Alopecia areata (AA) is a common inflammatory nonscarring hair loss, characterized by well-demarcated patches of hair loss. It can progress to complete loss of hair from the scalp (alopecia totalis) or from the whole body in severe cases (alopecia universalis) 1.
AA has major effects on the quality of life and self-esteem, especially in the young patients, constituting the commonly affected group. AA is considered an organ-specific autoimmune disease. Therefore, therapies are mostly immunosuppressive; nevertheless, treatment is still a challenge in AA, and no treatment is either curative or preventive 2.
Platelet-rich plasma (PRP) is an autologous, nonallergic preparation of platelets in concentrated plasma obtained from the patient’s own blood after centrifugation 3.
It has recently attracted the attention of plastic surgeons and dermatologists, because of the ability of growth factors contained in the alpha granules of platelets, including platelet-derived growth factor, transforming growth factor, vascular endothelial growth factor, and insulin-like growth factor, to stimulate human dermal fibroblasts, improve wrinkling and rejuvenate the skin 4.
PRP has been found to be beneficial in dermatology, for example, in acne scarring, wound healing and fat transplantation 5. It has also been shown to promote hair growth and survival both in vivo and in vitro6,7.
The principle of use of PRP in hair loss depends on its high concentration of growth factors (GFs) 8. GFs stimulate the formation of hair epithelium and the differentiation of stem cells into HF cells, through an upregulation of b-catenin, strongly expressed in the bulge region of the human anagen HF 9. In addition, they prolong the anagen phase of hair cycle, through an increase in expression of fibroblast growth factor-7 3.
Different studies were conducted for the efficacy of PRP in AA with controversial results and no consensus on the optimum standards for preparation 6,10–12. Furthermore, it is not yet known whether the PRP effect is caused by the platelets and its growth factors or the needling. Therefore, the present study was carried out to evaluate the efficacy and safety of PRP in the treatment of AA in comparison with placebo (similarly injected saline) and to explore the role of needling in the effect of PRP.
Patients and methods
This open-labeled, nonrandomized placebo-controlled study was carried out on 41 patients complaining of multiple patches of AA from February 2015 to January 2016. The patients were recruited from Outpatient Clinic of Dermatology, Andrology and STDs Department of Mansoura University Hospital, Mansoura, Egypt.
The inclusion criteria included patients of both sexes with multiple bilateral and symmetrical patches of AA of less than 6 months duration and who were at least 18 years of age.
The Research Ethics Committee for experimental and clinical studies at faculty of Medicine, Mansoura University approved the study.
The exclusion criteria included the following: pregnant and nursing female individuals; hemoglobin of less than 10 g/dl; patients with systemic diseases (thyroid diseases, chronic liver disease, and blood clotting disorders) and other autoimmune diseases. The exclusion criteria also included the following: patients on drugs affecting bleeding and/or clotting mechanisms; recent fever or illness within the last 3 months; use of ultraviolet radiation, including tanning beds and PUVA. Therapy for treatment of acne, psoriasis or any other skin condition within 3 months before study initiation and the use of a topical medication within 6 weeks before the study were other exclusion criteria.
All patients were subjected to history taking including age, sex, duration of current episode of AA, history of relapse, family history of atopic dermatitis, asthma, thyroid disease, vitiligo, rheumatoid arthritis, psoriasis, and other autoimmune diseases.
Diagnosis of AA was based on having circumscribed, hairless, patches with normal-appearing skin area, exclamation mark hair (distal segment of hair shaft is broad than its proximal segment) and a positive pull test at the margins of lesions 13.
Evaluation of hair loss was determined using Severity of Alopecia Tool score (SALT score). The scalp was divided into four parts on the basis of the surface area, top (40%), posterior (24%), right side (18%), and left side of scalp (18%). Percentage of hair loss in each area was determined independently and was multiplied by the percentage of scalp covered in that area of the scalp, and summing the products of each area gives the SALT score. Patients were divided into four grades according to disease severity: S1<25% hair loss, S2=25–49% hair loss, S3=50–74% hair loss, and S4=75–99% hair loss 14.
