RAYNAUD'S DISEASE

Raynaud's disease (Primary Raynaud's) is a rare, vasospastic disorder that typically affects women between the ages of 15-45 years with onset typically before age 30. Patients typically experience pain, numbness, and loss of finger function when exposed to cold temperatures. Vasospastic attacks may be accompanied by a triphasic color changes in the hands. The term Raynaud’s disease is often confused with Raynaud’s phenomenon; however, it is incredibly important to distinguish them. The main difference is that the cause of Raynaud’s disease is idiopathic, while patients with Raynaud’s phenomenon have an underlying collagen vascular disease that is responsible for the underlying vascular abnormalities. Management of Raynaud’s disease should be initially conservative and consist of reducing exposure to cold, smoking cessation, and stress management. For patients that fail to improve with these strategies, drug therapy may be helpful; in extreme cases, surgical intervention might be considered.^1-9

Pathophysiology

• In 1862, Maurice Raynaud theorized that the disorder was due to sympathetic nervous system overactivity, and more specifically, elevated level of circulating neurotransmitters that result in an exaggerated vasoconstriction in the peripheral circulation¹
• Another theory proposes that there is a local fault at the digital artery level, with digital blood vessels having an abnormal sensitivity to cold temperatures¹
• A third theory suggests that increased blood viscosity and plasma fibrinogen levels may result in a stasis of the digital circulation in response to cold¹
• One of the most recent theories concerns alpha-2 receptors, as individuals with Raynaud’s disease appear to have an extreme alpha-2 response to cold exposure, which results in a vasospasm and produces symptoms; it is not clear why this response is amplified, but it may be due to multiple forms of vascular stress^2,4
• A fault in the local histaminergic vasodilating system has also been proposed as a possible underlying mechanism, while emotional stress and chronic exposure to vibration are believed to play a role in eliciting vasospasm^2,5

Related Anatomy

• Vasospastic attacks most commonly involve the fingers and not the thumb
• Patients may also experience symptoms involving the toes, nose, ears, face, and tongue; it is uncommon for Raynaud's disease to affect only the toes and not the fingers¹

Incidence and Related Conditions

• The reported incidence of Raynaud's disease is between 5-10% of the general population, making it more common than Raynaud’s phenomenon⁶
• Raynaud’s disease most commonly occurs in females aged 15-45 years; up to 22% of healthy young women may experience symptoms of the disorder at some point; this makes Raynaud’s disease about 4 times more common in females than in males⁶
• Children are rarely affected by Raynaud’s disease ^7-8

Related syndromes:

• Sjögren's, 
• Scleroderma (CREST)
• Thoracic outlet
• Buerger’s disease
• Angina pectoris 
• Arterial obstruction 
• Cryoglobulinemia 
• Cold agglutinins 
• Cryofibrinogenernia 
• Dermatomyositis 
• Dysproteinemia 
• Frostbite 
• Hemoglobinopathies Polycythernia vela 
• Polyarteritis nodosa 
• Rheumatoid arthritis 
• Vibration white finger 
• Upper extremity trauma 

Differential Diagnosis

• Raynaud’s phenomenon (differentiating signs/symptoms):
  • Onset in the mid-20s and later
  • More equal distribution between male and female patients
  • Usually not related to stress
  • Often begins in a single digit instead of most digits
  • An ischemic injury is usually involved
  • Finger edema and periungual erythema are common
  • No other vasomotor syndromes¹

For the past 2 years, a 17-year-old girl has been dealing with a particular set of symptoms every time she goes outside in cold weather. Symptoms include burning sensations, pain and numbness in both of her hands, which interferes with her ability to grab items tightly and perform many other tasks that require dexterity. She also noticed that the color of her hands changes during these attacks, first to white and then to blue, and after coming back inside to a warmer environment, to red with an accompanied swelling and tingling sensation. These symptoms may also occur to a lesser degree when she grabs very cold items or spends time in highly air-conditioned rooms.  Helping control her stress level and her exposure to cold control her symptoms significantly.

