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Raynaud Phenomenon

Raynauds Syndrome

Raynaud phenomenon is a clinical condition caused by vasospasm in the hand or foot parts due to cold or emotional stress, which may result in a reversible pain and observable color change, manifesting in the form of a pallor, erythema nodosum, or cyanosis in one or more digits. Sometimes, it may involve other body parts such as nose and tongue. This clinical disorder may either be primary or secondary in the development and the diagnosis is made mainly by clinical examination.


Presentation

Common manifestations of Raynaud phenomenon include paresthesia, abnormal sensation of coldness or burning pain, periodic color changes in one or more finger digits stimulated in response to a cold condition, emotional stress, and vibration. These changes may be reversed when the stimulus causing the effect is removed. The introduction of warm condition assists in resolving the body skin color and normal sensation.

There may be skin color change of the affected digit usually with distinct demarcation. The color changes appear in the progression from white to blue and then red due to pallor, cyanosis and hyperemia respectively. These can either be triphasic (pallor, cyanosis, and hyperemia), biphasic (cyanosis and erythema), or uni-phasic (either pallor or cyanosis) in nature. These changes are usually reversible. In severe cases, these changes may result in a localized ischemia and ulceration. Raynaud phenomenon commonly involves the index, middle and ring finger and may not affect the thumb particularly those at the proximal end of the metacarpophalangeal joints. The period of vasospasm development in primary Raynaud phenomenon may range from few minutes to hours usually without any significant effect such as tissue loss. Raynaud phenomenon which develops secondary to a disorder involving connective tissue and systemic sclerosis may result into an inflamed digital gangrene and infected finger ulcers. Affected patients with Raynaud syndrome sometimes report vasospastic episodes stimulated by cold condition or emotional stress. These episodes commonly affect the fingers or toes and rarely involve the nose, ears, (including nipples,and lips). There may be numbness and pain in the affected body parts.

The previous history of the patient and the observed symptoms may guide in identifying any underlying clinical disorder. This may include symptoms of any vasospastic episodes which include, migraines.

