4.  Found in 95% of pts with SSc  Digital arteries of fingers and toes Also tongue, nose, ears, nipples  Appears suddenly as attacks Cold temperatures or stress  Color changes Pallor  Cyanosis  Redness

5. CONDITIONS ASSOCIATED WITH RAYNAUD'S PHENOMENON Immune mediated Systemic sclerosis (90%) Mixed connective tissue disease (85%) Sjögren's syndrome (33%) Systemic lupus erythematosus (10–45%) Polymyositis/dermatomyositis (20%) Rheumatoid arthritis (10–15%) Cryoglobulinemia and cryofibrinogenemia (10%) Arteritis (e.g. giant cell arteritis, Takayasu's arteritis) Antiphospholipid syndrome Occupation related Vibration exposure Cold injury (e.g. frozen-food packers) Polyvinyl chloride exposure Ammunition workers (outside work) Obstructive vascular disease Atherosclerosis Thromboangiitis obliterans (50%) Diabetic microangiopathy Thoracic outlet syndrome (e.g. cervical rib) Drug induced β -blockers (particularly non-selective) Antimigraine compounds Sulfasalazine Cytotoxic drugs Cocaine abuse Metabolic disorders Hypothyroidism Carcinoid syndrome Infections Chronic viral liver diseases (hepatitis B and C) Cytomegalovirus Parvovirus B19 Miscellaneous Neoplasm Complex regional pain syndrome type 1 Polycythemia Arteriovenous fistula Fibromyalgia syndrome % values are percentage of patients with disease who have Raynaud's phenomenon

6.  Vasoconstriction, cyanosis, hyperemia Neurogenic  A and B adrenergic receptors have increase sensitivity or density  A2C receptor felt to be major pathway for cold induced vasoconstriction  SNS has role – vibration of one hand, stress, CGRP  Infusions of adrenergic agonist do not produce pathology Endothelium  Endothelium dependant vasoconstriction abnormal in 2” Raynauds  Asymmetric DiMethylArginine (ADMA) inhibits NO synthase  Level increased in 2” Raynauds  Endothelin I, angiotensin II, vWF levels high in 2” Raynauds

7.  Blood Cells Platelets aggregate, Tx A2, TGF beta RBCs stiff WBCs produce ROS Inflammatory/immune  TNF, lymphotoxin, IC abnormalities seen

8.  Definite Repeated episodes Biphasic color changes on cold exposure  Possible Uniphasic change plus numbness or paresthesia

9.  Primary 4-15% of the general population Usually mild and not associated with structural vascular changes or ischemic tissue damage Onset typically occurs between 15-25 years  Secondary Age of onset usually after 30 yrs old More severe symptoms Ischemic injury Enlarged capillary loops and loss of normal capillaries in the nail folds

10. FEATURES SUGGESTIVE OF PROGRESSION OF RAYNAUD'S PHENOMENON TO CTD Clinical Older age at onset (>35 years) Vasospasm all year round Asymmetric attacks Sclerodactyly Digital ulceration Finger pulp pitting scars Laboratory Increased inflammatory markers Detection of autoantibodies Increased Von Willebrand factor antigen Nailfold microscopy Abnormal vessels

14.  H&P Concern for CTD? Aggravating drugs? Occupational or Hx suggesting a cause?  50% vibration workers  60% pts over 60 ASVD Nailfold Capillaries  Labs CBC, CMP, TSH, ESR, CRP Apropriate serologies

16.  BetaBlockers  Vasoconstrictors Clonidine, sympathomimetics, narcotics, ergotomines, serotonin agonists  Chemotherapy agents Bleomycin, cisplatin/carboplatin, vinblastine/vincristine  Other Cyclosporin, interferons, estrogens  Exposures Nicotine, cocaine, polyvinyl chloride

18.  Raynaud’s phenomenon Avoid cold exposure, layer clothing Stop smoking Vasodilator therapy  Nifedipine>Diltiazem>prazosin  Topical nitroglycerin paste Other agents Ischemic lesions  IV PGE 1 or PGI 2  Sympathetic blocks, amputation  Bosentan, sildenafil, SSRIs,

