Oral chronic graft-versus-host disease: current pathogenesis, therapy, and research

Abstract

Optimal management of complex autoimmune diseases requires a multidisciplinary medical team including dentists to care for lesions of the oral cavity. In this review, we discuss the presentation, prevalence, diagnosis, and treatment of oral manifestations in chronic graft-versus-host disease (cGVHD), which is a major late complication in patients treated by allogeneic hematopoietic stem cell transplantation. We assess current general knowledge of systemic and oral cGVHD and present general treatment recommendations based on literature review and our clinical experience. Additionally, we review areas where the understanding of oral cGVHD could be improved by further research and address tools with which to accomplish the long-term goal of providing better health and quality of life to patients with cGVHD.

Figure 1

The spectrum of the clinical presentation of oral cGVHD includes (a) erythema of the oral mucosa and tongue, (b) lichenoid lesions that occur on the buccal mucosa, lips and other areas of the oral cavity, (c) oral ulcerations, (d) mucoceles on the hard palate and occasionally lower labial mucosa, and (e) peri-oral sclerosis that limits mouth-opening.

Figure 2

Salivary gland dysfunction results in extreme dry mouth (a). This contributes to increased susceptibility to opportunistic infections and fungal overgrowth (b), and reduced remineralization of tooth enamel, resulting in cervical carious lesions (c). Patient-reported oral dryness, pain, and sensitivity scales, used for oral cGVHD symptom measurement (d).

Figure 3

Oral histopathologic changes in cGVHD include alterations in the minor salivary glands (MSG) and buccal mucosa. In the MSG, (a) sialadentis is often present, and fibrosis and atrophy of the gland are frequently observed. Lymphocytic infiltration (small arrow) and apoptotic cells (large arrow) may be observed in active stages of disease. (b) In late cGVHD, MSGs may have marked atrophy with only mild residual inflammation and few to no observable apoptotic cells. Destroyed glandular acini are often replaced by loose fibrotic stroma with associated lymphocytes (large arrow). In the buccal mucosal tissue, (c) generalized or band-like lymphocytic infiltration (large arrow) may be observed in the submucosa, near the junction of nonkeratinized squamous mucosa. Apoptotic cells (small arrows), often associated with lymphocytes, and may be observed in active stages of disease. (d) In severe cases, separation or clefting of the basal epithelial layer may be observed (large arrow), often in conjunction with heavy lymphocytic infiltrate and apoptotic bodies (small arrow). Original magnification 20×.

Figure 4

Clinical and research focused rating tools used for assessment of oral GVHD. (a) The NIH cGVHD Activity Scale scores the oral cavity for percent of surface area involved with erythema, lichenoid lesions and hyperkeratosis, ulceration and mucoceles (Pavletic et al., 2006b). (b) The Oral Mucositis Rating Scale (OMRS) rates 13 locations and 7 types of lesions (Schubert et al., 1992).

Figure 5

NIH oral cGVHD scale breakdown by type of mucosal change. The frequency and severity of mucosal changes in (a) erythema, (b) lichenoid lesions, (c) ulceration and (d) mucoceles were assessed in patients with and without oral cGVHD. Reprinted with permission (Fassil et al., 2012).

Figure 6

Patient-Reported Symptoms of oral cGVHD. The distribution of self-reported symptoms is compared here in patients with and without oral cGVHD (n=187 total). The oral cGVHD status is compared across the distribution of the Lee Symptom Scale (a) on the degree of bother from the avoidance of food and (b) degree of bother from ulceration. (c) Mouth pain and (d) mouth sensitivity are grouped by the patient-reported 0–10 score to show the percentage of each group affected at that level. Reprinted with permission (Fassil et al., 2012).