Intralesional Methotrexate Enters Direct Comparison With Triamcinolone in Nail Psoriasis
A phase 2 trial at Tanta University set out to answer a question that matters at the bedside: which intralesional agent does more for nail psoriasis when systemic therapy is off the table and topical treatment has already failed. The study compared methotrexate with triamcinolone acetonide in a within-participant, left-to-right design, giving one affected side methotrexate and the opposite side triamcinolone acetonide. The approach is unusually efficient for a disease in which a single patient may carry two simultaneously diseased nails that behave differently, even under the same immune and environmental pressures.
Nail psoriasis can be stubborn. Pitting, discoloration, thickening, and onycholysis are not cosmetic nuisances alone; they reflect chronic inflammation in the nail matrix and nail bed, where small structural changes translate into visible distortion and functional discomfort. In that setting, local treatment carries a clear biological logic. Drug delivered directly into the diseased nail unit can expose the inflamed compartment to higher concentrations while limiting whole-body exposure, a tradeoff that often makes intralesional therapy attractive when diffuse therapy is undesirable or has already disappointed.
A Side-by-Side Design Built Around the Same Patient
The trial enrolled 25 participants with bilateral, clinically significant nail psoriasis that had not responded well to prior treatment. Each participant served as their own comparator. One side received intralesional methotrexate at a concentration of 25 mg/mL, while the opposite side received intralesional triamcinolone acetonide at 10 mg/mL. Sessions were scheduled every two weeks, for up to six treatments or until improvement occurred.
That structure matters because it reduces between-person noise. Age, immune background, psoriasis severity, disease duration, and pain tolerance can all complicate interpretation in parallel-arm dermatology studies. By comparing opposite sides in the same participant, the investigators narrowed the clinical question to the treatment effect itself, rather than the patient’s baseline biology. The tradeoff is familiar in single-blinded local therapy studies: the hands-on practicalities are strong, while the design still depends on careful measurement and a disciplined follow-up schedule.
Participants came from the Dermatology and Venereology Outpatient Clinic at Tanta University Hospital in Gharbia Governorate, Egypt. The age range was 16 to 50 years, and all sexes were eligible. Pregnancy and lactation were excluded, as were onychomycosis, concurrent nail disorders such as trauma, other dermatologic disease, systemic disease, and any concomitant drug therapy that could affect the nail. Patients also had to avoid topical or systemic treatment for nail psoriasis for three months before enrollment and throughout the study. Those criteria created a relatively clean read on the nail unit itself.
What the Trial Measured at the Nail Unit
The primary endpoint was change from baseline in the target nail Nail Psoriasis Severity Index, or NAPSI, at 3 and 6 months after the first treatment session. Each target nail was scored from 0 to 8, with higher values reflecting more severe disease. Because the same nail was tracked over time, the endpoint could capture whether improvement emerged early and whether it persisted after the treatment period ended.
Secondary measures went beyond the visible surface. Ultrasound assessed nail plate thickness, nail bed thickness, and nail matrix thickness at baseline, 3 months, and 6 months. Dermoscopy added a magnified clinical readout of psoriatic change across the treatment period. The study also tracked treatment-related adverse events, including injection-site pain, depigmentation, subungual hematoma, and yellow discoloration.
Those measures reflect how nail psoriasis behaves in real life. The disease is layered anatomically, and a visible change in the nail often lags behind microscopic inflammation. Ultrasound and dermoscopy can detect structural and surface changes earlier than casual inspection, which is useful when the clinician is trying to judge whether a local intervention is modifying the disease process or merely changing appearance.
Safety Monitoring Centered on Known Intralesional Risks
The trial did not treat safety as an afterthought. Each participant was asked to report pain, discomfort, bleeding beneath the nail, or other medical problems during follow-up. Local numbing injections and ice packs were built into the protocol to reduce discomfort during treatment visits. Monthly follow-up continued for three months after the last session, extending observation beyond the active treatment window.
This is a sensible design choice in a small nail study. Intralesional therapy can be effective, but the nail unit is unforgiving to procedural misadventure. Pain is expected, and a small subungual bleed or pigment change can matter disproportionately to patients who are already bothered by visible nail disease. In a condition where patients often weigh symptom relief against the nuisance of repeated injections, tolerability may determine whether a regimen survives outside a trial setting.
Why Methotrexate vs Triamcinolone Is a Clinically Relevant Question
Triamcinolone acetonide has long been used in localized inflammatory nail disease because corticosteroids blunt the immune cascade that drives psoriatic change. Methotrexate operates through a different anti-inflammatory pathway and may offer a distinct local effect on proliferating keratinocytes and immune activation within the nail unit. Comparing the two directly inside the same patient gives clinicians a more precise sense of whether one mechanism better fits the biology of nail psoriasis, rather than relying on extrapolation from skin plaques or broader psoriasis management.
The study’s single-blinded design suggests that participants were blinded, while the left-right allocation was not randomized. No results were posted in the record reviewed here, so no efficacy or safety conclusion can be drawn from the registry entry alone. Even so, the protocol signals a practical attempt to answer a narrow therapeutic question with a measurable endpoint, and the use of NAPSI plus ultrasound raises the likelihood that any signal of benefit would be captured across both clinical and structural domains.
Why the Record Stops Short of a Practice Change
The trial began on 2023-05-01, reached primary completion on 2025-03-10, and completed on 2025-06-15. Enrollment was 25. Those numbers define a focused exploratory study rather than a definitive comparative standard. The sample size is small, the treatment allocation is non-randomized, and the design is limited to a specific group of patients with bilateral nail psoriasis and no competing nail or systemic disease.
For clinicians, the most useful takeaway is narrower than a headline efficacy claim. This study is a well-defined attempt to compare two intralesional strategies in a difficult-to-treat manifestation of psoriasis, using lesion-specific scoring, imaging, and side-effect tracking over six months. The unanswered question is not whether nail psoriasis needs better local therapy; it does. The remaining task is to learn whether methotrexate can match or outperform triamcinolone acetonide in the diseased nail unit without introducing a worse procedural burden or a less acceptable safety profile.