplan SJ.: Pemphigus vegetans: its relationship to eosinophilic spongiosis and favorable response to dapsone. Arch Dermatol. 1980;116(1):65-68.

15. Piamphongsant T, Ophaswongse S.: Treatment of pemphigus. Int J Dermatol. 1991;30(2):139-146.

16. Ahmed AR, Hombal S.: Use of cyclophosphamide in azathioprine failures in pemphigus. J Am Acad Dermatol. 1987;17(3):437-442.

17. Heaphy MR, Albrecht J, Werth VP.: Dapsone as a glucocorticoid-sparing agent in maintenance-phase pemphigus vulgaris. Arch Dermatol. 2005;141(6):699-702.

18. Baum S, Debby A, Gilboa S, Trau H, Barzillai A.: Efficacy of dapsone in the treatment of pemphigus vulgaris: a single-center case study. Dermatology. 2016;232(5):578-585.

19. Alkeraye S, AlZamil LR, Alenazi S.: Dapsone in the management of pemphigus and pemphigoid: rediscovery of its long-lost efficacy. Cureus. 2020;12(6):e8805.

20. Azizi A, Lawaf S.: The management of oral pemphigus vulgaris with systemic corticosteroid and dapsone. J Dent Res Dent Clin Dent Prospects. 2008;2(1):33-37.

21. Werth VP, Fivenson D, Pandya AG, et al.: Multicenter randomized, double-blind, placebo-controlled, clinical trial of dapsone as glucocorticoid-sparing agent in maintenance-phase pemphigus vulgaris. Arch Dermatol. 2008;144(1):25-32.

22. El-Darouti M, Marzouk S, Abdel Hay R, et al.: The use of sulfasalazine and pentoxifylline (low-cost antitumor necrosis factor drugs) as adjuvant therapy for the treatment of pemphigus vulgaris: a comparative study. Br J Dermatol. 2009;161(2):313-319.

23. Dogra D, Dogra N, Gupta N, Gupta V.: Sulfasalazine and pentoxifylline, a new adjuvant in young pemphigus patients: A pilot study. Indian J Dermatol Venereol Leprol. 2015;81(6):640-642.

24. Navarro-Navarro I, Jiménez-Gallo D, Villegas-Romero I, Valenzuela-Ubiña S, Linares-Barrios M.: Sulfasalazine treatment for persistent pemphigus vulgaris oral lesions after rituximab treatment. Australas J Dermatol. 2021;62(2):e303-306.

25. Gürcan HM, Ahmed AR. Efficacy of dapsone in the treatment of pemphigus and pemphigoid: analysis of current data.: Am J Clin Dermatol. 2009;10(6):383-396.

26. Khalilzadeh M, Shayan M, Jourian S, Rahimi M, Sheibani M, Dehpour AR.: A comprehensive insight into the anti-inflammatory properties of dapsone. Naunyn Schmiedebergs Arch Pharmacol. 2022;395(12):1509-1523.

27. Mushtaq S, Sarkar R. Sulfasalazine in dermatology: a lesser explored drug with broad therapeutic potential.: Int J Womens Dermatol. 2020;16(3):191-198.

28. Moreno ACL, Santi CG, Gabbi TVB, Aoki V, Hashimoto T, Maruta CW.: IgA pemphigus: case series with emphasis on therapeutic response. J Am Acad Dermatol. 2014;70(1):200-201.