Zoya Kuzmina, MD
,
Graft-versus-Host and Autoimmunity Unit, Experimental Transplantation and Immunology Branch, National Institutes of Health, National Cancer Institute NCI, Bethesda, MD
Galen O Joe, MD
,
Rehabilitation Medicine Department Clinical Research Center, National institutes of Health,, Bethesda, MD
Kristin Baird, MD
,
Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, MD
Edward W Cowen, MD
,
Dermatology Branch, National Cancer Institute, NIH, Bethesda, MD
Haley Bharat Naik, MD
,
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
Seth Steinberg, PhD
,
Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Rockville, MD
Leora Comis, MPA, OTR/L, FAOTA
,
Rehabilitation Medicine Department Clinical Research Center, National Institutes of Health, Bethesda, MD
Judy L Baruffaldi
,
Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD
Daniele Avila, CRNP
,
Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD
Tiffani Taylor, PA-C
,
Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD
Kristen Cole, RN, BSN, OCN
,
Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD
Sandra Mitchell, PhD, CRNP
,
Outcomes Research Branch; Division of Cancer Control and Population Sciences, National Institutes of Health, Rockville, MD
Steven Z. Pavletic, MD
,
Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD
Background: Involvement of joints and fascia by chronic GVHD (cGVHD) is a prominent contributor to cGVHD-associated disability. NIH cGVHD Joint and Fascia Score (JFS, range 0-3) consists of three measurements: tightness, restriction in measured range of motion (ROM) and limitations in activities of daily living (ADL). The NIH consensus criteria did not distinguish the contributions to JFS made by isolated joint involvement vs. joint restrictions caused by sclerosis of overlying skin, as well as most studies fail to distinguish it. The purpose of this study was to compare patients with isolated joint-fascia (JF) involvement to JF involvement with overlying skin and soft tissue sclerosis, and to identify predictive factors for isolated joint involvement in a cohort of cGVHD patients.
Patients and methods: In a cross-sectional cGVHD natural history study (n=283, median age 43 years, range 4-70), 169 (60%) had JF involvement at the time of enrollment; mild (n=60), moderate (n=78), severe (n=31). Only 27 (16%) patients with JFS involvement had no (n=11) or mild (n=16) skin score (NIH 0-1). Clinical assessments included measured active assisted ROM, grip strength, 2 minute walk, Lee cGVHD symptom scale, Human Activity Profile (HAP) and selected laboratory parameters. JFS-positive patients (NIH JFS score 1-3) with joint restrictions and no sclerotic skin changes (n=43) were compared to JFS-positive sclerotic cGVHD (n=126).
Results: JFS-positive patients (n=169) had significantly more skin erythema, dermal and deep sclerosis. Only 27 (16%) of JFS-positive patients had NIH skin scores of 0 (n=11) or 1 (n=16). JFS-positive patients without evidence of sclerotic cGVHD had significantly shorter duration of cGVHD (p<.001) and were considered to have more active cGVHD based on therapeutic intent (p<.0001), but had lower NIH global severity scores when compared to JFS-positive patients with sclerotic features (p<.0001). Restriction in ROM at most severely affected joints was greater in patients with sclerotic features compared to those without observable sclerotic changes (p<0.0001). JFS-positive patients with sclerotic features were more likely to have self-reported limitations in joint movement (p<0.001). In those with isolated joint involvement, ankles (88%) and shoulders (44%) were most frequently affected. In multivariable analysis, shorter duration of cGVHD, less impairment in measured ROM and lower maximum individual organ score were able to identify 77% of patients with positive JFS without sclerotic features.
Conclusion: Although JFS involvement is common in cGVHD, the incidence of joint involvement in the absence of detectable skin or fascial sclerosis is low. Future refinements of the NIH criteria may need to recognize separately joint restrictions that occur without evidence of sclerotic involvement within the JFS NIH scale.
