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ORIGINAL ARTICLE
Year : 2023 | Volume
: 41
| Issue : 2 | Page : 111-115
Platelet-rich plasma in the treatment of alopecia areata: A retrospective evaluation of 17 patients
Yusuf Kelleci1, Fatma Aydin2, Gokhan Sahin2, Esra Pancar Yuksel2
1 Estethica Ataşehir, Istanbul, Turkey
2 Ondokuz Mayis University, Medical Faculty, Department of Dermatology, Samsun, Turkey
Correspondence Address:
Dr. Gokhan Sahin
Ondokuz Mayis University, Medical Faculty, Department of Dermatology, 55139, Kurupelit, Samsun
Turkey
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/ds.DS-D-22-00205
Background: Alopecia areata (AA) is a disease of unknown etiology which is thought to be autoimmune, that presents challenges in terms of treatment. Platelet-rich plasma (PRP) can induce the development of new hair follicles through various growth factors it contains. PRP could be a treatment option for patients with AA. Objectives: We aim to evaluate the effectiveness and safety of PRP treatment in patients with patch-type AA. Methods: The study included 17 patients diagnosed with patch-type AA who received PRP treatment at least 3 sessions every 4 weeks. Treatment response was evaluated by calculating the severity of alopecia tool (SALT) scores. Results: The mean age of patients was 29.70 ± 10.09, and the mean disease duration was 18.17 ± 39.46 months. The mean SALT score of 17 patients was 6.82 ± 4.96 and 4.35 ± 4.58 before treatment and at the end of the 3rd month, respectively. The reduction in SALT scores was statistically significant (P = 0.01). At the end of the 3rd month, six patients (35.3%) had an excellent response, one patient (5.9%) had a good response, one patient (5.9%) had a partial response, and nine patients (52.9%) showed no response. The mean SALT scores of four patients who received six sessions of PRP of treatment were 6.00 ± 2.94 and 1.75 ± 2.06 at the end of the 6th month. No serious side effects were noted. Relapse was observed in one patient within 1 year of follow-up. Conclusion: As a result of our study, PRP treatment was found to be an effective and reliable treatment method in patients with mild AA.
Keywords: Alopecia areata, efficacy, platelet-rich plasma, side effects, treatment
Alopecia areata (AA) is a chronic, autoimmune disease that causes noncicatricial hair loss that targets anagen hair follicles.[1] The estimated prevalence of the disease is 0.1%, and a person's lifetime risk of developing the disease is about 2%.[2] Topical and intralesional steroids, topical minoxidil, and contact immunotherapy can be recommended in mild AA, whereas systemic steroids, systemic cyclosporine, and oral tofacitinib are among the treatments used in severe disease.[3] In recent years, platelet-rich plasma (PRP) has become popular in the treatment of AA. PRP is autologous blood plasma enriched with platelets. During PRP preparation, the venous blood drawn from the patient is put into a special tube and then centrifuged. The platelet density is increased above approximately 1,000,000 platelets/μL and then injected into the diseased areas.[4] PRP contains various growth factors and cytokines, and it was reported to induce the development of new hair follicles. However, the main mechanism of action of PRP in the development of hair follicles has not been fully elucidated. Hair follicles are the regions with immune privilege, and molecules such as transforming growth factor β1, insulin-like growth factor 1 (IGF-1), and α-melanocyte-stimulating hormone play a local immunosuppressive role in providing this privilege.[5]
AA occurs in genetically predisposed individuals due to loss of follicular immune privilege and is associated with increased expression of major histocompatibility complex class I (MHC Class 1) polypeptide-related sequence A on hair follicle cells. As a result, natural-killer (NK) cells are activated, and the secretion of interferon-γ (IFN-γ) and interleukin-15 (IL-15) increases. IFN-γ stimulates the expression of MHC-1 protein in hair follicles, while IL-15 promotes the proliferation of NK cells and T-cells.[6] Furthermore, IFN-γ and IL-15 activate target immune cells through the Janus kinase-signal transducer and activator of transcription signaling pathway.[7] Eventually, with increased inflammation, the anagen phase follicles prematurely enter the telogen phase, this is likely in response to an immune-mediated stimulus.
