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 Table of Contents  
BRIEF REPORT
Year : 2022  |  Volume : 8  |  Issue : 2  |  Page : 73-78

Platelet-rich plasma for the treatment of vitiligo: A case series


1 Department of Dermatology, Venereology and Leprosy, Indira Gandhi Medical College, Shimla, India
2 Department of Community Medicine, Dr. Rajendra Prasad Government Medical College, Tanda, Kangra, Himachal Pradesh, India

Date of Submission14-Feb-2021
Date of Decision02-Jun-2022
Date of Acceptance29-Nov-2022
Date of Web Publication5-Jan-2023

Correspondence Address:
Sakshi Bhota
Department of Community Medicine, Dr. Rajendra Prasad Government Medical College, Tanda, Kangra, Himachal Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_3_21

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  Abstract 

Vitiligo is a multifactorial disorder characterized by the loss of functional melanocytes. Even though not a life-threatening disorder, many suffer enormous stigma and psychiatric comorbidities. The treatment of vitiligo still remains a challenge. To get therapeutic success, there has been a continuous search for newer treatment modalities. We hereby report the case series of five patients of stable vitiligo who were resistant to topical therapies. These patients were given intradermal platelet-rich plasma at 4-week interval for a total of four injections. Out of five patients, two showed excellent response and two patients showed moderate response to the treatment, whereas there was no response seen in one patient.

Keywords: Melanocytes, PRP, stable vitiligo


How to cite this article:
Mehta P, Verma G, Tegta GR, Bhota S. Platelet-rich plasma for the treatment of vitiligo: A case series. Indian J Drugs Dermatol 2022;8:73-8

How to cite this URL:
Mehta P, Verma G, Tegta GR, Bhota S. Platelet-rich plasma for the treatment of vitiligo: A case series. Indian J Drugs Dermatol [serial online] 2022 [cited 2023 May 28];8:73-8. Available from: https://www.ijdd.in/text.asp?2022/8/2/73/367122




  Introduction Top


Vitiligo is a multifactorial polygenic disorder with a complex pathogenesis.[1]

The exact prevalence of vitiligo has not been known but is considered to lie between 0.4% and 4%.[2] It has a major impact on the quality of life and self-esteem. Depression, anxiety, and other psychiatric comorbidities are common in vitiligo patients.[3] The pathogenesis remains incompletely understood and is believed to be caused by dynamic interplay between genetic and environmental factors that initiate an autoimmune attack on melanocytes in the skin. The main hypothesis includes autoimmune hypothesis, neural hypothesis, self-destruct hypothesis, and biochemical hypothesis.[4]

The various therapies have been proposed for treating vitiligo, but none of these have shown desirable therapeutic effect. Platelet-rich plasma (PRP) has been emerging as a new treatment modality in many dermatological diseases. The usage of PRP in vitiligo is still in its initial stages.


  Materials and Methods Top


A total of five patients of stable vitiligo (without any activity since 1 year) who were not responding to topical therapies were included.

Each patient was given intradermal injections of freshly prepared autologous PRP. PRP was prepared by manual double-spin technique. The venous blood approximately (8–10 mL) was drawn into a tube containing anticoagulant acid citrate dextrose/sodium citrate to avoid platelets activation and degranulation. The blood was then processed for the first centrifugation (soft spin) for 5 min at 1500 rpm approximately, which separated blood into three layers, namely bottom-most red blood cell (RBC) layer (around 55% of total volume), topmost a cellular plasma layer (platelet-poor plasma [PPP]), which was around 40% of a total volume, and an intermediate PRP layer (around 5% of total volume) called the buffy coat. Using a sterile syringe, PPP, PRP, and some RBCs were transferred into another tube without an anticoagulant. This tube was then processed for the second centrifugation (hard spin) for 15 min at around 2500 rpm. This allowed the platelets (PRP) to settle at the bottom of the tube with a very few RBCs. PPP (80% of the volume) was formed at the top. Most of the PPP was removed with a syringe and discarded, and the remaining PRP was shaken well. The PRP formed was collected into an insulin syringe, already containing calcium gluconate, which acts as an activator by nullifying the action of anticoagulant. The ratio of calcium gluconate and PRP in insulin syringe was 1:9, respectively.

PRP formed was injected intradermally in a dose of 0.1–0.2 mL per injection approximately 1 cm apart in depigmented patches at a 4-week interval for a total of four injections. The patients were also advised to apply topical tacrolimus 0.1% ointment daily at night. The final results were evaluated at the end of 4 months by using a quartile grading scale (grade 1: <25%, no or minimal improvement; grade 2: 25%–49%, moderate; grade 3: 50%–74%, marked; grade 4: >75%–99%, excellent; and grade 5: 100%, complete).

