Hospitalization Risks for Neurological Disorders in Primary Sjögren’s Syndrome Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. National Database Characteristics
2.2. Primary Sjögren’s Syndrome Patients (pSS)
2.3. Control Group of Non-pSS Hospitalized Patients
2.4. Outcomes
2.5. Adjustment Factors
2.6. Statistical Analysis
3. Results
3.1. Population
3.2. Incidental Hospitalization Risk for Dementia
3.3. Incidental Hospitalization Risk for Associated Neurological Disorders
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Maciel, G.; Servioli, L.; Nannini, C.; Berti, A.; Crowson, C.S.; Achenbach, S.J.; Matteson, E.L.; Cornec, D. Hospitalisation Rates among Patients with Primary Sjögren’s Syndrome: A Population-Based Study, 1995–2016. RMD Open 2018, 4, e000575. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Manzo, C.; Martinez-Suarez, E.; Kechida, M.; Isetta, M.; Serra-Mestres, J. Cognitive Function in Primary Sjögren’s Syndrome: A Systematic Review. Brain Sci. 2019, 9, 85. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Delalande, S.; de Seze, J.; Fauchais, A.-L.; Hachulla, E.; Stojkovic, T.; Ferriby, D.; Dubucquoi, S.; Pruvo, J.-P.; Vermersch, P.; Hatron, P.-Y. Neurologic Manifestations in Primary Sjögren Syndrome: A Study of 82 Patients. Medicine 2004, 83, 280–291. [Google Scholar] [CrossRef] [PubMed]
- Morreale, M.; Marchione, P.; Giacomini, P.; Pontecorvo, S.; Marianetti, M.; Vento, C.; Tinelli, E.; Francia, A. Neurological Involvement in Primary Sjögren Syndrome: A Focus on Central Nervous System. PLoS ONE 2014, 9, e84605. [Google Scholar] [CrossRef]
- Blanc, F.; Longato, N.; Jung, B.; Kleitz, C.; Di Bitonto, L.; Cretin, B.; Collongues, N.; Sordet, C.; Fleury, M.; Poindron, V.; et al. Cognitive Dysfunction and Dementia in Primary Sjögren’s Syndrome. ISRN Neurol. 2013, 2013, 501327. [Google Scholar] [CrossRef]
- Koçer, B.; Tezcan, M.E.; Batur, H.Z.; Haznedaroğlu, Ş.; Göker, B.; İrkeç, C.; Çetinkaya, R. Cognition, Depression, Fatigue, and Quality of Life in Primary Sjögren’s Syndrome: Correlations. Brain Behav. 2016, 6, e00586. [Google Scholar] [CrossRef]
- Faurholt-Jepsen, M.; Miskowiak, K.W.; Frost, M.; Christensen, E.M.; Þórarinsdóttir, H.; Bardram, J.E.; Vinberg, M.; Kessing, L.V. Patient-Evaluated Cognitive Function Measured with Smartphones and the Association with Objective Cognitive Function, Perceived Stress, Quality of Life and Function Capacity in Patients with Bipolar Disorder. Int. J. Bipolar Disord. 2020, 8, 31. [Google Scholar] [CrossRef]
- Epstein, L.C.; Masse, G.; Harmatz, J.S.; Scott, T.M.; Papas, A.S.; Greenblatt, D.J. Characterization of Cognitive Dysfunction in Sjögren’s Syndrome Patients. Clin. Rheumatol. 2014, 33, 511–521. [Google Scholar] [CrossRef]
- Chen, H.-H. Risk of Dementia among Patients with Sjogren’s Syndrome: A Nationwide Population-Based Cohort Study in Taiwan. Semin. Arthritis Rheum. 2019, 48, 895–899. [Google Scholar] [CrossRef]
