Fatigue severity in anti-nuclear antibody-positive individuals does not correlate with pro-inflammatory cytokine levels..., 2019, Hafiz et al

[Sly Saint]

Fatigue severity in anti-nuclear antibody-positive individuals does not correlate with pro-inflammatory cytokine levels or predict imminent progression to symptomatic disease

• Waleed Hafiz,
• Rawad Nori,
• Ariana Bregasi,
• Babak Noamani,
• Dennisse Bonilla,
• Larissa Lisnevskaia,
• Earl Silverman,
• Arthur A. M. Bookman,
• Sindhu R. Johnson,
• Carolina Landolt-Marticorena &
• Joan Wither
  
  • 
    
  • Published: 04 November 2019
    
    

    Abstract
    Background
    
    Fatigue is a common symptom of systemic autoimmune rheumatic disease (SARD). Patients with SARD have a protracted pre-clinical phase during which progressive immunologic derangements occur culminating in disease. In this study, we sought to determine when fatigue develops and whether its presence correlates with inflammatory factors or predicts disease progression.
    
    Methods
    Anti-nuclear antibody (ANA)-negative healthy controls (HCs) and ANA-positive participants with no criteria, at least one clinical criteria (undifferentiated connective tissue disease, UCTD), or meeting SARD classification criteria were recruited. Fatigue was assessed using a modified version of the FACIT-F questionnaire and the presence of fibromyalgia determined using a questionnaire based on the modified 2010 ACR criteria. Peripheral blood expression of five IFN-induced genes was quantified by NanoString and the levels of IL-1β, IL-6, or TNF-α by ELISA.
    
    Results
    Fatigue was as prevalent and severe in individuals lacking SARD criteria as it was in UCTD and SARD. Overall, ~ 1/3 of ANA+ subjects met fibromyalgia criteria, with no differences between sub-groups. Although fatigue was more severe in these individuals, those lacking fibromyalgia remained significantly more fatigued than ANA− HC. However, even in these subjects, fatigue correlated with the widespread pain index and symptom severity scores on the fibromyalgia questionnaire. Fatigue was not associated with elevated cytokine levels in any of the ANA+ sub-groups and did not predict imminent disease progression.
    
    Conclusions
    Fatigue is common in ANA+ individuals lacking sufficient criteria for a SARD diagnosis, correlates with fibromyalgia-related symptoms, and is not associated with inflammation or predictive of disease progression.

    
    https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-019-2013-9
  
  

 

[rvallee]

I checked the FACIT-F questionnaire (https://www.facit.org/FACITOrg/Questionnaires).

Not half-bad, but has a bunch of questions that poorly distinguish can't and won't. However, it's miles above the CFQ as it asks additional relevant questions and is an absolute scale. Big question mark on what the modifications were, especially as there already is a 13-item version specific for fatigue.

But without an accurate and reliable standardized test it's very hard to build a useful body of evidence of anything. As usual it's hard to say whether fatigue was measured, or some ersatz combination of various things that could relate to the actual symptom experience. Especially as some people use seriously weird definitions of fatigue.

 

[Woolie]

Who smelt a rat here? These "lack of direct link between fatigue and biomarkers" studies are always a pretext for suggesting the fatigue is psychologically constructed and/or due to activity avoidance. And lo and behold, here is the article's concluding statement:

Our findings have important clinical implications. Firstly, clinicians can reassure their fatigued ANS patients that their fatigue does not indicate that they are at increased risk for imminent progression; secondly, the presence of significant fatigue should not prompt initiation of treatment with DMARDs; and thirdly, our findings suggest that treatments that have been shown to improve fatigue, such as exercise programs, promotion of good sleep hygiene, addressing life stressors and depression [54], or drug therapy for fibromyalgia, may be more appropriate therapies for these individuals.

Usual stuff.

Hey, just 'cos something can't be measured using a few limited biomarkers does not make it behavioural/psychological... One does not necessarily follow from the other. Why do people continue to think that biomedical explanations require evidence, whereas psychological ones require no actual postive supporting evidence at all?

At least they mention drug therapy for fibro, that's something I suppose.

Also, the usual stuff about how doctors can "reassure" their patients that their fatigue doesn't imply worsening of their disease. If the fatigue is not linked to anything measurable, that means its not fixable, and there's nothing reassuring about that!

 

[Jonathan Edwards]

They should probably have known enough immunology to know that antinuclear antibodies are not expected to activate cytokines. They either form large immune complexes, which interact with complement, or interfere with DNA function within the cell, silently.

 

[Sid]

Who smelt a rat here? These "lack of direct link between fatigue and biomarkers" studies are always a pretext for suggesting the fatigue is psychologically constructed and/or due to activity avoidance. And lo and behold, here is the article's concluding statement:

I read a review about fatigue in lupus a few years ago and the treatment recommendation was antidepressant drugs based on the fact that there is no correlation between fatigue and 'objective' disease markers like inflammation. Lol.