Out of five patients, two showed excellent response and two patients showed moderate response to the treatment, whereas there was no response seen in one patient. No side effects were noted during the treatment.


  Case Reports Top


Case 1

A 17-year-old female patient presented with a single localized depigmented patch over the left upper eyelid since 3 years. The lesion was asymptomatic, initially started as a pea-sized depigmented macule, which increased in size gradually to its present size [Figure 1] during the course of the first year. The lesion has remained stable since then, i.e., the absence of any new lesions and no extension of preexisting lesions. There was no familial history, and her routine blood investigations and thyroid function tests were within normal limits. She had received topical steroids and calcineurin inhibitors for a long period of time (6 months) in the past, but no improvement was seen. The patient was off-medication since 1 year. She was started with PRP and topical tacrolimus 0.1% ointment application at night. A total of four injections of PRP at 4-week interval were given intradermally. After the first session of PRP, no significant improvement was there, but after the second session, repigmentation started to appear with mild decrease in the size of the lesion. At the end of 4 months, the patient demonstrated repigmentation >75% improvement from the baseline [Figure 1] and [Figure 2].
Figure 1: Depigmented patch over the left upper eyelid before treatment (patient 1)

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Figure 2: Significant repigmentation achieved after a total of four injections of PRP at 4-week interval (patient 1)

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Case 2

A 20-year-old female patient with a single vitiligo patch over the left cheek was included in the study. It started at the age of 15 years, initially a small depigmented dot, which gradually increased to the present size over a period of 2 years [Figure 3]. The lesion was nonprogressive since then and the patient did not report appearance of any new lesions. The patient was prescribed topical steroids, oral levamisole, and calcineurin inhibitors by a dermatologist in the past but left medications on her own after 4 months when no improvement was seen. She was off-medications since then (6 months). Her routine investigations and thyroid profile were in normal limits. PRP along with topical tacrolimus was started, and after four sessions of PRP, lesion resolved significantly (grade 4) without any noted side effects [Figure 3] and [Figure 4].
Figure 3: Vitiligo patch over the left cheek (patient 2)

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Figure 4: Repigmentation after PRP (patient 2)

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Case 3

A 35-year-old woman had depigmented lesion over the anterior aspect of the left wrist since the age of 27 years. The lesion started as a pin-head sized macule, which gradually increased to its present size over a period of 5 years. There was no increase in the size of lesion since 3 years. The patient had applied topical steroids, deca-peptide solution in the past, but no improvement was seen. She was given intradermal PRP injections and advised to apply topical tacrolimus at night. The improvement was visible as there is a decrease in size of the lesion (grade 2) with pigmentation starting from the periphery and gradually extending toward the center of the lesion [Figure 5] and [Figure 6].
Figure 5: Lesion over the anterior aspect of the left wrist (patient 3)

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Figure 6: Decrease in size of lesion after PRP (patient 3)

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Case 4

A 38-year-old woman with stable vitiligo lesion over the dorsum of the left foot was included. Since 3 years, there was no extension of the existing lesion. In the past, she had been treated with topical tacrolimus ointment and steroids, but there was no response. Thereafter, she took homeopathic medications, but again there was no improvement. Her routine blood investigations and thyroid tests were within normal limits. After two sessions of PRP, no significant improvement was seen, but after receiving four sessions of PRP injections, repigmentation started from the periphery of the lesion with a decrease in size more than 25% from the baseline [Figure 7] and [Figure 8].
Figure 7: Lesion over dorsum of the left foot (patient 4)

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Figure 8: Improvement in lesion after PRP (patient 4)

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Case 5

A 46-year-old man presented with depigmented patch around the right foot since the age of 27 years. During the first 2–3 years, the lesion increased in size to its present size but remained stable since then. In the family history, his grandfather had also suffered from vitiligo. The thyroid function tests and routine blood tests were within normal limits. The lesion was not responding to the topical treatments, which the patient had applied in the past. The patient was planned for PRP, but even after four sessions of PRP, no sign of repigmentation was seen.