- Liliang, P.-C.; Liang, C.-L.; Lu, K.; Yang, S.-N.; Hsieh, M.-T.; Tai, Y.-C.; Wang, K.-W. Population-Based Study Suggests an Increased Risk of Alzheimer’sdisease in Sjögren’s Syndrome. Clin. Rheumatol. 2017, 37, 935–941. [Google Scholar] [CrossRef] [Green Version]
- Goulabchand, R.; Roubille, C.; Montani, D.; Fesler, P.; Bourdin, A.; Malafaye, N.; Morel, J.; Arnaud, E.; Lattuca, B.; Barateau, L.; et al. Cardiovascular Events, Sleep Apnoea, and Pulmonary Hypertension in Primary Sjögren’s Syndrome: Data from the French Health Insurance Database. J. Clin. Med. 2021, 10, 5115. [Google Scholar] [CrossRef] [PubMed]
- Goulabchand, R.; Malafaye, N.; Jacot, W.; Viel, P.W.D.; Morel, J.; Lukas, C.; Rozier, P.; Lamure, S.; Noel, D.; Molinari, N.; et al. Cancer Incidence in Primary Sjögren’s Syndrome: Data from the French Hospitalization Database. Autoimmun. Rev. 2021, 20, 102987. [Google Scholar] [CrossRef]
- Fang, M.; Mirutse, G.; Guo, L.; Ma, X. Role of Socioeconomic Status and Housing Conditions in Geriatric Depression in Rural China: A Cross-Sectional Study. BMJ Open 2019, 9, e024046. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Freeman, A.; Tyrovolas, S.; Koyanagi, A.; Chatterji, S.; Leonardi, M.; Ayuso-Mateos, J.L.; Tobiasz-Adamczyk, B.; Koskinen, S.; Rummel-Kluge, C.; Haro, J.M. The Role of Socio-Economic Status in Depression: Results from the COURAGE (Aging Survey in Europe). BMC Public Health 2016, 16, 1098. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Austin, P.C.; Lee, D.S.; Fine, J.P. Introduction to the Analysis of Survival Data in the Presence of Competing Risks. Circulation 2016, 133, 601–609. [Google Scholar] [CrossRef] [PubMed]
- Lin, T.-M.; Chen, W.-S.; Sheu, J.-J.; Chen, Y.-H.; Chen, J.-H.; Chang, C.-C. Autoimmune Rheumatic Diseases Increase Dementia Risk in Middle-Aged Patients: A Nationwide Cohort Study. PLoS ONE 2018, 13, e0186475. [Google Scholar] [CrossRef] [Green Version]
- Hou, T.-Y.; Hsu, H.-C.; Lin, T.-M.; Chang, Y.-S.; Chen, W.-S.; Kuo, P.-I.; Lin, Y.-C.; Chang, C.-C.; Chen, J.-H. Higher Risk of Dementia in Primary Sjogren’s Syndrome. Ann. Clin. Transl. Neurol. 2019, 6, 633–641. [Google Scholar] [CrossRef]
- Alexander, E.L.; Malinow, K.; Lejewski, J.E.; Jerdan, M.S.; Provost, T.T.; Alexander, G.E. Primary Sjögren’s Syndrome with Central Nervous System Disease Mimicking Multiple Sclerosis. Ann. Intern. Med. 1986, 104, 323–330. [Google Scholar] [CrossRef]
- Mekinian, A.; Tennenbaum, J.; Lahuna, C.; Dellal, A.; Belfeki, N.; Capron, J.; Januel, E.; Stankoff, B.; Alamowitch, S.; Fain, O. Primary Sjögren’s Syndrome: Central and Peripheral Nervous System Involvements. Clin. Exp. Rheumatol. 2020, 38 (Suppl. S126), 103–109. [Google Scholar]
