- Open Access
Long-term follow-up in primary Sjögren’s syndrome reveals differences in clinical presentation between female and male patients
- Jorge I. Ramírez Sepúlveda1,
- Marika Kvarnström1,
- Per Eriksson2,
- Thomas Mandl3,
- Katrine Brække Norheim4,
- Svein Joar Johnsen4,
- Daniel Hammenfors5, 6,
- Malin V. Jonsson5, 7,
- Kathrine Skarstein8, 9,
- Johan G. Brun5, 6,
- the DISSECT consortium,
- Lars Rönnblom10,
- Helena Forsblad-d’Elia11,
- Sara Magnusson Bucher12,
- Eva Baecklund10,
- Elke Theander3,
- Roald Omdal4,
- Roland Jonsson5, 6,
- Gunnel Nordmark10 and
- Marie Wahren-Herlenius1Email authorView ORCID ID profile
© The Author(s). 2017
Received: 29 April 2017
Accepted: 26 July 2017
Published: 8 August 2017
Despite men being less prone to develop autoimmune diseases, male sex has been associated with a more severe disease course in several systemic autoimmune diseases. In the present study, we aimed to investigate differences in the clinical presentation of primary Sjögren’s syndrome (pSS) between the sexes and establish whether male sex is associated with a more severe form of long-term pSS.
Our study population included 967 patients with pSS (899 females and 68 males) from Scandinavian clinical centers. The mean follow-up time (years) was 8.8 ± 7.6 for women and 8.5 ± 6.2 for men (ns). Clinical data including serological and hematological parameters and glandular and extraglandular manifestations were compared between men and women.
Male patient serology was characterized by more frequent positivity for anti-Ro/SSA and anti-La/SSB (p = 0.02), and ANA (p = 0.02). Further, men with pSS were more frequently diagnosed with interstitial lung disease (p = 0.008), lymphadenopathy (p = 0.04) and lymphoma (p = 0.007). Conversely, concomitant hypothyroidism was more common among female patients (p = 0.009).
We observe enhanced serological responses and higher frequencies of lymphoma-related extraglandular manifestations in men with pSS. Notably, lymphoma itself was also significantly more common in men. These observations may reflect an aggravated immune activation and a more severe pathophysiological state in male patients with pSS and indicate a personalized managing of the disease due to the influence of the sex of patients with pSS.
It has been widely established that women are more prone to develop autoimmune diseases . Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by inflammation of the salivary and lacrimal glands, causing a reduction in exocrine secretion that ultimately leads to the clinical presentation of sicca symptoms. The reported population-based female to male ratio is 14:1 . Many hypotheses have been proposed to explain the overall marked sex bias in autoimmunity and pSS , including genetic and epigenetic factors [4, 5], sex hormones , and X-chromosome aberrances [7, 8]. However, the molecular mechanisms that drive this sex skewing still remain elusive.
Interestingly, the differences between the sexes likewise extend to the clinical manifestations, where female and male patients differ in disease presentation and severity. Despite being less prone to develop autoimmune diseases, male patients have been reported to have a more severe disease and a worse prognosis. In systemic lupus erythematosus (SLE), men present more renal disease  and serositis . Further, Andrade et al.  identified male sex as a strong predictor for poorer long-term prognosis due to accelerated damage accrual, while Manger et al.  reported male sex as a risk factor for increased SLE mortality. Male sex is also deemed as a factor for accelerated disease progression in multiple sclerosis (MS)  and associated with a significantly higher prevalence of comorbidities  such as diabetes, epilepsy, depression, and anxiety. Although less clear, sex differences in rheumatoid arthritis (RA) severity and extra-articular manifestations have also been described; women appear more prone to present sicca symptoms and men to have erosive joint disease, rheumatoid nodules, and interstitial lung disease [15, 16].
Regarding pSS, several studies have addressed sex differences in clinical presentation [17, 18]. As reviewed by Brandt et al. , some authors have identified differences in extraglandular manifestations and serological markers, with a focus on female prevalence. However, there is no clear consensus on whether male sex is associated with a more severe disease. Our group has described that at diagnosis, male patients more frequently present with extraglandular manifestations, more concomitant extraglandular manifestations, and higher anti-Ro52 levels by investigation in two independent cohorts . To understand if there are sex differences in the clinical presentation of pSS also after a long-standing disease and whether risk for comorbidities vary between the sexes, we assessed glandular and extraglandular manifestations, serological parameters, and comorbidities of pSS in men and women years after diagnosis in a large Scandinavian cohort.
