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Platelet-Rich Plasma in the Treatment of Alopecia Areata: A Review

      Platelet-rich plasma (PRP) is an autologous preparation of plasma with concentrated platelets containing various growth factors and cytokines that enhance the body’s inherent capacity to repair and regenerate hair follicles. A few studies and case reports support the use of PRP for the treatment of alopecia areata (AA). Further large-scale studies are needed to evaluate the efficacy of PRP as monotherapy or in association with other therapeutic modalities for AA. Although PRP is relatively safe and potentially effective, there is no standardized protocol or recommendations for the number of PRP sessions required to treat and maintain hair growth.

      Abbreviations:

      AA (alopecia areata), AT (alopecia totalis), AU (alopecia universalis), FGF (fibroblast growth factor), PRP (platelet-rich plasma), TAC (triamcinolone acetonide)

      Introduction

      Alopecia areata (AA) causes nonscarring alopecia through an autoimmune mechanism targeting the hair follicles. The estimated lifetime incidence of AA is around 2%, with no difference in incidence between genders (
      • Fricke A.C.V.
      • Miteva M.
      Epidemiology and burden of alopecia areata: a systematic review.
      ,
      • Mirzoyev S.A.
      • Schrum A.G.
      • Davis M.D.P.
      • Torgerson R.R.
      Lifetime incidence risk of alopecia areata estimated at 2.1% by Rochester Epidemiology Project, 1990–2009.
      ). AA has an unpredictable course, with 34–50% of patients recovering within 1 year, and 14–25% of patients progressing to alopecia totalis (AT) or alopecia universalis (AU) (
      • Gip L.
      • Lodin A.
      • Molin L.
      Alopecia areata. A follow-up investigation of outpatient material.
      ,
      • Tosti A.
      • Bellavista S.
      • Iorizzo M.
      Alopecia areata: a long term follow-up study of 191 patients.
      ). Approximately 24.2% of patients with AT and/or AU reported hair regrowth ≥90% over 10 years (
      • Jang Y.H.
      • Hong N.S.
      • Moon S.Y.
      • Eun D.H.
      • Lee W.K.
      • Chi S.G.
      • et al.
      Long-term prognosis of alopecia totalis and alopecia universalis: a longitudinal study with more than 10 years of follow-up: better than reported.
      ). Poor prognostic factors include the onset of AA at a younger age, family history of AA, history of atopy, ophiasis type, nail dystrophy, extensive hair loss, or the presence of other autoimmune diseases (
      • Madani S.
      • Shapiro J.
      Alopecia areata update.
      ). Treatment of AA is challenging, and hair loss may remit naturally, although spontaneous hair regrowth may take months to years (
      • Pratt C.H.
      • King Jr., L.E.
      • Messenger A.G.
      • Christiano A.M.
      • Sundberg J.P.
      Alopecia areata.
      ). Traditional therapeutic modalities include corticosteroids, immunosuppressants, topical immunotherapy, and light therapy (
      • Pratt C.H.
      • King Jr., L.E.
      • Messenger A.G.
      • Christiano A.M.
      • Sundberg J.P.
      Alopecia areata.
      ;
      • Park K.Y.
      • Jang W.S.
      • Son I.P.
      • Choi S.Y.
      • Lee M.Y.
      • Kim B.J.
      • et al.
      Combination therapy with cyclosporine and psoralen plus ultraviolet a in the patients with severe alopecia areata: a retrospective study with a self-controlled design.
      ). Several new treatments are under investigation, including IL-2 agonist, IL-17 inhibitors, abatacept, Jak inhibitors, and platelet-rich plasma (PRP) (
      • Darwin E.
      • Hirt P.A.
      • Fertig R.
      • Doliner B.
      • Delcanto G.
      • Jimenez J.J.
      Alopecia areata: review of epidemiology, clinical features, pathogenesis, and new treatment options.
      ). Although an IL-4 receptor antagonist has been reported to induce AA (
      • Flanagan K.
      • Sperling L.
      • Lin J.
      Drug-induced alopecia after dupilumab therapy.
      ,
      • Mitchell K.
      • Levitt J.
      Alopecia areata after dupilumab for atopic dermatitis.
      ), it also showed efficacy in treating AA (
      • Barroso-García B.
      • Rial M.J.
      • Molina A.
      • Sastre J.
      Alopecia areata in severe atopic dermatitis treated with dupilumab.
      ,
      • Darrigade A.S.
      • Legrand A.
      • Andreu N.
      • Jacquemin C.
      • Boniface K.
      • Taïeb A.
      • et al.
      Dual efficacy of dupilumab in a patient with concomitant atopic dermatitis and alopecia areata.
      ,
      • Penzi L.R.
      • Yasuda M.
      • Manatis-Lornell A.
      • Hagigeorges D.
      • Senna M.M.
      Hair regrowth in a patient with long-standing alopecia totalis and atopic dermatitis treated with dupilumab.
      ).
      PRP was introduced to the medical field as a possible hemostatic agent used in surgery and for chronic nonhealing wounds (
      • Cieslik-Bielecka A.
      • Choukroun J.
      • Odin G.
      • Dohan Ehrenfest D.M.
      L-PRP/L-PRF in esthetic plastic surgery, regenerative medicine of the skin and chronic wounds.
      ,
      • DelRossi A.J.
      • Cernaianu A.C.
      • Vertrees R.A.
      • Wacker C.J.
      • Fuller S.J.
      • Cilley Jr., J.H.
      • et al.
      Platelet-rich plasma reduces postoperative blood loss after cardiopulmonary bypass.
      ). After that, PRP gained attention in other areas, including plastic surgery, orthopedics, and maxillofacial surgery for its usage in the wound healing process and tissue repair (
      • Albanese A.
      • Licata M.E.
      • Polizzi B.
      • Campisi G.
      Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration.
      ). Recently, new indications for PRP have been developed in dermatology, including scar revision, skin rejuvenation, wound healing, and striae distensae (
      • Arshdeep
      • Kumaran M.S.
      Platelet-rich plasma in dermatology: boon or a bane?.
      ). Moreover, PRP has been implemented to regrow hairs in treating androgenetic alopecia and AA and to boost graft survival in hair transplantation (
      • Schiavone G.
      • Raskovic D.
      • Greco J.
      • Abeni D.
      Platelet-rich plasma for androgenetic alopecia: a pilot study.
      ). This review summarizes the efficacy, safety, and mechanism of action of PRP injections in treating AA.

