O OftalmopediaAn open ophthalmology reference ⌕

Flammer syndrome

AI overview

Flammer syndrome is a described clinical entity comprising a complex of clinical features caused mainly by dysregulation of the blood supply.

Key points
  • It was previously known as vascular dysregulation.
    source quote
    It was previously known as vascular dysregulation
  • The syndrome is named after Swiss ophthalmologist Josef Flammer.
    source quote
    Flammer syndrome is named after the Swiss ophthalmologist Josef Flammer
  • Most symptoms result from impaired regulation of blood supply.
    source quote
    Most of the symptoms of Flammer syndrome result from an impaired regulation of the blood supply
  • It is associated with or predisposes to normal tension glaucoma.
    source quote
    In certain cases it is associated with or predisposes to the development of diseases such as a normal tension glaucoma
  • Most affected individuals remain healthy and certain diseases like arteriosclerosis may be rarer.
    source quote
    Most of those affected are and remain healthy. Certain diseases such as arteriosclerosis and its consequences are probably even rarer
  • It is more prevalent in women, people with lower blood pressure, Asians compared to Caucasians, and academics compared to blue-collar workers.
    source quote
    in women compared to men in people with lower blood pressure in Asians compared with Caucasians in academics compared with blue collar-workers
Symptoms
  • Cold hands and feet.
    source quote
    cold hands and feet
  • Low blood pressure.
    source quote
    low blood pressure
  • Occasional white and red patches on the face or neck.
    source quote
    occasional white and red patches on the face or neck
  • Migraine-like pain or a feeling of pressure behind the upper eyelid.
    source quote
    migraine-like pain or a feeling of pressure behind the upper eyelid
  • Prolonged time needed to fall asleep.
    source quote
    a prolonged time needed to fall asleep
  • Reduced feeling of thirst.
    source quote
    a reduced feeling of thirst
  • High sensitivity to cold, odors, vibrations, psychological stress, or certain medications.
    source quote
    high sensitivity not only to cold but also to odors, vibrations, psychological stress, or certain medications (e.g., calcium antagonists, beta blockers)
  • Pain and muscle spasms are common.
    source quote
    Pain and muscle spasms are common
  • Tinnitus and sometimes acute hearing loss can occur.
    source quote
    Tinnitus and sometimes even acute hearing loss can occur
  • Reversible patchy white or red discoloration of the skin.
    source quote
    reversible patchy white or red discoloration of the skin
Diagnosis
  • Diagnosis is primarily based on patient history with typical features and nail fold capillaroscopy findings.
    source quote
    The diagnosis of Flammer syndrome is primarily based on the patient's history with its typical features as well as the findings of nail fold capillaroscopy
  • Nail fold capillaroscopy shows excessive constriction of capillaries in fingers in response to cold.
    source quote
    an excessive constriction (narrowing) in the smallest blood vessels (capillaries) of the fingers in response to being exposed to cold
  • Patients show unique gene expression when lymphocytes undergo gene expression profiling.
    source quote
    a unique gene expression when their lymphocytes underwent gene expression profiling
Treatment
  • No therapy is needed as long as the individual does not experience symptoms or pathological sequelae.
    source quote
    Flammer syndrome requires no therapy as long as the individual does not experience the symptoms or pathological sequelae occur
  • Treatment is based on three pillars: lifestyle interventions, diet, and medication.
    source quote
    The treatment is based on three pillars: lifestyle interventions, diet, and medication
  • Lifestyle interventions include regular sleep, weight stabilization, avoiding fasting, and avoiding trigger factors such as cold.
    source quote
    A healthy lifestyle should include regular sleep, weight stabilization (in the sense of not being underweight), avoiding periods of fasting, and avoidance of known trigger factors such as cold
  • Nutrition should contain many antioxidants found in green tea, black filter coffee, red wine, blueberries, and fruits.
    source quote
    Nutrition should contain many antioxidants, such as those found in green tea, black filter coffee, red wine, blueberries, and fruits
  • Omega-3 fatty acids and ginkgo improve regulation of blood flow.
    source quote
    Omega-3 fatty acids, especially in the form of fish, improve the regulation of blood flow, as well as ginkgo
  • Salt intake should be increased if blood pressure is very low.
    source quote
    If blood pressure is very low, salt intake should be increased
  • Drugs that lead to vasoconstriction should be avoided.
    source quote
    Drugs that can lead to vasoconstriction should be avoided
  • Calcium antagonists like magnesium may help against vascular dysregulation.
    source quote
    Calcium antagonists like magnesium may help against the vascular dysregulation
  • Medical treatment is necessary when normal tension glaucoma is present, including addressing low blood pressure.
    source quote
    Medical treatment is necessary when normal tension glaucoma is present
  • Nightly blood pressure dips can be prevented with dietary measures such as salt intake and sometimes low-dose steroids.
    source quote
    With dietary measures such as salt intake and sometimes with low-dose steroids, a drop in blood pressure, especially during sleep, can often be prevented
Red flags
  • Higher risk of normal tension glaucoma.
    source quote
    Best known is the higher risk of normal tension glaucoma
  • Glaucomatous damage occurring or progressing despite normal intraocular pressure may indicate Flammer syndrome.
    source quote
    If glaucomatous damage occurs despite normal eye pressure or if glaucomatous damage is progressive despite normalized intraocular pressure, frequently Flammer syndrome is the cause
  • May predispose to central serous retinopathy.
    source quote
    central serous retinopathy
  • Nightly blood pressure dips in normal tension glaucoma patients can significantly damage retinal sensory cells.
    source quote
    These nightly "dips" of blood pressure in normal tension glaucoma patients with Flammer syndrome can significantly damage the sensory cells of the retina
  • Insufficient data on suspected cases in sudden, unexpected deaths of young athletes.
    source quote
    There is currently insufficient data available on cases where Flammer syndrome is suspected like in the sudden, unexpected deaths of young athletes
Prognosis