Demographic and basic characteristics of the cohort
Women n = 899% (frequency)
Men n = 68% (frequency)
Age at symptom onset (years, mean ± SD)
46.16 ± 14.79
47.88 ± 14.71
Age at diagnosis (years, mean ± SD)
52.65 ± 13.75
52.63 ± 13.52
Follow-up time from diagnosis (years, mean ± SD)
8.76 ± 7.62
8.48 ± 6.15
Item IV. Histopathologya
Salivary gland biopsy
Positive (focus score ≥1)
For the comparison of continuous variables, the Mann–Whitney U test was used. The chi-square test was used when analyzing categorical data, and Fisher’s exact test was employed if the observed frequency of any given cell was <5 and/or the total number of analyzed individuals in any group was <40. Data was analyzed with GraphPad Prism 6, and p values <0.05 were considered statistically significant.
Basic characteristics of the cohort
The cohort consisted of 967 pSS patients, of which 899 were women (93%) and 68 were men (7%) (Table 1). The female/male ratio was 13:1. The mean age at symptom onset for the female group was 46 years ± 14.8 (95% CI) and 48 years ± 14.7 (95% CI) for the male group. There was no significant difference with regard to the age at diagnosis between women and men (52.6 and 52.6 years, respectively), or the follow-up time from diagnosis between female and male patients (8.8 years ± 7.6, 95% CI and 8.5 years ± 6.1, 95% CI, respectively).
We also compared the histopathological parameters of the salivary gland biopsy from all the included patients (Table 1). Although women tended to more frequently undergo a salivary gland biopsy than men (p = 0.06), the histological findings revealed no significant differences in terms of a positive focus score or presence of germinal center-like structures.
Serological differences between female and male patients with pSS
Serological characteristics in female and male patients with pSS
Women n = 899% (frequency)
Men n = 68% (frequency)
Item VI.a Autoantibodies
Ro/SSA and/or La/SSB positive
Ro/SSA and La/SSB positive
Anti-Ro/SSA positivity was observed in 68% of the women and 76% of the men; SSB autoantibodies were detected in 41% of the women and 57% of the men (p = 0.01) and positivity for both anti-Ro/SSA and anti-La/SSB was found in 38% of the women and 52% of the men (p = 0.02) (Table 2). Furthermore, ANA positivity was significantly more frequent in male patients (p = 0.02). Thus, the stratified analysis indicated that the male group presents significantly higher frequencies of positivity towards ANA, La/SSB, and Ro/SSA + La/SSB.
Frequencies of clinical manifestations differ between female and male pSS patients
Frequency of pSS-associated clinical manifestations and comorbidities in female and male patients with pSS
Women n = 899% (frequency)
Men n = 68% (frequency)
Interstitial lung disease
Lymphadenopathy and lymphoma
Enlarged lymph nodes
Major salivary gland swelling
Presence of EGM
Number of EGM
(mean + SD)
0.44 ± 0.69
0.51 ± 0.74
Other common comorbidities and clinical manifestations
Frequencies of subtypes of lymphoma in women and men with pSS
n = 32% (frequency)
n = 7% (frequency)
Autoantibody-positive pSS female and male patients differ in terms of clinical manifestations
Frequency of comorbidities, extraglandular, and other common clinical manifestations in SSA- and/or SSB-positive female and male patients with pSS
Women n = 640% (frequency)
Men n = 54% (frequency)
Interstitial lung disease
Enlarged lymph nodes
Primary Sjögren’s syndrome represents the autoimmune disease with the highest female bias, ranging from a ratio of 10–20:1 . Besides the overwhelming sex bias observed in disease susceptibility, previous studies have also aimed to investigate whether the disease manifests differently between female and male patients. Earlier observations have not reached a clear consensus as to whether male pSS patients have a distinct clinical course and a more severe presentation of the disease . In a recent study, though, we reported that men with pSS, from a population-based incident case cohort, displayed significantly higher levels of anti-Ro52, were diagnosed at an earlier age than their female counterparts, presented more concomitant extraglandular manifestations, and had a higher frequency of pulmonary complications and cutaneous vasculitis. Similarly, an Italian cohort revealed a significant male propensity towards extraglandular manifestation presentation . These findings strongly suggest that men affected by pSS have a more severe disease at time of diagnosis. In the present study, we addressed whether differences between the sexes are also present several years after diagnosis.