It is hypothesized that the mechanism of action of PRP is multifactorial. First, PRP prolongs the shortened anagen phase and induces hair growth in the anagen phase in AA through the platelet-derived growth factor and vascular endothelial growth factor it contains.[8],[9],[10] PRP application also prolongs the life of dermal papilla (DP) cells during the hair cycle by activating anti-apoptotic regulators such as the bcl-2 protein and Akt-signaling pathway. In addition, it stimulates the proliferation of DP cells by increasing the production of fibroblast growth factor 7. Second, PRP contains transforming growth factor β1, a potent immunosuppressive cytokine, and IGF-1 might contribute to the restoration of immune privilege, which is impaired in AA.[11] With PRP treatment, imbalances between T-helper cells that play an important role in AA may be corrected. In a study evaluating the effect of PRP application on mRNA expression in lesional skin in patients with AA, it was shown that IFN-γ and IL-17 cytokine mRNA expressions decreased and IL-10 expression increased after PRP treatment.[12] Finally, it has been shown that PRP improves blood flow in the skin and boosts the growth of blood vessels near the hair follicle.[13]
In recent years, PRP has emerged as a new treatment option in AA, but studies on its effectiveness are still limited with some studies reporting poor responses.[14],[15] Therefore, our goal in this study was to evaluate the efficacy and safety of PRP treatment in AA patients who applied to our outpatient clinic.
Materials and MethodsStudy population
Seventeen clinically diagnosed patch-type AA patients who were admitted to our dermatology outpatient clinic from August 2017 to August 2019 and received at least three sessions of PRP treatment every 4 weeks were included in this study. The severity of hair loss in all patients was under the S1 (<25% hair loss) group according to the criteria defined by the AA investigational assessment guideline, estimating the percentage of the scalp surface that all the alopecic areas would occupy.[16] Patients with body hair loss, patients who received another treatment in the last 3 months before PRP treatment, and patients who were pregnant or younger than 18 years were excluded. PRP treatment had not been combined with another systemic or topical agent. The patients included in the study had been treated only by PRP and before the first session of the PRP treatment, the patients in the study had wash-out periods of at least 3 months in which they did not use any topical or systemic treatments.
Gender, age, disease duration, family history, nail changes, comorbidities, previous treatments for AA, and side effects were obtained through the hospital information management system and recorded for each patient.
The study was approved by Local Ethics Committee (Ondokuz Mayis University Clinical Research Ethics Committee, B.30.2.ODM.0.20.08/728, September 27, 2019). Participants provided written informed consent.
Preparation and application of platelet-rich plasma
S and M PRP UNIQUE branded PRP kit was used for the PRP application. First, 15 ml of venous blood was drawn from the patients. The collected blood was centrifuged at 3200 rpm for 8 min with the ELEKTRO·MAG M415P centrifugation device in our department. Platelet-poor plasma, PRP, and erythrocyte layers were obtained from the top to bottom after centrifugation. At the end of the procedure, approximately 2.5–3 ml of PRP was collected with the help of an 18 G injector. It had been observed that the platelet concentration in the PRP sample increased approximately four times compared to the normal blood of the patients. The PRP obtained without an activator was injected into the alopecic areas of the skin as interfollicular, in an amount of 0.05–0.1 ml/cm2, from deep to the surface, at every centimeter along the treated area with a 27G injector. PRP application was performed and repeated every 4 weeks according to the patient's request and clinical response for AA patients in our department.
Evaluation
The clinical response was evaluated by calculating the Severity of Alopecia Tool (SALT) score before and after treatment based on the photographs taken with a Canon EOS 450D (Rebel XSi) digital camera. The clinical photographs were obtained from the patient photographs archive at the department of dermatology.
Treatment responses were classified as follows:
Excellent response: 75% or more reduction in SALT scoreGood response: 50%–74% decrease in SALT scorePartial response: 25%–49% decrease in SALT scoreNo response: No change in score or <25% decrease in SALT score.[16]The patients were followed up 1 year after treatment ended.
Whether relapse occurred or not was detected from the hospital database or the phone numbers registered in our system.
Statistical analysis
Data analysis was performed using the Statistical Package for the Social Sciences software for Windows (version 22.0; SPSS Inc. Chicago, IL, USA). Descriptive statistical evaluations of all the variables in the study were made by calculating the mean and standard deviation values. The difference between before and after treatment values was evaluated by t-test or Wilcoxon signed-rank test in dependent groups. P < 0.05 was considered statistically significant.
ResultsThis study included 17 AA patients (8 males and 9 females) with a mean age of 29.70 ± 10.09 in the range of 12–45 years.