      PRP Mechanism of Action and Preparation

      PRP is an emerging technology that uses an autologous preparation of plasma with concentrated platelets to stimulate hair growth. PRP is composed of several growth factors and cytokines that stimulate hair follicle repair and regeneration (
      • Dhillon R.S.
      • Schwarz E.M.
      • Maloney M.D.
      Platelet-rich plasma therapy - future or trend?.
      ,
      • Marwah M.
      • Godse K.
      • Patil S.
      • Nadkarni N.
      Is there sufficient research data to use platelet-rich plasma in dermatology?.
      ). Recent evidence suggests that PRP may positively impact wound repair, angiogenesis, cellular differentiation, and the proliferation of adipose precursor cells (
      • Marwah M.
      • Godse K.
      • Patil S.
      • Nadkarni N.
      Is there sufficient research data to use platelet-rich plasma in dermatology?.
      ). The efficacy of PRP as adjuvant therapy for nonscarring alopecias is supported by the literature (
      • Aasly J.
      • Anke I.M.
      Erfaringer med poliklinisk radikulografi [Experiences with ambulatory radiculography].
      ,
      • El Taieb M.A.
      • Ibrahim H.
      • Nada E.A.
      • Seif Al-Din M.
      Platelets rich plasma versus minoxidil 5% in treatment of alopecia areata: a trichoscopic evaluation.
      ,
      • Trink A.
      • Sorbellini E.
      • Bezzola P.
      • Rodella L.
      • Rezzani R.
      • Ramot Y.
      • et al.
      A randomized, double-blind, placebo- and active-controlled, half-head study to evaluate the effects of platelet-rich plasma on alopecia areata.
      ).
      PRP consists of over 20 growth factors secreted by a high concentration of platelets. Hair regrowth is stimulated by these growth factors, which include PGDF, VEGF, TGF, fibroblast growth factor (FGF), connective tissue growth factor, EGF, and IGF-1 (
      • Akiyama M.
      • Smith L.T.
      • Holbrook K.A.
      Growth factor and growth factor receptor localization in the hair follicle bulge and associated tissue in human fetus.
      ). These growth factors bind to the corresponding receptors expressed by stem cells in the hair follicle bulge and surrounding tissues. Ligand binding stimulates the proliferation phase of the hair follicle, giving rise to the anagen follicular unit and promoting hair growth (
      • Akiyama M.
      • Smith L.T.
      • Holbrook K.A.
      Growth factor and growth factor receptor localization in the hair follicle bulge and associated tissue in human fetus.
      ,
      • Gkini M.A.
      • Kouskoukis A.E.
      • Tripsianis G.
      • Rigopoulos D.
      • Kouskoukis K.
      Study of platelet-rich plasma injections in the treatment of androgenetic alopecia through an one-year period.
      ). In addition, the growth factors in PRP initiate pathways, which cause angiogenesis and the development of adnexal structures. Anagen-associated angiogenesis has been linked to VEGF secreted by keratinocytes located in the outer root sheath and fibroblasts of the dermal papilla (
      • Cervelli V.
      • Garcovich S.
      • Bielli A.
      • Cervelli G.
      • Curcio B.C.
      • Scioli M.G.
      • et al.
      The effect of autologous activated platelet rich plasma (AA-PRP) injection on pattern hair loss: clinical and histomorphometric evaluation.
      ).
      • Li Z.J.
      • Choi H.I.
      • Choi D.K.
      • Sohn K.C.
      • Im M.
      • Seo Y.J.
      • et al.
      Autologous platelet-rich plasma: a potential therapeutic tool for promoting hair growth.
      demonstrated that in vitro, PRP affects the dermal papilla cells by increasing cell proliferation, increasing the phosphorylation of extracellular signal-regulated kinases and Akt, increasing Bcl-2 expression, increasing β-catenin activity, and increasing FGF-7 expression. The activation of extracellular signal-regulated kinases is associated with promoting cell growth, whereas Akt activation promotes cell survival and inhibits apoptosis. In addition, Bcl-2 is involved in the inhibition of apoptosis (
      • Schenk R.L.
      • Strasser A.
      • Dewson G.
      BCL-2: long and winding path from discovery to therapeutic target.
      ). β-catenin has an important role in the formation of hair placodes and the differentiation of stem cells into hair follicle cells (
      • Sohn K.C.
      • Shi G.
      • Jang S.
      • Choi D.K.
      • Lee Y.
      • Yoon T.J.
      • et al.
      Pitx2, a beta-catenin-regulated transcription factor, regulates the differentiation of outer root sheath cells cultured in vitro.
      ), supporting the theory that PRP contributes to hair growth by inducing the differentiation of stem cells to hair follicle cells. β-catenin is also involved in signaling for melanocyte differentiation (
      • Luciani F.
      • Champeval D.
      • Herbette A.
      • Denat L.
      • Aylaj B.
      • Martinozzi S.
      • et al.
      Biological and mathematical modeling of melanocyte development.
      ). FGF-7 contributes to hair growth by prolonging the anagen phase and delaying entry to the catagen phase (
      • Danilenko D.M.
      • Ring B.D.
      • Yanagihara D.
      • Benson W.
      • Wiemann B.
      • Starnes C.O.
      • et al.
      Keratinocyte growth factor is an important endogenous mediator of hair follicle growth, development, and differentiation. Normalization of the nu/nu follicular differentiation defect and amelioration of chemotherapy-induced alopecia.
      ). Related to FGF-7, basic FGF (also called FGF-2) is present in PRP (
      • Krüger J.P.
      • Freymannx U.
      • Vetterlein S.
      • Neumann K.
      • Endres M.
      • Kaps C.
      Bioactive factors in platelet-rich plasma obtained by apheresis.
      ); basic FGF promotes melanin synthesis by melanocytes (
      • Puri N.
      • van der Weel M.B.
      • de Wit F.S.
      • Asghar S.S.
      • Das P.K.
      • Ramaiah A.
      • et al.
      Basic fibroblast growth factor promotes melanin synthesis by melanocytes.
      ). The effects of β-catenin and basic FGF on melanocyte differentiation and melanin synthesis may contribute to the ability of PRP to promote the growth of pigmented hairs in AA. Ki-67, a marker of cellular proliferation, is present in significantly higher levels in hair taken from patients treated with PRP (
      • Trink A.
      • Sorbellini E.
      • Bezzola P.
      • Rodella L.
      • Rezzani R.
      • Ramot Y.
      • et al.
      A randomized, double-blind, placebo- and active-controlled, half-head study to evaluate the effects of platelet-rich plasma on alopecia areata.
      ).
      PRP may also be effective in AA through anti-inflammatory mechanisms owing to its ability to suppress MCP-1, and owing to the presence of TGFβ (β1 and β2) (
      • Amable P.R.
      • Carias R.B.
      • Teixeira M.V.
      • da Cruz Pacheco I.
      • Corrêa do Amaral R.J.
      • Granjeiro J.M.
      • et al.
      Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors.
      ,
      • El-Sharkawy H.
      • Kantarci A.
      • Deady J.
      • Hasturk H.
      • Liu H.
      • Alshahat M.
      • et al.
      Platelet-rich plasma: growth factors and pro- and anti-inflammatory properties.
      ). MCP-1 is a chemotactic cytokine involved in monocyte and T lymphocyte recruitment (
      • Noris M.
      • Bernasconi S.
      • Casiraghi F.
      • Sozzani S.
      • Gotti E.
      • Remuzzi G.
      • et al.
      Monocyte chemoattractant protein-1 is excreted in excessive amounts in the urine of patients with lupus nephritis.
      ). Moderate expression of MCP-1 in the hair bulb is associated with AA, which is hypothesized to play a role in the pathogenesis of AA by recruiting T lymphocytes and monocytes to the hair bulb, resulting in a local inflammatory reaction around the hair bulb (
      • Benoit S.
      • Toksoy A.
      • Goebeler M.
      • Gillitzer R.
      Selective expression of chemokine monokine induced by interferon-gamma in alopecia areata.
      ). TGFβ is a known immune modulator, which inhibits T lymphocyte proliferation (
      • Kehrl J.H.
      • Wakefield L.M.
      • Roberts A.B.
      • Jakowlew S.
      • Alvarez-Mon M.
      • Derynck R.
      • et al.
      Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.
      ). Levels of TGFβ1 in the serum were found to be significantly reduced in patients with AA (
      • Tembhre M.K.
      • Sharma V.K.
      T-helper and regulatory T-cell cytokines in the peripheral blood of patients with active alopecia areata.
      ). The hair follicle locally produces TGFβ1, whose immunosuppressant action acts with other mechanisms to create a local “immune privileged” environment, the disruption of which is hypothesized to contribute to the pathogenesis of AA (
      • Paus R.
      • Ito N.
      • Takigawa M.
      • Ito T.
      The hair follicle and immune privilege.
      ).
      No consensus exists for the standardized protocol of the PRP preparation and procedure. Many techniques have been described, and several PRP systems are commercially marketed. Currently, there is no evidence-based information comparing the protocol of administration, the frequency of injections, or the number of treatment sessions (
      • Maria-Angeliki G.
      • Alexandros-Efstratios K.
      • Dimitris R.
      • Konstantinos K.
      Platelet-rich plasma as a potential treatment for noncicatricial alopecias.
      ). Generally, 8–60 ml of fresh venous blood is collected from an individual subject, and the blood sample undergoes centrifugation. The centrifuge separates the red blood cells from lighter plasma with a buffy coat at the interface. After that, the plasma and buffy coat are aspirated (
      • Lynch M.D.
      • Bashir S.
      Applications of platelet-rich plasma in dermatology: a critical appraisal of the literature.
      ). Protocols yield an increase in the concentration of platelet ranging from three to 8-fold (
      • Trink A.
      • Sorbellini E.
      • Bezzola P.
      • Rodella L.
      • Rezzani R.
      • Ramot Y.
      • et al.
      A randomized, double-blind, placebo- and active-controlled, half-head study to evaluate the effects of platelet-rich plasma on alopecia areata.
      ,
      • Eppley B.L.
      • Woodell J.E.
      • Higgins J.
      Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing.
      ). A review of the literature has revealed that seven studies showed preliminary evidence for the potential effect of PRP in treating AA.