- Ramos-Casals, M.; Brito-Zerón, P.; Solans, R.; Camps, M.-T.; Casanovas, A.; Sopeña, B.; Díaz-López, B.; Rascón, F.-J.; Qanneta, R.; Fraile, G.; et al. Systemic Involvement in Primary Sjögren’s Syndrome Evaluated by the EULAR-SS Disease Activity Index: Analysis of 921 Spanish Patients (GEAS-SS Registry). Rheumatology 2014, 53, 321–331. [Google Scholar] [CrossRef] [Green Version]
- Fauchais, A.-L.; Magy, L.; Vidal, E. Central and Peripheral Neurological Complications of Primary Sjögren’s Syndrome. Presse Med. 2012, 41, e485–e493. [Google Scholar] [CrossRef] [PubMed]
- Manly, J.J.; Tang, M.-X.; Schupf, N.; Stern, Y.; Vonsattel, J.-P.G.; Mayeux, R. Frequency and Course of Mild Cognitive Impairment in a Multiethnic Community. Ann. Neurol. 2008, 63, 494–506. [Google Scholar] [CrossRef] [Green Version]
- Massara, A.; Bonazza, S.; Castellino, G.; Caniatti, L.; Trotta, F.; Borrelli, M.; Feggi, L.; Govoni, M. Central Nervous System Involvement in Sjögren’s Syndrome: Unusual, but Not Unremarkable—Clinical, Serological Characteristics and Outcomes in a Large Cohort of Italian Patients. Rheumatology 2010, 49, 1540–1549. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jamilloux, Y.; Magy, L.; Hurtevent, J.-F.; Gondran, G.; de Seze, J.; Launay, D.; Ly, K.H.; Lambert, M.; Hachulla, E.; Hatron, P.-Y.; et al. Immunological Profiles Determine Neurological Involvement in Sjögren’s Syndrome. Eur. J. Intern. Med. 2014, 25, 177–181. [Google Scholar] [CrossRef] [PubMed]
- Pego-Reigosa, J.M.; Restrepo Vélez, J.; Baldini, C.; Rúa-Figueroa Fernández de Larrinoa, Í. Comorbidities (Excluding Lymphoma) in Sjögren’s Syndrome. Rheumatology 2021, 60, 2075–2084. [Google Scholar] [CrossRef]
- Manzo, C.; Serra-Mestres, J.; Isetta, M. Comment on: Comorbidities (Excluding Lymphoma) in Sjögren’s Syndrome. Rheumatology 2021, 60, e453–e454. [Google Scholar] [CrossRef] [PubMed]
- Seeliger, T.; Jacobsen, L.; Hendel, M.; Bönig, L.; Kristian Prenzler, N.K.; Thiele, T.; Ernst, D.; Witte, T.; Stangel, M.; Kopp, B.; et al. Cognitive Impairment in Patients with Neuro-Sjögren. Ann. Clin. Transl. Neurol. 2020, 7, 1352–1359. [Google Scholar] [CrossRef]
- Segal, B.M.; Rhodus, N.; Moser Sivils, K.L.; Solid, C.A. Validation of the Brief Cognitive Symptoms Index in Sjögren Syndrome. J. Rheumatol. 2014, 41, 2027–2033. [Google Scholar] [CrossRef]
- Riega-Torres, J.C.L.; Treviño-Castro, M.A.; de Jesus Hernandez-Galarza, I.; Garza-Martinez, M.J.; Vera-Pineda, R.; Cardenas-de la Garza, J.A.; Rodriguez-de la Garza, P.; Skinner-Taylor, C.M.; Galarza-Delgado, D.A. Cognitive Dysfunction in Sjögren’s Syndrome Using the Montreal Cognitive Assessment Questionnaire and the Automated Neuropsychological Assessment Metrics: A Cross-Sectional Study. Int. J. Rheum. Dis. 2020, 23, 1019–1023. [Google Scholar] [CrossRef]
