Monday, August 1, 2016

MedPage today: Fatigue in Sjogren's: A Paradoxical Response

I want to thank Dr. Sarah Schafer for essentially writing my posts for the last three days! She sent an email containing this intriguing article today. It explains a great deal of my frustration for inability of the medical community to find the cause of my crushing fatigue. Check it out:

This article is by a researcher in the UK who studies Sjogrens, especially fatigue-  Wan-Fai Ng   He found in previous study in the UK that 70 % of patients have disabling fatigue.    (My comment:  disabling can mean you need to  reduce activities,  or you are too sick to work, or you are profoundly debilitated-  all of those in the 70 %) 
It came through on MedPage today, titled:

Fatigue in Sjogren's: A Paradoxical Response

Decreased proinflammatory cytokine levels tied to higher levels of fatigue

Excerpts with Main points: 
Inflammation has been postulated to have a central role in fatigue associated with chronic autoimmune disease as part of a phenomenon termed sickness behavior.

"Sickness behavior is considered an evolutionarily adaptive behavioral response to infection facilitating speedy recovery, minimizing energy expenditure, and reducing environmental risks when an organism is in a weakened state during and following an infection," Ng and colleagues explained.

Because this response is mediated by proinflammatory cytokines, it has been assumed that inflammation would be responsible for fatigue in chronic disease.

However, the finding that proinflammatory cytokine levels were lower among patients with high levels of fatigue "does not ... support a simple concept of higher levels of inflammation leading to worse fatigue,"  

Previous research has found that inflammatory burden does not necessarily correlate with fatigue scores in diseases such as Sjogren's syndrome, rheumatoid arthritis, and lupus, "suggesting that there may be a complex range of positive and negative feedback loops contributing to fatigue in autoimmune conditions," they wrote.

As to why lower levels of inflammatory markers would be associated with worse fatigue, the authors suggested that there might be a negative feedback loop where inflammatory markers are reduced but fatigue persists.

"Thus, although fatigue is induced by proinflammatory cytokines as part of an 'adaptive behavior response,' which has evolved as a protective motivational state during and following an infection, a potentially maladaptive immune response may contribute to the maintenance of persistent fatigue after clearance of a pathogen or in a chronic inflammatory state," Ng and colleagues wrote.

In a healthy patient, they explained, exposure to an infectious agent leads to an immune response triggering inflammatory pathways resulting in sickness behavior, followed by restoration of immune homeostasis and normalization of the behavioral response. But in a patient whose immune response is dysregulated, the anti-inflammatory response becomes excessive and continues to upregulate the immune system "in a pathological feedback loop," and the sickness behavior persists.

This reinforces that there remains  no clear explanation for Sjogren’s fatigue.  There are no measurements to prove how bad you feel.   Some people who are quite sick with organ involvement feel better than others who have “uncomplicated” Sjogren’s.  So here you have another reason for feeling awful and hearing  “you don’t look that sick” comments from medical providers or lay people.

You can read the complete article here.

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