RAYNAUD’S PHENOMENON Christina Page, M.D. Olive View-UCLA Internal Medicine Epidemiology Approximately 5-10% of the US population have Raynaud’s Phenomenon Affects mostly women and usually appears between the ages of 15-20 (almost always before the age of 40) More prevalent in colder climate In over 80% of patients with Raynaud’s Phenomenon who are seen by an internist, the condition is simply an exaggeration of the physiologic response to cold temperatures Definition of Raynaud’s Phenomenon Maurice Raynaud (1862): people exposed to cold temperatures have transient digital ischemia secondary to exaggerated response of CNS Term is used to represent these episodic events that represent vasoconstriction of the digital arteries, precapillary arterioles and cutaneous arteriovenous shunts What happens with Raynaud’s Phenomenon? The ischemic phase of the attack is evidenced by demarcated pale or cyanotic skin limited to the digits. Starts in one or several digits after exposure to the cold or a stressful situation and then spreads symmetrically to all fingers of both hands Ends with rapid reflow of blood into the digits, shown as erythematous skin (reactive hyperemia) Mechanism of color changes in Raynaud’s Raynaud’s Phenomenon Diagnosis of Raynaud’s Phenomenon Patient must have history of sensitivity to the cold and have episodic pallor or cyanosis of the distal portions of the digits (or both) after exposure to the cold Photographs of the hands can be obtained during an attack and be used to confirm the history Discarded provocative test: immersion of the patient’s hand in ice water (cruel, and inhuman punishment) Active Raynaud’s Phenomenon Panel A shows sharply demarcated pallor resulting from the closure of digital arteries Panel B shows digital cyanosis of the fingertips Primary versus Secondary Raynaud’s Phenomenon Clinical criteria are used to distinguish patients with uncomplicated or primary Raynaud’s Phenomenon from those with Raynaud’s Phenomenon secondary to another illness. In Primary Raynaud’s Phenomenon, about one quarter of patients have a family history of Raynaud’s Phenomenon in a first-degree relative and usually the symptoms are generally milder than in Secondary Raynaud’s Phenomenon Criteria for the Diagnosis of Primary Raynaud’s Phenomenon Vasospastic attacks precipitated by cold or emotional stress Symmetric attacks involving both hands Absence of tissue necrosis, ulceration or gangrene No history or physical findings suggestive of a secondary cause Normal ESR Negative serologic findings, Particularly Negative ANA Normal nail-fold capillaries Secondary Raynaud’s Phenomenon Criteria Age at onset of more than 30 years Episodes are intense, painful, asymmetric or associated with ischemic skin lesions Clinical features suggestive of a connective- tissue disease Specific autoantibodies (i.e., centromere, SCL-70, Smith, dsDNA) Evidence of microvascular disease on microscopy of nail-fold capillaries Nail-Fold Capillaries in a Patient with CREST Syndrome or Limited Scleroderma The capillaries are dilated and enlarged, and some areas are devoid of normal capillaries, a typical characteristic of scleroderma. Nailfold capillaroscopy Supplies Nailfold capillaroscopy Technique Nailfold capillary abnormalities Normal SSc Adult DM Childhood DM SSc-specific antibodies Readily available •Anti-centromere •Anti-SCL 70 •Anti-PM/Scl Not so available •Anti-Th/To •Anti-RNA polymerase III •Anti-fibrillarin Anti-centromere antibody Evaluating a Patient for Raynaud’s Phenomenon Ask the following screening questions: 1. Are your fingers unusually sensitive to cold? 2. Do your fingers change color when they are exposed to cold temperatures? 