Seasonal Effect on Fatigue, Pain and Dryness in Primary Sjögren's Syndrome

Pierre-Marie Duret; Nicolas Meyer; Alain Saraux; Valérie Devauchelle-Pensec; Raphaele Seror; Véronique Le-Guern; Claire Larroche; Aleth Perdriger; Jean Sibilia; Vianney Guardiolle; Xavier Mariette; Jacques-Eric Gottenberg


Arthritis Res Ther. 2020;22(39) 

In This Article


The present study performed on a large population of patients and on a long duration did not show any seasonal effect on the main symptoms of pSS, pain, fatigue and dryness.

The pathogenesis of pSS is, not unlike other auto-immune diseases, considered multifactorial. A complex relationship between environmental and immunological factors affecting a peculiar genetic background may interact and sustain disease onset in susceptible individuals.

A seasonal pattern of several suspected environmental triggers, such as viral infections (EBV and CMV in winter and HBV and HCV in spring and summer) as well as sunshine exposure (through UV-B radiation, governing blood levels of inactive 25OH-vitamin D3), might suggest an association between disease activity and season changes. Of note, previous studies have postulated that low levels of vitamin D, because of its immunomodulatory effects, could affect clinical manifestations in patients with pSS,[17] as demonstrated in other IMIDs, especially in LES[18] and RA.[19] Nevertheless, vitamin D influence on pSS activity remains controversial.

Otherwise, weather-related ocular and oral dryness enhancement has been reported in patients outside autoimmune context, mainly in spring and summer, but this has never been specifically analysed in pSS.

Indeed, to our knowledge, there is no study available in the literature investigating a seasonal impact on symptoms and outcomes in primary Sjögren's syndrome.

In the present study, all the fluctuations observed were not statistically significant and were not clinically relevant either, since they were well lower than the minimal clinically important improvements (MCIIs) for dryness, pain and fatigue, which are − 10, − 10 and − 20 on a 100-point scale, respectively.[15]

Nevertheless, this study has several limitations. First, patients included in the ASSESS cohort underwent an annual evaluation of their symptoms and activity, mostly at the same period every year. However, the three trials lasted 1 year and visits were scattered all over the year. In addition, the statistical analysis not only focused on the intra-individual but also assessed the inter-individual seasonal variability of symptoms.

Several confounding factors, such as age, symptomatic treatments of dryness and immunomodulatory treatments assumed by patients, could have hampered the interpretation of the results. To address this point, linear mixed models were adjusted to take into account the influence of age and treatments on objective assessment of ocular and oral dryness and on PROs, in the ASSESS cohort. Adjusted analyses on age, immunomodulatory drug exposure and symptomatic treatments of dryness did not reveal any statistically significant effect of seasons on objective dryness outcomes. Furthermore, even when adjusted on age and treatments, there was no significant effect of seasons on fatigue, pain and dryness VASs or on the ESSPRI score either.

Other limitations include the unavailability of weather variables such as temperature, relative humidity, barometric pressure, sunshine exposure, precipitations and the variability of geographic locations (multicentric studies). A longitudinal study involving meteorological features and assessing pSS outcomes every months during several years, as recently performed in RA,[20] could be the most accurate way to investigate the effect of seasonality in pSS.