We identified significant sex differences in terms of serological parameters and frequencies of some organ involvement. Our results indicate that the humoral response between women and men is different; particularly, men present more often with La/SSB, Ro/SSA + La/SSB and ANA positivity. This increased immune activity observed among the male patients is of special interest since in a healthy state, men mount a lower antibody response in comparison with women [23–25]. Although the pathogenic effect of autoantibodies has not been clearly established, the presence of certain autoantibodies has been associated with organ manifestations. Noteworthy, SSA antibodies are related to pulmonary diseases [26, 27], an extraglandular manifestation we observed overrepresented in the male patients from our cohort. Further, a recent study proposed that anti-La/SSB antibodies are a risk factor associated with increased mortality in pSS patients . Thus, even though the pathogenic role of pSS-associated autoantibodies remains unknown, seropositivity has a strong correlation with organ involvement and worse prognosis, supporting the conclusion that the disease course is more severe in male patients than in female patients.
Interstitial lung disease has been extensively studied in the context of pSS [29, 30]. Male sex is widely recognized as a risk factor for developing interstitial lung disease [26, 31]. In accordance with more recent studies , our extended cohort shows that male patients with pSS are indeed more prone to develop interstitial lung disease. The reasons for this male preponderance are poorly understood; however, this might be due to increased seropositivity, environmental exposure to certain pollutants  and smoking  in the male pSS group. In fact, idiopathic pulmonary fibrosis, which represents a usual interstitial pneumonia histopathological pattern, is one of the most common forms of interstitial lung disease detected in pSS  and has a higher prevalence in men, as epidemiological studies have previously described [33, 34]. In other words, regardless of pSS diagnosis, men in general are more frequently affected by a type of interstitial lung disease that is associated with a worse prognosis. This susceptibility, thus, might be augmented in pSS, driven by other pathophysiological factors that enhance this propensity to develop pulmonary disease.
It is well known that pSS patients have an increased risk for developing non-Hodgkin lymphoma [35–38]. Sex-specific risk for lymphoma development in patients with rheumatic disease has been seldom studied, mainly due to the inclusion of mostly female patients. Nevertheless, Ansell et al. have reported a significantly higher incidence of lymphoma in male RA patients. Despite the increased association of autoimmune diseases and lymphoma in men , earlier studies of sex differences in lymphoproliferative malignancies in pSS have not shown a clear sex-specific predominance [40, 41]. In contrast, our present study is the largest pSS cohort to report a significantly increased risk for male patients to present lymphoma in comparison with female patients. This is in accordance with the results from a smaller patient sample from which an increased risk for men affected with pSS, SLE, RA, and autoimmune hemolytic anemia to develop lymphoma was reported .
Since the male bias observed in pSS-associated malignancies has only recently been described, it is not fully understood. However, considering the reported predictive factors of lymphoma development, an increased risk of lymphoma in male patients is logical. As reviewed by Nocturne and Mariette , the main clinical manifestations and parameters associated with this type of cancer are swelling of salivary glands, lymphadenopathy, palpable purpura, cryoglobulinemia, lymphopenia, low complement levels, and a monoclonal component in serum or urine. Interestingly, the male pSS patients from our cohort presented more frequently with lymphadenopathy. Although not included in the data analysis due to the high amount of missing data, cryoglobulinemia was also more commonly observed in the male patients (20/151 in females vs 3/7 in males, p = 0.03).
The only clinical manifestation that was more significantly represented in the female pSS patients from our cohort was hypothyroidism. Endocrine problems are not uncommon in patients with autoimmune disorders , and the female bias towards thyroid diseases has been extensively documented [45–48]. Furthermore, since the predominantly female incidence of hypothyroidism corresponds with the female susceptibility to autoimmune diseases, the thyroid gland has been proposed as a decisive organ to explain the sex skewness in autoimmune diseases. The effect of adipokines, which comprise a number of different cytokines including, e.g., leptins, adiponectins, TNF-α, and IL-6, on thyroid tissue has been suggested as a triggering mechanism for autoimmune thyroiditis, which probably precedes or coincides with the diagnosis of another systemic autoimmune disease such as pSS and SLE. . This emphasizes the need for a comprehensive screening and close monitoring of thyroid function in suspected patients because it might be an important marker for autoimmune disease development. As for the thyroid gland being responsible for female-preponderant diseases, further studies should be performed to clarify its role.