Most affected individuals are and remain healthy; certain diseases such as arteriosclerosis may even be rarer, though there is a higher risk of normal tension glaucoma.

AI-synthesized from the Wikipedia article “Flammer syndrome”. Not medical advice. Verify source →
Flammer syndrome
SpecialtyAngiology

Flammer syndrome is a described clinical entity comprising a complex of clinical features caused mainly by dysregulation of the blood supply. It was previously known as vascular dysregulation.[1] It can manifest in many symptoms, such as cold hands and feet, and is often associated with low blood pressure. In certain cases it is associated with or predisposes to the development of diseases such as a normal tension glaucoma.[2] Flammer syndrome is named after the Swiss ophthalmologist Josef Flammer.

Most of the symptoms of Flammer syndrome result from an impaired regulation of the blood supply. How these symptoms affect the patient depends on to which organs or body parts blood supply is inhibited. Typical symptoms of Flammer syndrome are cold hands or feet, low blood pressure, occasional white and red patches on the face or neck, and migraine-like pain or a feeling of pressure behind the upper eyelid. In addition, there are symptoms not directly resulting from dysregulations of the blood supply, such as a prolonged time needed to fall asleep,[3] a reduced feeling of thirst, and high sensitivity not only to cold but also to odors, vibrations, psychological stress, or certain medications (e.g., calcium antagonists, beta blockers). Pain and muscle spasms are common.[4]

In many people with glaucoma, the cause of the disease is perfusion issues of the optic nerve and retina, while intraocular pressure is normal. Many patients with normal tension glaucoma have a basic constitution, which corresponds to the Flammer syndrome. Some of its features were formerly summarized under the term "primary vascular dysregulation syndrome".[5]

Signs of Flammer syndrome include:[citation needed]

  • cold hands or feet, or both
  • arterial hypotension
  • lower body mass index
  • decreased feeling of thirst
  • prolongation of time to fall asleep
  • increased sensitivity to pain and odors
  • sensitivity to certain drugs
  • migraine
  • tinnitus
  • reversible patchy white or red discoloration of the skin
  • excessive response to mental or physical stimuli such as stress or cold

The disease is more prevalent in the following groups:

  • in women compared to men
  • in people with lower blood pressure
  • in Asians compared with Caucasians
  • in academics compared with blue collar-workers

People with Flammer syndrome sleep poorly[6] and have a decreased sensation of thirst.[7]

The diagnosis of Flammer syndrome is primarily based on the patient's history with its typical features as well as the findings of nail fold capillaroscopy. This test shows an excessive constriction (narrowing) in the smallest blood vessels (capillaries) of the fingers in response to being exposed to cold. Patients with vasospastic symptoms characteristic of Flammer syndrome have shown a unique gene expression when their lymphocytes underwent gene expression profiling.[8]

Clinical significance

Having Flammer syndrome does not necessarily mean that an individual is sick. Most of those affected are and remain healthy. Certain diseases such as arteriosclerosis and its consequences are probably even rarer. Best known is the higher risk of normal tension glaucoma, a disease with an impaired regulation of blood flow in a large number of patients.[9] If glaucomatous damage occurs despite normal eye pressure or if glaucomatous damage is progressive despite normalized intraocular pressure, frequently Flammer syndrome is the cause. In these eyes, an elevated pressure in the retinal veins has been observed.[10]

