Salivary Gland Involvement in Chronic Graft-Versus-Host Disease: Prevalence, Clinical Significance, and Recommendations for Evaluation

Abstract

Although xerostomia is a commonly reported complaint in patients with chronic graft versus host disease (cGVHD), criteria for evaluating the prevalence and characteristics of salivary gland involvement have not been well defined in this patient population. Prior studies also do not make distinction between salivary and mucosal oral cGVHD. We have systematically evaluated sicca symptoms and signs in a large cohort of patients with cGVHD (N=101) using instruments widely used to study Sjogren’s Syndrome. Xerostomia was reported by 77% of the patients and was associated with xerophthalmia in all cases but one. Twenty-seven percent had salivary flow rates of ≤0.2 ml/min, 16% had rates ≤0.1 ml/min. Histopathological changes consisting of mononuclear infiltration and/or fibrosis/atrophy, were present in all patients with salivary dysfunction. Importantly, there was no correlation of salivary and oral mucosal involvement in cGVHD. Patients with cGVHD-associated salivary gland involvement had lower oral cavity-specific quality of life and body mass index. In conclusion, salivary gland involvement is a common and clinically distinct manifestation of cGVHD. Formal evaluation of salivary function using standardized criteria is necessary and may be incorporated as outcome measure in clinical trials of cGVHD.

The impact of morphological and immunohistological changes in minor salivary glands on the health of the oral cavity in HSCT patients

“…Severe involvement of the MSG in cGVHD results in marked destruction of the secretory units and, thus, in permanent and profound oral dryness. 27,28 Unlike our results, Soares et al 14 found increased CD68 þ cell number in cGVHD patients, compared with non-cGVHD HSCT patients. This discrepancy might be explained by the previous development of acute GVHD.…”

Sicca symptoms and their impact on quality of life among very long-term survivors after hematopoietic SCT

“…Recent studies on HSCT recipients with GVHD have reported the prevalence of pathological Schirmer's scores of B70% during the observation periods of 6 months to 3 years. 11,39 The present study indicates that this complication has an irreversible nature and that conditioning regimen may have a major role, as past or present GVHD did not correlate with sicca symptoms nor with a pathological Schirmer's test. The impact of the conditioning regimen (TBI) in the development of other ocular late effects, such as cataracts, has been well described.…”

“…6,17 Moreover, general malnutrition and even vitamin A deficiency can be encountered, causing dehydration with oral and ophthalmological symptoms. 11,18,19 So far only a few studies have addressed the functional well-being of survivors after HSCT. In a retrospective multicenter analysis in patients surviving 5 years or more after HSCT, a Karnofsky score X90% was reported in 93% and only 6% of these patients did not return to school or work after HSCT.…”

“…GVHD is a common complication of HSCT that can directly compromise salivary gland and lacrimal functions. [11][12][13] The occurrence of keratoconjunctivitis sicca has been shown to vary between 38 and 10% in HSCT recipients with and without cGVHD, respectively. 7 In addition to GVHD, HSCT may cause other long-term comorbidities, in particular infections, which may require a broad repertoire of therapeutic agents.…”

<b>Pivotal role of duct epithelia in salivary gland </b><b>GVHD </b>

“…In graft-versus host disease (GVHD), salivary glands are one of the primary target organs besides skin and gastrointestinal tracts (Imanguli et al, 2010;Nagler et al, 2004), and impaired secretion of saliva affects patients' quality of life through oral filthiness, caries and decreased appetite. Although this symptom is well-known, pathophysiology and mechanism of salivary gland injury have been poorly investigated.…”