      PRP in the Treatment of AA

      Overview

      • El Taieb M.A.
      • Ibrahim H.
      • Nada E.A.
      • Seif Al-Din M.
      Platelets rich plasma versus minoxidil 5% in treatment of alopecia areata: a trichoscopic evaluation.
      and
      • Trink A.
      • Sorbellini E.
      • Bezzola P.
      • Rodella L.
      • Rezzani R.
      • Ramot Y.
      • et al.
      A randomized, double-blind, placebo- and active-controlled, half-head study to evaluate the effects of platelet-rich plasma on alopecia areata.
      conducted high quality randomized, placebo-controlled trials that showed significant improvement of AA after PRP treatment compared with placebo, providing particularly strong evidence of the efficacy of PRP in the treatment of AA. Two nonrandomized trials showed improvement in hair regrowth with PRP treatment (
      • Shumez H.
      • Prasad P.V.S.
      • Kaviarasan P.K.
      • Deepika R.
      Intralesional platelet rich plasma vs intralesional triamcinolone in the treatment of alopecia areata: a comparative study.
      ,
      • Singh S.
      Role of platelet-rich plasma in chronic alopecia areata: our centre experience.
      ). In addition, two case reports support the efficacy of PRP (
      • Donovan J.
      Successful treatment of corticosteroid-resistant ophiasis-type alopecia areata (AA) with platelet-rich plasma (PRP).
      ,
      • Mubki T.
      Platelet-rich plasma combined with intralesional triamcinolone acetonide for the treatment of alopecia areata: a case report.
      ). A case series showed some improvement in regrowth with PRP treatment, though regrowth was not maintained at further follow-up (
      • d’Ovidio R.
      • Roberto M.
      Limited effectiveness of platelet-rich-plasma treatment on chronic severe alopecia areata.
      ).

