Fatigue in ANCA-associated vasculitis (AAV) and systemic sclerosis (SSc): similarities with ME/CFS. review 2022


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Systemic autoimmune rheumatic diseases (SARDs) such as systemic sclerosis (SSc, or scleroderma) and ANCA-associated vasculitis (AAV) are rare with annual incidences estimated at 1.4 (1.1–1.9) per 100.000 for SSc [Citation3] and 3–5 cases per 100,000 for AAV [Citation4,Citation5]. SSc is characterized by systemic immune dysregulation, vasculopathy, and/or fibrosis [Citation6].

In contrast, AAV is associated with the formation of pathogenic anti-neutrophil cytoplasmic antibodies (ANCA) which directly promote vascular inflammation and subsequent loss of organ function [Citation7,Citation8].

The mechanisms promoting the formation of ANCA are multifactorial, and it is being recognized that patients with SSc and severe vascular complications also generate ANCA [Citation9,Citation10] – suggesting a potential overlap in both diseases.
ME/CFS, Systemic Sclerosis, and Vasculitides are unique diseases with vastly different presentations. However, their pathogenesis shares a multitude of inflammatory, immune, and metabolic perturbations. In particular, mitochondrial dysregulation, Th2 polarization, low IgG levels and reduced NK cell cytotoxicity have been highlighted in all three groups – suggesting that in patients with ME/CFS and SSc or vasculitis, common mechanisms may be present. Patients with these diseases also present with high levels of persistent, debilitating fatigue.
We have identified that patients with early SSc and AAV patients with fatigue fulfill the diagnostic criteria for ME/CFS. Although these patients cannot be diagnosed as having ME/CFS, the criteria surrounding the diagnosis of ME/CFS have been very well researched. Using ME/CFS criteria as a standardized approach to identifying persistent fatigue in SARDs may help streamline research, including the identification of potential biomarkers as well as improved treatment strategies.


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Hello @pattismith. This is an idle question compared to what you're dealing with....but would you happen to know what Fibromyalgia is now classified under since CFS, etc., became ME. This has me puzzled. Thanks!
Yours, Lenora


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Exercice Intolerance in Systemic Sclerosis may be interesting to understand for us:
Respiratory compensation for metabolic acidosis occurred in all patients.
However, the Global Peripheral Chemoreflex Drive was diminished in diffuse cutaneous SSc patients, suggesting an altered control of breathing. Its assessment may help the clinician to better understand reported EI and exertional dyspnea in dcSSc patients.



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This study is interesting to me

Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the basis of the co-DEGs using the R package ClusterProfiler, which showed that hypoxia and cross talk of hypoxia with other pathogenic factors are involved in the pathogenesis of SSc.
I don't fully understand this complexe genetic study, but I feel peripheral hypoxia may be involved both in ME/CFS and Systemic sclerosis pathology.

Peripheral hypoxia may induce CO2 to raise (respiratory alkalosis) and Bicarbonate and Citrate to be retained in blood (fully compensated respiratory alkalosis), leading to acidic urine and oxalate lithiasis.

Oxalate lithiasis happens in Systemic Sclerosis, but was only supposadly linked to a small intestine issue with decreased intestine oxalate excretion. I think the pathogenic pathway involves also peripheral hypoxia.

Peripheral hypoxia is linked with peripheral hypoperfusion and endothelial dysfunction.

There is a simple test to observe the phenomenon, because there is a discrepancy between capillary glycemia (at the finger for example) and venous glycemia, and idem with lactatemia.
Both glycemia and lactatemia are lowered at the finger because the blood flow is reduced and the local stasis allow cells to empty all the O2 available and all the glucose available. At least that was the explanation I read about pseudo-hypoglycemia which is recognized phenomenon.


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from the same team​

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia: PR3-versus MPO-ANCA-associated vasculitis, an exploratory cross-sectional study 2023



Persistent fatigue is a common complaint in ANCA-vasculitis (AAV) patients and has a profound impact on patient's quality of life.
The symptoms associated with this fatigue mirror those found in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia.
Etiologic and pathophysiologic differences exist between PR3- and MPO-ANCA disease, yet differences in their fatigue manifestations have not been well researched.
We compared fatigue and its associations in healthy controls, AAV patients and fibromyalgia controls.


The Canadian consensus criteria were used for ME/CFS diagnosis, and American College of Rheumatology criteria for fibromyalgia diagnosis.
Factors such as cognitive failure, depression, anxiety, and sleep disturbances were assessed by patient reported questionnaires.
Clinical factors such as BVAS, vasculitis damage index, CRP and BMI were also collected.


Our AAV cohort comprised 52 patients, with a mean age of 44.7 (20–79), 57% (30/52) of the patients were female.
We found 51.9% (27/52) of patients fulfilled the diagnostic criteria for ME/CFS, with 37% (10/27) of those having comorbid fibromyalgia.
Rates of fatigue were higher in MPO-ANCA patients, than in PR3-ANCA patients, and their symptoms were more similar to the fibromyalgia controls.
Fatigue in PR3-ANCA patients was related to inflammatory markers.
These differences may be due to the varied pathophysiology of the PR3- and MPO-ANCA serotypes.


A large proportion of AAV patients suffer from debilitating fatigue consequential enough to meet the diagnostic criteria for ME/CFS.
Fatigue associations were not the same between PR3- and MPO-ANCA patients, suggesting that the underlying mechanisms may be different.
Future studies should consider ANCA serotype, as further research may inform different clinical treatment strategies for AAV patients suffering from ME/CFS.