Glaucoma patients with Flammer syndrome show some specific clinical signs like increased frequency of optic disc haemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization, and fluctuating diffuse visual field defects.[11] The association of normal tension glaucoma with the syndrome has recently been confirmed by a group of Chinese researchers.[12] In a 2016 review on the risk factors for normal tension glaucoma by ophthalmologists from Asia (where this form of glaucoma is much more prevalent than in Europe or North America), Flammer syndrome has been attributed to increase the likelihood of ganglion cell damage in these patients, with disc hemorrhages as a characteristic clinical sign.[13] Migraine attacks, a common feature of Flammer syndrome, have been described as a risk factor for glaucoma progression, in open-angle glaucoma as well as in normal tension glaucoma.[14] Flammer syndrome may also predispose to other eye diseases such as vascular occlusion (especially retinal vein occlusion)[15] in relatively young people or central serous retinopathy. Muscle spasms and tension are common among individuals with Flammer syndrome. Tinnitus and sometimes even acute hearing loss can occur. There is currently insufficient data available on cases where Flammer syndrome is suspected like in the sudden, unexpected deaths of young athletes. People with retinitis pigmentosa seem to have Flammer syndrome quite frequently, and possible associations with the vascular factor endothelin-1 are under investigation.[16]

Flammer syndrome requires no therapy as long as the individual does not experience the symptoms or pathological sequelae occur. The treatment is based on three pillars: lifestyle interventions, diet, and medication. A healthy lifestyle should include regular sleep, weight stabilization (in the sense of not being underweight), avoiding periods of fasting, and avoidance of known trigger factors such as cold. Regular physical exercise is beneficial, while extreme sports might be detrimental. Nutrition should contain many antioxidants, such as those found in green tea, black filter coffee, red wine, blueberries, and fruits. Omega-3 fatty acids, especially in the form of fish, improve the regulation of blood flow, as well as ginkgo. If blood pressure is very low, salt intake should be increased. Drugs that can lead to vasoconstriction should be avoided. If blood pressure is too low, sleeping pills should be taken cautiously. Calcium antagonists like magnesium may help against the vascular dysregulation. With lifestyle interventions, attacks—particularly pronounced symptoms such as massive cold extremities, tinnitus, or migraine-like episodes—can be avoided or reduced. Stabilizing weight (i.e. not being underweight) and the avoidance of periods of fasting are important.[17]

Medical treatment is necessary when normal tension glaucoma is present. In these cases, in addition to the ophthalmologic treatment of glaucoma, the patient's usually low blood pressure should be addressed. With dietary measures such as salt intake and sometimes with low-dose steroids, a drop in blood pressure, especially during sleep, can often be prevented. These nightly "dips" of blood pressure in normal tension glaucoma patients with Flammer syndrome can significantly damage the sensory cells of the retina.[18]

For over 100 years vasospasms have been known, particularly in the vessels supplying the retina with blood. These vasospasms are temporary narrowings of arteries or arterioles, resulting in insufficient supply of blood to the corresponding organs or parts of organs. Such spasms can occur at various locations in the human body; in this case medical terminology calls it "vasospastic syndrome". Over the years, it has been established that these spasms are usually part of a general dysregulation of blood vessels. These dysregulations can occur in spasms as well as in excessive or insufficient dilation of arteries, veins, and capillaries. The blood vessels of individuals with vasospastic syndrome respond to stimuli insufficiently. If an identifiable disease does not cause this, it is called a primary vascular dysregulation (PVD); in case of an underlying disease, it is called secondary PVD. PVD is almost always associated with other vascular and non-vascular symptoms and signs.[19] This entire complex (PVD and accompanying symptoms) is today called Flammer syndrome.[20]