SALT score would be determined at baseline (BL), and follow-up (FU) last visit and the percentage change from BL is determined by the following equation:
SALT score improvement of more than 50% (SALT>50) was considered as an effective response.
Assessment of qualify of life was carried out using the Arabic version questionnaire of dermatology quality of life scales (DQOLs) 15. It is a self-explanatory 10-item questionnaire and has responses ranging from very much (score 3), a lot (score 2), a little (score 1), to not at all (score 0). The patient fills it in without the need for detailed explanation. DQOLS is calculated by summing the score of each question, resulting in a maximum of 30 and a minimum of zero. The higher the score, the more the quality of life is impaired: 0–1: no effect at all on patient’s life; 2–5: small effect on patient’s life; 6–10: moderate effect on patient’s life; 11–20: very large effect on patient’s life; and 21–30: extremely large effect on patient’s life 16. Digital photographs were taken before and after treatment.
PRP was prepared according to Kim et al. 17. In short, 10–30 ml of venous blood was collected from patients under complete aseptic condition into tubes containing sodium citrate as anticoagulant, and then the citrated blood was centrifuged at two steps. The initial step consisted of 3000 rpm for 7 min, and the second step consisted of 4000 rpm for 5 min, leading to separation of plasma into two portions, platelet-poor plasma and PRP. The lower 1–3 cm3 of plasma was taken as PRP. The PRP was activated by adding calcium chloride immediately before the injections.
PRP injection technique
The patients were placed in an appropriate comfortable position; all necessary materials for injection were placed on a sterile table adjacent and easily accessible to physician. The treatment areas were cleaned with local antimicrobial agent such as betadine solution. Local anesthetic cream (Lidocaine gel; The Nile Co. For Pharmaceuticals and Chemical Industries, Cairo, Egypt) was topically applied to the treatment area for 45–60 min before treatment. Anesthetic cream was washed off by saline solution. The patients (with bilateral and symmetrical patches of AA) were injected with PRP on one side and with saline on the other side as a control. PRP and saline were injected by multiple injections intradermally 20 mm apart every 2 weeks for a total of 10 injections or shorter if hair regrowth occurred. Patients were educated about postoperative skin care; no scalp coverage unless in prolonged direct sun light or rain; in this event, the scalp may be covered with a loose-fitting hat or headscarf. Patients were strongly advised to decrease touching the site of injection for the first 48 h to reduce the chance of infection.
Safety assessment was evaluated by recording possible side effects including pain, tenderness, erythema, and infection.
All data were collected, tabulated and statistically analyzed using SPSS 18.0 for windows (SPSS Inc., Chicago, Illinois, USA). Continuous data are expressed as the mean±SD, and the categorical data are expressed as n (%). Continuous variables were checked for normality by using the Shapiro–Wilk test. Percent of categorical variables was compared using the χ2-test. Mann–Whitney U-test was used to compare the age and duration between PRP responders and nonresponders. All tests were two tailed, and P less than 0.05 was considered statistically significant.
This study included 41 patients with AA. The mean age was 26.68±4.49 years, and the range was 18–33 years. They comprised 32 (78%) male patients and nine (22%) female patients. The duration of the disease was 2.66±1.89 months, and the range was 0.3–5.5 months. A total of 32 (78%) patients had a history of relapse, whereas nine (22%) had no history of relapse. The number of patients were 23, seven, four, and seven in grade S1, S2, S3, and S4, respectively.
Hair regrowth measured as SALT of more than 50 occurred in 13 (31.7%) patients in the areas injected with PRP, whereas regrowth of hair in placebo areas occurred in two (4.9%) patients. There was a statistically significant difference between treatment side and placebo side (P=0.002) (Table 1).
