Intradermal tranexamic acid versus PRP for melasma: A comparative randomized trial

Inclusion criteria

• Patients with clinically diagnosed epidermal/dermal or mixed melasma

• Patients aged ≥18 years old and <50 years old.

Exclusion criteria

• Used any form of melasma treatment, whether oral or topical, within the past 3 months

• Patients with established platelet dysfunction disorder/known cases of bleeding disorders

• Patients on oral contraceptive pills/anticoagulants

• Pregnant and lactating females.

Eligible patients were randomized into two parallel groups (Group A and Group B) using the sequentially numbered opaque sealed envelopes (SNOSEs) technique. A random allocation sequence was generated using a computer-generated random number table. The allocation sequence was placed in SNOSE prepared by a staff member who was not involved in patient recruitment or assessment. At the time of enrolment, the treating investigator opened the next envelope in sequence to determine treatment allocation. The use of opaque sealed envelopes ensured allocation concealment.

• Group A (n = 24): Intradermal TXA

• Group B (n = 24): Intradermal PRP

The total sample size of 48 patients was determined based on the availability of eligible patients presenting to our center during the predetermined study period.

Operative procedure

Patients were laid in Fowler’s position, and the area involved was then covered in a thin layer of a eutectic mixture of local anesthetics (EMLAs) containing 2.5% lidocaine and 2.5% prilocaine for 45–50 min under occlusion.

Preparation of TXA

TXA ampoules of 500 mg/ml were diluted using normal saline in the ratio 1:25 so as to obtain a concentration of 4 mg/mL, similar to the RCT by Abd Elraouf et al.³

Preparation of PRP

20 mL of venous blood was drawn and placed in tubes containing acid citrate dextrose- A under completely aseptic conditions. The PRP was prepared using a standard double centrifugation technique. In the present study, platelet counts were not measured after preparation; therefore, the final platelet concentration or fold increase could not be quantified. Approximately 3 mL of PRP was injected per session using intradermal microinjections over the affected areas. Calcium chloride or any other activation methods were not used. The prepared PRP was injected directly, relying on endogenous activation after injection into the dermal tissue.

Post-procedure care

The EMLA was cleaned, followed by sterilizing the involved area with a 10% povidone-iodine solution. A 31-gauge needle was then used for the administration of the respective treatment modality. Post-procedure, a thin layer of Mupirocin ointment was applied to the area treated. The patient was asked to avoid the application of possible irritants such as soap, cosmetic products, homemade remedies, and moisturizers/serums for the next 24 h. Patients were advised to apply a broad-spectrum sunscreen with a minimum SPF of 30, thrice a day till the last follow-up session. The formulation recommended was of physical blockers such as zinc oxide and/or titanium dioxide, with or without chemical filters.

Pain and erythema were recorded at 1 h and 6 h after the procedure. If it persisted beyond 6 h, then it was managed with analgesics and antihistamines.

Clinical assessment and followup

4 sessions, each at an interval of 4 weeks, were performed with meticulous photographic (using iPhone 14 Pro) and dermoscopic (using DermaIndia M10A30) workup. The patient was then followed up 3 months after the last treatment session. Hence, assessment was done at week 0, week 4, week 8, week 12, and week 24, using the modified MASI score. Along with this, at week 4, week 8, week 12, and week 24, PGA was implemented.

Dermoscopic score of the pigmentary and vascular elements was calculated at week 0 and week 24. This scoring system evaluates five specific pigmentary patterns – pseudoreticular, globular, dotted, arcuate, perifollicular pigmentation, and telangiectasia. Each of these clinical findings is graded on a qualitative four-point scale ranging from 0 (not detected) to 3 (obvious). Data thus compiled were used to assess and compare the two procedures.

Statistical analysis of data

Statistical analysis was done using the statistical package for the social sciences software version 26.0 (IBM, Chicago). Descriptive and inferential statistics were done. Continuous variables were expressed as mean ± standard deviation and categorical variables as frequencies and percentages. Appropriate statistical tests (e.g., independent t-test/Chi-square test/repeated measures analysis of variance with post hoc comparisons) were used for within-group and between-group comparisons. A p ≤ 0.05 was considered statistically significant.

The primary endpoint of the study was the change in mMASI score at the end of 24 weeks. Secondary endpoints included changes in PGA scores, dermoscopic score of the pigmentary and vascular elements, and safety outcomes (pain, erythema, and recurrence) at 24 weeks. Analysis type was of the Per-Protocol type and 95% confidence intervals were reported. As this was an exploratory comparative study, a prior power calculation based on an assumed effect size was not performed.

