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Choi, Yoo, Oh, Jang, Lee, and Song: Extraglandular Manifestations in Korean Patients with Primary Sjögren′s Syndrome
Original Article

J Rheum Dis 2015;22(3):167-174.

Published online: 31 October 2015

DOI: https://doi.org/10.4078/jrd.2015.22.3.167

Extraglandular Manifestations in Korean Patients with Primary Sjögren′s Syndrome

Byoong Yong Choi1, Jong Jin Yoo2, Hye Jin Oh3, Yu Jin Jang3, 4, Yun Jong Lee2, Yeong Wook Song3, 4

1Department of Internal Medicine, Seoul Medical Center, Seoul, Korea

2Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul, Korea

3Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

4Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Medical Research Center, Seoul National University, Seoul, Korea

Corresponding to: Yeong Wook Song, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea. E-mail: ysong@snu.ac.kr

Received 16 February 2015       Revised 8 April 2015       Accepted 9 April 2015

Copyright © 2015 The Korean College of Rheumatology

This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objectives

To investigate the clinical findings upon initial diagnosis and extraglandular manifestations in Korean patients with primary Sjögren's syndrome (pSS).

Methods

We collected clinical and laboratory data from 238 pSS patients enrolled at Seoul National University Hospital, Seoul National University Bundang Hospital and Seoul Medical Center from March 2011 to December 2014. All patients met the American-European Consensus Group criteria for pSS.

Results

Upon initial diagnosis, sicca symptoms (xerophthalmia or xerostomia) as the chief complaint were only observed in 129 (54.2%) pSS patients, while extraglandular manifestation was more common as the chief complaint in male patients or those with younger age (＜40 years) than female or older patients (both p＜0.05). Extraglandular manifestations were found in 178 (74.8%) patients, with musculoskeletal manifestations being most common (53.8%). Peripheral neuropathy in pSS patients was associated with Raynaud phenomenon and elevated serum total immunoglobulin G (IgG) levels (both p＜0.05). Serum β2-microglobulin (β2-M) levels were significantly correlated with European League against Rheumatism (EULAR) Sjögren's syndrome disease activity index, erythrocyte sedimentation rate and serum total IgG (all p＜0.001), and were higher in patients with extraglandular manifestations than those without (p＜0.05). Serum C3 levels were decreased in patients with extraglandular manifestation, compared to those without (p＜0.05). Malignant lymphoma was found in Korean pSS patients (1.7%) and associated with elevated serum β2-M levels (p＜0.0001).

Conclusion

Extraglandular manifestations were common in pSS patients and may be a diagnostic tool for male or younger pSS patients. Serum β2-M levels can be useful markers for monitoring pSS patients.

Keywords: Sjögren's syndrome, Extraglandular manifestation, Beta 2-microglobulin, Lymphoma

