Baseline Dermoscopic Vascular Score and Response to Oral Tranexamic Acid in Facial Melasma

Design: prospective, single-centre, single-arm interventional study with prognostic-factor assessment.

Exposure: a study-defined dermoscopic vascular score. In each affected facial region (forehead, right malar, left malar, chin), one field in the most densely pigmented area is graded 0-3 for erythema and telangiectatic vessels, giving a total of 0-12 (prorated when fewer than four regions are graded). Dermoscopy uses a DermLite DL4 in polarised contact mode with minimal or no pressure, after removal of cosmetics and sunscreen and a 5-minute rest.

Outcome assessment: mMASI is scored at every visit by a dermatologist unaware of the vascular score; at baseline and week 12 it is completed before dermoscopy.

Sample size: precision-based. 102 participants with complete data give a 95% confidence interval of total width 0.40 for the adjusted correlation; 128 will be recruited to allow 20% non-evaluability.

Analysis: multiple linear regression of week-12 mMASI on baseline vascular score, adjusted for baseline mMASI, duration of melasma, age and Fitzpatrick skin type. Missing week-12 outcomes will be handled by multiple imputation, with prespecified sensitivity analyses, including adjustment for prior topical corticosteroid use. Inter-observer reliability will be assessed by intraclass correlation on stored baseline images of the first 40 participants.

Safety: participants are screened for thromboembolic risk and given written stop-and-attend instructions. Rescue treatment is offered if mMASI rises by 25% or more above baseline. Serious adverse events are reported to the Ethical Review Committee.

• Tranexamic acid (Drug), also known as TXA: 250 mg orally twice daily for 12 weeks, dispensed monthly.
• Standardised sunscreen and emollient (Other): Broad-spectrum SPF 50+ sunscreen each morning and reapplied during the day; plain ceramide-based emollient at night. Both are free of depigmenting or brightening agents.

Primary outcomes

• Week-12 mMASI in relation to baseline dermoscopic vascular score [Baseline and week 12]: Association between the baseline dermoscopic vascular score (range 0-12; higher = more vascular) and the modified Melasma Area and Severity Index (mMASI; range 0-24; higher = more severe) at week 12. Estimated by multiple linear regression adjusted for baseline mMASI, duration of melasma, age and Fitzpatrick skin type, and reported as the adjusted difference in week-12 mMASI per one-point higher baseline vascular score.

Secondary outcomes

• Change in mMASI from baseline [Baseline, weeks 4, 8 and 12]: mMASI score (range 0-24; higher = more severe) at weeks 4, 8 and 12 compared with baseline.
• Percentage reduction in mMASI and proportion of responders [Baseline and week 12]: Change in total dermoscopic vascular score (range 0-12) from baseline to week 12 in matched facial regions, and its association with absolute change in mMASI.
• Treatment response by dermoscopic phenotype [Week 12]: Exploratory descriptive comparison of week-12 mMASI response between pigmentary (vascular score below 4) and pigmentary-vascular (vascular score 4 or more) phenotypes.
• Inter-observer reliability of the dermoscopic vascular score [Baseline]: Intraclass correlation coefficient (two-way mixed effects, absolute agreement, single measure) between two dermatologists independently scoring stored baseline dermoscopic images of the first 40 participants.
• Adherence to tranexamic acid [Weeks 4, 8 and 12]: Percentage of prescribed tablets taken, calculated from tablet counts of returned strips.
• Adverse events, treatment discontinuation and rescue treatment [Baseline to week 12]: Number of participants with adverse events (including thromboembolic events), number discontinuing treatment, and number receiving rescue treatment.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age 18 years or above, either sex
* Clinically diagnosed facial melasma
* Fitzpatrick skin type III, IV or V
* Baseline mMASI of 4 or greater
* Treatment-naive, or no topical or systemic melasma treatment for at least 2 weeks
* Willing to take oral tranexamic acid and attend all follow-up visits
* Written informed consent

Exclusion Criteria:

* Pregnancy, lactation or planned pregnancy during the study
* History of deep venous thrombosis, pulmonary embolism, stroke, myocardial infarction or other significant thromboembolic disease
* Known thrombophilia or coagulation disorder, or clinically relevant family history
* Current oestrogen-containing contraceptive or other oestrogen-containing treatment
* Current anticoagulant treatment
* Renal impairment or serum creatinine above the reference range
* Active malignancy, or major surgery within 3 months
* Known hypersensitivity to tranexamic acid
* Other facial pigmentary disorder that may interfere with assessment (exogenous ochronosis, lichen planus pigmentosus, acquired dermal macular hyperpigmentation, prominent post-inflammatory hyperpigmentation)
* Active rosacea, facial eczema, inflammatory acne or other facial inflammatory dermatosis
* Dermoscopic vascularity ungradable in two or more affected facial regions
* Chemical peel, microneedling, laser or other procedural melasma treatment within 3 months
* Any other contraindication to oral tranexamic acid

• Amara Safdar, MBBS, FCPS, Principal investigator, Allied Hospital, Faisalabad Medical University