The studied cohort offers a valuable large group of clinically carefully characterized patients with pSS, allowing for analysis of parameters that differ between men and women affected by the syndrome. The long follow-up time is essential for identifying clinical manifestations at different time points of the disease course. However, the patients included in this cohort were mostly included at tertiary referral centers of university hospital clinics. A possible limitation of the study is that the study population might therefore not mirror the general pSS patient population and that the patients described in this study represent cases with an overall more severe disease phenotype, both female and male patients. A further possibility is that male patients with mild symptoms and less severe disease are less often referred, as the primary health care doctor may not be as likely to suspect Sjögren’s syndrome due to its rarity in men, resulting in only men with more severe disease being included in the study. As the evaluation of extraglandular manifestations was dependent on doctors’ clinical assessments and did not include specific laboratory or physiologic tests unless the patient had symptoms, it is also possible that subclinical extraglandular manifestations may have been missed. However, the mean number of extraglandular manifestations diagnosed did not differ significantly between centers, nor did the proportion of men and women contributed. A further limitation is the lack of EULAR primary Sjögren’s syndrome disease activity (ESSDAI) and patient-reported (ESSPRI) indexes  at diagnosis, as well as information on other common extraglandular manifestations such as neurological diseases.
In summary, our findings provide compelling evidence that the clinical presentation of pSS differs between women and men. The sex-specific preference of some clinical manifestations hints at divergent pathophysiological mechanisms between women and men with pSS. Consequently, management of the disease will benefit from sex-specific tailored clinical programs to address complications that are common or expected in the respective sex.
DISSECT consortium members:
Agneta Zickert, Stockholm; Albin Björk, Stockholm; Anders A. Bengtsson, Lund; Andreas Jönsen, Lund; Andrei Alexsson, Uppsala; Anna Tjärnlund, Stockholm; Ann-Christine Syvänen, Uppsala; Antonella Notarnicola, Stockholm; Argyri Mathioudaki, Uppsala; Åsa Karlsson, Uppsala; Carin Backlin, Uppsala; Christine Bengtsson, Umeå; Christopher Sjöwall, Linköping; Dag Leonard, Uppsala; Daniel Hammenfors, Bergen; Elisabet Svenungsson, Stockholm; Elke Theander, Malmö; Eva Baecklund, Uppsala; Eva Murén, Uppsala; Fabiana Farias, Uppsala; Gerli Pielberg, Uppsala; Guðný Ella Thorlacius, Stockholm; Gunnel Nordmark, Uppsala; Hector Chinoy, Manchester; Helena Andersson, Oslo; Helena Enocsson, Linköping; Helena Forsblad-d’Elia, Gothenburg; Ingrid E. Lundberg, Stockholm; Iva Gunnarsson, Stockholm; Janine Lamb, Manchester; Jennifer Meadows, Uppsala; Jessika Nordin, Uppsala; Johan G Brun, Bergen; Johanna Dahlqvist, Uppsala; Johanna K. Sandling, Uppsala; John Mo, Gothenburg; Jonas Carlsson Almlöf, Uppsala; Jonas Wetterö, Linköping; Jorge I. Ramírez Sepúlveda, Stockholm; Juliana Imgenberg-Kreuz, Uppsala; Karin Bolin, Uppsala; Karin Hjorton, Uppsala; Karl A. Brokstad, Bergen; Karolina Tandre, Uppsala; Kathrine Skarstein, Bergen; Katrine Brække Norheim, Stavanger; Kerstin Lindblad-Toh, Uppsala; Lars Rönnblom, Uppsala; Leonid Padyukov, Stockholm; Lilian Vasaitis, Uppsala; Lina Hultin-Rosenberg, Uppsala; Louise Pyndt Diederichsen, Odense; Maija-Leena Eloranta, Uppsala; Malin V. Jonsson, Bergen; Marie Wahren-Herlenius, Stockholm; Marika Kvarnström, Stockholm; Maryam Dastmalchi, Stockholm; Matteo Bianchi, Uppsala; Niklas Hagberg, Uppsala; Outi Vaarala, Gothenburg; Øyvind Molberg, Oslo; Per Eriksson, Linköping; Roald Omdal, Stavanger; Robert G. Cooper, Liverpool; Roland Jonsson, Bergen; Sara Magnusson Bucher, Örebro; Sergey Kozyrev, Uppsala; Silke Appel, Bergen; Simon Rothwell, Manchester; Solbritt Rantapää-Dahlqvist, Umeå; Svein Joar Johnsen, Stavanger; Thomas Mandl, Malmö.