      Randomized, Placebo-controlled clinical trials

      • Trink A.
      • Sorbellini E.
      • Bezzola P.
      • Rodella L.
      • Rezzani R.
      • Ramot Y.
      • et al.
      A randomized, double-blind, placebo- and active-controlled, half-head study to evaluate the effects of platelet-rich plasma on alopecia areata.
      conducted a randomized, double-blind, placebo-, and active-controlled, half-head parallel-group study to evaluate the efficacy and safety of PRP on AA. A total of 45 subjects were randomized to one of three groups: PRP, triamcinolone acetonide (TAC, 2.5 mg/cm3), or placebo. Three treatments with a 1-month interval were administered. All subjects were evaluated at baseline, 2 months, 6 months, and 12 months. The results of the study revealed that intralesional TAC and PRP resulted in significant hair regrowth in AA lesions compared with placebo or to baseline. Results were sustained at a 1-year follow-up. PRP and TAC decreased the number of dystrophic hairs as evaluated by dermoscopic findings and also minimized the itching or burning sensation of treatment. Nonetheless, PRP revealed significantly better dermoscopy results than having intralesional TAC. This study supports the use of PRP in AA to stimulate hair regrowth, especially of pigmented hairs, with a lower chance of relapse. Of note, the method of centrifugation that has been used in this study produced a platelet count that was, on average, 3.5 times higher than whole blood. No adverse effects were noted with PRP, TAC, or placebo administration (
      • Trink A.
      • Sorbellini E.
      • Bezzola P.
      • Rodella L.
      • Rezzani R.
      • Ramot Y.
      • et al.
      A randomized, double-blind, placebo- and active-controlled, half-head study to evaluate the effects of platelet-rich plasma on alopecia areata.
      ).
      • El Taieb M.A.
      • Ibrahim H.
      • Nada E.A.
      • Seif Al-Din M.
      Platelets rich plasma versus minoxidil 5% in treatment of alopecia areata: a trichoscopic evaluation.
      conducted a randomized controlled study to investigate the efficacy of PRP in treating AA. A total of 90 patients with patchy AA and/or AT and/or AU were included with ages between 10 and 40 years, with no therapy for at least 3 months before the study. Patients were randomized into three groups, each of which included 30 patients. The first group was treated with topical minoxidil 5% twice daily (six pubs per time) as a monotherapy. The second group was treated with three PRP treatment sessions every 4 weeks. The third group received topical panthenol cream twice daily as a placebo. Digital photography and dermoscopic examination were done before treatment and monthly after treatment for 3 months. For PRP preparation, 10 ml of blood was drawn from each patient and placed in two test tubes as 5 ml each. The collected blood was centrifuged at 3,000 r.p.m. for 10 minutes, and blood was separated into an inferior red phase and superior plasma supernatant phase. The PRP fraction was separated and suspended with calcium gluconate. The total volume of collected PRP was about 4 ml. Significant hair regrowth was noticed in patchy AA (70%) and AU (30%) after three sessions of PRP; however, AT did not respond to PRP. PRP led to significant, fully pigmented hair growth in AA lesions. Short vellus hair and yellow dots were significantly decreased after PRP treatment. Minoxidil group showed improvement of patchy AA (81%) more than AT and/or AU. Only 30% of patients in the control group experienced a significant hair growth of patchy AA type. Although both PRP and minoxidil 5% showed a significant increase in hair growth, subjects treated with PRP exhibited a significant decrease in short vellus hair, unlike patients treated with minoxidil and control who showed a significant increase in short vellus hair. Participants who underwent PRP treatments had better and an earlier response than participants treated with minoxidil 5% in terms of hair regrowth, reduction of short vellus hair, broken hairs, and yellow dots (
      • El Taieb M.A.
      • Ibrahim H.
      • Nada E.A.
      • Seif Al-Din M.
      Platelets rich plasma versus minoxidil 5% in treatment of alopecia areata: a trichoscopic evaluation.
      ).

      Nonrandomized clinical trials

      • Shumez H.
      • Prasad P.V.S.
      • Kaviarasan P.K.
      • Deepika R.
      Intralesional platelet rich plasma vs intralesional triamcinolone in the treatment of alopecia areata: a comparative study.
      conducted a nonrandomized controlled study on 74 patients with AA (excluding AA with more than 25% involvement). Subjects were divided into two groups; the first group involved 48 participants who received TAC 10 mg/ml, and the second group included 26 patients that underwent PRP injections. PRP was prepared with a double centrifugation technique, where 20 ml of whole blood was drawn and centrifugated at 5,000 r.p.m. for 15 minutes. PRP was separated, and the residual plasma above the buffy coat was centrifugated again at 2,000 r.p.m. for 5–10 minutes. This soft spin collects the residual PRP. Calcium chloride (10%) was added as an activator (0.3 ml for 1 ml PRP). Three sessions were performed to each patient at 3-week intervals. Patients were evaluated at 3 months by “assessment of overall improvement” scale, serial photographs, and dermoscopic examination. The results showed a remission rate of 52.8% and 35.4% in PRP and TAC, respectively, at week 6. However, this difference was statistically insignificant (P = 0.597). The overall improvement at week 9 and week 12 showed complete hair regrowth of all patients in both groups (
      • Shumez H.
      • Prasad P.V.S.
      • Kaviarasan P.K.
      • Deepika R.
      Intralesional platelet rich plasma vs intralesional triamcinolone in the treatment of alopecia areata: a comparative study.
      ).
      A prospective study was carried out to evaluate the efficacy of PRP in AA. A total of 20 patients with AA were enrolled in this study. A total of 25 ml of peripheral blood was drawn, then PRP was separated and injected in the subfollicular plane. All patients received six sessions at 4-week intervals. The subjects were evaluated at 6 months and 1 year. The results revealed that good hair regrowth was noticed by most of the participants except for one patient who had a relapse and minimal hair regrowth. None of the patients developed serious side effects (
      • Singh S.
      Role of platelet-rich plasma in chronic alopecia areata: our centre experience.
      ).

