Sjögren's syndrome (SS) is a chronic autoimmune disease that causes serocytic symptoms due to lymphocyte infiltration and inflammation of the lacrimal and salivary glands, and various autoantibodies such as anti-SSA antibodies, anti-SSB antibodies, and RF can be present in serum. SS may also affect other organs outside the exocrine glands, such as autoimmune inflammation can affect the ductal epithelium of various organs, such as the liver and kidneys, similar to inflammation in the salivary and lacrimal glands, also known as "autoimmune epitheliitis". In addition, SS can also have multi-system involvement of the skin, joints, muscles, lungs, kidneys, nervous system, and blood system. Fifteen percent of patients also develop serious systemic complications, including lymphoma, during the course of the disease. Parotid gland enlargement, splenomegaly, lymphadenopathy, purpura, neutropenia, monoclonal immunoglobulin, cryoglobulinemia, low C4, RF positivity, ectopic parasalivary gland germinal center, and ESSDAI score >5 are risk factors for lymphoma in patients with pSS.
The incidence of Sjögren's syndrome is 0.1-0.6%, and it is more common in women, with a male-to-female ratio of 1:9~20. It can occur at any age, more common in 40-60 years old, and only about 10% of cases occur before the age of 30. What are the characteristics and differences between early-onset Sjögren's syndrome and late-onset syndrome, which are summarized from two literatures below.
Literature I
Objectives: We sought to determine whether early-onset SS is associated with a specific phenotype and whether its prognosis is worse.
Methods A national prospective study in France from 2006 to 2009 involving 393 patients with primary Sjögren's syndrome was included to determine factors predicting systemic involvement of primary Sjögren's syndrome. The study included 55 patients with early-onset Sjögren's syndrome (18 years ≤ age ≤ 35 years) and 338 patients with late-onset Sjögren's syndrome (age > 35 years). Clinical and biological symptoms were compared at baseline and 5 years after diagnosis. Disease activity was assessed using the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI).
Results In terms of clinical features at initial diagnosis, patients with early-onset Sjögren's syndrome had enlarged salivary glands compared with the late-onset group (47.2 versus 33.3 percent; P = 0.045), lymphadenopathy (25.5 versus 11.8 percent; P = 0.006), purpura (23.6 versus 9.2 percent; P = 0.002) and renal involvement (16.4 versus 4.4 percent; P = 0.003); There was no difference in the proportion of patients with dry eyes, dry mouth, joint involvement, central nervous system involvement, peripheral nervous system involvement, or lung involvement between the two groups, and the incidence of lymphoma was similar between the two groups.
Laboratory tests at initial presentation: Hyperglobulinemia in early-onset Sjögren's syndrome compared with the late-onset group (60.8 versus 26.6 percent; P < 0.001), and there was no difference between the two groups in the proportion of CRP, lymphocyte count, and cryoglobulinemia.
In terms of immune markers at initial diagnosis, patients with early-onset Sjögren's syndrome were positive for rheumatoid factor (41.5% vs 20.2%, P < 0.001) and ANA (86.5% vs 73.1%; P = 0.038), anti-SSA antibody (84.6% vs 54.4%; P < 0.001) and anti-SSB antibodies (57.7 versus 29.7 percent; P <0.001); Complement C3 (18.9 versus 9.1 percent; P = 0.032) and C4 (54.7% vs 40.2%; P = 0.048).
There was no difference in ESSDAI scores between the two groups at initial diagnosis; The ESSDAI score 5 years after diagnosis showed a significant improvement in the late-onset group (-1.27; P <0.0001), and the disease in the early-onset group had a tendency to worsen (0.72; P = 0.27）。
ConclusionsEarly-onset primary SS is associated with risk factors for predicting severe systemic disease of SS. The study also found that patients with different age groups of onset had different trends in ESSDAI scores, with patients with early onset tending to worsen over time. Therefore, age may be one of the risk factors for severe SS.
Literature II
ObjectiveTo investigate the clinical, serological and histologic characteristics of patients with early (age≤35 years) and advanced (age>65 years) primary Sjögrens syndrome (pSS), and to explore the differences in the development trend of lymphoma between the two groups.
MethodsFrom 1997 multicenter pSS study populations, 379 patients with early-onset (age≤35 years) and 293 patients with late-onset (age>65 years) primary Sjögrens syndrome (pSS) were screened and compared with healthy controls of corresponding ages, and the clinical and laboratory test characteristics of the two groups were analyzed, as well as the risk factors associated with lymphoma.
Results Patients with early-onset pSS (19%, n = 379) had higher rates of salivary gland disease (SGE), lymphadenopathy, Raynaud's phenomenon, autoantibodies, C4 hypocomplementemia, hypergammaglobulinemia, leukopenia, and lymphoma (10.3% vs 5.7%, p = 0.030, OR = 1.91, 95% CI: 1.11-3.27) compared with healthy controls of the same age.
和同年龄健康对照组相比，老年发病pSS患者(15%，n =293)更频繁地出现口干、间质性肺病和淋巴瘤(6.8% vs 2.1%,p = 0.011, OR = 3.40, 95% CI: 1.34-8.17)。
In patients with early-onset pSS, cryoglobulinemia, C4 hypocomplementemia, lymphadenopathy, and SGE are considered independent risk factors for lymphoma. SGE, C4 hypocomplementemia, and male sex are independent risk factors for lymphoma in older-onset patients with pSS. The peak incidence of lymphoma in patients with early-onset pSS occurred within 3 years and 10 years after the onset of pSS, while the peak incidence of lymphoma in elderly patients with pSS occurred within 6 years of onset.
Figure 1: Distribution pattern of lymphoma development during the course of pSS: (A) time to lymphoma in early-onset pSS patients and healthy controls (n = 24), (B) time to lymphoma in elderly patients with pSS and healthy controls (n = 12).
Figure 2: Calculation of the prevalence and classical predictors of lymphoma using simple statistical and data-driven methods. (A) Comparison of lymphoma prevalence and classical predictors of lymphoma in patients with early-onset pSS and their matched healthy controls, and (B) in older patients with early-onset pSS and their matched healthy controls. Independent predictors of lymphoma after data-driven analysis by multivariate logistic regression analysis based on FCBF are indicated by asterisks. Two asterisks indicate negative associations.
ConclusionsThere are different clinical phenotypes of PSS with early onset and late onset. They both have a high prevalence of lymphoma, but the causes and timing of lymphoma are different.
Summarizing the above two literatures, it can be seen that patients with early-onset pSS have obvious systemic changes and worse prognosis, and lymphoma occurs earlier, while in general, patients with early-onset pSS have less obvious dry mouth and tooth decay, which is easier to be ignored, so it is necessary to pay attention to the diagnosis and treatment of early-onset pSS patients, and closer follow-up is required.
整理自：1. A Céline, Eric H , Franois M , et al. Is early-onset primary Sjgren's syndrome a worse prognosis form of the disease? [J]. Rheumatology (Oxford, England), 2018(7):7.2. Goules A V , Argyropoulou O D , Pezoulas V C , et al. Primary Sjgren's Syndrome of Early and Late Onset: Distinct Clinical Phenotypes and Lymphoma Development[J]. Frontiers in Immunology, 2020, 11:594096.
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