- Rollot, F.; Fauvernier, M.; Uhry, Z.; Vukusic, S.; Bossard, N.; Remontet, L.; Leray, E.; OFSEP Investigators. Effects of Age and Disease Duration on Excess Mortality in Patients With Multiple Sclerosis From a French Nationwide Cohort. Neurology 2021, 97, e403–e413. [Google Scholar] [CrossRef]
- Masi, G.; Annunziata, P. Sjögren’s Syndrome and Multiple Sclerosis: Two Sides of the Same Coin? Autoimmun. Rev. 2016, 15, 457–461. [Google Scholar] [CrossRef] [PubMed]
- de Seze, J.; Devos, D.; Castelnovo, G.; Labauge, P.; Dubucquoi, S.; Stojkovic, T.; Ferriby, D.; Vermersch, P. The Prevalence of Sjögren Syndrome in Patients with Primary Progressive Multiple Sclerosis. Neurology 2001, 57, 1359–1363. [Google Scholar] [CrossRef] [PubMed]
- Annunziata, P.; De Santi, L.; Di Rezze, S.; Millefiorini, E.; Capello, E.; Mancardi, G.; De Riz, M.; Scarpini, E.; Vecchio, R.; Patti, F. Clinical Features of Sjogren’s Syndrome in Patients with Multiple Sclerosis. Acta Neurol. Scand. 2011, 124, 109–114. [Google Scholar] [CrossRef] [PubMed]
- Akasbi, M.; Berenguer, J.; Saiz, A.; Brito-Zerón, P.; Pérez-De-Lis, M.; Bové, A.; Diaz-Lagares, C.; Retamozo, S.; Blanco, Y.; Perez-Alvarez, R.; et al. White Matter Abnormalities in Primary Sjögren Syndrome. QJM 2012, 105, 433–443. [Google Scholar] [CrossRef] [Green Version]
- McCoy, S.S.; Baer, A.N. Neurological Complications of Sjögren’s Syndrome: Diagnosis and Management. Curr. Treat. Opt. Rheumatol. 2017, 3, 275–288. [Google Scholar] [CrossRef]
- Kuo, C.-F.; Grainge, M.J.; Valdes, A.M.; See, L.-C.; Luo, S.-F.; Yu, K.-H.; Zhang, W.; Doherty, M. Familial Risk of Sjögren’s Syndrome and Co-Aggregation of Autoimmune Diseases in Affected Families: A Nationwide Population Study. Arthritis Rheumatol. 2015, 67, 1904–1912. [Google Scholar] [CrossRef] [Green Version]
- Lopes, A.P.; Bekker, C.P.J.; Hillen, M.R.; Blokland, S.L.M.; Hinrichs, A.C.; Pandit, A.; Kruize, A.A.; Radstake, T.R.D.J.; van Roon, J.A.G. The Transcriptomic Profile of Monocytes from Patients With Sjögren’s Syndrome Is Associated With Inflammatory Parameters and Is Mimicked by Circulating Mediators. Front. Immunol. 2021, 12, 701656. [Google Scholar] [CrossRef]
- Soret, P.; Le Dantec, C.; Desvaux, E.; Foulquier, N.; Chassagnol, B.; Hubert, S.; Jamin, C.; Barturen, G.; Desachy, G.; Devauchelle-Pensec, V.; et al. A New Molecular Classification to Drive Precision Treatment Strategies in Primary Sjögren’s Syndrome. Nat. Commun. 2021, 12, 3523. [Google Scholar] [CrossRef]
- Roy, E.R.; Wang, B.; Wan, Y.-W.; Chiu, G.; Cole, A.; Yin, Z.; Propson, N.E.; Xu, Y.; Jankowsky, J.L.; Liu, Z.; et al. Type I Interferon Response Drives Neuroinflammation and Synapse Loss in Alzheimer Disease. J. Clin. Investig. 2020, 130, 1912–1930. [Google Scholar] [CrossRef]
- Cafaro, G.; Perricone, C.; Carubbi, F.; Baldini, C.; Quartuccio, L.; Priori, R.; Berardicurti, O.; Ferro, F.; Gandolfo, S.; Gattamelata, A.; et al. Peripheral Nervous System Involvement in Sjögren’s Syndrome: Analysis of a Cohort From the Italian Research Group on Sjögren’s Syndrome. Front. Immunol. 2021, 12, 615656. [Google Scholar] [CrossRef]