Toe Pain
  • When Raynaud's syndrome is associated with scleroderma (Systemic Sclerosis) problems may involve skin ulcers (sores) or gangrene (tissue death) in the fingers or toes. Painful ulcers and gangrene are fairly common and can be difficult to treat.[medic8.com]
Cyanosis
  • Methemoglobinemia and sulfhemoglobinemia are rare causes of cyanosis that can be medication-induced. Both are known complications of therapy with phenazopyridine.[ncbi.nlm.nih.gov]
  • These can either be triphasic (pallor, cyanosis, and hyperemia), biphasic (cyanosis and erythema), or uni-phasic (either pallor or cyanosis) in nature. These changes are usually reversible.[symptoma.com]
  • The triple color change includes pallor (indicating ischemia), cyanosis (indicating deoxygenation), and erythema (indicating reperfusion); the double color change may present as pallor plus cyanosis or cyanosis plus erythema.[clinicaladvisor.com]
  • , cyanosis; paroxysmal digital , Raynaud; phenomenon , paroxysmal; digital cyanosis , phenomenon; Raynaud , Raynaud's syndrome (disorder) [Ambiguous] , Raynaud Phenomenon , Raynaud's phenomenon, secondary , raynauds phenomenon , Raynaud's phenomenon[fpnotebook.com]
Vascular Disease
  • Therapies directed at the vascular disease continue to focus on the alleviation of vascular spasm. However, immunosuppressive therapy may influence the levels of vascular injury markers and thus may have an effect on the vascular disease itself.[ncbi.nlm.nih.gov]
  • BACKGROUND: Raynaud's phenomenon (RP) is a functional vascular disease, presenting with recurrent episodes of ischemia of extremities in response to cold and emotional stress.[ncbi.nlm.nih.gov]
  • Likewise, RP is not a contraindication for hormone replacement therapy (HRT), as HRT may protect women against the development of vascular disease in general.[academic.oup.com]
  • This book will be a valuable asset to the internist and should be mandatory reading for any physician or surgeon interested in vascular diseases."[amazon.com]
Acrocyanosis
  • Occasionally, an alternate explanation is revealed such as acrocyanosis. Methemoglobinemia and sulfhemoglobinemia are rare causes of cyanosis that can be medication-induced. Both are known complications of therapy with phenazopyridine.[ncbi.nlm.nih.gov]
  • To help differentiate benign acrocyanosis from acrocyanosis associated with other serious conditions, the differential diagnosis of unilateral and bilateral acrocyanosis in infants is also discussed.[ped-rheum.biomedcentral.com]
  • Also, unlike Raynaud phenomenon, acrocyanosis exhibits no trophic changes including ulcer.[symptoma.com]
  • Symptoms Hypersensitivity to cold Temperature s Color changes of digits during cold or stress exposure "White attacks" suggest severe ischemia Mottling with acrocyanosis is more common and benign Sensation of numbness, clumsiness or "pins and needles"[fpnotebook.com]
Foot Pain
  • Commodes and Accessories Grab Bars Shower Chairs Transfer Benches Walk In Tubs Braces Back Supports & Braces Cervical Neck Pain Comfort Cool Tennis Elbow Braces - Elbow Wraps, Sleeves & Bands Finger - Thumb Supports Foot and Ankle Braces - Supports Foot[activeforever.com]
Paresthesia
  • The attacks may be associated with pain, paresthesia, and complicate with nonhealing ulceration often leading to amputation. To date, there are no clear-cut therapeutic guidelines and many medications are used off-label.[ncbi.nlm.nih.gov]
  • Raynaud's phenomenon [ ra-nōz ] intermittent bilateral attacks of ischemia of the fingers or toes and sometimes the ears or nose, marked by severe pallor, and often accompanied by paresthesia and pain; it is brought on characteristically by cold or emotional[medical-dictionary.thefreedictionary.com]
  • It causes pallor followed by cyanosis and/or redness, often with pain and, at times, paresthesia. On rare occasions, it can lead to ulceration of the fingers and toes and, in some cases, of the ears or nose.[aafp.org]
  • Raynauds sykdom Portuguese Doença de Raynaud Ontology: Raynaud Phenomenon (C0034735) Definition (NCI_FDA) Intermittent bilateral attacks of ischemia of the fingers or toes and sometimes of the ears or nose, marked by severe pallor, and often accompanied by paresthesia[fpnotebook.com]
Aura
  • We report the case of a patient who developed typical migraine with aura and Raynaud phenomenon at the age of 14, 12 years after onset of Kawasaki disease.[ncbi.nlm.nih.gov]

Workup

Most often, Raynaud phenomenon is commonly diagnosed clinically. This has been proven to be more sensitive compared to other diagnostic technique such as imaging test. A similar condition called acrocyanosis commonly affects the finger digits with the visible color change due to cold , however, it is different from Raynaud phenomenon because of the persistence, and difficult irreversibility of the condition. Also, unlike Raynaud phenomenon, acrocyanosis exhibits no trophic changes including ulcer.

Clinically, both primary and secondary types are differentiated based on the symptoms and by special technique (vascular imaging studies) including laboratory investigations such as blood screening. Laboratory investigations are usually required to assess clinical conditions that are similar to primary or secondary Raynaud phenomenon. The choice of the appropriate laboratory test is determined by the clinical findings. Blood investigations primarily can be done for collagen vascular diseases. These include erthrocyte sedimentation rate, C-reactive protein estimation, rheumatoid factor test, anti-DNA or antinuclear screening. Other tests such as anticentromere antibody and anti-Scl-70 antibody screening are done to rule out any underlying disorders.

Imaging techniques such as isotope studies, infra-red thermography, and angiography can also be used, although with less sensitivity when compared with clinical assessment. This is usually recommended for patients with symptoms of permanently fixed, cyanotic lesion.