With regard to the relation between improvement and grade severity of AA, grade1 (S1) showed the best improvement [12/23 (52.3%)], whereas only one patient [1/7 (14.3%)] with grade 2 (S2) had hair regrowth. In contrast, no response occurred in both grade 3 and grade 4 (S3 and S4) (Table 2). Figure 1a and b showed an example of PRP responders, whereas Fig. 2a and b showed an example of PRP nonresponders. No significant differences were found between PRP responders and nonresponders with regard to age, duration of the disease, presence or absence of relapse and associated diseases (P>0.05) (Table 3).
Using DQOLS, 15 (36.6%) patients suffered a very large effect on impairment of quality of life before treatment whereas, after treatment, it became six (14.6%). Twelve (29.3%) patients had moderate degree, whereas, after treatment, it became seven (17.1%). Twelve (29.3%) patients had mild degree before treatment, whereas, after treatment, it became 11 (26.8%) patients. Two (4.9%) had small effect on impairment of quality of life, whereas, after treatment, it became 15 (36.6%). There was a statistically significant difference in the mean value of DQOLS after treatment compared with that before treatment (P=0.002) (Table 4).
With regard to the occurrence of side effects in the studied patients, 31 (75.6%) patients felt tolerable pain with a duration of not more than half hour. A total of six (14.6%) patients experienced tenderness and burning sensation. All the patients developed erythema at the site of injections only for few hours after the session. No patient developed infection.
Multiple therapies have been used for AA, such as corticosteroids (topical, intralesional, and systemic), minoxidil, anthralin, contact sensitizers, topical tacrolimus, psoralen ultraviolet A, cyclosporine A, methotrexate, and sulfasalazine. However, none has been shown to alter the course of the disease 2.
This is an open-labeled, nonrandomized placebo-controlled study, aimed to examine the efficacy and safety of PRP for the treatment of AA. Our protocol was carried out according to the study of Kim et al.17. However, it was dissimilar to the studies of others 6,10–12.
We observed significant hair regrowth in 31.7% of patients injected with PRP compared with those injected with saline 4.9% as placebo after 10 sessions. Furthermore, grade 1 (S1) AA was the best in showing improvement [12 (52.3%)], whereas only one (14.3%) patient with grade 2 (S2) had hair regrowth. In contrast, no response occurred in both grade 3 (S3) and grade 4 (S4). This response is in agreement with previous reports, indicating that the prognosis and treatment response is poor in patients with severe AA and longer disease duration 18,19. However, our study did not find a significant difference with regard to the duration of the disease between PRP responders and nonresponders. This could be due to the short duration of AA in our patients, which was less than 6 months. This was in agreement with Nakajima et al.20 who found a good response was achieved in patients with recent-onset disease with duration of AA of up to 6 months.
Trink et al.6 performed a randomized double-blind, placebo active-controlled, half-head study on 45 patients. In total, three treatments were administered to each patient, with an interval of 1 month from each other. Administration of both triamcinolone acetonide and PRP led to significant hair regrowth in AA lesions compared with placebo. Furthermore, patients treated with PRP had significantly increased hair regrowth (60%), compared with those treated with triamcinolone (27%), at 12 months after start of the study. They reported that PRP is considered an effective option for treatment of AA. They also concluded that PRP significantly increased Ki-67 levels, and decreased hair dystrophy, compared with placebo. Yet, this study neglected to report the concentration of platelets, inclusion or exclusion of WBCs, and anticoagulant usage 6.
Another study was carried out by Singh 21 in 2015, including 20 patients with chronic AA (>2 years) treated with PRP, reporting hair regrowth of his patients, with failure of only one patient.
Shumez et al.10 treated 48 patients with triamcinolone injections and 26 patients with PRP injections. PRP was prepared using a double centrifugation technique. Patients treated with PRP had an earlier response at the end of 6 weeks than patients treated with triamcinolone. However, this difference was statistically insignificant. The overall improvement at the end of 9 weeks was 100% for all patients in both groups. They concluded that PRP is a safe, simple, and effective procedure for the treatment of AA.
