Ablative fractional laser resurfacing for treatment of sclerosis and contractures in chronic graft-versushost disease: A pilot study

To the Editor

Cutaneous sclerosis is a disabling complication of chronic graft-versus-host disease (cGVHD) that leads to joint contractures and reduced range of motion (ROM). Current therapies are limited by adverse effects and poor efficacy, and no systemic treatment successfully reverses cGVHD-induced sclerotic skin changes.¹ There is an urgent need for therapies to address the debilitating effects of cutaneous sclerosis in cGVHD.

The ablative fractional CO₂ laser remodels collagen and reduces fibrosis. It has been used for treatment of scars and contractures secondary to linear morphea, burns, and traumatic injury, conditions resembling the sclerosis of cGVHD.^2,3 We evaluated the safety, tolerability, and efficacy of the ablative fractional CO₂ laser for cGVHD-related sclerosis and joint contractures.

Six patients with cGVHD-related sclerosis were enrolled prospectively and completed the study. Eligible patients had clinically severe, refractory sclerosis from longstanding cGVHD, with demonstrable ROM limitation and contractures across a joint amenable to laser therapy. After administration of topical anesthesia, patients had 3 monthly treatments of an approximately 10 × 6-cm area of skin at the target joint using the 10 600-nm fractional Ultrapulse CO₂ laser (Ultrapulse Encore; Lumenis, Inc, Santa Clara, CA) in Deep FX mode (energy settings, 20–25 mJ; density, 5%−15%). Photographs, ROM measurements, and high-resolution ultrasonography were recorded at baseline, 1 week after each laser session, and 3 months after the final session. Punch biopsy and patient and provider assessments, including validated health and disability questionnaires, were performed at baseline and 3 months after the final session. The study was approved by the University of Pennsylvania institutional review board, and all patients provided written informed consent.

Before enrollment, patients had received a mean of 5.5 systemic therapies for cGVHD-related sclerosis. Laser treatments were well tolerated, without infectious or other serious complications. ROM measurements, particularly the twisting motions of supination and pronation, improved in all patients (Table I). Immunohistochemical analysis of skin biopsy specimens showed decreased thickened collagen bundles, decreased intensity of collagen staining, and greater abundance of type III collagen in treated areas (Fig 1).³ Dermal echogenicity measured via high-resolution ultrasonography increased after the laser treatment, suggestive of collagen remodeling. Less haphazard organization of collagen is postulated to produce increased echogenicity.⁴ Patient photographs and disability assessments similarly showed evidence of improvement.

Table I.

Change in degrees of range of motion from baseline to 3 months after the final laser treatment

Range of motion	Patient 1 (right wrist)	Patient 2 (left foot)	Patient 3 (right elbow)	Patient 4 (left elbow)	Patient 5 (left elbow)	Patient 6 (right wrist)
Wrist extension	−1	—	—	—	—	+0.5
Wrist flexion	+25	—	—	—	—	+5
Forearm pronation	+11	—	+28	+14.5	+19	+66
Forearm supination	+14	—	+19.5	+14.5	+2	+2.5
Elbow extension	—	—	+16.5	+1	0	—
Ankle dorsiflexion	—	+21	—	—	—	—
Ankle plantarflexion	—	+4.5	—	—	—	—
Ankle inversion	—	+21	—	—	—	—
Ankle eversion	—	+6.5	—	—	—	—

Fig 1.

Trichrome staining of punch biopsy specimen (A) before and (B) after laser therapy, showing decreased intensity of staining, consistent with collagen remodeling. Herovici stain of punch biopsy (C) before and (D) after laser therapy, showing an increase in the abundance of blue-staining type III ( fetal) collagen, consistent with collagen remodeling.

The results of this pilot study highlight the safety, tolerability, and potential efficacy of the fractional ablative CO₂ laser for treatment of cGVHD-related sclerosis and joint contracture, resulting in small but measurable histologic, radiologic, and functional improvements. Small sample size, small treatment area, and imperfect objective response measures are limitations. Longer follow-up, larger treatment areas, use of other laser settings, and laser-assisted delivery of topical medications should be evaluated in future studies.⁵

In summary, the fractional ablative CO₂ laser was safe and well tolerated in a small group of medically complex patients with treatment-refractory cGVHD. Treatment of a target area of sclerotic skin appeared to induce collagen remodeling, with resulting modest improvement in ROM and joint function. These findings suggest that the fractional ablative CO₂ laser may be an effective novel therapy for disabling sclerotic joint contractures in some patients with cGVHD.