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RiittaLuosujärvi

Raynaud's Phenomenon (RP) or White Finger Disease

Essentials

  • Most patients have benign primary Raynaud's phenomenon.
  • Identify the patients who may have a treatable underlying disease. Secondary Raynaud's phenomenon should be diagnosed as early as possible and the underlying cause effectively treated.
  • An extended RP episode will cause hypoxia in target organ tissues.
  • Prepare to treat the patient in cooperation with specialized care and primary health care. Severe RP should be treated in specialized care.
  • Remember to provide the patient with lifestyle guidance.

Definition

  • Maurice Raynaud described Raynaud's phenomenon in 1862. The phenomenon is called by several names, such as Raynaud's phenomenon, Raynaud's disease and Raynaud's syndrome.
  • RP is a phenomenon where, due to paroxysmal constriction of small vessels, most often in the fingers or toes, the skin turns first pale, then bluish and finally red (”tricolour”).
  • Primary RP (pRP) is an independent condition that is usually benign.
  • Secondary RP (sRP) is due to some other disease (see Table T3).

Aetiology and prevalence

  • Primary RP often runs in the maternal side of the family, and there is often also migraine in the family.
  • The exact mechanism behind the phenomenon is unknown but there may be abnormal self-regulation of capillary function or increased secretion of transmitters constricting blood vessels.
  • In pulmonary RP, in particular, endothelial function is disturbed.
  • The prevalence of primary RP is 3-15%.
    • More than 20% of young women may have RP.
    • Its prevalence is higher in women than in men.
  • The prevalence of secondary RP is high in patients with systemic autoimmune diseases, in particular: for example, 95% of patients with systemic sclerosis have sRP.

Symptoms

  • Both pRP and sRP usually occur symmetrically in both hands and/or both feet. Nevertheless, RP may occur in just a few or one finger or toe, the nose, the navel or nipples.
  • RP with a mechanical cause or nerve entrapment often occurs in organs innervated by that nerve (e.g. median nerve entrapment in patients with carpal tunnel syndrome).
  • In patients with systemic autoimmune diseases, such as systemic sclerosis, RP may also occur in visceral organs, such as kidneys or lungs, or in coronary vessels.
  • Stages of RP episodes
    • The skin first turns white and, at the same time, numbness and tingling occur in the area, and the finger, for instance, becomes clumsy.
    • When the vasospasm starts to subside, the skin becomes warm. At the same time, it turns blue, sometimes really deep blue, and severe pain occurs in the area.
    • When the spasm subsides completely, the skin turns bright red.
    • The various stages may last only a moment but may sometimes continue for several hours.
  • Factors triggering RP episodes
    • Wind, cold exposure, change of temperature (e.g. going into an air-conditioned space or into a refrigerated department at a store)
    • In the summer, wind blowing from the sea, even if not cold, is a common triggering factor.
    • Ingesting cold food or beverages may trigger an episode, as can handling frozen goods or coins with bare hands.
    • Emotional stress

History and examination

  • Careful history taking
    • Age at onset of symptoms
    • Medication
    • Smoking
    • Working conditions
    • Family background
  • RP in the hands or any other visible area of the body is easy to detect by careful observation, interview and clinical examination (see Symptoms here). Visceral RP is hard to detect.
  • Check the general condition of the skin and check for ulceration on fingertips.
  • Note possible sausage fingers.
  • Check the blood pressure and consider cardiac disorders.
  • The formerly recommended test where, in the doctor's office, the patient immersed his/her hands or feet in ice water should not be used. There is a risk of severe vasospasm and development of gangrene.
  • It is important to distinguish between primary and secondary RP and, in the case of the latter, to target the treatment at its cause. Secondary RP should be suspected if
    • the symptom appears at an age of over 30 years
    • the patient has abnormal autoantibodies in his/her blood
    • the patient is found to have or develops during follow-up other symptoms suggestive of an autoimmune disease, such as ulceration on fingertips or butterfly rash on the face.
    • In patients with autoimmune diseases, videocapillaroscopy shows typical changes in eponychial capillaries (see Table T1).
    • sRP may also be associated with many other diseases and conditions (Table T3).