Epidemiological data

The mean age of participants was slightly higher in Group A (30.4 ± 7.19 years) compared to Group B (28.91 ± 7.86 years), suggesting a comparable distribution in Group A and Group B. The majority of participants were females, accounting for 85.4% of the total sample, while males constituted only 14.6%, indicating a female predominance in both groups. In terms of skin phototype, the majority of participants belonged to Fitzpatrick skin type V (64.6%), while type IV constituted 33.3%, and type III only 2.1%. Regarding the type of melasma, the mixed type was most common (39.6%), followed by epidermal (33.3%) and dermal (27.1%) types. Most participants had melasma for 1–3 years (50%), whereas 37.5% reported a duration of 4–6 years, and 12.5% had melasma for 7–10 years. The malar pattern was the predominant site (64.6%), followed by the centrofacial pattern (35.4%). Overall, both groups were well matched demographically, minimizing confounding effects related to baseline characteristics [Table 1].

Comparision of mean percentage reduction in mMASI scores between Group A and Group B at different time intervals

At week 4, Group A showed a higher mean percentage reduction (14.80 ± 12.32%) compared to Group B (8.14 ± 3.55%), with a mean difference of 6.67% (p = 0.014), indicating an early response in Group A. However, by week 8, Group B exhibited a greater reduction (25.10 ± 9.66%) than Group A (21.30 ± 13.66%), though the difference was not statistically significant (p = 0.273). At week 12, Group B continued to show improvement (35.58 ± 9.90%) compared to Group A (28.59 ± 12.91%), with the difference reaching statistical significance (p = 0.041). By week 24, this trend became more evident, as Group B demonstrated a higher mean percentage reduction (44.74 ± 12.21%) than Group A (35.59 ± 16.86%) (p = 0.037). These findings suggest that while Group A responded faster initially, Group B achieved a more sustained reduction in melasma severity over time, highlighting its efficacy [Figures 1 and 2, Graph 1, Table 2].

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Figure 1: 32-year-old female with melasma. (a) Clinical picture before starting intradermal platelet-rich plasma (PRP) therapy. (b) Clinical picture after four sessions of PRP therapy. (c) Dermoscopy before intradermal PRP therapy (non polarized, 10x). (d) Dermoscopy after completion of intradermal-PRP therapy(non polarized, 10x).

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Figure 2: 35-year-old female with melasma. (a) Clinical picture before starting intradermal tranexamic acid (TXA) therapy. (b) Clinical picture after four sessions of TXA therapy. (c) Dermoscopy before intradermal TXA therapy (non polarized, 10x). (d) Dermoscopy after completion of intradermal TXA therapy (non-polarized, 10x).

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Graph 1: Comparison of mean percentage reduction of modified Melasma area and severity index(mMASI) scores between Group A and Group B at different time intervals.

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Comparison between groups and PGA scores

While Group A (TXA) provided a faster clinical response by week 4 (p = 0.002), this advantage disappeared by week 8 as progress equalized. Ultimately, response in Group B (PRP) proved better, yielding higher patient satisfaction by week 24 (p = 0.016) and a 16.7% “good” response rate with no reported worsening of the condition. Ultimately, response in group B (PRP) proved better, yielding higher patient satisfaction by week 24 (p= 0.016) and a 16.7% “good” response rate with no reported worsening of the condition [Graph 2].

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Graph 2: Patient global assessment scores (PGA) in both groups at every visit.

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Erythema, pain, and recurrence

Both groups showed similar, short-term discomfort and redness that resolved within 24 h.

Group B demonstrated comparative stability with a 0% recurrence rate, while Group A had a higher recurrence rate of 20.8% (n = 5, p = 0.018). While both treatments were equally well-tolerated and safe, Group B was more effective at preventing the return of melasma.

Comparison of the percentage reduction of mMASI scores based on the type of lesion

The intra-group comparison of mean percentage reduction of mMASI scores in Groups A and B based on the type of lesion revealed progressive improvement across all lesion types from week 4 to week 24, indicating that the extent of improvement in melasma severity was similar regardless of lesion depth or type, reflecting a uniform treatment response across all lesion categories [Graphs 3 and 4].

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Graph 3: Intra-group comparison of the percentage reduction of modified melasma area and severity index(mMASI) scores in Group A based on the type of lesion.

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Graph 4: Intra-group comparison of the percentage reduction of modified melasma area and severity index scores in Group B based on the type of lesion.

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Comparison of mean dermoscopic score at different time intervals

Both groups began with nearly identical baseline dermoscopic scores (Group A: 10.92 ± 2.75; Group B: 10.63 ± 2.86), confirming comparable pigmentation patterns at week 0 (p = 0.720). By the end of the 24-week study, both interventions successfully improved melasma features, as evidenced by a noticeable decrease in scores for all participants. Although Group B (PRP) achieved a lower final mean score of 7.75 ± 2.25 compared to Group A (8.83 ± 2.71), this trend toward better clinical response did not reach statistical significance (p = 0.139).