      Case reports and/or series

      • Donovan J.
      Successful treatment of corticosteroid-resistant ophiasis-type alopecia areata (AA) with platelet-rich plasma (PRP).
      reported a case of a 41-year-old woman with AA (ophiasis type) for 2 years that had failed intralesional TAC. Treatment was performed with autologous PRP (anthrax angel system) after drawing 120 ml from the patient’s blood and processing it according to the manufacturer’s instructions. PRP was mixed with platelet-poor plasma to achieve a final platelet concentration of 3.5 times above baseline. A total of 9 ml of PRP was injected into the patient’s occipital area. Mild tenderness was controlled with acetaminophen on the procedure day and the following 2 days. The patient experienced that hair regrowth started 1 month after the procedure with minimal side effects (
      • Donovan J.
      Successful treatment of corticosteroid-resistant ophiasis-type alopecia areata (AA) with platelet-rich plasma (PRP).
      ).
      Another case report supports the positive effect of PRP, where
      • Mubki T.
      Platelet-rich plasma combined with intralesional triamcinolone acetonide for the treatment of alopecia areata: a case report.
      used a combination of PRP and intralesional TAC on half of the scalp of a patient with long-standing AA and intralesional TAC alone in the other half of the scalp. The right side of the scalp was treated with both intralesional TAC (2.5 mg/ml a total of 4 ml) and intradermal injections of PRP (2–3 ml), and the left half of the scalp was treated with intralesional TAC only (2.5 mg/ml a total of 4 ml). Eight sessions were performed on the right scalp over 16 weeks (four sets of PRP alternating with four sessions of intralesional TAC at 2 weeks interval), whereas four treatment sessions were performed on the left side of the scalp with intralesional TAC only. Regarding the PRP preparation, 18 ml of whole blood was drawn from the patient in vacutainers (Pure PRP System, Seoul, Korea) containing ACD-A (trisodium citrate, citric acid, and dextrose). The tube was centrifuged at 1,500 g for 4 minutes. The PRP fraction was separated and suspended with calcium chloride. Assessment of hair regrowth was carried out by using global photography and digital trichoscopy. Two square areas were anatomically marked, each measuring 1 cm × 1 cm over both right and left parietal scalp located at the midpupillary line, 10 cm proximal to the corresponding eyebrow. The patient’s response was assessed at baseline and 2 weeks after the last treatment. Both treatment modalities showed an increase in terminal hair number (16% for PRP and TAC combination vs. 12% for TAC alone). There was an increase in mean hair shaft diameter (+35%) with combination therapy and a decline (−4%) with TAC monotherapy. (
      • Mubki T.
      Platelet-rich plasma combined with intralesional triamcinolone acetonide for the treatment of alopecia areata: a case report.
      ).
      In Contrast,
      • d’Ovidio R.
      • Roberto M.
      Limited effectiveness of platelet-rich-plasma treatment on chronic severe alopecia areata.
      reported a case series of nine patients with chronic AA (> 50 of the scalp involved) who received PRP. The patients underwent three treatment sessions with a 45–60 days interval. The protocol for PRP preparation was similar to the study of
      • Trink A.
      • Sorbellini E.
      • Bezzola P.
      • Rodella L.
      • Rezzani R.
      • Ramot Y.
      • et al.
      A randomized, double-blind, placebo- and active-controlled, half-head study to evaluate the effects of platelet-rich plasma on alopecia areata.
      . The platelet concentration was about 3–4 times higher than the quantity found in the blood. A total of 2–4 ml PRP was injected intradermally. The patients were evaluated at baseline, 8 months, and 1 year. In the eighth month, six subjects had obtained regrowth of terminal pigmented hair, and the others noted nonpigmented vellus hairs in the seats of infiltration after the second session of PRP infusion. At an average follow-up of 1 year, none of the patients still had the hair regrown (
      • d’Ovidio R.
      • Roberto M.
      Limited effectiveness of platelet-rich-plasma treatment on chronic severe alopecia areata.
      ).