- Seeliger, T.; Gingele, S.; Bönig, L.; Konen, F.F.; Körner, S.; Prenzler, N.; Thiele, T.; Ernst, D.; Witte, T.; Stangel, M.; et al. CIDP Associated with Sjögren’s Syndrome. J. Neurol. 2021, 268, 2908–2912. [Google Scholar] [CrossRef] [PubMed]
- Seeliger, T.; Prenzler, N.K.; Gingele, S.; Seeliger, B.; Körner, S.; Thiele, T.; Bönig, L.; Sühs, K.-W.; Witte, T.; Stangel, M.; et al. Neuro-Sjögren: Peripheral Neuropathy With Limb Weakness in Sjögren’s Syndrome. Front. Immunol. 2019, 10, 1600. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Sjögren’s Syndrome Patients (n = 25,661) | Matched Patients (n = 252,543) | ||||
---|---|---|---|---|---|
Number of Patients | % of pSS Patients | Number of Matched Patients | % of Matched Patients | Comparison (p Value) | |
Sex (female) (n, %) | 22,489 | 87.66% | 224,887 | 87.65% | 0.995 |
Low socio-economic status (n, %) | 1224 | 4.77% | 8482 | 3.31% | <0.001 |
Mean age (mean, SD) | 60.2 | ±16.3 | 60.0 | ±16.3 | 0.075 |
Age ranks, years (n, %) | 1 | ||||
00–17 | 106 | 0.41% | 1070 | 0.42% | |
18–29 | 881 | 3.43% | 8812 | 3.43% | |
30–39 | 2123 | 8.27% | 21,219 | 8.27% | |
40–49 | 3374 | 13.15% | 33,737 | 13.15% | |
50–59 | 5287 | 20.61% | 52,874 | 20.61% | |
60–69 | 5933 | 23.13% | 59,338 | 23.13% | |
70–79 | 4697 | 18.31% | 46,965 | 18.31% | |
80–89 | 2878 | 11.22% | 28,774 | 11.22% | |
>90 | 377 | 1.47% | 3771 | 1.47% | |
Mean number of hospitalizations before index date (mean, SD) | 3.7 | ± 9.0 | 0.21 | ±1.1 | <0.001 |
Annual rate of hospitalizations before index date (n, %) | |||||
≤0.25 per year | 10,245 | 39.93% | 244,107 | 95.15% | <0.001 |
between 0.25 and 0.5 per year | 5959 | 23.23% | 8679 | 3.38% | |
between 0.5 and 1 per year | 5430 | 21.16% | 2807 | 1.09% | |
between 1 and 5 per year | 3704 | 14.44% | 908 | 0.35% | |
More than 5 per year | 318 | 1.24% | 59 | 0.02% | |
Deaths (incidence #, CI) | 14.4 | (13.7–15.2) | 10.5 | (10.3–10.7) | <0.001 |
Follow-up time after index date (median, (IQR), years) | 3.96 | (1.96–5.96) | 3.96 | (1.96–6.04) | 0.003 * |
Diseases’ codes reported in hospitalization stays prior to incidence study period (used as adjustment covariates) | |||||
High blood pressure | 274 | 1.07% | 884 | 0.34% | <0.001 |
Diabetes | 657 | 2.56% | 2852 | 1.11% | <0.001 |
Obesity | 294 | 1.15% | 1395 | 0.54% | <0.001 |
Cardiovascular diseases | 1360 | 5.30% | 8828 | 3.44% | <0.001 |
Parkinson’s disease | 56 | 0.22% | 154 | 0.06% | <0.001 |
Multiple sclerosis | 194 | 0.76% | 264 | 0.10% | <0.001 |
Encephalitis | 107 | 0.42% | 48 | 0.02% | <0.001 |
pSS Patients | Matched Patients | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Incident Cases # | Py | Incidence | CI | Incident Cases # | Py | Incidence | CI | Crude HR | Crude CI | Crude p Value | Adjusted HR | Adjusted CI | Adjusted p Value | |