In medical history and physical examination, two patients had a family history of AA. Only 3 (17.6%) patients had comorbidities which were obsessive-compulsive disorder in one patient, epilepsy in one, type 2 diabetes mellitus, and chronic gastritis in one. None of the patients had nail involvement. When we reviewed the therapeutic agents received by the patients before the wash-out period, 11 out of 17 patients used topical steroids and/or intralesional steroids, one was treated by topical and systemic steroid combination, and one was treated by systemic steroid and cyclosporine combination, whereas four patients did not use any treatment.
The mean disease duration of patients was 18.17 ± 39.46 months. However, only three patients had disease duration longer than 12 months, 18, 96, and 144 months, respectively. When these three patients were excluded, the mean disease duration of the remaining 14 patients was 3.64 ± 2.40 months.
The mean SALT score of 17 patients before the treatment was 6.82 ± 4.96; the mean SALT score at the end of the 3rd month was 4.35 ± 4.58. There was a statistically significant difference between the two values (P = 0.01). Considering response rates at the end of the 3rd month, six patients (35.3%) had excellent responses, one (5.9%) partial response, one (5.9%) good response, and nine (52.9%) patients had no response. When three chronic AA patients were excluded who were unresponsive to PRP treatment, the rate of patients with at least a good response increased to 64.3%.
Among 17 patients, three sessions of PRP were applied to 13 (76.5%) patients, whereas treatment continued until six sessions in 4 (23.5%) patients.
The mean SALT score of 13 patients who received only three sessions of PRP was 7.07 ± 5.51 before and 4.07 ± 5.13 after treatment, and the difference was statistically significant (P = 0.01). At the end of the 3rd month, among these patients, six patients (46.2%) had excellent responses, 1 (7.7%) had a good response, and 6 (46.2%) patients had no response to treatment. Moreover, the treatment success was preserved at the 6th month in the patients who received three treatment sessions.
When the response rates of the remaining four patients who received six sessions of PRP patients were evaluated at the end of the 3rd month, it was observed that three of the patients were unresponsive to treatment, and one had a partial response. However, at the end of the 6th month of PRP treatment, only one out of three unresponsive patients remained unresponsive to treatment; the other two were evaluated as excellent and good, respectively. The patient with a partial response was evaluated as excellent, too. The mean SALT score of these four patients was 6.00 ± 2.94 prior to the treatment and 1.75 ± 2.06 at the end of the 6th month. No statistical analysis was performed for these patients due to the low sample size. The photographs of the patients before and after PRP treatment are shown in [Figure 1].
Figure 1: This figure shows the photographs of three different patients before and after (a-f) PRP treatment. Excellent response was seen in (b) and (d) (dyed hair) after 3 PRP sessions, (f) after 6 PRP sessions. PRP: Platelet-rich plasma.No severe side effects were observed other than minor side effects, such as pain and ecchymosis. Relapse was observed in only one of the patients who responded to treatment within 1 year of follow-up.
DiscussionAA is a chronic, relapsing autoimmune disease that causes a great psychosocial burden on patients. Although various topical and systemic agents are used in the treatment, there is currently no curative treatment method. In recent years, PRP has been suggested to have a beneficial role in hair growth, and usage in the treatment of AA has increased. However, knowledge about the efficacy of this treatment is still limited and warrants further research.
The mechanisms of action of PRP on AA patients are not fully understood. It has been proposed to regulate the growth and differentiation of stem cells, prolong the anagen phase, promote vascularization and angiogenesis, and prevent apoptosis by containing various cytokines and growth factors.[17],[18],[19] In a randomized, double-blind, placebo and active controlled, half-head study; Ki-67 levels, which serve as markers for cell proliferation, were found to be significantly higher with PRP.[20] Dermal papilla (DP) cells produce growth factors such as IGF-1, fibroblast growth factor 7, hepatocyte growth factor, and vascular endothelial growth factor which are responsible for keeping the hair follicle in the anagen phase of the hair cycle.[10] PRP increases the proliferation of DP cells and the level of these growth factors and might prolong the anagen phase. PRP also stimulates vascularization and angiogenesis by increasing the effect of Wnt/β-catenin, extracellular-signal regulated kinase, protein kinase B (Akt) signaling pathways, induces hair follicles to enter the anagen phase, and lengthens the anagen phase. In addition, regarding cell survival and preventing apoptosis, the extracellular signal-regulated kinase, and protein kinase B (Akt) signaling were also reported to be stimulated by PRP.[13],[21]
There are a few studies evaluating the effects of PRP in AA patients. In a randomized controlled study conducted by Trink et al., PRP injection was reported as the most effective treatment method in stimulating hair growth among PRP, triamcinolone acetonide or placebo. Injections were administered randomly three times with intervals of 1 month on 45 patients with chronic, recurrent AA lasting at least 2 years.[20] In another randomized controlled study, PRP was compared with 5% topical minoxidil and placebo in the treatment of AA with three sessions of PRP treatment every 4 weeks and resulted in a significant increase in hair growth, similar to minoxidil.[22] However, in a randomized double-blind study, the efficacy of intralesional corticosteroid and PRP injections administered every 4 weeks was compared, and they observed no statistically significant difference between treatments.[23] In another randomized controlled study by Gupta et al., PRP administration was found to be associated with a significant increase in SALT score compared to the placebo group.[12] In addition, in this study, alterations in IL expressions in the lesional skin were shown that PRP might be effective in balancing the immune dysregulation in AA.