Features distinguishing between primary and secondary RP

FeaturePrimarySecondary
Prevalence in women/men20:14:1
Age at onset (years)Below 30Above 30
Associated diseaseNoYes
AutoantibodiesNoOften
Eponychial capillariesNormalPathological
Endothelial damageNoOften
Ischaemic damageNoOften

Differential diagnosis

Primary RP

  • Table T2 lists conditions to be considered in differential diagnosis. In these conditions, the tricolour phenomenon is absent, but they are still sometimes difficult to distinguish from RP. These conditions should also be considered when investigating sRP.
  • If the patient is a young woman who has developed no other symptoms during the first couple of years of follow-up, it is normally the benign primary form.
  • It should be kept in mind that in elderly women and men, in particular, RP may precede a systemic disease by as many as 20 years.

The most common conditions to be considered in the differential diagnosis of RP.

Disease/conditionDescriptionFurther information
AcrocyanosisHereditary and often congenital condition
Peripheral body parts are evenly bluish and there are no tricolour changes.		New onset in an adult may be associated with an autoimmune disease or anorexia nervosa, for example.
Chilblains As a result of prolonged cold exposure, purplish spots appear on the skin or a firm swelling can be felt in the skin.The lesions often heal slowly.
Cold urticaria Hives (Urticaria)A typical, itchy urticarial rash appears after cold exposure.Antihistamines can be used to treat itching.
Most importantly, the skin must be protected from cold.
ErythromelalgiaHeat, severe erythema and burning, most commonly affecting the feet.
Livedo reticularis, or a net-like pattern on the skinNet-like pattern on the skin
The pattern is non-blanchable.		Occurs in association with conditions such as systemic autoimmune diseases.
Symptoms of acute onset, in particular, always require medical assessment.
ErythrocyanosisA benign, typical colour change occurring on the legs of young or middle-aged women in association with cold exposure and subsiding with ageThis is due to slowing of the circulation in the skin and the subcutaneous fatty tissue.

Secondary RP

  • There are many types of diseases and conditions that cause secondary RP.
  • It is important to identify such conditions because the symptom can often be completely cured or at least alleviated by effective treatment of the underlying cause.
  • Table T3 lists various causes of sRP. Careful clinical examination is important to identify the underlying cause. If any of the conditions listed below are suspected, they should be investigated separately.

Causes of secondary RP

Type of disease or conditionAetiology
Systemic connective tissue disorderScleroderma Systemic Sclerosis (in 90%)
Systemic lupus erythematosus (SLE) Systemic Lupus Erythematosus (Sle) (in 40%)
Rheumatoid arthritis Rheumatoid Arthritis (in 10%)
Dermatomyositis and polymyositis Myositis (in 25%)
Mixed connective tissue disease (MCTD) Mixed Connective Tissue Disease (MCTD) (in 85%)
Eating disorderAnoreksia nervosa
Obstructive vascular diseaseAtherosclerosis
Buerger's disease
Takayasu arteritis Vasculitides
Aneurysm of the subclavian artery
Thoracic outlet syndrome Thoracic Outlet Syndrome
Exposure to external factorsWork where an individual is subjected to vibration or shaking (may be compensated as an oocupational disease) Hand-Arm Vibration Syndrome (Vibration-Induced White Fingers)
Exposure to vinyl chloride, mercury or cold
Other diseasesSevere mental trauma
Lyme disease Lyme Borreliosis (LB)
Hypothyroidism Hypothyroidism
Cryoglobulinaemia Vasculitides
Malignant disease
Chronic fatigue syndrome
Complex regional pain syndrome (CRPS) Complex Regional Pain Syndrome (CRPS)
Carpal tunnel syndrome Carpal Tunnel Syndrome (CTS)
Magnesium deficiency Magnesium Deficiency
MS Multiple Sclerosis (Ms)
Erythromelalgia
Idiopathic PAH Increased Pulmonary Blood Pressure: Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension (10-14% have RP)
Cholesterol embolization Cholesterol Embolization
Endocarditis Infective Endocarditis
Polycythaemia vera Polycythaemia Vera (PV)
Hyperviscosity syndrome
Myxoma
Drug-induced RPBeta blockers
Sulfasalazine
Ciclosporin
Sympathomimetics
Ergotamine derivatives
Cocaine
Hormonal contraceptives