      Adverse effects

      The PRP procedure is a relatively effective and safe intervention with minimal adverse effects, including temporary and tolerable pain during treatment, mild headache which may regress with acetaminophen, minimal itching, transient erythema and edema, and desquamation (
      • Alves R.
      • Grimalt R.
      Randomized placebo-controlled, double-blind, half-head study to assess the efficacy of platelet-rich plasma on the treatment of androgenetic alopecia.
      ,
      • Anitua E.
      • Pino A.
      • Martinez N.
      • Orive G.
      • Berridi D.
      The effect of plasma rich in growth factors on pattern hair loss: a pilot study.
      ,
      • Gentile P.
      • Garcovich S.
      • Bielli A.
      • Scioli M.G.
      • Orlandi A.
      • Cervelli V.
      The effect of platelet-rich plasma in hair regrowth: a randomized placebo-controlled trial.
      ,
      • Gkini M.A.
      • Kouskoukis A.E.
      • Tripsianis G.
      • Rigopoulos D.
      • Kouskoukis K.
      Study of platelet-rich plasma injections in the treatment of androgenetic alopecia through an one-year period.
      ,
      • Kachhawa D.
      • Vats G.
      • Sonare D.
      • Rao P.
      • Khuraiya S.
      • Kataiya R.
      A spilt head study of efficacy of placebo versus platelet-rich plasma injections in the treatment of androgenic alopecia.
      ,
      • Kang J.S.
      • Zheng Z.
      • Choi M.J.
      • Lee S.H.
      • Kim D.Y.
      • Cho S.B.
      The effect of CD34+ cell-containing autologous platelet-rich plasma injection on pattern hair loss: a preliminary study.
      ,
      • Khatu S.S.
      • More Y.E.
      • Gokhale N.R.
      • Chavhan D.C.
      • Bendsure N.
      Platelet-rich plasma in androgenic alopecia: myth or an effective tool.
      ,
      • Singhal P.
      • Agarwal S.
      • Dhot P.S.
      • Sayal S.K.
      Efficacy of platelet-rich plasma in treatment of androgenic alopecia.
      ). An unpublished anecdotal report of three patients who developed telogen effluvium with psoriasiform scalp dermatitis 2–6 weeks after being treated with PRP was seen by Dr Tosti (
      • de Sousa I.C.V.D.
      • Tosti A.
      New investigational drugs for androgenetic alopecia.
      ). To date, there are no reports of infections, folliculitis, panniculitis, hematoma, or seroma formation (
      • Badran K.W.
      • Sand J.P.
      Platelet-rich plasma for hair loss: review of methods and results.
      ). Patients who received PRP in the
      • Trink A.
      • Sorbellini E.
      • Bezzola P.
      • Rodella L.
      • Rezzani R.
      • Ramot Y.
      • et al.
      A randomized, double-blind, placebo- and active-controlled, half-head study to evaluate the effects of platelet-rich plasma on alopecia areata.
      study demonstrated the reduction of burning and itching compared with baseline. Contraindications to PRP procedure include platelet dysfunction, thrombocytopenia, coagulation disorders, anticoagulant therapy, hepatitis, hemodynamic instability, local infection at the site of blood harvest or PRP injection, and patients who are prone to keloid formation (
      • Badran K.W.
      • Sand J.P.
      Platelet-rich plasma for hair loss: review of methods and results.
      ).

      Conclusion

      There is initial supporting evidence to use PRP for the treatment of AA; however, the lack of standardized protocol precludes any recommendations for the number of PRP sessions required to treat AA. PRP is relatively safe and potentially effective for the regrowth of pigmented hairs in AA. Further large-scale studies are needed to evaluate the efficacy of the PRP procedure as monotherapy and whether it is superior over current therapeutic modalities for AA.

      Conflict of Interest

      AT is a consultant for P&G, DS Laboratories, Monat, Pfizer, Thirty Madison, and Almirall, Principal Investigator for Incyte, Pfizer, Aclaris, Eli Lilly, and Nutrifol and serves on the advisory board of Leo Pharma. HMA, AAA, and JWG state no conflict of interest.

      Acknowledgments

      This article is published as part of a supplement sponsored by the National Alopecia Areata Foundation .
      Funding for the Summit and publication of this supplement was provided by the National Alopecia Areata Foundation. This Summit was supported (in part) by the National Institute of Arthritis and Musculoskeletal and Skin Diseases under award number R13AR074890 . The opinions or views expressed in this professional supplement are those of the authors and do not necessarily reflect the official views, opinions, or recommendations of the National Institutes of Health or the National Alopecia Areata Foundation.

      Author Contributions

      Writing - Original Draft Preparation: HMA, AAA, JWG; Writing - Review and Editing: AT