The study was supported by grants from the Swedish Research Council, the Heart-Lung Foundation, the Stockholm County Council, Karolinska Institutet, the Swedish Rheumatism association, and the King Gustaf the Vth 80-year foundation. The DISSECT study is supported by an AstraZeneca Science for Life Laboratory Research Collaboration grant.
Availability of data and materials
JIRS and MWH conceived and designed the study. DISSECT consortium: MK, PE, KBN, SJJ, DH, MVJ, KS, HFdE, EB, SMB, ET, TM, RO, RJ, and GN managed the study participant recruitment and clinical data acquisition. Data was analyzed by JIRS and GN. JIRS and MWH wrote the first draft of the manuscript, and all authors participated in the revision until its final stage. All authors read and approved the final manuscript.
Ethics approval and consent to participate
The study was approved by the regional ethical committee for respective study center, and patients gave informed written consent.
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Whitacre CC. Sex differences in autoimmune disease. Nat Immunol. 2001;2:777–80.View ArticlePubMedGoogle Scholar
- Kvarnstrom M, Ottosson V, Nordmark B, Wahren-Herlenius M. Incident cases of primary Sjogren's syndrome during a 5-year period in Stockholm County: a descriptive study of the patients and their characteristics. Scand J Rheumatol. 2015;44:135–42.View ArticlePubMedGoogle Scholar
- Brandt JE, Priori R, Valesini G, Fairweather D. Sex differences in Sjogren's syndrome: a comprehensive review of immune mechanisms. Biol Sex Differ. 2015;6:19.View ArticlePubMedPubMed CentralGoogle Scholar
- Lessard CJ, Li H, Adrianto I, et al. Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjogren's syndrome. Nat Genet. 2013;45:1284–92.View ArticlePubMedGoogle Scholar
- Imgenberg-Kreuz J, Sandling JK, Almlöf JC, Nordlund J, Signér L, Norheim KB, Omdal R, Rönnblom L, Eloranta ML, Syvänen AC, Nordmark G. Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren's syndrome reveals regulatory effects at interferon-induced genes. Ann Rheum Dis. 2016;75(11):2029–36. doi:10.1136/annrheumdis-2015-208659.
- Cutolo M, Capellino S, Sulli A, et al. Estrogens and autoimmune diseases. Ann N Y Acad Sci. 2006;1089:538–47.View ArticlePubMedGoogle Scholar
- Liu K, Kurien BT, Zimmerman SL, et al. X chromosome dose and sex bias in autoimmune diseases: increased prevalence of 47,XXX in systemic lupus erythematosus and Sjogren's syndrome. Arthritis Rheumatol. 2016;68:1290–300.PubMedPubMed CentralGoogle Scholar
- Harris VM, Sharma R, Cavett J, et al. Klinefelter's syndrome (47,XXY) is in excess among men with Sjogren's syndrome. Clin Immunol. 2016;168:25–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Boodhoo KD, Liu S, Zuo X. Impact of sex disparities on the clinical manifestations in patients with systemic lupus erythematosus: a systematic review and meta-analysis. Medicine (Baltimore). 2016;95:e4272.View ArticleGoogle Scholar
- Voulgari PV, Katsimbri P, Alamanos Y, Drosos AA. Gender and age differences in systemic lupus erythematosus. A study of 489 Greek patients with a review of the literature. Lupus. 2002;11:722–9.View ArticlePubMedGoogle Scholar
- Andrade RM, Alarcon GS, Fernandez M, et al. Accelerated damage accrual among men with systemic lupus erythematosus: XLIV. Results from a multiethnic US cohort. Arthritis Rheum. 2007;56:622–30.View ArticlePubMedGoogle Scholar
- Manger K, Manger B, Repp R, et al. Definition of risk factors for death, end stage renal disease, and thromboembolic events in a monocentric cohort of 338 patients with systemic lupus erythematosus. Ann Rheum Dis. 2002;61:1065–70.View ArticlePubMedPubMed CentralGoogle Scholar