  Discussion Top


PRP is an autologous preparation of platelets in concentrated plasma with platelets concentration five times more than the baseline values. PRP has a high concentration of growth factors such as fibroblast growth factor-7 and beta-catenin.[5] It plays an important role in maintaining tissue repair through the release of growth factors by the degranulation of α-granule.[6] These factors promote cellular proliferation and differentiation. PRP also causes the activation of phosphatidylinositol 3-kinase; protein kinase B (Akt) signaling enhances cell survival and reduces apoptosis.[7]

In vitiligo, it has been proposed that these growth factors in PRP may stimulate melanocyte proliferation and repigmentation in the vitiligo lesions.[6]

Studies have shown that melanocytes in patients with vitiligo have defects in the Wnt/β-catenin signal pathway, which promotes the differentiation of melanocytes precursors in the skin. The growth factors released by PRP stimulate protein kinase B (Akt) by binding to growth factor receptors on the cell membrane. Akt prevents melanocyte apoptosis by inhibiting B-cell lymphoma 2 and inhibits glycogen synthase kinase-3 (an enzyme that degrades β-catenin) to promote β-catenin accumulation in the cytoplasm, leading to the survival and proliferation of melanocytes.[8]

It was also found that PRP induces accelerated proliferation and migration of fibroblasts through the upregulation of cyclin E and cyclin-dependent kinase 4, which is important in cell migration and proliferation.[7]

Huang et al.[9] suggested the apoptosis hypothesis in vitiligo, which proposes that cytokines such as interleukin 1, interferon gamma (IFN-γ) or tumour necrosis factor alpha (TNF-α), released by lymphocytes, keratinocytes, and melanocytes, can initiate apoptosis. The growth factors of PRP suppress cytokine release, limit inflammation, and limit apoptosis of melanocytes.[10] Interleukin 17, matrix metalloproteinase-2, matrix metalloproteinase-9, various types of cytokines, and growth factors enhance migration and mitogens of melanocytes.[11]

There have been very few studies about the role of PRP in vitiligo.

Lim et al.[12] treated 16 vitiligo patients by giving intradermal injections of PRP into lesions spacing 0.5 cm between each injection (0.05 mL/each injection) by using a 1 mL syringe with a 26-gauge needle weekly for 10 weeks. In this study, only few patients responded and they suggested that PRP does not effectively induce repigmentation in vitiligo. However, in the present case series, 80% of patients showed improvement.

Kadry et al. (2018)[13] conducted a prospective study of 30 patients with stable nonsegmental vitiligo. The patients received six treatment sessions with 2-week interval for 3 months. It was observed that a combination of PRP with fraction carbon dioxide laser was more effective in producing repigmentation than PRP alone or fraction carbon dioxide laser alone. Interestingly, they observed that the trunk lesions showed higher response with PRP and lower limbs showed the highest improvement with Fr:CO2 laser.

Abdelghani et al.[14] evaluated a combined treatment with fractional carbon dioxide laser, autologous PRP (four sessions of PRP injections with 3-week interval), and narrowband ultraviolet B in different body sites, in 80 patients with vitiligo for 12 months. Patients included in combined fractional CO2 laser + PRP reached the best results regarding repigmentation; specifically 60% of the patients developed a repigmentation >50% and 40% of patients developed a repigmentation >75%.

Garg et al. (2019)[15] conducted a pilot study of 10 patients with stable vitiligo and evaluated the extent of repigmentation with noncultured trypsinized fragmented epidermal suspension using PRP and pixel erbium yttrium aluminum garnet laser for 6 months. The repigmentation was observed as early as 2 weeks with an excellent response in 60% of patients of stable vitiligo in 8 weeks. In an another study by Ibrahim et al.,[16] 60 stable vitiligo patients were enrolled; the left side of the body was treated with narrow band ultraviolet-B (NB-UVB) alone (control side), whereas the right side was treated with NB-UVB therapy in addition to intradermal injection of PRP, every 2 weeks for 4 months. Compared with NB-UVB side, 55% of patients in the PRP group achieved excellent repigmentation and 20% achieved good repigmentation in 4-month duration. Hence a significant improvement in the repigmentation was there in the combination group (PRP plus NB-UVB) compared with the NB-UVB group.

Variable improvement has been seen in vitiligo patches treated by different study modalities. In most studies conducted previously, PRP had been used as an adjuvant for treating stable vitiligo with lasers such as NB-UVB and fractional CO2 laser. However, contrary to previous studies, PRP has been used as the main treatment modality in the present case series report.

