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Monitoring Response to Platelet-Rich Plasma in Patients with Alopecia Areata with Optical Coherence Tomography: A Case Series

      Alopecia areata (AA) is an autoimmune hair loss condition that is difficult to treat and frequently disruptive to the psychosocial well-being of patients. Platelet-rich plasma (PRP) is an innovative therapy that provides concentrated GFs that impart anti-inflammatory effects. Optical coherence tomography (OCT) is a noninvasive imaging modality with the potential for providing quantitative monitoring of AA response to PRP. Our objective is to share our experience using OCT to monitor the therapeutic progress of patients with AA treated with PRP. Two patients with patchy AA and one with alopecia universalis were treated with PRP three times at 6-week intervals as part of a larger clinical trial. Patients were followed from baseline to week 24 with OCT imaging. OCT demonstrates an increase in hair density associated with improvement in inflammation at week 24. Conversely, the patient with alopecia universalis did not experience any significant change in follicular activity. This case series exemplifies the potential of PRP in inflammatory regulation as well as hair regrowth in patchy AA, whereas there is no notable advantage in alopecia universalis. Our findings add evidence on the possible value of OCT in quantitatively assessing hair growth progress throughout a treatment course.

      Abbreviations:

      AA (alopecia areata), OCT (optical coherence tomography), PRP (platelet-rich plasma)

      Introduction

      Alopecia areata (AA) is an inflammatory, autoimmune, nonscarring hair loss condition affecting 0.1–0.2% of the American population and 2% of the world (
      • Renert-Yuval Y.
      • Guttman-Yassky E.
      The changing landscape of alopecia areata: the therapeutic paradigm.
      ,
      • Strazzulla L.C.
      • Wang E.H.C.
      • Avila L.
      • Lo Sicco K.
      • Brinster N.
      • Christiano A.M.
      • et al.
      Alopecia areata: disease characteristics, clinical evaluation, and new perspectives on pathogenesis.
      ). Disease severity ranges from isolated bald patches of the scalp to complete body hair loss. AA’s characteristically unpredictable relapse and remission pattern frequently devastate patients, greatly impact self-esteem and social development in youth, as well as increase the likelihood of psychiatric comorbidities (
      • Wohlmuth-Wieser I.
      • Osei J.S.
      • Norris D.
      • Price V.
      • Hordinsky M.K.
      • Christiano A.
      • et al.
      Childhood alopecia areata-data from the National Alopecia Areata Registry.
      ).
      Advances in understanding AA’s pathophysiology have motivated clinical trials using anti-inflammatory systemic and topical therapies (
      • Jabbari A.
      • Petukhova L.
      • Cabral R.M.
      • Clynes R.
      • Christiano A.M.
      Genetic basis of alopecia areata: a roadmap for translational research.
      ,
      • Wang E.H.C.
      • Sallee B.N.
      • Tejeda C.I.
      • Christiano A.M.
      JAK inhibitors for treatment of alopecia areata.
      ). With the development of these additional treatments for AA, tools able to quantitatively discern effective therapeutic evidence are needed to better guide and advise patients. Optical imaging is an increasingly accessible, noninvasive technique that can be used for cross-sectional visualization of the skin’s microstructures. Optical coherence tomography (OCT) uses near-infrared, low-coherence interferometry to detect backscattered photons at varying tissue depths to form high-resolution grayscale images analogous to those of ultrasound. This technology has been pivotal in the exploration of adjunct instruments for the diagnosis of both melanoma and nonmelanocytic lesions (
      • Boone M.A.
      • Norrenberg S.
      • Jemec G.B.
      • Del Marmol V.
      High-definition optical coherence tomography imaging of melanocytic lesions: a pilot study.
      ). OCT images reach 1.3 mm depth, provide a clear distinction between epidermal and dermal layers, as well as skin appendages such as hair follicles and also uphold comparable image quality for manual analysis of all Fitzpatrick skin types (
      • Boone M.
      • Jemec G.B.
      • Del Marmol V.
      High-definition optical coherence tomography enables visualization of individual cells in healthy skin: comparison to reflectance confocal microscopy.
      ,
      • Ekelem C.
      • Yu J.
      • Heydarlou D.
      • Heidari E.
      • Csuka E.
      • Chen Z.
      • et al.
      The effect of melanin on in vivo optical coherence tomography of the skin in a multiethnic cohort.
      ). Acquired data may be manipulated to provide horizontal en face viewing or vertical sections, synonymous with histology. Owing to its ability to visualize subepidermal structures, OCT can theoretically provide valuable information on the number of active hair follicles, associated appendageal structures, presence of a hair shaft, and hair shaft width.
      Platelet-rich plasma (PRP) was first introduced as a regenerative aid for musculoskeletal injury and maxillofacial surgery in the 1960s (
      • Alves R.
      • Grimalt R.
      A review of platelet-rich plasma: history, biology, mechanism of action, and classification.
      ). In vitro and in vivo studies show that VEGF, PDGF, and TGFβ lead to angiogenesis as well as differentiation and proliferation of fibroblasts to enhance wound repair (
      • Alves R.
      • Grimalt R.
      A review of platelet-rich plasma: history, biology, mechanism of action, and classification.
      ,
      • 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.
      ). The ability of PRP to induce synthesis of collagen and extracellular matrix proteins make its benefits applicable to numerous inflammatory processes, including AA (
      • Lynch M.D.
      • Bashir S.
      Applications of platelet-rich plasma in dermatology: a critical appraisal of the literature.
      ). The largest trial of PRP in patients with AA demonstrated a 60% complete remission rate after PRP, compared with only 29% receiving intralesional triamcinolone only (
      • 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.
      ). We present a case series of patients with AA treated with PRP whose treatment response was monitored both longitudinally and quantitatively using OCT.