3. Do they turn white, blue, or both? The diagnosis of Raynaud’s phenomenon is excluded if the response to questions 2 and 3 is negative. The diagnosis is confirmed by positive response to all three questions. Evaluating a Patient for Raynaud’s Phenomenon If all three questions are positive, you next need to exclude potential causative or aggravating factors. Drugs and toxins Chemo agents, interferon, estrogen, nicotine, narcotics, sympathomimetic agents, cyclosporine, cocaine, ergotamines, clonidine Environmental agents and injury Frostbite, repetitive occupational stress, hypothenar hammer syndrome Neuropathy Carpal tunnel syndrome Evaluating a Patient for Raynaud’s Phenomenon Patients with: 1. Normal findings on review of history and physical exam 2. No digital lesions or gangrene 3. Normal nail-fold capillaries can be considered to have Primary Raynaud’s Phenomenon Evaluating a Patient for Raynaud’s Phenomenon Patient’s with a history of any of the following: 1. Single digit or asymmetric attacks 2. Absent pulses 3. Asymmetry of blood pressure 4. Evidence of critical ischemia Obtain: Angiography, Arterial Doppler Ultrasonography or Digital plethysmography Abnormal findings indicate the presence of conditions causing large-artery disease such as Vasculitis, Atherosclerosis, Thromboangiitis obliterans, Embolic Disease or Thoracic Outlet Syndrome Evaluating a Patient for Raynaud’s Phenomenon Patient’s with symptoms or signs suggestive of systemic disease (Myalgias, arthralgias, fever, weakness, weight loss, rash, arthritis or symptoms of heart or lung disease) Obtain: CBC, Chemistry panel, Urinalysis, ANA, ESR, Rheumatoid Factor, C3 and C4 Complement levels and tests for disease specific auto-antibodies Evaluating a Patient for Raynaud’s Phenomenon Patient with negative initial laboratory results, should undergo the following: 1. Thyroid-function tests 2. Serum protein electrophoresis 3. Test for cryoglobulins If results are negative, patient has PRIMARY RAYNAUD’S PHENOMENON If results are positive, patient has other systemic disease, Hypothyroidism, Cancer, Cryoglobulinemia, Cryofibrinogenemia, Cold agglutinin syndrome Evaluating a Patient for Raynaud’s Phenomenon Patient’s with positive initial laboratory results have rheumatic disease: Scleroderma Systemic lupus erythematosus Mixed connective-tissue disease Dermatomyositis/Polymyositis Sjogren’s Syndrome Undifferentiated connective-tissue disease Non-pharmacological Treatments for Raynauld’s Phenomenon Quit Smoking Nicotine causes skin temperature to drop, which may lead to an attack Control Stress Emotional upsets may trigger an attack Keep Warm Avoid cold temperatures Dress warm: gloves, headgear, layers Air conditioning can trigger attacks Pharmacologic Treatment of Raynaud’s Phenomenon Calcium-Channel Blockers (Nifedipine, Amlodipine, Felodipine) Placebo-controlled trials indicate benefit 50-66% reduction in frequency of attacks SE: tachycardia, edema, flushing, HA, dizziness, constipation, orthostatic hypotension Pharmacologic Treatment of Raynaud’s Phenomenon Effective Calcium-Channel Blockers † Nifedipine XL 30-120 mg QD (Procardia, Adalat-CC) Amlodipine 5-20 mg QD (Norvasc) Felodipine 2.5-10 mg QD (Plendil) Isradapine 2.5-5.0 mg QD (DynaCirc) Diltiazem 30-120 mg TID (Cardizem, Dilacor) * Diltiazem XR 120-300 mg QD (Cardizem SR or CD) * * Diltiazem is the least effective of the bunch † Not all CCB effective: verapamil is not effective Other Pharmacologic Options for Treatment of Raynaud’s Disease Prazosin Crossover trial found it to more effective than placebo Losartan Reduced severity of attacks in patients with scleroderma Fluoxetine Controlled study showed improved symptoms Nitroglycerin Ointment effective--apply proximal 2/3 of finger Oral long-acting; patches--not well studied References 1. Wigley,F. Raynaud’s Phenomenon. NEJM 2002;347(23):1001-1008 2. Thompson SE, et al. Calcium-channel blockers for Raynaud’s phenomenon in systemic sclerosis. Arthritis Rheum 2001,44:1841-7. 3. Dziadzio M, et al. Losartan therapy for Raynaud’s phenomenon and scleroderma: clinical and biochemical findings in a fifteen week, randomized, parallel-group, controlled trial. Arthritis Rheum 1999, 42:2646:55. 4. Coleiro B, et al. Treatment of Raynaud’s phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford) 2001,40:1038-43. 5. Pope J, et al. Prazosin for Raynaud’s phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev 2000;2:CD000956.