Methods: Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n=212), underwent oral exam evaluating: 1) mucosal cGVHD (Oral Mucositis Rating Scale), 2) salivary dysfunction (saliva flow and xerostomia), and 3) trismus (maximum mouth opening). These oral cGVHD parameters (flow ≤2mL/5min, mouth opening ≤35mm) were analyzed for association with oral mucosal disease, lacrimal dysfunction (Schirmer’s tear test, xerophthalmia) and skin cGVHD involvement (erythema and sclerosis), as well as Lee cGVHD Symptom Scores, FACT-BMT, and NIH organ scores, and nutritional status (Mann-Whitney U, Fisher’s exact contingency, Cochran-Armitage trend tests).
Results: Table: Significant associations were found between decreased salivary flow (51% prevalence) and xerostomia/xerophthalmia and salivary flow and poorer emotional status. A non-significant trend was seen between salivary and lacrimal dysfunction. Trismus (17% prevalence), was significant associated with oral mucosal cGVHD, mouth pain, low oral-related quality-of-life, skin-related symptoms and skin sclerosis, joint cGVHD, and poor nutritional status.
Conclusion: This analysis supports the understanding of oral cGVHD as a triad of distinct diseases: mucosal lesions, salivary dysfunction, and trismus, and provides the first analysis of trismus in cGVHD. The independent association between salivary and lacrimal dysfunction and between trismus and dermal sclerosis further suggests tissue-type specific cGVHD expression in the oral cavity: mucosal, secretory, and sclerotic. Trismus may impact highly on the morbidity of oral cGVHD.
Table. Patients with cGVHD: Data presented as medians (range of values) or as number affected (percentage) |
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|
Trismus and Sclerosis Associations |
Salivary and Lacrimal Dysfunction Associations |
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Variable |
Limited Mouth Opening (≤35mm) |
Normal Range of Mouth Opening |
p-value |
Limited Salivary Function (<2mL/5min) |
Normal Salivary Function |
p-value |
Number of Patients |
37 |
175 |
- |
50 |
47 |
- |
Age (years) |
45 (21-65) |
49 (18-70) |
0.68 |
50 (18-70) |
45 (19-68) |
0.39 |
Gender (# males, %) |
17 (46%) |
96 (55%) |
0.37 |
27 (54%) |
33 (70%) |
0.14 |
Schirmer’s Tear Test (mm) |
2.5 (0.6-26) |
3.5 (0-35) |
0.70 |
1.5 (0-18) |
3 (0-35) |
0.09 |
Eye Symptoms (0-10) |
5 (1-10) |
5 (0-10) |
0.47 |
6 (0-10) |
4 (0-10) |
0.019 |
Saliva Flow (mL/5min) |
2.8 (0.8-15) |
1.9 (0.2-5.6) |
0.08 |
1.1 (0.2-2.0) |
3.3 (2.2-14.8) |
- |
Maximum Mouth Opening (mm) |
32 (10-35) |
46 (36-70) |
- |
44 (25-58) |
45 (13-70) |
0.30 |
Oral Mucositis Rating Scale |
17 (0-152) |
9 (0-108) |
0.003 |
18 (0-79) |
13 (0-152) |
0.27 |
Mouth Pain (0-10) |
2 (0-10) |
0 (0-10) |
0.007 |
1 (0-10) |
0.5 (0-10) |
0.88 |
Oral Health Impact Profile |
16 (2-48) |
10 (0-40) |
0.032 |
14 (2-29) |
7 (0-30) |
0.36 |
Mouth Dryness (0-10) |
2 (0-8) |
3 (0-10) |
0.87 |
4 (0-10) |
1 (0-7) |
0.0003 |
Skin Erythema |
1.7 (0-39) |
0.36 (0-80) |
0.10 |
0.50 (0-76) |
0.09 (0-43) |
0.24 |
Skin Sclerosis |
20 (0-95) |
0.54 (0-92) |
0.009 |
5.6 (0-92) |
5.0 (0-85) |
0.51 |
Skin Itching (0-10) |
3.5 (0-10) |
1 (0-10) |
0.0012 |
2 (0-10) |
2 (0-10) |
0.98 |
Body Mass Index |
22 (15-32) |
29 (15-44) |
0.030 |
24 (12-36) |
24 (17-35) |
0.65 |
Nutritional PG-SGA Score |
7 (1-20) |
5 (1-21) |
0.038 |
6 (1-21) |
6 (1-20) |
0.41 |
Lee cGVHD Symptoms Scale Total |
41 (7-76) |
33 (1-80) |
0.017 |
34 (12-76) |
37 (3-58) |
0.69 |
Skin |
9 (2-18) |
5 (0-19) |
0.001 |
6 (0-18) |
6 (1-18) |
0.42 |
Eyes/Mouth |
9 (1-21) |
8 (0-20) |
0.25 |
10 (0-16) |
7 (0-20) |
0.06 |
Eating/Digestion |
2 (0-11) |
1 (0-10) |
0.036 |
1 (0-9) |
1 (0-11) |
0.98 |
Mental/Emotional |
4 (0-10) |
3 (0-12) |
0.83 |
4 (0-12) |
2 (0-8) |
0.026 |
Functional Assessment of Cancer Therapy – Bone Marrow Transplant: Emotional |
18 (9-24) |
18 (1-24) |
0.91 |
16 (1-24) |
19 (9-24) |
0.023 |
Average NIH Score |
1.25 (0.43-2.1) |
0.9 (0.14-2.0) |
0.004 |
1.13 (0.3-2.0) |
1 (0.14-2.0) |
0.37 |
NIH Score Joints |
29 (78%) |
100 (57%) |
0.016 |
34 (68%) |
30 (64%) |
0.84 |