Flammer syndrome

Abstract

The new term Flammer syndrome describes a phenotype characterized by the presence of primary vascular dysregulation together with a cluster of symptoms and signs that may occur in healthy people as well as people with disease. Typically, the blood vessels of the subjects with Flammer syndrome react differently to a number of stimuli, such as cold and physical or emotional stress. Nearly all organs, particularly the eye, can be involved. Although the syndrome has some advantages, such as protection against the development of atherosclerosis, Flammer syndrome also contributes to certain diseases, such as normal tension glaucoma. The syndrome occurs more often in women than in men, in slender people than in obese subjects, in people with indoor rather than outdoor jobs, and in academics than in blue collar workers. Affected subjects tend to have cold extremities, low blood pressure, prolonged sleep onset time, shifted circadian rhythm, reduced feeling of thirst, altered drug sensitivity, and increased general sensitivity, including pain sensitivity. The plasma level of endothelin-1 is slightly increased, and the gene expression in lymphocytes is changed. In the eye, the retinal vessels are stiffer and their spatial variability larger; the autoregulation of ocular blood flow is decreased. Glaucoma patients with Flammer syndrome have an increased frequency of the following: optic disc hemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization, fluctuating diffuse visual field defects, and elevated oxidative stress. Further research should lead to a more concise definition, a precise diagnosis, and tools for recognizing people at risk. This may ultimately lead to more efficient and more personalized treatment.

Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences

“…Historically, the first two dots of FS's diverse symptoms were connected by the observation that some glaucoma patients had conspicuously cold hands [97,98] Crucially, people with FS seem less prone to atherosclerosis but exhibit signs of endothelial dysfunction. Endothelial dysfunction appears to take on a different role in vascular dysregulation than in atherosclerotic etiology.…”

“…In normal-tension glaucoma (NTG), for which FS is an important risk factor [97,98], circulating ET-1 is elevated and even more so than in high-tension glaucoma (HTG) [118]. ET-1, on the other hand, reduces ocular blood flow but does not interfere with autoregulation.…”

“…Cold acra have been found in FS similar to Raynaud's phenomenon (CREST) or even Raynaud's disease, yet less pronounced [98]. The role of endothelial dysfunction in primary and secondary Raynaud's phenomenon has been demonstrated with evidence from various modalities including autonomic nervous stress tests like the cold pressor test [121][122][123][124][125].…”

Postmenopausal breast cancer: European challenge and innovative concepts

“…FS phenotype [11] is described for both healthy individuals in sub-optimal health condition [12] and severely diseased patients [13]. FS is particularly relevant for females [11].…”

“…FS phenotype [11] is described for both healthy individuals in sub-optimal health condition [12] and severely diseased patients [13]. FS is particularly relevant for females [11]. It is characterised by local and systemic hypoxic effects caused by vascular dysregulation [11] as well as molecular patterns which are evidently relevant for the BC cancer advancement [14][15][16] as described earlier.…”