19.  Cold avoidance  Warm clothing, gloves  Stop smoking  Withdraw medications  Avoid vibration  Avoid stress  Rewarm with warm water or body heat

21.  Nifedipine, amlodipine, ditiazem, others  XR nifedipine preferred 30-180 mg/day  XR amlodipine second choice 5-20mg/day  Verapamil ineffective

22.  Prazosin Effective in cochrane review, may lose effect  PDE5 inhibitors Small studies, sildenafil, tadalafil, verdenafil  Fluoxetine Crossover, conflicting case reports  Losartan One blinded study, reduced attacks, ACE data conflicting  Topical nitrates Effective, many side effects (HA,dizzy)  Statin, NAC, Botox, gingko biloba  Bosentan Approved in UK, 2 controlled trials, fewer NEW ulcers only

23.  16 patients with disease resistant to vasodilators 78% with systemic sclerosis 11% with MCTD 11% with no CTD 33% had digital ulcers  50 mg sildenafil vs. placebo BID for 4 weeks  Frequency of attacks 35 vs. 52 (p=0.0064)  Duration of attack 581 vs. 1046 minutes (p=0.0038)  Nailfold capillary blood flow velocity quadrupled (p=0.0004) Fries R et al. Circulation 2005;112:2980

24.  Iloprost has the most trials 6-10ng/kg/min x 72 hrs or 0.5-2ng/kg/min x 6hr x 5 days  Prostacyclin (PGI2) also effective 7.5 – 10 ng/kg/min x 5 hr x 3 days  Epoprostanol not significant 0.5 to 2 ng/kg/min for 1-3 days  Alprostadil (PGE1) ineffective  Oral forms ineffective

25.  Medical emergency  hospitalization  Rest in warm environment  Pain control  Titrate CCB to full tolerated dose  Local lidocaine or bupivicaine for rapid chemical sympathectomy and pain relief (local block)  Heparin/LMWH for 24-72 hours  Parenteral prostaglandin  Surgical sympathectomy

28.  Temp – lidocaine/bupivocaine (no epi!!) Digital or wrist local block If shows temporary effect, then surgery may help  Surgical digital Local, less invasive  Surgical cervical Open or endoscopic

29.  Exposure to cold above freezing  On cold exposed skin Fingers, toes, feet, nose, knees, elbows  Results in edematous, inflammatory lesions  Painful or pruritic  Seen more in women, children, elderly  Most idiopathic and self limited

31.  Associated with SLE A less common form of Chronic Cutaneous SLE Increased mucin, +DIF on biopsy Up to 20% may develop SLE  Especially if have DLE  TREX1 mutation Familial chillblain and SLE DNAse, blocks type 1 interferon response

33.  Tissue damage from freezing  Direct cell death and inflamation  Ice crystals lyse cells  Inflammatory reaction Thromboxane A2, Prostaglandin F2, bradykinin, histamine Tissue ischemia and necrosis

34.  First Degree Skin pallor and anesthesia  Second Degree Blisters within 24 h, erythema  Third Degree Hemorrhagic blisters - eschar  Fourth Degree Involves muscle/bone – complete necrosis  Superficial/Deep

37.  EXPOSURE!!!  Prior cold injury  Alcohol  Tobacco  Exhaustion  Malnutrition  Peripheral vascular disease  Diabetes  Mental illness

38.  Ears, nose, cheeks, fingers, toes  Cold, numb, clumsy  Pallor, insensate  Hard or waxy

39.  Move to warm area  Do NOT rewarm if may refreeze  Avoid trauma, rubbing, harsh rewarming  Warm with warm water or body heat  Transport for treatment  Avoid walking on frostbitten feet if possible

40.  Rewarm 40-42C 104-108F water  Anesthesia (opioids)  Bulky dressing, elevation  Infection control  TPA if <24h from injury 2-4mg bolus, 0.5-1mgh infusion Angiogram q8-12 H Continue to perfusion or 48H