      References

        • Aasly J.
        • Anke I.M.
        Erfaringer med poliklinisk radikulografi [Experiences with ambulatory radiculography].
        Tidsskr Nor Laegeforen. 1989; 109 ([in Norwegian]): 951-952
        • Akiyama M.
        • Smith L.T.
        • Holbrook K.A.
        Growth factor and growth factor receptor localization in the hair follicle bulge and associated tissue in human fetus.
        J Invest Dermatol. 1996; 106: 391-396
        • Albanese A.
        • Licata M.E.
        • Polizzi B.
        • Campisi G.
        Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration.
        Immun Ageing. 2013; 10: 23
        • Alves R.
        • Grimalt R.
        Randomized placebo-controlled, double-blind, half-head study to assess the efficacy of platelet-rich plasma on the treatment of androgenetic alopecia.
        Dermatol Surg. 2016; 42: 491-497
        • Amable P.R.
        • Carias R.B.
        • Teixeira M.V.
        • da Cruz Pacheco I.
        • Corrêa do Amaral R.J.
        • Granjeiro J.M.
        • et al.
        Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors.
        Stem Cell Res Ther. 2013; 4: 67
        • Anitua E.
        • Pino A.
        • Martinez N.
        • Orive G.
        • Berridi D.
        The effect of plasma rich in growth factors on pattern hair loss: a pilot study.
        Dermatol Surg. 2017; 43: 658-670
        • Arshdeep
        • Kumaran M.S.
        Platelet-rich plasma in dermatology: boon or a bane?.
        Indian J Dermatol Venereol Leprol. 2014; 80: 5-14
        • Badran K.W.
        • Sand J.P.
        Platelet-rich plasma for hair loss: review of methods and results.
        Facial Plast Surg Clin North Am. 2018; 26: 469-485
        • Barroso-García B.
        • Rial M.J.
        • Molina A.
        • Sastre J.
        Alopecia areata in severe atopic dermatitis treated with dupilumab.
        J Investig Allergol Clin Immunol. 2018; 28: 420-421
        • Benoit S.
        • Toksoy A.
        • Goebeler M.
        • Gillitzer R.
        Selective expression of chemokine monokine induced by interferon-gamma in alopecia areata.
        J Invest Dermatol. 2003; 121: 933-935
        • Cervelli V.
        • Garcovich S.
        • Bielli A.
        • Cervelli G.
        • Curcio B.C.
        • Scioli M.G.
        • et al.
        The effect of autologous activated platelet rich plasma (AA-PRP) injection on pattern hair loss: clinical and histomorphometric evaluation.
        Biomed Res Int. 2014; 2014: 760709
        • Cieslik-Bielecka A.
        • Choukroun J.
        • Odin G.
        • Dohan Ehrenfest D.M.
        L-PRP/L-PRF in esthetic plastic surgery, regenerative medicine of the skin and chronic wounds.
        Curr Pharm Biotechnol. 2012; 13: 1266-1277
        • Danilenko D.M.
        • Ring B.D.
        • Yanagihara D.
        • Benson W.
        • Wiemann B.
        • Starnes C.O.
        • et al.
        Keratinocyte growth factor is an important endogenous mediator of hair follicle growth, development, and differentiation. Normalization of the nu/nu follicular differentiation defect and amelioration of chemotherapy-induced alopecia.
        Am J Pathol. 1995; 147: 145-154
        • Darrigade A.S.
        • Legrand A.
        • Andreu N.
        • Jacquemin C.
        • Boniface K.
        • Taïeb A.
        • et al.
        Dual efficacy of dupilumab in a patient with concomitant atopic dermatitis and alopecia areata.
        Br J Dermatol. 2018; 179: 534-536
        • Darwin E.
        • Hirt P.A.
        • Fertig R.
        • Doliner B.
        • Delcanto G.
        • Jimenez J.J.
        Alopecia areata: review of epidemiology, clinical features, pathogenesis, and new treatment options.
        Int J Trichology. 2018; 10: 51-60
        • de Sousa I.C.V.D.
        • Tosti A.
        New investigational drugs for androgenetic alopecia.
        Expert Opin Investig Drugs. 2013; 22: 573-589
        • DelRossi A.J.
        • Cernaianu A.C.
        • Vertrees R.A.
        • Wacker C.J.
        • Fuller S.J.
        • Cilley Jr., J.H.
        • et al.
        Platelet-rich plasma reduces postoperative blood loss after cardiopulmonary bypass.
        J Thorac Cardiovasc Surg. 1990; 100: 281-286
        • Dhillon R.S.
        • Schwarz E.M.
        • Maloney M.D.
        Platelet-rich plasma therapy - future or trend?.
        Arthritis Res Ther. 2012; 14: 219
        • Donovan J.
        Successful treatment of corticosteroid-resistant ophiasis-type alopecia areata (AA) with platelet-rich plasma (PRP).
        JAAD Case Rep. 2015; 1: 305-307
        • d’Ovidio R.
        • Roberto M.
        Limited effectiveness of platelet-rich-plasma treatment on chronic severe alopecia areata.
        Hair Ther Transplant. 2014; 4: 116
        • El Taieb M.A.
        • Ibrahim H.
        • Nada E.A.
        • Seif Al-Din M.
        Platelets rich plasma versus minoxidil 5% in treatment of alopecia areata: a trichoscopic evaluation.
        Dermatol Ther. 2017; 30: e12437
        • El-Sharkawy H.
        • Kantarci A.
        • Deady J.
        • Hasturk H.
        • Liu H.
        • Alshahat M.
        • et al.
        Platelet-rich plasma: growth factors and pro- and anti-inflammatory properties.
        J Periodontol. 2007; 78: 661-669
        • Eppley B.L.
        • Woodell J.E.
        • Higgins J.
        Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing.
        Plast Reconstr Surg. 2004; 114: 1502-1508
        • Flanagan K.
        • Sperling L.
        • Lin J.
        Drug-induced alopecia after dupilumab therapy.
        JAAD Case Rep. 2019; 5: 54-56
        • Fricke A.C.V.
        • Miteva M.
        Epidemiology and burden of alopecia areata: a systematic review.
        Clin Cosmet Investig Dermatol. 2015; 8: 397-403
        • Gentile P.
        • Garcovich S.
        • Bielli A.
        • Scioli M.G.
        • Orlandi A.
        • Cervelli V.
        The effect of platelet-rich plasma in hair regrowth: a randomized placebo-controlled trial.
        Stem Cells Transl Med. 2015; 4: 1317-1323
        • Gip L.
        • Lodin A.
        • Molin L.
        Alopecia areata. A follow-up investigation of outpatient material.
        Acta Derm Venereol. 1969; 49: 180-188
        • Gkini M.A.
        • Kouskoukis A.E.
        • Tripsianis G.
        • Rigopoulos D.
        • Kouskoukis K.
        Study of platelet-rich plasma injections in the treatment of androgenetic alopecia through an one-year period.
        J Cutan Aesthet Surg. 2014; 7: 213-219
        • Jang Y.H.
        • Hong N.S.
        • Moon S.Y.
        • Eun D.H.
        • Lee W.K.
        • Chi S.G.
        • et al.
        Long-term prognosis of alopecia totalis and alopecia universalis: a longitudinal study with more than 10 years of follow-up: better than reported.
        Dermatology. 2017; 233: 250-256