PGA scores at different time intervals

At week 4, a statistically significant association was observed between the treatment groups (p = 0.002). However, by week 24, PRP demonstrated fitter outcomes, with 16.7% of patients rating their improvement as “good” compared to 4.2% in the TXA group (χ² = 10.264, p = 0.016). These findings align with those of Sitaula et al.,⁹ who conducted a randomized split-face study comparing PRP delivered by microneedling and microinjection in 62 patients with melasma. It produced significantly higher PGA scores (p < 0.001), with 73.33% of patients achieving more than 50% improvement compared to only 18.33% in the microinjection group. In comparison, while our PRP group (delivered intradermally) showed delayed but significant subjective improvement by week 24, Sitaula et al.⁹ observed more rapid and pronounced PGA gains with microneedling. This difference likely reflects the enhanced penetration and uniform delivery achieved with microneedling.

Mean dermoscopic score at different time intervals

TXA and PRP both demonstrated improvement in dermoscopic scores over 24 weeks. However, the intergroup difference did not reach statistical significance (p = 0.139). These findings are in agreement with those reported by Rout et al.,¹⁰ who conducted a clinical and dermoscopic evaluation of intradermal PRP in patients with melasma and observed significant improvement in both clinical and dermoscopic parameters after 12 weeks of treatment in Fitzpatrick skin types IV–V. While Rout et al.¹⁰ did not provide specific numeric dermoscopic score values, their results support the effectiveness of PRP in reducing dermoscopic pigmentation features. The lack of statistical significance between the two treatment arms in the present study may be attributed to the relatively small sample size, differences in treatment duration, and variability inherent to dermoscopic scoring.

Pain and erythema

Both TXA and PRP were well tolerated, with minimal adverse effects limited to transient pain and erythema at the injection site. These findings are consistent with Patil and Bubna,⁷ Abd Elraouf et al.,³ and Mumtaz et al.,⁶ who similarly documented mild transient erythema and edema in both treatment arms. All these studies, along with the present data, reaffirm that both TXA and PRP are safe, well-tolerated treatment options for melasma.

Recurrence

A statistically significant difference in recurrence was noted between the two treatment groups (p = 0.018), with 20.8% of patients in the TXA group experiencing recurrence, whereas Lueangarun et al.,¹¹ observed a 60% recurrence rate at 48 weeks following intradermal TXA monotherapy. In the present study, no recurrence was seen in the PRP group. These results were similar to Sitaula et al.,⁹ who reported no significant recurrence during follow-up in PRP therapy. Deng et al.⁸ also found durable improvement in PRP-treated patients with no relapse at 12-week post-treatment.

Comparison of mMASI percentage reduction in different lesion types

Pairwise comparison of mMASI percentage reduction among different lesion types (dermal, epidermal, and mixed) within the PRP and TXA group revealed no statistically significant differences at any follow-up interval (p > 0.05 for both groups); both groups produced a consistent therapeutic effect irrespective of melasma depth or classification. Abd Elraouf et al.³ after PRP/TXA therapy, followed by mixed and dermal types, indicating better responsiveness of superficial pigmentation. Contradictory to the above-mentioned studies, the results of the present study showed no difference in the type of lesions. This could be due to a small sample size and short period of follow-up.

Comparison of dermoscopic scores in different lesion types

Dermoscopic evaluation across different melasma types – dermal, epidermal, and mixed – showed improvement in both TXA and PRP groups over 24 weeks, though none of the intergroup differences reached statistical significance (p > 0.05).

This score was first introduced by Abdel Hay et al.,¹² who applied the same six-feature dermoscopic scoring system, and similar trends emerge. The study reported a statistically significant reduction in total dermoscopic score (p < 0.001) following five sessions of low-fluence 1064-nm Q-switched Nd: YAG laser. Importantly, they observed greater improvement in epidermal melasma compared to dermal and mixed variants, due to the laser’s limited penetration depth. In the study by Rout et al.,¹⁰ dermoscopic assessments demonstrated significant improvement following three sessions of PRP therapy. These dermoscopic changes correlated with a significant clinical improvement (p < 0.05), confirming PRP’s efficacy in reducing both pigmentary and vascular components of melasma.

Limitations

• A prior power calculation based on an assumed effect size was not performed

• The use of subjective outcome measures such as mMASI and PGA without assessor blinding may introduce observer bias

• A follow-up duration of 3 months may be insufficient to fully evaluate recurrence in melasma, and longer follow-up periods are recommended for future studies.