D’Ovidio and Roberto 11 treated 25 patients affected by severe (>50% of the scalp involved) chronic (>2 years) AA with PRP. Their protocol was almost similar to the study of Trink et al.6, using the single-spin technique (Technica Centric 90), with calcium gluconate as a platelet activator. Only nine of 25 patients completed the protocol. The most common reason for discontinuation of treatment was the absence of significant results after the second and fourth months. None of the patients achieved noticeable cosmetic results. Of the nine patients, at the eighth month, six (66.6%) have obtained regrowth of terminal pigmented hair; the others noted nonpigmented vellus in the seats of infiltration after the second session of PRP. This treatment regimen does not seem to be able to give persistent results, and fails to inhibit the appearance of new relapses during treatment, and all patients lost their regrown hairs at an average of 1 year 11. A case report of successful treatment of corticosteroid-resistant ophiasis type AA with PRP has been declared with no further similar cases 22. In a controlled study, 90 patients were allocated into three groups; the first was treated with topical minoxidil 5% solution, the second with PRP injections, and the third with placebo. Diagnosis and follow-up were carried out by serial digital camera photography of lesions and trichoscopic scan before and every month after treatment for 3 months. Eltaieb et al.12 concluded that PRP is a more effective therapy for treatment of AA than minoxidil 5% in the same period of treatment. PRP showed a significant decrease in yellow dots and short vellus hair, whereas minoxidil showed an increase in short vellus hair. Moreover, PRP has no side effects such as those of minoxidil 5%. The method of PRP preparation, study methodology and patients’ population could explain the differences in the efficacy of PRP in different studies 6,10–12.
The mechanism of action of PRP in promoting hair growth and survival is largely attributed to its content of growth factors, including platelet-derived growth factor, transforming growth factor, vascular endothelial growth factor, and insulin-like growth factor 4,6,7. However, the mechanical stimulation by needling itself creates a biologic response that is expected to stimulate mesodermal changes 23. Our study results indicated that the efficacy of PRP is mostly not caused by needling, as the saline injection showed less significant improvement.
There was statistically significant improvement in the mean value of DQOLS after treatment. These findings may be attributable to the better understanding, adjustment and acceptance of open and active management of AA. In addition, the wearing of headpieces such as, wigs, hats, beanies, and/or scarfs help to improve the quality of life and self-esteem. These assumptions are supported by the findings of Mazter et al.24 and Cartwright et al.25, wherein neither AA severity nor status influenced the participant’s quality of life, mood and self-worthiness. In contrast, several studies 26–29 have shown that individuals with AA are more likely to exhibit aberrant psychosocial traits, such as increased anxiety, depression, and aggression.
The reported side effects were few, minor and of shorter duration. Pain was tolerable, without the need for analgesics, after treatment or discontinuation of the sessions. No patients complained of any erythema or tenderness for more than the first few hours after the session. PRP is safe, easy to perform, with minimal tolerable side effects, and with no restriction to normal daily activities. Our results agree with other studies 6,21. However, D’Ovidio and Roberto 11 stated that most of their patients did not complete the study because of significant discomfort and pain caused by infiltration. In addition, Betsi et al.29 reported that the main side effects after PRP were drowsiness and a sensitive scalp that disappeared after the second injection.
Our study has some limitations, including the relatively small number and the lack of more objective methods of evaluation, such as videomicroscopy or trichoscopy.
PRP treatment for AA is effective, safe, and easy to perform, improving the patients’ DQOL, with minimal tolerable side effects. It is effective in mild cases of AA. The efficacy of PRP is mostly not caused by needling, as the saline injection showed less significant improvement. However, further studies are needed to clarify the optimum parameters for PRP preparation, the dose, the number of sessions needed and the interval between them.
No financial support.
Conflicts of interest
There are no conflicts of interest.
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Keywords:© 2018 Egyptian Women's Dermatologic Society
alopecia areata; dermatology quality of life; PRP