Treatment of immunoglobulin G4-related sialadenitis: outcomes of glucocorticoid therapy combined with steroid-sparing agents

Abstract

Background: Immunoglobulin G4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated systemic disease. Despite its good response to steroid therapy, its treatment protocol is not standardized and the long-term outcome is controversial. The study was conducted to determine the short-term and long-term outcomes of IgG4-RS patients treated with glucocorticoids and steroid-sparing immunosuppressive agents, to analyze secretory function, serological and radiological changes in salivary glands and to assess the usefulness of serum IgG4 level as an indicator of disease activity.

Methods: IgG4-RS patients who were treated for more than 3 months were enrolled. Serological tests, salivary gland function assessment and computed tomography (CT) were performed before treatment and during follow up. The treatment outcomes in the short and the long term were evaluated, and the relationship between serum IgG4 level and salivary gland volume was analyzed.

Results: Glucocorticoids were used in all 43 patients and steroid-sparing immunosuppressive agents in 38 patients (88.4%). The follow-up period was 24.6 ± 14.9 months. Clinical remission was achieved in all patients after induction therapy. During short-term observation, salivary gland secretion significantly increased, and the serum IgG4 levels, the volumes and CT values of submandibular and parotid gland decreased significantly (P < 0.001). For long term, relapse occurred in 32.5% patients within 55 months in the regularly treated group, while all seven irregularly treated patients relapsed. However, the relapse-free survival curves were not significantly different between the steroid monotherapy and the combination therapy groups (P = 0.566). Submandibular glands, lacrimal glands, sublingual glands, nasal and paranasal cavity were commonly relapsing organs. In clinically stable patients, a serologically unstable condition occurred in 54.9% patients within 55 months and medication adjustment was performed accordingly. Volume changes in the submandibular and parotid glands were associated with serum IgG4 levels and time of follow up (R²_adjusted = 0.905, P < 0.0001 and R²_adjusted = 0.9334, P < 0.0001, respectively).

Conclusions: The combination of glucocorticoid and steroid-sparing agents could be effective for treating IgG4-RS, and restoring salivary gland function. Serum IgG4 levels could predict disease activity.

Keywords: Glucocorticoid; IgG4-related sialadenitis; Serum IgG4 level; Steroid-sparing agents; Treatment.

Fig. 1

Kaplan–Meier analysis of treatment outcomes in patients with immunoglobulin G4 (IgG4)-related sialadenitis. a Partial or complete relapse occurred in 32.5% of patients within 55 months in the regularly treated group, while in the irregularly treated group, all the patients relapsed. b The relapse-free survival curves for the groups of patients treated with or without steroid-sparing agents are not significantly different (P = 0.566). c The serologically stable survival curve shows that a serologically unstable condition occurred in 54.9% patients within 55 months in regularly treated patients

Fig. 2

Association between serum immunoglobulin G4 (IgG4) levels and volumes of the submandibular gland and parotid gland. a Mean volume (S.D. in dotted curves) of the submandibular gland (SMG), parotid gland (PG) and log₂ serum IgG4 at each follow up time point exhibit similar variation. Three-dimensional scatter plot and regression function shows the correlation between SMG volume and log₂ serum IgG4 and the parallel time of follow up (P < 0.0001 (b)), and correlation between PG volume and log₂ serum IgG4, time of follow up, and their interaction term (P < 0.0001 (c))