Raynaud syndrome

• 1. Introduction

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  Raynaud syndrome is a condition in which the smallest arteries in the body clamp down and starve a patch of tissue of blood. It is also called Raynaud's phenomenon. About 4% of people have it, which makes it far more common than most people guess. A physician named Auguste Gabriel Maurice Raynaud first described it in his doctoral thesis in 1862, and his name has been attached to it ever since. The condition usually strikes the fingers. A hand that was fine a moment ago can change in a matter of minutes, and the cause may be nothing more than a cold room or a stressful thought. For some people it is a nuisance that comes and goes. For others it is the first quiet signal of a serious illness that has not yet announced itself. Why do the vessels overreact? What separates the harmless form from the dangerous one? And what can anyone do about it?

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• 2. Three Colors

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  A classic attack on the fingers or toes unfolds in a fixed order of colors. In the first stage, cold shrinks the blood supply to the fingertips. The skin goes white, a change doctors call pallor, and it turns cold and numb. The nose and the earlobes can go the same way, and in rare cases so can the lips. The source describes the white phase as followed by blue, and that dull blue marks the stretch when the tissue is short of oxygen.

  The second stage comes when the attack ends or the area warms up. Blood rushes back, and the skin first turns red, which doctors call rubor. The flush is reactive hyperemia, the body flooding tissue that was deprived. The red area often burns and swells. It tingles, and it can ache with a sharp pins and needles feeling. Episodes typically last minutes, though some stretch to several hours.

  Not everyone sees every color. In milder cases a person may notice only some of the changes, and not in every episode. The condition is not limited to hands and feet. Raynaud's has been seen in breastfeeding mothers, whose nipples turned white and painful. Pregnancy, on the other hand, normally makes the color change disappear, because more blood flows near the surface of the body.

  The colors tell a story about plumbing, but they do not say why the plumbing fails. That depends on which of two quite different forms a person has.

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• 3. Two Forms

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  Doctors divide the condition into primary Raynaud's, called Raynaud's disease, and secondary Raynaud's, called Raynaud's phenomenon. In the primary form, the word that matters is idiopathic. It means the attacks occur on their own, with no other disease behind them and no known cause. Some people describe it as being allergic to coldness. It often begins in young women in their teens and early adulthood, and the usual onset falls between the ages of 15 and 30.

  Heredity seems to play a part. A large genetic study identified two genes that predispose people to the condition. One is ADRA2A, which codes for the alpha-2A-adrenergic receptor that responds to adrenaline. The other is IRX1, a transcription factor, meaning a protein that switches other genes on and off.

  Secondary Raynaud's behaves differently. It tends to appear at an older age, and its attacks are more likely to be painful and uneven between the two sides of the body. They are also more likely to progress to ulcers on the fingers. A telling clue is attacks limited to a single hand or foot. That uncommon pattern, called unilateral Raynaud's, is always secondary to a local or regional disease of the blood vessels, and it usually spreads to other limbs within several years as that disease advances.

  The long list of conditions behind secondary Raynaud's is where the stakes rise.

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• 4. An Early Warning

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  For 70% of people with scleroderma, a disease of the skin and joints, Raynaud's is the very first symptom they notice. That figure shows why the condition matters beyond cold fingers. Secondary Raynaud's can precede the illness behind it by many years, and the same is true in CREST syndrome, of which Raynaud's is a component.

  The list of associated conditions is long. Connective tissue disorders head it, including scleroderma, systemic lupus erythematosus, rheumatoid arthritis, Sjögren's disease, dermatomyositis, polymyositis and mixed connective tissue disease. Ehlers-Danlos syndrome and cold agglutinin disease appear there too. Anorexia nervosa is on the list. So are blocked or narrowed vessels, as in atherosclerosis, Buerger's disease, Takayasu's arteritis, subclavian aneurysms and thoracic outlet syndrome. Further entries include Lyme disease, hypothyroidism, cancer, multiple sclerosis, carpal tunnel syndrome and magnesium deficiency.

  Medications and workplaces can also cause it. Drugs implicated include beta-blockers, cyclosporin, bromocriptine, ergotamine and sulfasalazine, and chemotherapy drugs, most especially bleomycin. Stimulants used for ADHD, such as amphetamine and methylphenidate, are on the list, as are over-the-counter pseudoephedrine products such as Sudafed. So are anthrax vaccines whose main ingredient is the Anthrax Protective Antigen.

  Occupations matter as well. Drilling and long use of a string trimmer can produce vibration white finger. Exposure to vinyl chloride or mercury is a risk, and so is work in the cold, such as packing frozen food.

  Two conditions on the list look like mirror images of Raynaud's. Erythromelalgia leaves the extremities hot and red, and chilblains leave them hot and itchy in smaller areas, such as the tip of one toe. Both can co-exist with Raynaud's in the same patient, and the first one will matter again when treatment comes up.