      Results

      Case 1 is a 60-year-old Caucasian female with an 11-year history of patchy AA and stable hypothyroidism. She reported no active hair loss or regrowth in the past 6 months, did not respond to intralesional triamcinolone injections in the past, and was not using any other concomitant medications for hair loss. Throughout her PRP treatment course, we monitored three alopecic patches and three areas of clinically unaffected scalp. OCT data demonstrated a 9 hair (16.4%) increase in the right parietal region, a 21 hair (350%) increase in the left temporal region, and a 21 hair (51.2%) increase in the frontal hairline patch from baseline to week 24 (Figure 1). Both the frontal hairline and left parietal patches showed marked clinical improvement by week 12, which was maintained or improved by week 24. OCT also demonstrated increased follicular counts of unaffected scalp regions, including the crown (18 hairs; 40%), left parietal (17 hairs; 36.2%), and right temporal regions (6 hairs; 27.3%) from baseline to week 24.
      Figure thumbnail gr1
      Figure 1Case 1 right parietal patch response to PRP at (a) baseline (b) week 12, and (c) week 24 with a corresponding vertical section of OCT data. The patient provided written, informed consent for publication of these images. OCT, optical coherence tomography; PRP, platelet-rich plasma.
      Case 2 is an otherwise healthy 69-year-old Caucasian female with a 25-year history of AA and no regrowth in the past 6 years since developing alopecia universalis. Topical and intralesional steroids were tried in the past with moderate response but not within the last 6 years. We monitored six scalp regions during her PRP treatment: midline frontal, vertex, and parietal, as well as bilateral frontal and temporal scalp. This patient did not grow any terminal hair and lacked a significant clinical response to PRP. OCT images captured small follicles only in the midline parietal region, which increased from 1 to 3 at week 24, but this was not clinically visible to the naked eye or on trichoscopy (Figure 2).
      Figure thumbnail gr2
      Figure 2Case 2 midline parietal scalp lack of significant response to PRP at (a) baseline (b) week 12, and (c) week 24 with a corresponding vertical section of OCT data. The patient provided written, informed consent for publication of these images. OCT, optical coherence tomography; PRP, platelet-rich plasma.
      Case 3 is an otherwise healthy 58-year-old Hispanic female with patchy AA since age of 11 years, successfully treated with intralesional steroids without recurrence. In addition, she developed frontal fibrosing alopecia at age 54 years and had received intralesional and topical steroids and topical minoxidil in the past year. She discontinued all therapy before enrollment in the clinical trial with PRP for 3 months. On presentation, she had patchy AA on vertex in addition to frontal fibrosing alopecia pattern hair loss on her frontotemporal hairline. During the trial, the patient reported pruritus, tenderness, and shedding with worsening of AA peaking at week 12. At week 24, the patient reported decreased tenderness and minimal pruritus as well as hair regrowth in patchy areas of AA. OCT data demonstrated that her vertex hair count decreased by 13 hairs (29.5%) from baseline to week 12 at the scalp vertex and then increased by 25 hairs (80.6%) by week 24 (Figure 3).
      Figure thumbnail gr3
      Figure 3Case 3 crown and vertex scalp response to PRP at (a) baseline (b) week 12, and (c) week 24 with a corresponding vertical section of OCT data. The patient provided written, informed consent for publication of these images. OCT, optical coherence tomography; PRP, platelet-rich plasma.

