Fatigue in Sjogren's Syndrome

WHAT TO DO ABOUT FATIGUE: challenges and solutions

Fatigue is a frequent and disabling symptom of Sjogren's Syndrome. 

Fatigue is reported in up to 70% of SS patients and most patients are also affected by dryness and pain. 

Fatigue is defined by Staud as “a subjective, unpleasant symptom that incorporates total body feelings ranging from tiredness to exhaustion, creating an unrelenting overall condition that interferes with individuals’ ability to function in their normal capacity.”

The role of HCQ remains unclear; RTX is questionable; LEF, zidovudine, bortezomib, TGP, belimumab, epratuzumab, abatacept, etanercept, and anakinra require further research. Other treatments such as dehydroepiandrosterone, gamma-linolenic acid, doxycycline, and infliximab are not effective based on available data.

Read on for a more thorough report of what works and does not work for Sjogren's fatigue.

Trials have failed to demonstrate the efficacy of rituximab (RTX) in improving fatigue in SS.

Evidence supporting hydroxychloroquine (HCQ)  is weak, and its use is based largely on clinical experience and expert recommendations not science.

TNFα blockers, however, did not improve fatigue. Infliximab showed no efficacy

Gamma-linolenic acid, an essential omega-6 fatty acid, has shown no efficacy in reducing fatigue.

Small open-label studies have shown improvement in general fatigue using leflunomide (LEF) 20 mg daily in 15 patients after 24 weeks.

A recent Chinese multi-center clinical trial demonstrated the efficacy and safety of total glucosides of peony (TGP) in 320 patients with pSS who did not exhibit significant extra-glandular manifestations. 
TGP are extracted from the root of the Paeonia lactiflora pall and have been demonstrated to have *immunomodulatory effects, such as inhibition of dendritic cell maturation and function. 
The results showed that ESSPRI scores improved dramatically, significantly alleviated some dryness symptoms, and improved fatigue during the 24-week trial. 

Belimumab, a monoclonal anti-BAFF antibody, is a promising biological drug to treat pSS, since 60% of the patients achieved the primary endpoint, including fatigue Visual Analogue Scale (VAS) and systemic activity, at week 28 in a prospective 1-year open-label study including 30 SS patients with systemic complications.

Belimumab, a monoclonal anti-BAFF antibody, is a promising biological drug to treat pSS, since 60% of the patients achieved the primary endpoint, including fatigue VAS and systemic activity, at week 28 in a prospective 1-year open-label study including 30 SS patients with systemic complications. Ten mg/kg of belimumab was administered at weeks 0, 2, and 4 and then every 4 weeks up to week 24.

Another small, open-label study including 16 pSS patients with active disease investigated the use of epratuzumab, a humanized anti-CD22 monoclonal antibody, over 4 infusions of 360 mg/m2 once every 2 weeks, with 6 months of follow-up, showing efficacy in fatigue VAS.

Similarly, abatacept, a selective modulator of co-stimulation of T cells, seemed to be effective in improving Multidimensional Fatigue Inventory (MFI) scores. 

Despite their potential, the only published nonpharmacological intervention that appears to be effective, is aerobic exercise. Aerobic exercise seems to be effective and safe suggesting an important role for physical fitness in the pathogenesis of fatigue. Nonetheless, long-term RCTs are needed and other types of exercise should be explored too.

The vagus nerve may play a role in the regulation of fatigue and immune responses in pSS. However, a RCT* including a larger sample size is needed.

Robust studies using non-pharmacological approaches are urgently needed. 
Non-pharmacological approaches are inherently attractive offering fewer adverse effects than drug treatments, and there is some data to support their use from other rheumatic diseases. 

Managing fatigue in patients with primary Sjögren’s syndrome: challenges and solutions This article was published in the following Dove Press journal: Open Access Rheumatology: Research and Reviews in 2018.

* RCT is a randomised control trial:  a trial in which subjects are randomly assigned to one of two groups.

* immunomodulatory effects: that modifies the immune 

Fatigue is one of the most difficult symptoms in SS to manage

Treatment suggestions: The number 1 treatment option for fatigue in Sjogren's is EXERCISE. I know this sounds the opposite to what we would think (and feel). 

The importance of any exercise program is to start slowly and to gradually increase physical activity.

People who can help you with exercise include:

  • a doctor specialized in rehabilitation
  • an exercise physiologist or exercise therapist
  • a physiotherapist with interest in rehabilitation
  • community based exercise program tailored to individuals
  • a hydrotherapy program
  • tai chi instructor
  • pilates instructor
Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines.
"Our study demonstrates that patients with pSS with higher levels of fatigue had lower levels of the proinflammatory cytokines IP-10, TNF-α, LT-α and IFN-γ than patients with pSS with low levels of fatigue. It should be noted, however, that the serum levels of many cytokines among even the fatigued participants with pSS were still higher than non-fatigued healthy individuals." Read Original article


There is central fatigue associated with weariness - a worn out feeling. 

This is difficult to treat and can only be 'coped with' - strategies include a period of rest in the afternoon, no late nights, regular sleep time. 

Fatigue affects approximately 50% of patients with Sjögren's syndrome but is often brought on by hypothyroidismfibromyalgia, lymphoma, or underlying depression.

There is peripheral fatigue which can be due to inflammation of the muscles.

Genetic Determinants of Fatigue in Primary Sjögren`s Syndrome – a Genome Wide Association Study


Fatigue is common in primary Sjögren`s syndrome (pSS), but what leads to that fatigue is not fully understood. They hypothesized that there is a genetic basis for fatigue, and that specific gene-variants influence the severity of fatigue.

To investigate this further they performed a genome wide association study of 367 Scandinavian pSS patients. 

They identified genetic variants in RTP4 exceeding the GWS level for association with fatigue. This gene encodes a protein involved in pain processing. Pain is known to influence fatigue, and this finding could point to a possible molecular explanation. ​​​​​​​

The present study is the largest GWAS of fatigue in autoimmune disease, and adds further evidence to a genetic regulation of fatigue.

Read Full Article here.

The Multidimensional Fatigue Inventory (MFI) is a 20-item self-report instrument designed to measure fatigue. 
It covers the following dimensions: General Fatigue, 
Physical Fatigue, 
Mental Fatigue, 
Reduced Motivation, 
Reduced Activity.