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

Abstract

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.1Dignan F.L. Amrolia P. Clark A. et al.Diagnosis and management of chronic graft-versus-host disease.Br J Haematol. 2012; 158: 46-61Crossref PubMed Scopus (126) Google Scholar 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.2Kineston D. Kwan J.M. Uebelhoer N.S. Shumaker P.R. Use of a fractional ablative 10.6-mum carbon dioxide laser in the treatment of a morphea-related contracture.Arch Dermatol. 2011; 147: 1148-1150Crossref PubMed Scopus (39) Google Scholar, 3Ozog D.M. Liu A. Chaffins M.L. et al.Evaluation of clinical results, histological architecture, and collagen expression following treatment of mature burn scars with a fractional carbon dioxide laser.JAMA Dermatol. 2013; 149: 50-57Crossref PubMed Scopus (135) Google Scholar 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).3Ozog D.M. Liu A. Chaffins M.L. et al.Evaluation of clinical results, histological architecture, and collagen expression following treatment of mature burn scars with a fractional carbon dioxide laser.JAMA Dermatol. 2013; 149: 50-57Crossref PubMed Scopus (135) Google Scholar 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.4Naouri M. Atlan M. Perrodeau E. et al.High-resolution ultrasound imaging to demonstrate and predict efficacy of carbon dioxide fractional resurfacing laser treatment.Dermatol Surg. 2011; 37: 596-603Crossref PubMed Scopus (30) Google Scholar Patient photographs and disability assessments similarly showed evidence of improvement.Table IChange in degrees of range of motion from baseline to 3 months after the final laser treatmentRange of motionPatient 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————+0.5Wrist flexion+25————+5Forearm pronation+11—+28+14.5+19+66Forearm supination+14—+19.5+14.5+2+2.5Elbow extension——+16.5+10—Ankle dorsiflexion—+21————Ankle plantarflexion—+4.5————Ankle inversion—+21————Ankle eversion—+6.5———— Open table in a new tab 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.5Waibel J.S. Wulkan A.J. Shumaker P.R. Treatment of hypertrophic scars using laser and laser assisted corticosteroid delivery.Lasers Surg Med. 2013; 45: 135-140Crossref PubMed Scopus (173) Google Scholar 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. We are grateful for the support and collaboration of the Departments of Dermatology, Dermatopathology, Radiology, Physical Therapy, and Hematology/Oncology at the University of Pennsylvania, as well as for the patients who volunteered for this study.