Dementia | 207 | 101,420 | 2.04 | (1.76–2.32) | 1466 | 1,006,672 | 1.46 | (1.39–1.53) | 1.37 | (1.18–1.58) | 0.000 | 1.27 | (1.04–1.55) | 0.018 |
Multiple sclerosis | 58 | 101,894 | 0.57 | (0.42–0.72) | 128 | 1,014,654 | 0.13 | (0.11–0.15) | 4.58 | (3.35–6.25) | 0.000 | 3.66 | (2.35–5.68) | <0.001 |
Encephalitis | 25 | 102,410 | 0.24 | (0.15–0.33) | 54 | 1,019,787 | 0.05 | (0.04–0.06) | 4.68 | (2.9–7.55) | 0.000 | 2.66 | (1.22–5.80) | 0.014 |
Parkinson’s disease | 28 | 102,600 | 0.27 | (0.17–0.37) | 209 | 1,021,082 | 0.2 | (0.17–0.23) | 1.39 | (0.93–2.06) | 0.107 | 1.16 | (0.66–2.04) | 0.618 |
Migraine | 36 | 102,456 | 0.35 | (0.24–0.46) | 174 | 1,019,354 | 0.17 | (0.14–0.20) | 2.02 | (1.41–2.91) | 0.000 | 1.44 | (0.87–2.37) | 0.157 |
Inflammatory polyneuropathies | 67 | 101,892 | 0.66 | (0.5–0.82) | 36 | 1,016,623 | 0.04 | (0.03–0.05) | 18.04 | (12.0–27.1] | 0.000 | 23.22 | (12.2–44.5) | <0.001 |
Other polyneuropathies | 164 | 100,903 | 1.63 | (1.38–1.88) | 69 | 1,009,270 | 0.07 | (0.05–0.09) | 23.53 | (17.7–31.4) | 0.000 | 15.03 | (10.1–22.4) | <0.001 |
Polyneuropathies in other classified diseases | 63 | 102,095 | 0.62 | (0.47–0.77) | 5 | 1,018,421 | 0.00 | (0.00–0.00) | 150.39 | (54.8–413.8) | 0.000 | 101.1 | (31.7–324.3) | <0.001 |
Trigeminal neuralgia | 14 | 102,735 | 0.14 | (0.07–0.21) | 35 | 1,022,893 | 0.03 | (0.02–0.04) | 4.24 | (2.26–7.95) | 0.000 | 2.46 | (0.9–6.7) | 0.078 |
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Goulabchand, R.; Gabelle, A.; Ayrignac, X.; Malafaye, N.; Labauge, P.; Noël, D.; Morel, J.; Roubille, C.; Barateau, L.; Guilpain, P.; et al. Hospitalization Risks for Neurological Disorders in Primary Sjögren’s Syndrome Patients. J. Clin. Med. 2022, 11, 1979. https://doi.org/10.3390/jcm11071979
Goulabchand R, Gabelle A, Ayrignac X, Malafaye N, Labauge P, Noël D, Morel J, Roubille C, Barateau L, Guilpain P, et al. Hospitalization Risks for Neurological Disorders in Primary Sjögren’s Syndrome Patients. Journal of Clinical Medicine. 2022; 11(7):1979. https://doi.org/10.3390/jcm11071979
Chicago/Turabian StyleGoulabchand, Radjiv, Audrey Gabelle, Xavier Ayrignac, Nicolas Malafaye, Pierre Labauge, Danièle Noël, Jacques Morel, Camille Roubille, Lucie Barateau, Philippe Guilpain, and et al. 2022. "Hospitalization Risks for Neurological Disorders in Primary Sjögren’s Syndrome Patients" Journal of Clinical Medicine 11, no. 7: 1979. https://doi.org/10.3390/jcm11071979
APA StyleGoulabchand, R., Gabelle, A., Ayrignac, X., Malafaye, N., Labauge, P., Noël, D., Morel, J., Roubille, C., Barateau, L., Guilpain, P., & Mura, T. (2022). Hospitalization Risks for Neurological Disorders in Primary Sjögren’s Syndrome Patients. Journal of Clinical Medicine, 11(7), 1979. https://doi.org/10.3390/jcm11071979