  1. ↑ Konieczka, Katarzyna; Ritch, Robert; Traverso, Carlo Enrico; Kim, Dong Myung; Kook, Michael Scott; Gallino, Augusto; Golubnitschaja, Olga; Erb, Carl; Reitsamer, Herbert A; Kida, Teruyo; Kurysheva, Natalia; Yao, Ke (2014-07-08). "Flammer syndrome". The EPMA Journal. 5 (1): 11. doi:10.1186/1878-5085-5-11. ISSN 1878-5077. PMC 4113774. PMID 25075228.
  2. ↑ O'Brien, Colm (1998). "Vasospasm and glaucoma". British Journal of Ophthalmology. 82 (8): 855–856. doi:10.1136/bjo.82.8.855. PMC 1722712. PMID 9828764.
  3. ↑ Vollenweider, S; Wirz-Justice, A; et al. (Feb 2008). "Chronobiological characterization of women with primary vasospastic syndrome: body heat loss capacity in relation to sleep initiation and phase of entrainment". Am J Physiol Regul Integr Comp Physiol. 294 (2): R630–8. doi:10.1152/ajpregu.00609.2007. PMID 18046019. S2CID 4814596.
  4. ↑ Konieczka, Katarzyna; Ritch, Robert; et al. (2014). "Flammer syndrome". EPMA Journal. 5 (1): 11. doi:10.1186/1878-5085-5-11. PMC 4113774. PMID 25075228.
  5. ↑ Flammer, J.; Konieczka, K.; Flammer, A. J. (2013). "The primary vascular dysregulation syndrome: implications for eye diseases". The EPMA Journal. 4 (1): S14. doi:10.1186/1878-5085-4-14. PMC 3693953. PMID 23742177.
  6. ↑ Kräuchi, K; Gasio, PF; Vollenweider, S; et al. (Dec 2008). "Cold extremities and difficulties initiating sleep: evidence of co-morbidity from a random sample of a Swiss urban population". Journal of Sleep Research. 17 (4): 420–6. doi:10.1111/j.1365-2869.2008.00678.x. PMID 19021849. S2CID 205352251.
  7. ↑ Konieczka K, Fränkl S. Primary Vascular Dysregulation and Glaucoma.[Article in German] Zeitschrift für praktische Augenheilkunde 2013; 34:207-215
  8. ↑ Yeghiazaryan K, Flammer J, Orgül S, Wunderlich K, Golubnitschaja O.: Vasospastic individuals demonstrate significant similarity to glaucoma patients as revealed by gene expression profiling in circulating leukocytes. Mol Vis. 2009;15: 2339-48.
  9. ↑ Quill B, Henry E, Simon E, O'Brien C: Evaluation of the Effect of Hypercapnia on Vascular Function in Normal Tension Glaucoma. Biomed Res Int 2015, published online October 18
  10. ↑ Fang, Lei; Baertschie, Michael; Mozaffarieh, Manneli (2014). "The effect of flammer-syndrome on venous retinal pressure". BMC Ophthalmology. 14: 121. doi:10.1186/1471-2415-14-121. PMC 4216361. PMID 25312339.
  11. ↑ Wojcik-Gryciuka, A; Skup, M; Waleszczyk, M (2016). "Glaucoma – state of the art and perspectives". Restorative Neurology and Neuroscience. 34 (1): 107–123. doi:10.3233/rnn-150599. PMC 4927811. PMID 26684267.
  12. ↑ Fan, N; Wang, P; Tang, L; Liu, X (2015). "Ocular Blood Flow and Normal Tension Glaucoma". Biomed Res. Int. 2015 308505. doi:10.1155/2015/308505. PMC 4628977. PMID 26558263.
  13. ↑ Kim, KE; Park, KH (2016). "Update on the Prevalence, Etiology, Diagnosis, and Monitoring of Normal-Tension Glaucoma". Asia Pac. J. Ophthalmol. 5 (1): 23–31. doi:10.1097/apo.0000000000000177. PMID 26886116. S2CID 30907471.
  14. ↑ Nakazawa, T (2016). "Ocular Blood Flow and Influencing Factors for Glaucoma". Asia Pac. J. Ophthalmol. 5 (1): 38–44. doi:10.1097/apo.0000000000000183. PMID 26886118. S2CID 31765476.
  15. ↑ Fang, L; Baertschi, M; Mozaffarieh, M (Oct 2014). "The effect of Flammer syndrome on retinal venous pressure". BMC Ophthalmol. 14 (1): 121. doi:10.1186/1471-2415-14-121. PMC 4216361. PMID 25312339.
  16. ↑ Todorova, M.G.; et al. (2015). "Endothelin-1 Plasma Levels in Patients with both Retinitis Pigmentosa and Flammer Syndrome". Klin. Monatsbl. Augenheilkd. 232 (4): 514–518. doi:10.1055/s-0035-1545674. PMID 25902111. S2CID 23558601.
  17. ↑ Konieczka, Katarzyna; Ritch, Robert; et al. (2014). "Flammer syndrome". EPMA Journal. 5 (1): 11. doi:10.1186/1878-5085-5-11. PMC 4113774. PMID 25075228.
  18. ↑ Konieczka, K.; Fränkl, S.; et al. (2014). "Unstable oxygen supply and glaucoma. [Article in German]". Klinische Monatsblätter für Augenheilkunde. 231 (2): 121–126. doi:10.1055/s-0033-1360242. PMID 24532398. S2CID 206356894.
  19. ↑ Flammer, J; Konieczka, K; et al. (May 2013). "The Eye and the Heart". Eur. Heart J. 34 (17): 1270–8. doi:10.1093/eurheartj/eht023. PMC 3640200. PMID 23401492.
  20. ↑ Flammer, Josef; Konieczka, Katarzyna (2017). "The discovery of the Flammer syndrome: a historical and personal perspective". EPMA Journal. 8 (2): 88. doi:10.1007/s13167-017-0090-x. PMC 5486542. PMID 28725290.