Myocardial Fibrosis
  • Cardiac Raynaud's phenomenon (C-RP) was evaluated in a few clinical studies both as cold-induced transient myocardial ischaemia and as presence of advanced myocardial fibrosis and contraction band necrosis in autopsied patients.[ncbi.nlm.nih.gov]

Treatment

Treatment of Raynaud phenomenon depends on the type or form of the syndrome. Primary Raynaud phenomenon may not often require pharmacological therapy since it may be reversed, however, most secondary forms are better managed with drugs. Primary type is treated by identification and removal of the etiological factors. These include avoidance of cold temperature, stress management and cessation of the agent which causes vasoconstriction such as nicotine. The affected body part may be placed in a warm condition to reverse the disorder. Stress may be managed using different relaxation methods including biofeedback and patient counseling. Different drugs are recommended for convenience and also as psychological therapy. A vasodilating agent such as calcium ion channel blocker is used for treating primary Raynaud type. These drugs are generally recommended particularly dihydropyridines, which are known to be potent vasodilators [8]. Commonly administered, effective drugs include nifedipine, amlodipine, felodipine and isradipine[9] [10]. Most often nifedipine is always selected as the first drug of choice with a dosage of 30-120 mg/day to allow an extended-release and lasting effect. An initial treatment with the mentioned drugs may be followed by administering prazosin. Also, topical application of either or both of 1-2% nitroglycerine gel [11] (locally administered), pentoxifylline (taken with meals) have been found to be effective, although, no present evidence supports its use in clinical routine. β-Blockers such as clonidine and ergot alkaloids are strongly not recommended because they produce vasoconstriction which could stimulate or worsen the symptoms.

Secondary Raynaud phenomenon treatment targets the underlying clinical disorder that progresses to the disorder. It is important to know the patient's history to ascertain the underlying health challenge of the patient and determine the risk factors (such as occupational hazard or toxic compound exposure). Drugs such as calcium ion channel blockers and prazosin used in the management of the primary form can also be used. Cases of ischemic ulcers that develop from the condition may be managed by antibiotics, analgesics, or sometimes may require surgical debridement. Thrombosis may be prevented by a low dosage of aspirin. Presently, there are prostaglandins drugs such as alprostadil, epoprostenol, and iloprost which are reported to be effective and could be an alternative regimen for managing patients having ischemic digits, although, these drugs are generally unavailable. The use of a surgical technique such as local sympathectomy in managing Raynaud phenomenon is controversial and is majorly recommended for patients with symptoms of progressive disability who failed to respond to the therapeutic regimen. Although, patients who undergo sympathectomy recover from the symptoms, the effect is usually short-lived (lasting between 1-2 years).

Prognosis

In most patients with the primary type of Raynaud phenomenon, the prognosis is often encouraging, with reduced morbidity and no mortality rate. Very rarely, reported cases of ischemia may cause tissue necrosis, particularly in the affected body part. However, the prognosis of secondary Raynaud phenomenon in the affected patients depends on the underlying disease condition. The resolution of the finger digit with the disorder symptoms is associated with the type of method selected in restoring blood flow after ischemia.

Etiology

Although the mechanism of Raynaud phenomenon is not fully understood, it is suggested to be due to an increased effect of α 2 -adrenergic response that stimulates vasospasm. The primary Raynaud phenomenon is more common compared to the secondary type, accounting for more than > 80% of reported cases. The main cause of this type of Raynaud phenomenon is still unknown. It usually occurs without noticeable symptoms of other clinical disorders. However, among few 20% of the affected patients, there may be an underlying cause of the disease. These include systemic sclerosis which may be observed at the onset of the disease or diagnosed later.

Most often, the secondary Raynaud phenomenon occurs after an initial clinical disorder or condition, particularly those involving connective tissue. The possible causes of the secondary Raynaud phenomenon may be classified broadly into different groups which include, occupational effect, hematological influence, auto-immune disorder (collagen-vascular), drug-induced and other clinical disorder referred to as a miscellaneous syndrome. This syndrome includes acromegaly, Fabry's disease, pheochromocytoma (PCC), pulmonary adenocarcinoma, carpal tunnel syndrome (CTS), and myxedema.

Epidemiology

Generally, the prevalence of Raynaud phenomenon ranges from 3-5%, with women more commonly affected compared to men. Also, the disorder usually affects younger age groups than the older ones. Previous epidemiological study of Raynaud phenomenon among the Caucasian population in the United States revealed an exact prevalence value of 11% and 8% among women and men respectively, with incidence value of 2.2% among women and 1.5% in men occurring yearly [2]. Globally, the prevalence rate of primary Raynaud phenomenon varies with different populations and gender. It is more common among the women than men, ranging from 4.9-20.1% among women to 3.8-13.5% in men. Raynaud's disease is observed at a particular age, most commonly between the age of 20-30 years. As previously stated, secondary Raynaud phenomenon develops after the development of the primary underlying disorder.

