Sclerotic-type chronic GVHD of the skin: clinical risk factors, laboratory markers, and burden of disease

Abstract

Chronic GVHD is one of the most severe complications of allogeneic HSCT. The sclerotic skin manifestations of cGVHD (ScGVHD) result from inflammation and fibrosis of the dermis, subcutaneous tissue, or fascia, leading to significant functional disability. Risk factors and clinical markers associated with ScGVHD remain largely unexamined. By using a single-visit, cross-sectional design, we evaluated 206 patients with cGVHD at the National Institutes of Health. Most patients manifested severe (ie, 63% National Institutes of Health score "severe"), refractory disease (median treatments = 4). ScGVHD was detected in 109 (52.9%) patients. ScGVHD was associated with greater platelet count (P < .001) and C3 (P < .001), and decreased forced vital capacity (P = .013). Total body irradiation (TBI) was associated with development of ScGVHD (P = .002). TBI administered in reduced-intensity conditioning was most strongly associated with ScGVHD (14/15 patients, P < .0001). Patients with ScGVHD had significant impairments of joint range of motion and grip strength (P < .001). Greater body surface area involvement was associated with poorer survival (P = .015). We conclude that TBI, particularly in reduced-intensity regimens, may be an important risk factor for ScGVHD. Widespread skin involvement is associated with significant functional impairment, distressing symptoms, and diminished survival. This trial is registered at http://www.clinicaltrials.gov as NCT00331968.

Figures

Figure 1

The spectrum of cutaneous findings in ScGVHD. Localized bound-down thickened hyperpigmented plaques on the thigh (A) and forearms (B) resemble morphea/localized scleroderma. Widespread shiny indurated skin on the torso resembles generalized systemic sclerosis and may lead to restricted chest wall expansion (C). Subcutaneous and fascial fibrosis results in an irregular, rippled appearance to the skin, resembling eosinophilic fasciitis (D) and may result in joint contractures, including the prayer sign (E). Skin breakdown and poor wound healing is a complication of long-standing ScGVHD, particularly of the lower extremities, and may lead to increased risk of systemic infection (F).

Figure 2

TBI is associated with increased risk of development of ScGVHD. The association between TBI and ScGVHD was demonstrated most strongly among patients treated with reduced-intensity conditioning (RIC). Of 15 patients who received TBI as part of a RIC conditioning regimen, 14 demonstrated ScGVHD (P = .0114).

Figure 3

Percent BSA and survival. Survival among patients with ScGVHD with percent BSA involvement above and below the median (37.4%) for the entire ScGVHD group. Log-rank (P = .015). In multivariable analysis, after adjusting for NIH lung score, Karnofsky score, and lymphocyte count (factors associated with survival in this cohort on previous analyses), percent-BSA ScGVHD was no longer associated with survival.