A randomized double-blind placebo-controlled trial of autologous platelet-rich plasma intradermal injections for the treatment of vulvar lichen sclerosus

To the Editor: We performed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of autologous platelet-rich plasma (PRP) for the treatment of vulvar lichen sclerosus (LS). A total of 30 patients (mean age, 52.6 years; 29 whites and 1 Hispanic) with biopsy-proven active LS were recruited. One participant withdrew after randomization but before treatment, and 29 completed the study. Patients were randomized to receive either placebo (saline injections) (10 subjects) or 2 separate treatments of PRP separated by 6 weeks (20 subjects). There was no statistically significant difference in participant age or duration of symptoms between the PRP and placebo groups. Each treatment consisted of 5 mL of PRP injected subdermally and intradermally, infiltrating the areas affected by LS. The PRP was prepared by using a US Food and Drug Administration–cleared centrifuge that uses a laser to isolate the platelet-rich fraction of 60 mL of whole blood (Magellan Autologous Platelet Separator System, Isto Biologics, Hopkinton, MA). The PRP was collected in a blackened syringe so that neither the physician administering the PRP nor the study participants knew whether they were receiving the PRP or placebo. The primary efficacy variable was determined by a pathologist with expertise in vulvar pathology (D.H.), who was blinded to the treatment arms and evaluated the inflammatory infiltration on the pretreatment and post-treatment biopsy specimens (on a 0-3 scale). A secondary end point was change in score according to the Clinical Scoring System for Vulvar Lichen Sclerosus (CSS), which is a validated instrument that assesses both the investigator and patient impression of the severity of the LS.1Gunthert A.R. Duclos K. Jahns B.G. et al.Clinical scoring system for vulvar lichen sclerosus.J Sex Med. 2012; 9: 2342-2350Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar Of the 19 women receiving PRP, 5 had improvement in histopathologic inflammation between the pretest and post-test treatment biopsies, 10 had no change, and 4 had more inflammation. Of the 10 women receiving placebo, 5 had improvement, 4 had no change, and 1 had more inflammation (Mann-Whitney U test result, 109.0 [P = .542]). The mean difference in the CSS patient domain between the initial and final visits was −7.74 for patients receiving PRP and −9.44 for patients receiving placebo (Mann-Whitney U test result, 80.50 [P = .654]. Bruising was the only adverse event reported. A recent pilot study performed by our group showed that PRP reduced histopathologic inflammation in 7 of 12 patients with vulvar LS.2Goldstein A.T. King M. Runels C. Gloth M. Pfau R. Intradermal injection of autologous platelet-rich plasma for the treatment of vulvar lichen sclerosus.J Am Acad Dermatol. 2017; 76: 158-160Abstract Full Text Full Text PDF Scopus (26) Google Scholar However, the main limitations of that study was its lack of placebo control. In addition, Tedesco et al studied PRP injection in 31 patients with LS.3Tedesco M. Pranteda G. Chichierchia G. et al.The use of PRP (platelet-rich plasma) in patients affected by genital lichen sclerosus: clinical analysis and results.J Eur Acad Dermatol Venereol. 2019; 33: e58-e59Google Scholar They reported that 62% of patients had improvement in their LS, but their study was not placebo controlled, did not use validated measures of subjective or objective improvement, and did not include histopathologic evaluation. As LS is a premalignant condition and a reduction in inflammation with optimal use of corticosteroids lowers the rate of malignant transformation, it is essential that all studies of LS use reduction in inflammation as the primary efficacy measure.4Lee A. Bradford J. Fischer G. Long-term management of adult vulvar lichen sclerosus: a prospective cohort study of 507 women.JAMA Dermatol. 2015; 151: 1061-1067Crossref PubMed Scopus (190) Google Scholar One of the strengths of our current study is that it used this objective criterion as its primary end point. Additional strengths of our study are that it was blinded, was placebo-controlled, and used the validated CSS. A sample size calculation was performed before initiation of the study and determined that our study sample was powered to show a clinically significant effect of a 50% reduction in inflammation with a 2-sided significance of .05 and a power of 0.8. In conclusion, until further well-designed controlled studies with appropriate end points show positive results, the negative results of this study suggest that autologous PRP does not adequately treat vulvar LS.