Deterioration in saliva quality in patients with Sjögren's syndrome: impact of decrease in salivary epidermal growth factor on the severity of intraoral manifestations

Abstract

Background: Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration of the exocrine glands, especially the salivary and lacrimal glands. As a result of salivary gland dysfunction, most patients with SS have xerostomia related to a reduced salivary flow rate. In addition to the discomfort due to xerostomia, dry mouth can cause various intraoral manifestations such as refractory stomatitis, ulcer, and atrophic changes in the oral mucosa and tongue, and the patient's quality of life (QoL) is severely impaired. These manifestations are believed to be caused mainly by a decrease in the clearance in the oral cavity owing to hyposalivation. However, because saliva has several beneficial physiological effects on the intraoral environment, qualitative changes in sialochemistry should also be considered a cause of the refractory intraoral manifestations in SS.

Main text: Salivary epidermal growth factor (EGF) is considered an important cytoprotective factor against injuries. It contributes to wound healing in the oral cavity and to maintenance of mucosal integrity in the oral cavity and gastrointestinal tract. We evaluated changes in salivary EGF levels and assessed the association between salivary EGF levels and the severity of intraoral manifestations in patients with SS. The following novel findings were obtained: (1) salivary EGF levels in SS patients were significantly lower than those in non-SS patients; (2) salivary EGF levels as well as the salivary flow rate decreased with the progression of SS; (3) with prolonged SS disease duration, salivary EGF levels decreased more rapidly than the salivary flow rate; and (4) decreases in salivary EGF levels significantly correlated with exacerbation of the oral health-related QoL in patients with SS.

Conclusions: The deterioration in saliva quality as well as lower intraoral clearance by hyposalivation could play a role in the pathogenesis of refractory intraoral manifestations in patients with SS. Our findings suggest a new target for therapeutic intervention for SS.

Keywords: Dry mouth; Epidermal growth factor; Intraoral manifestation; Oral mucosal involvement; Quality of life; Saliva; Saliva quality; Sjögren’s syndrome; Xerostomia.

Fig. 1

Salivary epidermal growth factor (EGF) levels of the Sjögren’s syndrome (SS) and non-SS groups. a The SS group was divided into the long-duration group and short-duration groups depending on disease duration, and salivary EGF output levels were compared between these groups and the non-SS group. b The SS group was divided into the severe and mild groups according to the severity of intraoral manifestations determined using the Oral Health Impact Profile (OHIP)-14 score, and salivary EGF output levels were compared between these groups and the non-SS group. Statistical differences were assessed using the Mann−Whitney U test. *p < 0.001, **p < 0.01, ***p < 0.05; n.s., not significant

Fig. 2

Correlations between different factors and salivary epidermal growth factor (EGF) output in the Sjögren’s syndrome (SS) group. a Correlation of salivary flow rate with salivary EGF output (n = 13). b Correlation of disease duration with salivary EGF output (n = 24). c Correlation of the Oral Health Impact Profile (OHIP)-14 score with salivary EGF output (n = 10). Correlations were assessed using Spearman’s rank correlation coefficient

Fig. 3

Changes in the salivary flow rate and salivary epidermal growth factor (EGF) output according to the disease duration. a Short-duration Sjögren’s syndrome (SS) group. b Long-duration SS group. (1) Changes in the salivary flow rate. (2) Changes in the salivary EGF output. Statistical analysis was performed using the Wilcoxon signed-rank test. *p < 0.05; n.s., not significant

Fig. 4

Changes in the salivary flow rate and salivary epidermal growth factor (EGF) output according to the extent of changes in the Oral Health Impact Profile (OHIP)-14 score at 3-year re-evaluation. a Patient group in which the OHIP-14 score decreased or did not change (non-exacerbation group). b Patient group in which the OHIP-14 score increased (exacerbation group). (1) Changes in the salivary flow rate. (2) Changes in the salivary EGF output. Statistical analysis was performed using the Wilcoxon signed-rank test. *p < 0.05; n.s., not significant