- Tremlett H, Paty D, Devonshire V. Disability progression in multiple sclerosis is slower than previously reported. Neurology. 2006;66:172–7.View ArticlePubMedGoogle Scholar
- Marrie RA, Patten SB, Tremlett H, et al. Sex differences in comorbidity at diagnosis of multiple sclerosis: a population-based study. Neurology. 2016. [Epub ahead of print]Google Scholar
- Weyand CM, Schmidt D, Wagner U, Goronzy JJ. The influence of sex on the phenotype of rheumatoid arthritis. Arthritis Rheum. 1998;41:817–22.View ArticlePubMedGoogle Scholar
- Gossec L, Baro-Riba J, Bozonnat MC, et al. Influence of sex on disease severity in patients with rheumatoid arthritis. J Rheumatol. 2005;32:1448–51.PubMedGoogle Scholar
- Gondran G, Fauchais A, Lambert M, et al. Primary Sjogren's syndrome in men. Scand J Rheumatol. 2008;37:300–5.View ArticlePubMedGoogle Scholar
- Horvath IF, Szodoray P, Zeher M. Primary Sjogren's syndrome in men: clinical and immunological characteristic based on a large cohort of Hungarian patients. Clin Rheumatol. 2008;27:1479–83.View ArticlePubMedGoogle Scholar
- Ramirez Sepulveda JI, Kvarnstrom M, Brauner S, Baldini C, Wahren-Herlenius M. Difference in clinical presentation between women and men in incident primary Sjogren's syndrome. Biol Sex Differ. 2017;8:16.View ArticlePubMedPubMed CentralGoogle Scholar
- Vitali C, Bombardieri S, Jonsson R, et al. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61:554–8.View ArticlePubMedPubMed CentralGoogle Scholar
- Sakiani S, Olsen NJ, Kovacs WJ. Gonadal steroids and humoral immunity. Nat Rev Endocrinol. 2013;9:56–62.View ArticlePubMedGoogle Scholar
- Garcia-Carrasco M, Mendoza-Pinto C, Jimenez-Hernandez C, et al. Serologic features of primary Sjogren's syndrome: clinical and prognostic correlation. Int J Clin Rheumtol. 2012;7:651–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Klein SL, Jedlicka A, Pekosz A. The Xs and Y of immune responses to viral vaccines. Lancet Infect Dis. 2010;10:338–49.View ArticlePubMedGoogle Scholar
- Furman D. Sexual dimorphism in immunity: improving our understanding of vaccine immune responses in men. Expert Rev Vaccines. 2015;14:461–71.View ArticlePubMedGoogle Scholar
- Klein SL, Marriott I, Fish EN. Sex-based differences in immune function and responses to vaccination. Trans R Soc Trop Med Hyg. 2015;109:9–15.View ArticlePubMedPubMed CentralGoogle Scholar
- Boitiaux JF, Debray MP, Nicaise-Roland P, et al. Idiopathic interstitial lung disease with anti-SSA antibody. Rheumatology (Oxford). 2011;50:2245–50.View ArticleGoogle Scholar
- Ghillani P, Andre C, Toly C, et al. Clinical significance of anti-Ro52 (TRIM21) antibodies non-associated with anti-SSA 60kDa antibodies: results of a multicentric study. Autoimmun Rev. 2011;10:509–13.View ArticlePubMedGoogle Scholar
- Singh AG, Singh S, Matteson EL. Rate, risk factors and causes of mortality in patients with Sjogren's syndrome: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford). 2016;55:450–60.View ArticleGoogle Scholar
- Mira-Avendano IC, Abril A. Pulmonary manifestations of Sjogren syndrome, systemic lupus erythematosus, and mixed connective tissue disease. Rheum Dis Clin N Am. 2015;41:263–77.View ArticleGoogle Scholar
- Flament T, Bigot A, Chaigne B, et al. Pulmonary manifestations of Sjogren's syndrome. Eur Respir Rev. 2016;25:110–23.View ArticlePubMedGoogle Scholar
- Yazisiz V, Arslan G, Ozbudak IH, et al. Lung involvement in patients with primary Sjogren's syndrome: what are the predictors? Rheumatol Int. 2010;30:1317–24.View ArticlePubMedGoogle Scholar
