Abstract
This survey study explores the scope of chronic graft-vs-host disease among a cohort of patients with skin of color.
Chronic graft-vs-host disease (cGVHD) is a major complication of hematopoietic stem cell transplantation. The skin is the most commonly involved site and may present with a broad range of inflammatory and fibrotic manifestations that add to the complexity of diagnosis and management in patients with skin of color.1 Subtle erythema may be difficult to discern because of background skin pigmentation. In addition, current validated physician-reported and patient-reported cGVHD outcome measures offer limited insight into the effect of cGVHD-associated dyspigmentation, which may be of greater significance in patients with skin of color. This study explores the breadth and influence of cGVHD in a natural history cohort of patients with skin of color.
Methods
A total of 40 adult patients and 6 pediatric patients with nonwhite Fitzpatrick skin types (III-VI) and a diagnosis of cGVHD were evaluated at the National Institutes of Health between 2004 and 2013 as part of a cGVHD natural history research protocol (ClinicalTrials.gov identifier: NCT00331968). The protocol was approved by the institutional review board at the National Cancer Institute, and written informed consent was obtained from participants. Comprehensive skin assessment included skin examination, cGVHD scoring by body surface area, and photography. The cGVHD type was classified based on skin morphology as (1) no active skin disease/no dyspigmentation due to graft-vs-host disease (NoGVHDP−), (2) no active disease/with dyspigmentation (NoGVHDP+), (3) epidermal type (ET), (4) sclerotic type (ST), and (5) both epidermal type and sclerotic type (ET/ST). The primary outcome was the influence of cGVHD type on quality of life using validated measures, including Clinical Severity Score (CSS; 0-10 scale) as reported by both physicians and patients, and the skin domains of both the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT; 0-4 scale for 47 items [maximum score, 188]) and Lee Symptom Scale (LSS; 0-4 scale for 5 categories [maximum score, 20]) as reported by patients.
Results
The cohort consisted of 7 patients with NoGVHDP−, 9 with NoGVHDP+, 9 with ET, 8 with ST, and 13 with ET/ST. Clinical Severity Score responses were available for 34 patients (28 adult and 6 pediatric), FACT-BMT responses for 31 adults, and LSS responses for 34 adults (Tables 1 and 2).3 Patients with ET/ST reported the greatest clinical severity (mean, 7.0/10) on CSS, the most skin bother (mean, 3.6/4) on FACT-BMT, and the highest total LSS (14.0/20). Using the CSS, physicians overall rated patients with skin of color to be less severely affected than patients rated themselves (mean, 2.8/10 vs 3.7/10). In particular, self-rated severity of NoGVHDP+ was higher than the physician-rated severity (mean, 2.4/10 vs 0.1/10). Despite having no active cGVHD, the NoGVHDP+ group self-rated their skin disease as more severe than patients with ST (mean, 2.4/10 vs 1.1/10).
Table 1. Clinical Severity Scores and Skin-Focused FACT-BMT Responses in Patients With Skin of Color and cGVHDa.
| cGVHD Skin Morphology | CSSb | FACT-BMTb | ||||
|---|---|---|---|---|---|---|
| Patient Reported (0-10 scale) | Physician Reported (0-10 scale) | Patient-Physician Difference | Appearance (0-4 scale) | Skin Bother (0-4 scale) | Total (maximum score, 188) | |
| NoGVHDP− | 0.8 | 0 | 0.8 | 1.7 | 0.2 | 107.1 |
| NoGVHDP+ | 2.4 | 0.1 | 2.3 | 2.1 | 1.7 | 101.0 |
| ET | 5.2 | 3.1 | 2.0 | 0.5 | 3.5 | 56.5 |
| ST | 1.1 | 2.7 | −1.5 | 2.0 | 1.1 | 108.0 |
| ET/ST | 7.0 | 6.2 | 0.8 | 0.1 | 3.6 | 65.1 |
Abbreviations: cGVHD, chronic graft-vs-host disease; CSS, Clinical Severity Score; ET, epidermal type; ET/ST, epidermal type/sclerotic type; FACT-BMT, Functional Assessment of Cancer Therapy–Bone Marrow Transplant; NoGVHDP−, no active skin disease/no dyspigmentation due to graft-vs-host disease; NoGVHDP+, no active disease/with dyspigmentation; ST, sclerotic type.