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Figure 1.
The correlation of serum β2-microglobulin (β2-M) concentration with European League against Rheumatism (EULAR) Sjögren' s Syndrome Disease Activity Index (ESSDAI) (A), erythrocyte sediment rate (ESR) (B) and serum immunoglobulin G (IgG) (C) in 238 patients with primary Sjögren' s syndrome.
jrd-22-167f1.tif
Figure 2.
The comparison of serum β2-microglobulin (β2-M) levels (A) and erythrocyte sediment rate (ESR) (B) between primary Sjögren' s syndrome patients with and without extraglandular manifestation (EM).
jrd-22-167f2.tif
Table 1.
Chief complaints at diagnosis in 238 patients with primary Sjögren's syndrome
Symptom Frequency (%)
Sicca symptoms 54.2
 Dry mouth and eye 28.6
 Dry mouth only 14.7
 Dry eye only 10.9
Arthralgia 16.4
Raynaud phenomenon 7.6
Skin rash 4.2
Paresthesia 2.9
Oral ulcer 2.1
Parotid gland swelling 1.7
Positive anti-nuclear antibodies 4.6
Positive rheumatoid factor 2.5
Table 2.
The comparison of clinical and laboratory findings according to chief complaints at diagnosis in 238 patients with primary Sjögren's syndrome
Variable Sicca symptom (n=129) Extraglandular manifestation (n=109) p-value‡
Xerophthalmia 123 (95.3) 98 (89.9) 0.1313
 Positive Schirmer I test 83 (64.3) 54 (49.5) 0.0254
Xerostomia 115 (89.1) 92 (84.4) 0.3351
 Salivary gland involvement* 112 (86.8) 79 (72.5) 0.0085
Musculoskeletal involvement 71 (55.0) 57 (52.3) 0.6970
Raynaud phenomenon 23 (17.8) 31 (28.4) 0.0624
Abnormal chest radiograph 3 (2.3) 19 (17.4) ＜0.0001
Abnormal liver function test 2 (1.6) 9 (8.3) 0.0257
Positive anti-nuclear antibody 114 (88.4) 91 (83.5) 0.3470
Positive rheumatoid factor 85 (65.9) 79 (72.5) 0.3225
Positive anti-Ro/SSA 110 (85.3) 88 (80.7) 0.3871
Positive anti-La/SSB 82 (63.6) 60 (55.0) 0.1880
Histopathology of minor salivary glands† 25/42 (59.5) 34/51 (66.7) 0.5213

Values are presented as number (%).

* Unstimulated whole salivary flow (＜1.5 mL in 15 min) or positive salivary scintigraphy;

† Focal lymphocytic sialadenitis, with a focus score ≥1;

‡ by chi-square or Fisher's exact test.

Table 3.
Cumulative clinical and laboratory findingsin 238 patients with primary Sjögren's syndrome defined by revised European criteria proposed by the American-European Consensus Group
Variable Present study (n=238) Seo et al. [7] (n=125)
Xerophthalmia 221 (92.9) 122 (97.6)
 Positive Schirmer I test 137 (57.6) 114 (91.2)
Xerostomia 213 (89.5) 123 (98.4)
 Salivary gland involvement* 191 (80.3) 109/116 (93.6)
Musculoskeletal involvement 128 (53.8) NA
 Arthralgia/arthritis 114 (47.9) 82 (65.6)
 Myalgia 68 (28.6) 46 (36.8)
Raynaud phenomenon 54 (22.7) 30 (24.0)
Dry skin 48 (20.2) 24 (19.2)
Skin rash 23 (9.7) 7 (5.6)
Vasculitis 14 (5.9) 5 (4.0)
Central nervous system disease 11 (4.6) 8 (6.4)
Peripheral neuropathy 23 (9.7) 29 (23.2)
Lung nodule 7 (2.9) 6 (4.8)
Interstitial lung disease 15 (6.3) 6 (4.8)
Hepatobiliary involvement 12 (5.0) 7 (5.6)
Renal tubular acidosis 9 (3.8) 2 (1.6)
Hypothyroidism 29 (12.2) 16 (12.8)
Hyperthyroidism 10 (4.2) 4 (3.2)
Malignant lymphoma 4 (1.7) 2 (1.6)
Leukopenia 78 (32.8) NA
Thrombocytopenia 6 (2.5) NA
Positive anti-nuclear antibody 205 (86.1) 101 (80.8)
Positive rheumatoid factor 164 (68.9) 99 (79.2)
Positive anti-Ro/SSA 198 (83.2) 90 (72.0)
Positive anti-La/SSB 142 (59.7) 38 (30.4)
Positive anti-Ro/SSA or anti-La/SSB 209 (87.8) NA
Histopathology of minor salivary glands† 59/93 (63.4) 27/34 (75)

Values are presented as number (%). NA: not available.

* Unstimulated whole salivary flow (＜1.5 mL in 15 min) or positive salivary scintigraphy;

† Focal lymphocytic sialadenitis, with a focus score ≥1.

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