Hypothesis [ME/CFS] and Comorbidities: Linked by Vascular Pathomechanisms and Vasoactive Mediators? 2023, Wirth and Löhn

[Sly Saint]

Wirth and Lohn
Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is often associated with various other syndromes or conditions including mast cell activation (MCA), dysmenorrhea and endometriosis, postural tachycardia (POTS) and small fiber neuropathy (SFN). The causes of these syndromes and the reason for their frequent association are not yet fully understood. We previously published a comprehensive hypothesis of the ME/CFS pathophysiology that explains the majority of symptoms, findings and chronicity of the disease. We wondered whether some of the identified key pathomechanisms in ME/CFS are also operative in MCA, endometriosis and dysmenorrhea, POTS, decreased cerebral blood flow and SFN, and possibly may provide clues on their causes and frequent co-occurrence. Our analysis indeed provides strong arguments in favor of this assumption, and we conclude that the main pathomechanisms responsible for this association are excessive generation and spillover into the systemic circulation of inflammatory and vasoactive tissue mediators, dysfunctional ß2AdR, and the mutual triggering of symptomatology and disease initiation. Overall, vascular dysfunction appears to be a strong common denominator in these linkages.

https://www.mdpi.com/1648-9144/59/5/978

 

[Trish]

We previously published a comprehensive hypothesis of the ME/CFS pathophysiology that explains the majority of symptoms, findings and chronicity of the disease.

I think this might be the previous paper referred to:
A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Recognitions from the finding of autoantibodies against ß2-adrenergic receptors
By Wirth and Scheibenbogen, 2020
Thread here:
https://www.s4me.info/threads/a-uni...nst-ß2-adrenergic-receptors-wirth-2020.14476/

 

[Milo]

Post moved from duplicate thread

To associate dysmenorrhea and endometriosis at the same level as POTs is a new one for me. What about those without a uterus? (Men and women)

 

[SNT Gatchaman]

To associate dysmenorrhea and endometriosis at the same level as POTs is a new one for me. What about those without a uterus? (Men and women)

Interesting side-note, though a little tangential to your question: people without a uterus - but that previously had one - can have endometriosis. This could be due to residual endometriosis lesions or newly recurrent disease, especially affecting bowel. Less common post oophorectomy, but has been reported de novo post menopause (although HRT may have contributed in eg this case).

Furthermore, you can even be XX female, born without a normal uterus and still get endometriosis. See Clinical Features and Management of Endometriosis among Patients with MRKH and Functional Uterine Remnants (2021).

A case report: Endometriosis in a Patient with Mayer-Rokitansky-Küster-Hauser Syndrome and Complete Uterine Agenesis: Evidence to Support the Theory of Coelomic Metaplasia (2010) —

Endometriosis is a disease that is associated with chronic pelvic pain and infertility. Although its prevalence in the adolescent population has been widely documented, little is known about endometriosis in association with MRKH syndrome. To our knowledge, this is the first reported case of endometriosis in a patient with MRKH syndrome with complete uterine, cervical, and vaginal agenesis.

The patient underwent laparoscopy to evaluate her pain, at which time she was found to have no uterine structures and no fallopian tubes. A small band of flat Müllerian tissue was noted along the pelvic sidewall. Patent processus vaginalis were noted bilaterally, and both ovaries were located in the mid-abdomen. A single pelvic kidney occupied the left pelvis. Stage I endometriosis, with red and clear lesions, was visualized in the posterior cul-de-sac and destroyed using electrocautery.

Possible that that small band of Müllerian tissue had endometrial cells or their primitive precursors. In their discussion, the authors commented —

Another proposed theory that might explain the presence of endometriosis in this patient with MRKH syndrome is the embryonic Müllerian rest theory, which assumes that there are cell rests of Müllerian origin in the pelvis that are stimulated by ovarian steroids at puberty. However, our patient underwent thelarche at age 11 and did not develop pelvic pain until she was 20 years old. This 9-year time period between onset of puberty and diagnosis seems too long to justify the Müllerian rest theory, but it is quite sufficient to explain the development, and subsequent recurrence, of her endometriosis from transformation of totipotent cells.

Recent publication: Endometriosis in Patients with Mayer-Rokitansky-Küster-Hauser-Syndrome—Histological Evaluation of Uterus Remnants and Peritoneal Lesions and Comparison to Samples from Endometriosis Patients without Mullerian Anomaly (2022, Journal of Clinical Medicine)

 

[Yann04]

hypovolemia by microvascular leakage

If this indeed is found in ME-OI, as this paper seems to suggest (wihout much evidence), could it explain the excessive thirst some pwME report?

 

[Jonathan Edwards]

If this indeed is found in ME-OI, as this paper seems to suggest (wihout much evidence), could it explain the excessive thirst some pwME report?

No, because once you had corrected the hypovolaemia by drinking you would stopping thirsty.
Microvascular leakage can cause hypovolaemia, as in anaphylactic shock, over a short period, but fluid control mechanisms in the kidney will restore equilibrium within hours. And the leaked fluid gets back into the circulation in the end through the lymphatics.

 

[Yann04]

And the leaked fluid alleges backing the circulation in the end through the lymphatics.

I’m a bit brainfoggy, does this sentence mean the leaked fluid makes it back into the blood?

 

[Jonathan Edwards]

I’m a bit brainfoggy, does this sentence mean the leaked fluid makes it back into the blood?

Sorry, my computer has a problem with the space bar and the spell checker has a problem with making sense.

Yes, within an hour or so.