For CSS ratings, patients were asked to respond to the question, “How severe do you feel your skin problem is?” on a scale of 0 (not severe) to 10 (most severe). There were 34 CSS responses, including 9 pediatric patient responses. For the FACT-BMT ratings, patients were asked to respond to the question, “Do you like the appearance of your body?” on a scale of 0 (no) to 4 (very much). Higher scores for this question and the total FACT-BMT correlate with better quality of life. Patients also rated the statement “I am bothered by skin problems” on a scale of 0 (no) to 4 (very much). A higher score for this question indicates more bothersome symptoms or poorer quality of life. There were 31 FACT-BMT responses. Pediatric patients were not administered the FACT-BMT. Clinical significance of FACT-BMT was similar to the Functional Assessment of Cancer Therapy–General, in which a minimally important difference is defined as 4 to 7 points.3
Mean scores shown for each category.
Table 2. Lee Symptom Score Skin-Focused Responses in Patients With Skin of Color and cGVHDa,b.
| cGVHD Skin Morphology | Abnormal Skin Color (0-4 scale) | Rash (0-4 scale) | Thickened Skin (0-4 scale) | Sores (0-4 scale) | Itchy Skin (0-4 scale) | Total (0-20 scale) |
|---|---|---|---|---|---|---|
| NoGVHDP− | 0.2 | 0.3 | 0.3 | 0 | 0.7 | 1.5 |
| NoGVHDP+ | 2.0 | 1.0 | 1.0 | 0 | 1.0 | 4.0 |
| ET | 3.0 | 2.3 | 2.3 | 2.5 | 2.7 | 13.3 |
| ST | 1.6 | 0.3 | 1.9 | 0.9 | 1.3 | 5.4 |
| ET/ST | 3.1 | 2.4 | 2.7 | 2.9 | 3.2 | 14 |
Abbreviations: cGVHD, chronic graft-vs-host disease; ET, epidermal type; ET/ST, epidermal type/sclerotic type; NoGVHDP−, no active skin disease/no dyspigmentation due to graft-vs-host disease; NoGVHDP+, no active disease/with dyspigmentation; ST, sclerotic type.
Included were 6 patients with NoGVHDP−, 8 with NoGVHDP+, 3 with ET, 7 with ST, and 10 with ET/ST. For Lee Symptom Score, patients reported abnormal skin color, rashes, thickened skin, sores on skin, and itchy skin on a 6-point Likert scale: symptom not present (0), not bothered at all (0), slightly bothered (1), moderately bothered (2), quite a bit bothered (3), and extremely bothered (4). A higher score indicates more bothersome symptoms. Pediatric patients were not administered this survey.
Mean scores shown for each category.
The total FACT-BMT scores were similar among patients with NoGVHDP+ (mean, 101.0/188) and those with ST (mean, 108.0/188). Similarly, in all LSS categories (color, rash, thickness, sores, and itch), patients with ET were more bothered by their disease than patients with ST (mean, 13/20 vs 5.4/20).
Discussion
Self-reported measures provide the patient’s perspective of a condition’s effects and are unfiltered by physician opinion. This study was limited by the lack of a comparator group; however, the data suggest that patients with skin of color perceive the effect of pigment alteration to be significant when compared with sclerotic involvement, despite greater functional compromise associated with the latter. Given that dyspigmentation is generally considered a marker of damage rather than disease activity, the influence of dyspigmentation may be overlooked in skin scoring of disease burden.2 Indeed, patients with dyspigmentation, but no active disease, disliked the appearance of their skin as much as those with active sclerotic disease and were more bothered by their skin than those with active sclerotic disease. To our knowledge, this is the first study exploring the influence of cGVHD skin disease specifically in patients with skin of color. Data were collected systematically using validated tools recommended by the National Institutes of Health GVHD Consensus Group (ie, FACT-BMT, LSS). Although current cGVHD quality of life and symptom severity measures inquire about abnormal skin color, they do not specifically inquire about dyspigmentation. We believe that the effect of dyspigmentation in patients with skin of color may not be adequately captured in current GVHD skin scoring systems and should be expanded in quality of life assessments.
References
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