- Johannson KA, Balmes JR, Collard HR. Air pollution exposure: a novel environmental risk factor for interstitial lung disease? Chest. 2015;147:1161–7.View ArticlePubMedPubMed CentralGoogle Scholar
- Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183:431–40.View ArticlePubMedGoogle Scholar
- Hopkins RB, Burke N, Fell C, Dion G, Kolb M. Epidemiology and survival of idiopathic pulmonary fibrosis from national data in Canada. Eur Respir J. 2016;48:187–95.View ArticlePubMedGoogle Scholar
- Kassan SS, Thomas TL, Moutsopoulos HM, et al. Increased risk of lymphoma in sicca syndrome. Ann Intern Med. 1978;89:888–92.View ArticlePubMedGoogle Scholar
- Theander E, Henriksson G, Ljungberg O, et al. Lymphoma and other malignancies in primary Sjogren's syndrome: a cohort study on cancer incidence and lymphoma predictors. Ann Rheum Dis. 2006;65:796–803.View ArticlePubMedGoogle Scholar
- Dias C, Isenberg DA. Susceptibility of patients with rheumatic diseases to B-cell non-Hodgkin lymphoma. Nat Rev Rheumatol. 2011;7:360–8.View ArticlePubMedGoogle Scholar
- Nishishinya MB, Pereda CA, Munoz-Fernandez S, et al. Identification of lymphoma predictors in patients with primary Sjogren's syndrome: a systematic literature review and meta-analysis. Rheumatol Int. 2015;35:17–26.View ArticlePubMedGoogle Scholar
- Ansell P, Simpson J, Lightfoot T, et al. Non-Hodgkin lymphoma and autoimmunity: does gender matter? Int J Cancer. 2011;129:460–6.View ArticlePubMedGoogle Scholar
- Mellemkjaer L, Pfeiffer RM, Engels EA, et al. Autoimmune disease in individuals and close family members and susceptibility to non-Hodgkin's lymphoma. Arthritis Rheum. 2008;58:657–66.View ArticlePubMedGoogle Scholar
- Smedby KE, Askling J, Mariette X, Baecklund E. Autoimmune and inflammatory disorders and risk of malignant lymphomas--an update. J Intern Med. 2008;264:514–27.View ArticlePubMedGoogle Scholar
- Fallah M, Liu X, Ji J, et al. Hodgkin lymphoma after autoimmune diseases by age at diagnosis and histological subtype. Ann Oncol. 2014;25:1397–404.View ArticlePubMedGoogle Scholar
- Nocturne G, Mariette X. Sjogren syndrome-associated lymphomas: an update on pathogenesis and management. Br J Haematol. 2015;168:317–27.View ArticlePubMedGoogle Scholar
- Merrill SJ, Mu Y. Thyroid autoimmunity as a window to autoimmunity: an explanation for sex differences in the prevalence of thyroid autoimmunity. J Theor Biol. 2015;375:95–100.View ArticlePubMedGoogle Scholar
- Lu MC. Yin WY, Tsai TY, Koo M. Lai NS Increased risk of primary Sjogren's syndrome in female patients with thyroid disorders: a longitudinal population-based study in Taiwan PLoS One. 2013;8:e77210.PubMedGoogle Scholar
- Mavragani CP, Fragoulis GE, Moutsopoulos HM. Endocrine alterations in primary Sjogren's syndrome: an overview. J Autoimmun. 2012;39:354–8.View ArticlePubMedGoogle Scholar
- Appenzeller S, Pallone AT, Natalin RA, Costallat LT. Prevalence of thyroid dysfunction in systemic lupus erythematosus. J Clin Rheumatol. 2009;15:117–9.View ArticlePubMedGoogle Scholar
- Jara LJ, Navarro C, Brito-Zeron Mdel P, et al. Thyroid disease in Sjogren's syndrome. Clin Rheumatol. 2007;26:1601–6.View ArticlePubMedGoogle Scholar
- Seror R, Bootsma H, Saraux A, et al. Defining disease activity states and clinically meaningful improvement in primary Sjogren's syndrome with EULAR primary Sjogren's syndrome disease activity (ESSDAI) and patient-reported indexes (ESSPRI). Ann Rheum Dis. 2016;75:382–9.View ArticlePubMedGoogle Scholar