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• 5. The Overactive Switch

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  Behind every attack, the source points to the same culprit: an overactive sympathetic nervous system, the branch of the nervous system that prepares the body to react to danger. Mental stress and a cold atmosphere set it off. Three changes are seen in the mechanism. Blood flow falls, the vessels constrict, and nerve, inflammatory and immune responses join in.

  The two forms differ in how they get there. In the primary type, the vessels become unusually sensitive, and constriction follows. In the secondary type, the normal activity of the vessels is disrupted. The squeeze can then starve tissue of oxygen, a state called ischemia, and in the worst case the tissue dies.

  Smoking increases both the frequency and the intensity of attacks. A hormonal component also exists. Caffeine, estrogen and nonselective beta-blockers are often listed as aggravating factors, but the evidence that people should avoid them is not solid.

  Because a harmless attack and a warning sign can look identical to the eye, doctors need tests that look past the fingertip.

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• 6. Telling Them Apart

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  Diagnosis usually rests on the symptoms alone, and a careful medical history is meant to find or rule out secondary causes. Separating the primary form from the secondary form is the important step. Doctors look for signs of arthritis or vasculitis and order a number of laboratory tests.

  One of the most sensitive tools is a look at the tiny blood vessels at the base of the fingernail, called nail fold capillary examination or capillaroscopy. Under a microscope, it can objectively tell a secondary form tied to a connective tissue disorder from a primary one. If systemic sclerosis is suspected, thermography may help predict it.

  A cooling test offers a number. Pressures are measured in the arteries of the fingers before and after the hands are cooled, and a drop of at least 15 mmHg counts as a positive result. Doppler ultrasound can also assess blood flow.

  Blood work casts a wide net. A full blood count may show a normocytic anaemia, pointing to chronic disease or kidney failure. Tests of urea and electrolytes can reveal kidney impairment, and thyroid tests can reveal hypothyroidism. Other tests, including rheumatoid factor, C-reactive protein and an autoantibody screen, can point to a specific illness or an inflammatory process. Anti-centromere antibodies are common in limited systemic sclerosis, or CREST syndrome.

  Several sets of diagnostic criteria have been proposed over the years. More recently, a panel of experts in rheumatology and dermatology developed International Consensus Criteria for diagnosing primary Raynaud's phenomenon.

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• 7. Treatment

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  The first line of treatment costs nothing: stay away from cold. Doctors also advise avoiding emotional and environmental stress, vibration and repetitive motions. They recommend avoiding smoking, including passive smoking, and drugs that mimic the sympathetic nervous system. In secondary Raynaud's, the main task is treating the underlying disease.

  For moderate or severe cases, calcium channel blockers such as nifedipine or amlodipine, preferably slow-release versions, are often first-line medication. Their usual side effects are headache, flushing and ankle swelling, which rarely force a patient to stop. The evidence is mixed. Some limited findings show only a slight drop in how often attacks happen, while other studies suggest they ease the severity of attacks, pain and disability. Patients whose illness is tied to erythromelalgia often cannot take vasodilators at all, because the drugs can bring on flares that turn the extremities burning red.

  The list of alternatives is long. Aspirin may be prescribed for people prone to ulcers or large artery clots. Prazosin, an alpha-adrenergic blocker, may give temporary relief in secondary cases. Losartan and other angiotensin receptor blockers may reduce the frequency and severity of attacks, and some evidence suggests they do better than nifedipine. Iloprost manages critical ischemia, and bosentan helps prevent finger ulcers in scleroderma. Statins and SSRIs such as fluoxetine may help, though the data is weak. Sildenafil and tadalafil are used off-label for severe ischemia and ulcers, though as of 2016 their wider role was unclear.

  When drugs fail, surgeons have two options, and a newer injection is competing with both.

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• 8. Last Resorts and Outlook

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  In severe cases, surgeons can perform an endoscopic thoracic sympathectomy. This operation cuts the nerves that tell the blood vessels of the fingertips to constrict. Microvascular surgery on the affected areas is another possibility, but it is considered a last resort.

  A more recent option is botulinum toxin. A 2009 article studied 19 patients, aged 15 to 72, with severe Raynaud's. Sixteen of them, or 84%, reported less pain at rest. Thirteen felt relief immediately, and three more improved gradually over one to two months. All 13 patients who had chronic finger ulcers healed within 60 days. Only 21% needed repeat injections. A 2007 article reported similar improvement in a series of 11 patients, all of whom had significant pain relief.

  In contrast, alternative medicine fares poorly. The evidence does not support acupuncture, laser therapy or other alternative approaches.

  For most people the long-term picture is reassuring. The outlook for primary Raynaud's is often excellent, with no effect on life expectancy and little illness overall. Gangrene has developed only in some very rare cases. In the secondary form, the outcome follows the course of the underlying disease, and depends on how well blood flow can be restored. That is why a person's first cold-white fingertip can be worth a conversation with a doctor.

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