Laboratory tests

  • If a young woman has RP with mild symptoms and none suggesting a systemic connective tissue disease or other underlying disease, and if the symptom runs in the family, no laboratory investigations are needed. Primary health care can be responsible for her treatment.
    • Depending on the local guidelines, antinuclear antibodies, basic blood count with platelet count and ESR may be determined.
    • It should be kept in mind that about 10% of patients with scleroderma do not have antinuclear antibodies.
  • Examinations should be performed and treatment chosen in specialized care if
    • the patient is a child below the age of 16 years
    • the symptom appeared at an age of over 30 years
    • the symptom is severe, frequently recurring and slowly reversible
    • ulcers occur on fingertips.
  • In specialized care, laboratory examinations focus on the disease suspected based on the patient's clinical symptoms and examinations.
    • ESR: often elevated in patients with autoimmune disease or chronic inflammatory disease
    • Antinuclear antibodies (ANAAb): systemic autoimmune disease, SLE, systemic sclerosis, MCTD
    • Chemical screening of urine: changes in kidney function, such as proteinuria
    • RF: autoimmune disease, rheumatoid arthritis, cryoglobulinaemia, Sjögren's syndrome
    • Complete blood count: polycythaemia, autoimmune disorder
    • Creatinine: change in kidney function
    • fP-Gluc: diabetes
    • TSH: disorder of thyroid function
    • CK: polymyositis, dermatomyositis
    • Hepatitis serology: if there is clinical suspicion of hepatitis (cf. Viral Hepatitis)
    • Serum and urinary protein: to detect paraprotein

Videocapillaroscopy

  • Videocapillaroscopy of nailfold capillaries provides a picture of the capillaries and their function and may help to identify the underlying disease.
  • It can also be used to monitor the response to treatment and to define the prognosis.

Symptoms of systemic rheumatic disease

  • If RP is associated with a systemic disease (a rheumatic disease, for example), the treatment and the prognosis will depend on the disease.
  • Table T4 lists some of the most common autoimmune diseases with RP and their typical symptoms.

Typical symptoms of systemic autoimmune diseases

DiseaseTypical symptoms
SLE Systemic Lupus Erythematosus (Sle)Butterfly rash
Photosensitivity
Arthritis or joint and muscle pain
Nephritis, pleuritis or pericarditis
Prolonged fever
Systemic sclerosis Systemic SclerosisSwelling of the fingers (sausage fingers)
The skin later becoming thicker, shiny and stiff and being attached to the underlying tissue
Stiffening and loss of range of motion of joints; for example, being unable to clench the fist
Distension of and bleedings from nailfold capillaries
Mask-like facial appearance and puckered lips
Cutaneous telangiectasia
Dysphagia, impaired motility and strictures of the oesophagus
Dyspnoea and lung fibrosis on chest radiograph
Arthritis
Polymyositis and dermatomyositis MyositisProximal muscle weakness
Acute dysphagia
Purplish rash on the eyelids, neck and chest
Purplish, scaly, patchy rash on the extensor surfaces of the limbs
Prolonged fever
Arthritis
MCTD syndrome Mixed Connective Tissue Disease (MCTD)May be quite varied with features of conditions such as systemic sclerosis, polymyositis or rheumatoid arthritis.
Severe sausage-like swelling of the fingers is particularly typical.

Treatment

  • Holistic treatment is needed.
    • In secondary RP, it is essential to treat the underlying cause.
    • In primary RP, treatment should be targeted at the triggering factors that are known.
      • The same instructions apply to the treatment of sRP, as well.
  • The whole body should be kept warm and exposure to cold and sudden temperature changes avoided.
  • Smoking cessation is essential.
  • Work involving vibration should be stopped.
  • Release of nerve entrapment will usually cure RP restricted to a certain area.
  • Protection of the skin from knocks, inflammation and dryness
  • Careful treatment of the nails and cuticle skin
  • Effective treatment of underlying diseases, such as arteriosclerosis or diabetes, usually lessens the symptoms.
  • Work-related causes sustaining the symptom should be eliminated; for example, work that involves taking care of and reaching into a freezer is unsuitable for a patient with RP.
  • Air flowing with force from air-conditioning equipment towards the shoulders should be redirected.
  • If any drug (e.g. non-selective beta blocker, triptan, sympathomimetic; cf. Table T3) aggravates the symptom, its use should be avoided. However, drugs do not aggravate/trigger the symptoms in all patients.