Sex distribution
Age distribution

Pathophysiology

Patients with Raynaud phenomenon usually have one or more body sites affected with intense vasospasm and related skin color change along with hyperemia. Three phases of skin color change are observed, which include, early white skin color (due to vasoconstriction), then blue skin (caused by cyanosis), which later changes to a red color as a result of rapid reflow of the blood. The most affected body sites are the ones frequently susceptible to cold or injury. A distinct mark of separation is usually seen between an ischemic part and the unaffected area. These changes can be reversed and should be classified from other irreversible etiology of ischemia which includes vasculitis or thrombosis. Very rarely, there may be necrosis of the tissue distally situated to the affected blood vessel, particularly at the peripheral vasculature. It affects most frequently the fingers, sometimes the toes, nose, or ears and very rarely, it may involve the tongue.

The main pathophysiology of Raynaud phenomenon is probably due to an imbalance between vasoconstriction and vasodilation mechanism, which results from impairment in neural regulations of vascular tone, with the circulation of chemical mediators [3]. Raynaud phenomenon may be caused by an altered or impaired vasodilation. Chemical mediators involved in vasoconstriction are maintained by vasodilators which include, nitric oxide and prostaglandins. In addition, prostaglandins cause an increase in the fibrinolysis, which may subsequently influence the outcome of secondary Raynaud phenomenon in the affected patients [4]. A decrease in vasodilatory chemical mediators, such as nitric oxide, has been reported to stimulate the pathogenesis of Raynaud syndrome [5]. Also, a potent vasoconstrictor known as the endothelin-1, in the endothelial cells, has been shown to be detected in high amount among the patients having secondary Raynaud phenomenon [5] [6]. Increase episode of fibrosis and structural changes in blood vessels has also been observed in the patient with increased circulatory levels of the endothelin-1 mediators [5]. Therefore, impairment of endothelin-1 receptors simultaneously affects the vascular remodeling and development of smooth muscle cells including fibroblasts which is usually the primary drug target site in patients having systemic sclerosis [6]. A neuropeptide called calcitonin (gene-related peptide) is an active vasodilator released by the nerves that regulate blood supply in the vessels [7]. Another important vasoconstriction mediator that plays important roles in the pathogenesis of Raynaud phenomenon is angiotensin II.

These factors have been implicated to play important roles in the development of secondary Raynaud phenomenon particularly in connective tissue diseases such as systemic sclerosis.

Prevention

Raynaud phenomenon may be prevented by avoiding the risk factors. Although, treatment may be needed to reverse the condition, often, the use of non-drug therapy may be the only required regimen for managing the milder form of the primary Raynaud phenomenon. Patients managed using this approach may engage in self-treatment without the help of health caregiver. The preventive method used in the control of Raynaud phenomenon involves lifestyle and behavioral changes. This mainly includes avoidance of cold conditions. Direct exposure to cold temperature or objects should be discouraged including frozen foods. Also, people living in the colder regions are encouraged to wear hand gloves or socks and install home warming appliances such as a heater. Also, some substances rich in nicotine such as cigarette are known to stimulate vasospasm. Hence, they must be avoided. These lifestyle modifications are very important to control Raynaud phenomenon (both primary and secondary form). Among patients with symptoms of secondary Raynaud phenomenon, the diagnosis of the underlying disease is necessary with proper attention to any physical injuries or chemicals that can aggravate the condition.

Summary

Raynaud phenomenon usually presents with persistent vasospasm in the fingers or toes as a direct response to stress or cold condition exposure. The disorder is classified into either primary or secondary type. These two forms are different clinical conditions although with the same clinical name. The primary Raynaud phenomenon is also known as Raynaud's disease. Raynaud's disease has a feature of developing vasospasm only, with no relationship with any other condition. Secondary Raynaud phenomenon refers to a clinical situation where the vasospasm is associated with other diseases, particularly autoimmune diseases. This condition can also be described as a digital ischemic vasospasm stimulated by conditions such as cold or emotional stress resulting in a pale or cyanotic skin and post-ischemic form of hyperemia (typically known as tricolore phenomenon) [1].

