Oral disease profiles in chronic graft versus host disease.
At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials.
National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA carol.bassim@nih.gov.
C W
CW
Bassim
Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA Tufts University School of Dental Medicine, Boston, MA, USA.
H
H
Fassil
National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.
J W
JW
Mays
National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.
D
D
Edwards
Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
K
K
Baird
Biostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
S M
SM
Steinberg
Dermatology Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
E W
EW
Cowen
Dermatology Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
H
H
Naik
National Eye Institute, NIH, Bethesda, MD, USA.
M
M
Datiles
Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA.
P
P
Stratton
Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
R E
RE
Gress
Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
S Z
SZ
Pavletic
D000293:Adolescent; D000328:Adult; D000368:Aged; D001830:Body Surface Area; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D004890:Erythema / Q000209:etiology; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications*; D006801:Humans; D007766:Lacrimal Apparatus Diseases / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000473:pathology; D009059:Mouth Diseases / Q000209:etiology*; D009061:Mouth Mucosa / Q000473:pathology; D010146:Pain / Q000209:etiology; D012463:Saliva / Q000378:metabolism; D012466:Salivary Gland Diseases / Q000209:etiology; D012598:Sclerosis; D012636:Secretory Rate / Q000502:physiology; D012867:Skin / Q000473:pathology; D014985:Xerophthalmia / Q000209:etiology; D014987:Xerostomia / Q000209:etiology; D055815:Young Adult
autoimmune disease; clinical research; oral cGVHD; oral medicine; salivary dysfunction; stem cell transplantation