      Discussion

      Many advances in understanding AA pathophysiology and treatment have been made in recent years. Trichoscopy remains a pillar for AA diagnosis but is limited by its inability to penetrate the skin surface. In this clinical trial, OCT provides valuable quantitative data to bolster qualitative and subjective clinical and photographic evidence of treatment response.
      The cases presented highlight potential factors that may influence the PRP response rate in patients with AA. The two cases of patchy AA support the notion that patients with active inflammation or more recent patchy loss may respond to PRP, whereas longer standing diseases such as alopecia universalis with no acute activity may have limited to no response. Both cases of patchy AA demonstrate improvement in density, even in areas that were not clinically alopecic, which may represent normal hair growth or improvement of diffuse AA. The patient who concomitantly had frontal fibrosing alopecia also experienced improved inflammation and some hair regrowth in cicatricial areas. This patient also used a cooling measure with bagged ice applied to her scalp daily for 20 minutes for 3 months, the utility of which has been demonstrated with various cryotherapy tools in the literature (
      • Jun M.
      • Lee W.S.
      Therapeutic effect of superficial cryotherapy on alopecia areata: a prospective, split-scalp study in patients with multiple alopecia patches.
      ).
      Although PRP holds great therapeutic potential, standardized preparation methods to optimize platelet concentration and activation are not yet established. Differences exist in mean platelet volume and concentration, as well as the size of platelets and depth of scalp injection (
      • Ozer K.
      • Kankaya Y.
      • Çolak Ö.
      An important and overlooked parameter in platelet rich plasma preparation: the mean platelet volume.
      ). These factors may influence the efficacy of treatment in ways that are difficult to quantify and require further study to elucidate. The lack of internal control makes it difficult to determine with certainty whether the disease was slowed, stabilized, or improved. Other limitations in data analysis included confounding variables with concomitant therapies, possible human error in manual OCT image analysis, image artifact, or miscalibration in the relocation of scalp regions at follow-up imaging sessions. The challenges of OCT with limited depth were not relevant in this study as we were optimizing imaging for hair follicle quantification and calculation of epidermal thickness.

      Materials and Methods

      This pilot study is approved by the University of California, Irvine Institutional Review Board, and is registered on ClinicalTrials.gov as NCT03376581. All patients provided written, informed consent for trial participation and consent for publication of deidentified photographs in 2017. Patients were treated with three intradermal PRP treatments (Eclipse PRP HC 22 ml Patient Kit, Eclipse Aesthetics, The Colony, TX) over their entire scalp at 6-week intervals. Clinical assessments were completed at weeks 6, 12, and 24 after baseline PRP treatment.
      To quantitatively monitor PRP response, we used an in-line fiber-based swept-source OCT system (Thorlabs, Newton, NJ) with a 1,310 nm center wavelength and a spacer. OCT images were obtained of affected and unaffected areas, if applicable, at baseline, week 12, and 24. Scalp region relocation was achieved using individualized caps for each subject. Images were analyzed manually by two graders for follicular density using the program ImageJ (
      • Schneider C.A.
      • Rasband W.S.
      • Eliceiri K.W.
      NIH image to ImageJ: 25 years of image analysis.
      ).

      Data availability statement

      Datasets related to this article will be provided upon reasonable request submitted to the corresponding author.

      Conflict of Interest

      Zhongping Chen declares financial interests in OCT Medical Imaging, which did not provide any support for this study. The authors did not receive any monetary funding from agencies in the public, commercial, or not-for-profit sectors for this project. The remaining authors 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.
      Platelet-rich plasma kits were donated to this project by Eclipse Aesthetics, LLC.

      Author Contributions

      Conceptualization: NAM; Data Curation: CE, NAM, MJ, JY, AMH, EC, EH, ZC; Formal Analysis: CE, FC, CTP, AEH; Investigation: NAM; Methodology: NAM, MV; Project Administration: CE; Resources: JAR, ZC; Supervision: NAM; Visualization: CE; Writing - Original Draft Preparation: CE; Writing - Review and Editing: NAM, MJ

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