• Infection 
• Hematoma
• Thrombosis 
• Paresthesias

• Despite the wide array of promising treatments, the best and most basic management of Raynaud’s disease seems to be behavioral ²
• With appropriate education and lifestyle modifications, Raynaud’s disease is generally benign and self-limiting;¹most patients have a stable course, and nearly half will improve with time and steady reassurance²
• Calcium channel blockers have shown effectiveness in producing fingertip vasodilation within minutes in most patients experiencing an attack¹
• Intravenous ketanserin has been associated with considerable clinical improvements⁵
• Oral phenoxybenzamine has been reported to result in asymptomatic patients as a maintenance treatment for Raynaud’s disease⁵

• The triphasic color changes of Raynaud’s phenomenon or disease; pale (white), cyanotic (blue) and reperfusion hyperemia (red) are a key characteristic of Raynaud's disease and Raynaud's phenomenon.
• Patients with Raynaud's Disease typically are healthy females under age 20 at onset, have mild vasospastic attacks caused by cold or emotional stress, the color changes are symmetrical in both hands and they have no necrosis or gangrene.¹⁰
• Patients with Raynaud's Phenomenon typically have onset of symptoms around age 30, the vasospastic attacks are intensely painful, asymmetric in the hands and are associated ischemic skin changes. The patients also demonstrate signs suggestive of a connective tissue disease like scleroderma or rheumatoid arthritis.¹⁰
• Patients need to understand that drug therapy may help relieve symptoms but often will not eliminate them altogether¹
• Although there is no mortality associated with Raynaud’s disease, it is uncomfortable and can be embarrassing for many patients; the possibility of a more serious underlying condition may also lead to stress and highlights the importance of obtaining an accurate diagnosis²
• The ability to target endothelial cold receptors may lead to highly specific interventions for Raynaud’s disease in the future²
• One of the newest and most novel approaches to treating Raynaud’s disease follows a metabolic route over a vascular one, as the thermogenic steroid 7-oxodehydroepiandrosterone is used to boosts the basal metabolic rate, which can improve central warming and thus inhibit vasospasm²
• Angiography which provides the most objective evaluation of radial, ulnar, and digital vessel status³
• Laboratory tests including:
  • Urinalysis
  • Complete blood count
  • Serum chemistries
  • C-reactive protein
  • Erythrocyte sedimentation rate
  • Autoantibodies - Of patients with Raynaud’s disease, 25% have a positive antinuclear antibody titer⁴

Cited

1. Kaufman MW, All AC. Raynaud's disease: patient education as a primary nursing intervention. J Vasc Nurs1996;14(2):34-9. PMID: 8900768
2. Jackson CM. The patient with cold hands: understanding Raynaud's disease. JAAPA2006;19(11):34-8. PMID: 17124789
3. Kim YH, Ng SW, Seo HS, et al. Classification of Raynaud's disease based on angiographic features. J Plast Reconstr Aesthet Surg2011;64(11):1503-11. PMID: 21704575
4. Hodges H. Raynaud's disease: pathophysiology, diagnosis, and treatment. J Am Acad Nurse Pract1995;7(4):159-64. PMID: 7756043
5. Burns EC, Dunger DB, Dillon MJ. Raynaud's disease. Arch Dis Child1985;60(6):537-41. PMID: 3160308
6. Varon J, Gasman JD. Raynaud's disease: an update. Hosp Pract (Off ed) 1991;26:157-9. PMID: 1898940
7. Porter SB, Murray PM. Raynaud phenomenon.  J Hand Surg Am. 2013; 38A:375-378.
8. Butendieck RR, Murray PM.  Raynaud disease.  J Hand Surg Am. 2014; 39A:121-124.
9. Neumeister MW. Botulinum toxin type A in the treatment of Raynaud’s phenomenon.  J Hand Surg Am. 2010; 35A:2085-2092.
10. Wigley FM. Raynaud’s phenomenon. N Engl J Med 2002; 347(13); 1001-1008

Reviews

1. Kaufman MW, All AC. Raynaud's disease: patient education as a primary nursing intervention. J Vasc Nurs1996;14(2):34-9. PMID: 8900768
2. Hodges H. Raynaud's disease: pathophysiology, diagnosis, and treatment. J Am Acad Nurse Pract1995;7(4):159-64. PMID: 7756043
3. Jackson CM. The patient with cold hands: understanding Raynaud's disease. JAAPA2006;19(11):34-8. PMID: 17124789

Classics

1. Mouillot A. A Case of Raynaud's Disease. Br Med J1897;2(1917):806-7. PMID: 20757314