In present case series, out of five patients, two showed excellent response (grade 4) and two patient showed moderate response (grade 2) to the treatment, whereas there was no response seen in one patient [Figure 9]. No major side effects were noted during the treatment expect for mild pain at the site of injection. The lack of consensus regarding preparation methods and time interval to repeat PRP make it difficult to compare results from different clinical studies. As compared to the studies conducted previously, in the present study, PRP was given at 4-week interval rather than at biweekly interval.
Figure 9: Summary of pre-treatment and post-treatment images

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  Conclusions Top


The use of PRP in treating vitiligo is still in its initial stage and requires larger prospective controlled studies for further validation. This case series report demonstrates that PRP offers a safer, minimally invasive, effective treatment for stable vitiligo and may be combined with other treatment modalities.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Malhotra N, Dytoc M The pathogenesis of vitiligo. J Cutan Med Surg 2013;17:153-72.  Back to cited text no. 1
    
2.
Bidaki R, Haghighi FS Recurrent suicide attempt in two sisters with non-segmental vitiligo and obesity: A rare case report. Pigment Disord 2016;3:235.  Back to cited text no. 2
    
3.
Elbuluk N, Ezzedine K Quality of life, burden of disease, co-morbidities, and systemic effects in vitiligo patients. Dermatol Clin 2017;35:117-28.  Back to cited text no. 3
    
4.
Forschner T, Buchholtz S, Stockfleth E Current state of vitiligo therapy—Evidence-based analysis of the literature. J Dtsch Dermatol Ges 2007;5:467-75.  Back to cited text no. 4
    
5.
Landesberg R, Roy M, Glickman RS Quantification of growth factor levels using a simplified method of platelet-rich plasma gel preparation. J Oral Maxillofac Surg 2000;58:297-300; discussion 300-1.  Back to cited text no. 5
    
6.
Abuaf OK, Yildiz H, Baloglu H, Bilgili ME, Simsek HA, Dogan B Histologic evidence of new collagen formulation using platelet rich plasma in skin rejuvenation: A prospective controlled clinical study. Ann Dermatol 2016;28:718-24.  Back to cited text no. 6
    
7.
Li ZJ, Choi HI, Choi DK, Sohn KC, Im M, Sri YJ, et al. Autologous platelet rich plasma: A potential therapeutic tool for promoting hair growth. Dermatol Surg 2012;38:1040-6.  Back to cited text no. 7
    
8.
Bastonini E, Bellei B, Filoni A, Kovacs D, Iacovelli P, Picardo M Involvement of non-melanocytic skin cells in vitiligo. Exp Dermatol 2019;28:667-73.  Back to cited text no. 8
    
9.
Huang CL, Nordlund JJ, Boissy R Vitiligo: A manifestation of apoptosis? Am J Clin Dermatol 2002;3:301-8.  Back to cited text no. 9
    
10.
Bernuzzi G, Tardito S, Bussolati O, Adorni D, Cantarelli S, Fagnoni F, et al. Platelet gel in the treatment of cutaneous ulcers: The experience of the Immunohaematology and Transfusion Centre of Parma. Blood Transfus 2010;8:237-47.  Back to cited text no. 10
    
11.
Kumar R, Parsad D, Kanwar AJ, Kaul D Altered levels of Ets-1 transcription factor and matrix metalloproteinases in melanocytes from patients with vitiligo. Br J Dermatol 2011;165:285-91.  Back to cited text no. 11
    
12.
Lim K, Shin MK, Lee MH Clinical application of platelet-rich plasma in vitiligo: A pilot study. Poster presentation; Proceedings of the 21st International Pigment Cell Conference; Bordeaux. France. 20–24 September 2011.  Back to cited text no. 12
    
13.
Kadry M, Tawfik A, Abdallah N, Badawi A, Shokeir H Platelet-rich plasma versus combined fractional carbon dioxide laser with platelet-rich plasma in the treatment of vitiligo: A comparative study. Clin Cosmet Investig Dermatol 2018;11:551-9.  Back to cited text no. 13
    
14.
Abdelghani R, Ahmed NA, Darwish HM Combined treatment with fractional carbon dioxide laser, autologous platelet-rich plasma, and narrow band ultraviolet b for vitiligo in different body sites: A prospective, randomized comparative trial. J Cosmet Dermatol 2018;17:365-72.  Back to cited text no. 14
    
15.
Garg S, Dosapaty N, Arora AK Laser ablation of the recipient area with platelet-rich plasma-enriched epidermal suspension transplant in vitiligo surgery: A pilot study. Dermatol Surg 2019;45:83-9.  Back to cited text no. 15
    
16.
Ibrahim ZA, El-Ashmawy AA, El-Tatawy RA, Sallam FA The effect of platelet-rich plasma on the outcome of short-term narrowband-ultraviolet B phototherapy in the treatment of vitiligo: A pilot study. J Cosmet Dermatol 2016;15:108-16.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]



 

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