Background/Purpose: Fatigue is one of the most prevalent and impacting symptoms in primary Sjögren’s syndrome (pSS), significantly impairing the patient quality of life. To date, even though available measures of fatigue and other patient-reported symptoms (PROs) poorly correlate with pSS disease activity assessed by ESSDAI, therapeutic interventions reducing the burden of pSS disease activity showed utility in improving fatigue in pSS. The purpose of this study was to investigate if fatigue correlates to pSS features reflecting disease activity, by evaluating if a) higher fatigue severity is associated with a heavier involvement of mucosa-associated lymphoid tissue (MALT) in salivary gland (SG) as documented by histopathology or by the clinical presence of SG swelling, and b) if fatigue correlates to other pSS-related somatic symptoms, such as dryness and arthralgias.

Methods: 86 consecutive unselected pSS patients, fulfilling the latest ACR/EULAR pSS classification criteria, reported their degree of fatigue, general dryness, ocular dryness, oral dryness and pain on 10-cm VAS (range 0-100), and completed ESSPRI (range 0-10), PROFAD-SSI-SF (range 0-28) and EQ-5D-scale (0-100) questionnaires. Four subgroups of fatigue severity were studied (1): 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 (1), no significant difference between the four subgroups was observed in age, sex and prevalence of potential contributors to fatigue, such as autoimmune thyroiditis, anemia and fibromyalgia. Frequencies of peculiar pSS manifestations related to a heavier activity of MALT, at any time in the clinical history of patients, such as SG swelling, and a biopsy-proven myoepithelial sialadenitis (MESA) or pSS-related MALT lymphoma, were evaluated for each subgroup. Correlations between VAS fatigue and other PROs were finally performed.

Results: pSS patients with moderate or high fatigue VAS showed significantly higher frequencies of SG swelling (p=0.0274), and of MESA or lymphoma histological diagnosis (p=0.0397) compared to pSS patients with no or low levels of fatigue. VAS fatigue scores did not correlate with ESSDAI. Patients with higher levels of fatigue showed significant (p< 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, and reported worst scores in quality of life EQ-5D-scale.

Conclusion: Fatigue severity in pSS appears to mirror the degree of MALT involvement, which is the biological substrate of pSS itself where key pathogenetic events take place. A better definition of the immunobiological basis of pSS fatigue, starting from the study of the MALT, is therefore crucial to identify novel target therapies to treat fatigue, besides symptomatic agents. Since fatigue may also correlate with pSS somatic symptoms, such as dryness and arthralgia, the development of dedicated pSS scoring tools integrating both disease activity, in the MALT perspective, and PROs is definitely worthwhile.
(1) Gandolfo S et al, ARD 2018,77(Suppl 2).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/fatigue-in-primary-sjogrens-syndrome-as-a-manifestation-of-heavier-disease-activity-of-mucosa-associated-lymphoid-tissue-malt/