Patient Information

Raynaud phenomenon is a clinical condition in which there is vasospasm in blood vessels, supplying the fingers or toes, as a direct response to cold or emotional stress. There are two major forms of the disorder which include, primary and secondary Raynaud phenomenon. Primary type develops directly as a result of the vasospasm without any association with any other diseases, while secondary Raynaud phenomenon is a term used when the condition develops as a result of the establishment of another disease. The most common type of Raynaud phenomenon is the primary type accounting for about 60-90% cases among women between 15-40 years of age. The onset of the blood vessel constriction is very rapid, usually stimulated by direct exposure to cold and may last between minutes to hours. Commonly seen symptoms include a pale, bluish patch on fingers or toes. This may affect one or more fingers or toes in the affected limb. There may be tingling or burning sensations in the affected area, however, it is usually painless with a feeling of numbness. Most often, the finger or toe digits may become more reddish in color. Most cases of Raynaud phenomenon do not require serious medication because the condition is reversible following the removal of the risk factors. Placing the affected part in a warm temperature may restore the skin color and the sensation. However, in cases of prolonged Raynaud phenomenon, particularly in the patient with scleroderma, the affected finger or toe may be tender, shiny, or tight. There may be a painful ulceration at the tip of the affected finger or toe.
Depending on the observed symptoms, the clinician can, therefore, make the right diagnosis and recommend necessary treatment required. Various drugs are available for treatment of the disorder, however, mild cases may require a non-drug approach.

References

Article

  1. Raynaud M. London: New Sydenham Society. Local Asphyxia and Symmetrical Gangrene of the Extremities. 1862
  2. Suter LG, Murabito JM, Felson DT, Fraenkel L. The incidence and natural history of Raynaud's phenomenon in the community. Arthritis Rheum. 2005;52(4):1259-63.
  3. Rajagopalan S, Pfenninger D, Kehrer C, Chakrabarti A, Somers E, Pavlic R. Increased asymmetric dimethylarginine and endothelin 1 levels in secondary Raynaud's phenomenon: implications for vascular dysfunction and progression of disease. Arthritis Rheum. 2003;48(7):1992-2000.
  4. Kirchengast M, Munter K. Endothelin-1 and endothelin receptor antagonists in cardiovascular remodeling. Proc Soc Exp Biol Med. 1999;221(4):312-25.
  5. Bunker CB, Goldsmith PC, Leslie TA, Hayes N, Foreman JC, Dowd PM. Calcitonin gene-related peptide, endothelin-1, the cutaneous microvasculature and Raynaud's phenomenon. Br J Dermatol. 1996;134(3):399-406.
  6. Kahaleh B, Matucci-Cerinic M. Raynaud's phenomenon and scleroderma. Dysregulated neuroendothelial control of vascular tone. Arthritis Rheum. 1995;38(1):1-4.
  7. Bertelé V, Mussoni L, del Rosso G, Pintucci G, Carriero MR, Merati MG, Libretti A, de Gaetano G. Defective fibrinolytic response in atherosclerotic patients--effect of iloprost and its possible mechanism of action. Thromb Haemost. 1988;60(2):141-4.
  8. Generali J, Cada D. Nitroglycerin (topical): Raynaud's phenomenon. Hospital Pharmacy. 2008;43:980-981.
  9. Ennis H, Anderson ME, Wilkinson J, Herrick AL. Calcium channel blockers for primary Raynaud's phenomenon. Cochrane Database Syst Rev. 2014;1:CD002069.
  10. Bakst R, Merola JF, Franks AG Jr, Sanchez M. Raynaud's phenomenon: pathogenesis and management. J Am Acad Dermatol. 2008;59(4):633-53. doi:10.1016/j.jaad.2008.06.004. Epub 2008 Jul 24.
  11. Fries R, Shariat K, von Wilmowsky H, Böhm M. Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy. Circulation. 2005;112(19):2980-5.

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Last updated: 2018-06-22 05:57