        • Kachhawa D.
        • Vats G.
        • Sonare D.
        • Rao P.
        • Khuraiya S.
        • Kataiya R.
        A spilt head study of efficacy of placebo versus platelet-rich plasma injections in the treatment of androgenic alopecia.
        J Cutan Aesthet Surg. 2017; 10: 86-89
        • Kang J.S.
        • Zheng Z.
        • Choi M.J.
        • Lee S.H.
        • Kim D.Y.
        • Cho S.B.
        The effect of CD34+ cell-containing autologous platelet-rich plasma injection on pattern hair loss: a preliminary study.
        J Eur Acad Dermatol Venereol. 2014; 28: 72-79
        • Kehrl J.H.
        • Wakefield L.M.
        • Roberts A.B.
        • Jakowlew S.
        • Alvarez-Mon M.
        • Derynck R.
        • et al.
        Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.
        J Exp Med. 1986; 163: 1037-1050
        • Khatu S.S.
        • More Y.E.
        • Gokhale N.R.
        • Chavhan D.C.
        • Bendsure N.
        Platelet-rich plasma in androgenic alopecia: myth or an effective tool.
        J Cutan Aesthet Surg. 2014; 7: 107-110
        • Krüger J.P.
        • Freymannx U.
        • Vetterlein S.
        • Neumann K.
        • Endres M.
        • Kaps C.
        Bioactive factors in platelet-rich plasma obtained by apheresis.
        Transfus Med Hemother. 2013; 40: 432-440
        • Li Z.J.
        • Choi H.I.
        • Choi D.K.
        • Sohn K.C.
        • Im M.
        • Seo Y.J.
        • et al.
        Autologous platelet-rich plasma: a potential therapeutic tool for promoting hair growth.
        Dermatol Surg. 2012; 38: 1040-1046
        • Luciani F.
        • Champeval D.
        • Herbette A.
        • Denat L.
        • Aylaj B.
        • Martinozzi S.
        • et al.
        Biological and mathematical modeling of melanocyte development.
        Development. 2011; 138: 3943-3954
        • Lynch M.D.
        • Bashir S.
        Applications of platelet-rich plasma in dermatology: a critical appraisal of the literature.
        J Dermatolog Treat. 2016; 27: 285-289
        • Madani S.
        • Shapiro J.
        Alopecia areata update.
        J Am Acad Dermatol. 2000; 42 ([quiz 67–70]): 549-566
        • Maria-Angeliki G.
        • Alexandros-Efstratios K.
        • Dimitris R.
        • Konstantinos K.
        Platelet-rich plasma as a potential treatment for noncicatricial alopecias.
        Int J Trichology. 2015; 7: 54-63
        • Marwah M.
        • Godse K.
        • Patil S.
        • Nadkarni N.
        Is there sufficient research data to use platelet-rich plasma in dermatology?.
        Int J Trichology. 2014; 6: 35-36
        • Mirzoyev S.A.
        • Schrum A.G.
        • Davis M.D.P.
        • Torgerson R.R.
        Lifetime incidence risk of alopecia areata estimated at 2.1% by Rochester Epidemiology Project, 1990–2009.
        J Invest Dermatol. 2014; 134: 1141-1142
        • Mitchell K.
        • Levitt J.
        Alopecia areata after dupilumab for atopic dermatitis.
        JAAD Case Rep. 2018; 4: 143-144
        • Mubki T.
        Platelet-rich plasma combined with intralesional triamcinolone acetonide for the treatment of alopecia areata: a case report.
        J Dermatol Dermatol Surg. 2016; 20: 87-90
        • Noris M.
        • Bernasconi S.
        • Casiraghi F.
        • Sozzani S.
        • Gotti E.
        • Remuzzi G.
        • et al.
        Monocyte chemoattractant protein-1 is excreted in excessive amounts in the urine of patients with lupus nephritis.
        Lab Invest. 1995; 73: 804-809
        • Park K.Y.
        • Jang W.S.
        • Son I.P.
        • Choi S.Y.
        • Lee M.Y.
        • Kim B.J.
        • et al.
        Combination therapy with cyclosporine and psoralen plus ultraviolet a in the patients with severe alopecia areata: a retrospective study with a self-controlled design.
        Ann Dermatol. 2013; 25: 12-16
        • Paus R.
        • Ito N.
        • Takigawa M.
        • Ito T.
        The hair follicle and immune privilege.
        J Investig Dermatol Symp Proc. 2003; 8: 188-194
        • Penzi L.R.
        • Yasuda M.
        • Manatis-Lornell A.
        • Hagigeorges D.
        • Senna M.M.
        Hair regrowth in a patient with long-standing alopecia totalis and atopic dermatitis treated with dupilumab.
        JAMA Dermatol. 2018; 154: 1358-1360
        • Pratt C.H.
        • King Jr., L.E.
        • Messenger A.G.
        • Christiano A.M.
        • Sundberg J.P.
        Alopecia areata.
        Nat Rev Dis Primers. 2017; 3: 17011
        • Puri N.
        • van der Weel M.B.
        • de Wit F.S.
        • Asghar S.S.
        • Das P.K.
        • Ramaiah A.
        • et al.
        Basic fibroblast growth factor promotes melanin synthesis by melanocytes.
        Arch Dermatol Res. 1996; 288: 633-635
        • Schenk R.L.
        • Strasser A.
        • Dewson G.
        BCL-2: long and winding path from discovery to therapeutic target.
        Biochem Biophys Res Commun. 2017; 482: 459-469
        • Schiavone G.
        • Raskovic D.
        • Greco J.
        • Abeni D.
        Platelet-rich plasma for androgenetic alopecia: a pilot study.
        Dermatol Surg. 2014; 40: 1010-1019
        • Shumez H.
        • Prasad P.V.S.
        • Kaviarasan P.K.
        • Deepika R.
        Intralesional platelet rich plasma vs intralesional triamcinolone in the treatment of alopecia areata: a comparative study.
        Inte Jour of Medi Res & Health Sci. 2015; 4: 118-122
        • Singh S.
        Role of platelet-rich plasma in chronic alopecia areata: our centre experience.
        Indian J Plast Surg. 2015; 48: 57-59
        • Singhal P.
        • Agarwal S.
        • Dhot P.S.
        • Sayal S.K.
        Efficacy of platelet-rich plasma in treatment of androgenic alopecia.
        Asian J Transfus Sci. 2015; 9: 159-162
        • Sohn K.C.
        • Shi G.
        • Jang S.
        • Choi D.K.
        • Lee Y.
        • Yoon T.J.
        • et al.
        Pitx2, a beta-catenin-regulated transcription factor, regulates the differentiation of outer root sheath cells cultured in vitro.
        J Dermatol Sci. 2009; 54: 6-11
        • Tembhre M.K.
        • Sharma V.K.
        T-helper and regulatory T-cell cytokines in the peripheral blood of patients with active alopecia areata.
        Br J Dermatol. 2013; 169: 543-548
        • Tosti A.
        • Bellavista S.
        • Iorizzo M.
        Alopecia areata: a long term follow-up study of 191 patients.
        J Am Acad Dermatol. 2006; 55: 438-441
        • Trink A.
        • Sorbellini E.
        • Bezzola P.
        • Rodella L.
        • Rezzani R.
        • Ramot Y.
        • et al.
        A randomized, double-blind, placebo- and active-controlled, half-head study to evaluate the effects of platelet-rich plasma on alopecia areata.
        Br J Dermatol. 2013; 169: 690-694