Pharmacotherapy Nifedipine for Raynaud's Phenomenon, Calcium-Channel Blockers for Raynaud's Phenomenon in Systemic Sclerosis, Vasodilators for Primary Raynaud's Phenomenon, Iloprost and Cisaprost for Raynaud's Phenomenon in Progressive Systemic Sclerosis

  • Calcium channel blockers are the basic medication in all cases of RP and are often sufficient in pRP.
    • 10-20 mg nifedipine twice daily (up to 60 mg) is normally used.
  • Nitroglycerin patch, nitroglycerin cream (1 or 2%), extemporaneous prescription (2% glyceryl trinitrate in an emollient)
  • Diltiazem ointment, extemporaneous prescription
  • Effective and careful treatment of high blood pressure generally prevents the development of vascular damage.
  • Phosphodiesterase-5 inhibitors can be used under the supervision of a medical specialist.
  • Angiotensin receptor blockers (ARBs) may be tried.
  • Iloprost infusions can be used in courses, or in Finland, for example, all winter long.
    • They reduce and help to heal finger ulceration.
  • Bosentan has proved useful in preventing the recurrence of finger ulceration.
  • Serotonin reuptake inhibitors (SSRIs), particularly fluoxetine, have been used for the treatment of RP, for example in cases where calcium channel blockers cannot be used.

Other treatment

  • Heated gloves and socks to be used as personal aids can be prescribed in specialized care.
  • Face guards available in sports stores, for instance, protect the facial area from wind and cold, reducing RP episodes.

Treatment in severe cases

  • In severe cases, the patient should be referred to specialized care.
  • Sympathectomy will cure the symptom permanently.
  • Local nerve block anaesthesia of the finger will alleviate pain quickly and help to relieve the spasm.
  • Stem cell transplantation will cure RP in patients with underlying severe systemic sclerosis.
  • Amputation can be considered if there is necrosis not responding to treatment.
  • Courses of prostacyclin infusions can be used in wintertime, particularly.
  • Anticoagulants and aspirin are part of the treatment.
  • Specific drugs affecting the vascular wall (bosentan, phosphodiesterase-5 inhibitors) should be started if there is recurrent ulceration on fingertips or other places on the skin.
  • Topically administered botulinum toxin will relieve a severe RP episode and may save the finger from amputation.
  • Treatment of the underlying cause is of central importance.

Referral

  • Impending gangrene: the patient should be referred to a hospital as an emergency case.
  • The following patients should be non-urgently referred to a rheumatologist.
    • Patients with symptoms, findings or abnormal laboratory test results (e.g. ANA) suggestive of an underlying disease, such as a systemic connective tissue disease
    • Patients with symptoms constantly disturbing their everyday life
    • Patients with symptoms not responding to treatment
    • Patients who need assessment of working ability
    • Children below the age of 16 years
  • It is important to identify patients benefiting from treatment and requiring consultation of a rheumatologist.
  • There are treatments available to slow down or to prevent the development of finger ulceration and other late changes.

Prognosis

  • Primary RP will turn into secondary RP in 14-37% of cases, especially if antinuclear antibodies have been detected. About 99% of these patients will develop some systemic autoimmune disease, most commonly systemic sclerosis Systemic Sclerosis.
  • Particularly patients who have antinuclear antibodies at an early stage, elevated ESR or changes detected by videocapillaroscopy, have an increased risk of systemic sclerosis.
  • The prognosis of patients with secondary RP depends on the prognosis of the underlying cause or disease.

Pictures

    References

    • Bartelink ML, Wollersheim H, van de Lisdonk E et al. Prevalence of Raynaud's phenomenon. Neth J Med 1992;41(3-4):149-52. [PubMed]
    • Kowal-Bielecka O, Fransen J, Avouac J et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis 2017;76(8):1327-1339. [PubMed]
    • Hansen-Dispenza H, Narayanan SA, Oberto-Medinaet M. Raynaud Phenomenon. eMedicine http://emedicine.medscape.com/article/331197 (requires a user code). Updated on 27.9.2018.
    • Garner R, Kumari R, Lanyon P et al. Prevalence, risk factors and associations of primary Raynaud's phenomenon: systematic review and meta-analysis of observational studies. BMJ Open 2015;5(3):e006389. [PubMed]
    • Grassi W, Del Medico P. Atlas of capillaroscopy. EDRA 2004, Milan, Italy.
    • Maundrell A, Proudman SM. Epidemiology of Raynaud's Phenomenon. Kirjassa: Wigley FM, Herrick AL, Flavahan NA (toim.). Raynaud's Phenomenon -A Guide to Pathogenesis and Treatment. New York: Springer 2015;21-35.