THU0262 FATIGUE IN PRIMARY SJÖGREN’S SYNDROME AS A DISEASE MANIFESTATION REFLECTING THE DEGREE OF MUCOSA-ASSOCIATED LYMPHOID TISSUE (MALT) INVOLVEMENT
Authors: Saviana Gandolfo, Marco Binutti, Elena Doriguzzi Breatta, Cinzia Fabro, Salvatore De Vita
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> &nbsp;fatigue in primary Sjögren's syndrome (pSS) is a very common and complex symptom, heavily impairing a wide range of patient functions, quality of life and health policies. To date, measures of fatigue and other patient-reported symptoms/outcomes (PROs) poorly correlate with pSS disease activity assessed by ESSDAI. On the other hand, therapeutic interventions reducing pSS disease activity proved useful to improve fatigue burden in pSS. <h3>Objectives:</h3> &nbsp;to evaluate if fatigue correlates to other pSS disease manifestations which may also reflect disease activity, by investigating if: a) higher levels of fatigue shows a higher frequency of a heavier involvement of mucosa-associated lymphoid tissue (MALT) documented by histopathology, persistent glandular swelling, or cryoglobulinemia (1); and b) if fatigue correlates to other pSS-related somatic symptoms, such as dryness and arthralgias. <h3>Methods:</h3> &nbsp;among pSS patients undergoing clinical evaluation in our Sjögren's Clinic in a six-months period, 86 consecutive unselected patients, fulfilling the latest ACR/EULAR pSS classification criteria, accepted to report their degree of fatigue, general dryness, ocular dryness, oral dryness and pain on 10-cm VAS (range 0-100), and to complete the ESSPRI (range 0-10), the PROFAD-SSI-SF (range 0-28) and the EQ-5D-scale (0-100) questionnaires. Four subgroups of fatigue severity were preliminary defined (2), presenting, as previously described (3): no fatigue (VAS=0): 12.8% (n=11); low fatigue (VAS=1-24): 25.3% (n=19); moderate fatigue (VAS=25-74): 58.7% (n=44); high fatigue (VAS=75-100): 16% (n=12). As previously reported (3) no significant age or sex difference was present between subgroups, and potential contributors to fatigue, such as autoimmune thyroiditis, anemia and fibromylagia did not play a role. The frequencies of peculiar manifestations related to an increased activity in MALT involvement in pSS, such as persistent salivary gland swelling, cryoglobulinemia and biopsy-proven diagnosis of myoepithelial sialadenitis (MESA) or of pSS-related MALT lymphoma, at any time in the clinical history of patients, were evaluated for each subgroup. Secondly, the correlations between fatigue VAS and PROs reflecting somatic symptoms were performed. Results: pSS patients reporting moderate or high fatigue VAS showed significantly higher frequencies of salivary gland swelling (p=0.0274), of MESA or lymphoma proven by histological diagnosis (p=0.0397), if compared to pSS patients with no or low levels of fatigue. Cryoglobulinemia was not significantly increased, although more frequent, in patients with moderate or high fatigue (10.7%) compared to patients with no or low fatigue (6.6%). Fatigue VAS score did not correlate with ESSDAI. Patients with higher levels of fatigue showed significant (p&lt;0.0001) higher scores in total ESSPRI, dryness-ESSPRI, pain-ESSPRI, ocular dryness VAS, oral dryness VAS, pain VAS, somatic fatigue domain of PROFAD, arthralgia domain of PROFAD, total SSI and PROFAD-SSI-SF. Finally, patients with higher levels of fatigue reported worst scores in quality of life EQ-5D-scale. <h3>Conclusion:</h3> The severity of fatigue appears to mirror the degree of MALT involvement, and this involvement is the biological substrate of pSS itself. This represents a demonstration that fatigue is biologically related to pSS, and supports the notion that fatigue should be treated by disease-modifying drugs rather than only with symptomatic therapies in pSS. In addition, dedicated scores of pSS activity can be developed for pSS patients where fatigue is one of the dominant symptoms. Since fatigue may also correlate with pSS somatic symptoms, such as dryness and arthralgia, they could also be included. <h3>References:</h3> [1] De Vita S et al, Clin Exp Rheumatol 2018 [2] James K et al, PLoS one 2015 [3] Gandolfo S et al, Ann Rheum Dis 2018 <h3>Disclosure of Interests:</h3> Saviana Gandolfo: None declared, Marco Binutti: None declared, Elena Doriguzzi Breatta: None declared, Cinzia Fabro: None declared, Salvatore De Vita Grant/research support from: Roche, Pfizer, Abbvie, Novartis, BMS, MSD, Celgene, Janssen, Consultant for: Roche