When considering the nonrandomized controlled study, Shumez et al. compared forty-eight patients treated with triamcinolone and twenty-six patients treated with PRP. Although patients treated with PRP had an earlier response at the end of 6 weeks than patients treated with triamcinolone, the difference was reported as statistically insignificant. The patients were evaluated as mild AA, and the majority had a disease duration of 1–6 months.[24]
Other studies evaluated the PRP effects on AA patients before and after the treatment. In the study of Kumar, 70% of the patients were reported to have observable hair regrowth after three sessions of PRP at 4-week intervals. The mean duration of the disease was reported as 3.3 ± 1.8 months.[25] Khan et al. used three sessions of PRP treatment once a month and reported excellent response in 6 (30%) patients and good response in 5 (25%) patients at the end of the 6-month follow-up period in 20 patch-type AA patients.[26]
In the study by Khademi et al., a single session of PRP was applied to 10 patients with total alopecia for at least 3 years, and it was stated that hair growth was <10% in only 2 of the patients, while no change was observed in the other eight patients.[15] In another, 20 patients were followed up with the diagnosis of chronic AA, and PRP application every 4 weeks for 6 months resulted in remission in 19 patients (95%). PRP was suggested as a highly effective treatment method in chronic AA patients.[14] The reason for the difference in the results of these two studies conducted in patients with chronic AA may be that only one session of PRP was applied in the first study. In contrast, six sessions of PRP were applied once a month in the second study.
In our study, evaluating results before and after treatment, according to the response rates at the end of the 3rd month, one had a partial response, one had a good response, and six had excellent responses. Although our response rate is lower than the above studies, the rate of patients with shorter disease duration was observed as good-excellent with 64.3%. So, it is better to prefer new onset AA patients for PRP treatment. Another important point regarding the results of our study is the positive change in the treatment response after three more sessions in three of the four unresponsive patients who underwent six sessions of PRP. This might indicate the long-term use effect of PRP in treatment-refractory patients.
The family history was reported to have a worse prognosis on patch-type AA patients.[27] Only two of the patients in our study had a family history of AA. While one of these two patients did not respond to treatment, the other responded well. Nail involvement and thyroid dysfunction, which may be more frequently associated with AA, were not detected in our patients. We could not find any study presenting or comparing the PRP treatment with the history and clinical properties of AA patients. So, the role of prognostic factors on the efficacy of PRP treatment in AA patients could be considered in further studies.
AA is a disease with common relapses. It has been reported that spontaneous remission may occur in 34%–50% of AA patients within the 1st year, although most will experience multiple episodes.[28] We followed up the patients for 1 year after treatment. Relapse developed in only one of our patients who initially responded with a good response to treatment. The rarity of relapse in patients who recovered with PRP treatment can be considered as an indicator of the effectiveness of PRP treatment.
PRP application-related side effects were reported as postinflammatory hyperpigmentation and allergic reactions in case reports with non-AA indications.[29],[30] Similar to other studies from the literature, patients in our study had minor side effects such as pain, burning, erythema, ecchymosis, and local infection, and no major side effects were observed.
The absence of a control group was one of the limitations of our study. Since the improvement could be due to spontaneous healing or PRP-initiated immunological balance restoration, as reported by Gupta et al.[12] the absence of a control group made it difficult to evaluate spontaneous recovery. The other limitations of our study may be as follows: Most of our patients are mild and new-onset patients, and the number of patients is relatively small.
ConclusionPRP is an effective and safe method and can be considered as a therapy in AA patients with mild and short duration disease. Side effects are not serious, and relapse is rare. We recommend specific randomized controlled studies evaluating the relationship between prognostic factors, duration of treatment, and treatment success.
Data availability statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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