Raynaud’s

1. Raynaud’s

2. Raynaud’s Phenomenon

4. Raynaud’s Phenomenon • 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'sarteritis) Antiphospholipid syndrome Occupation related   Vibration exposure Cold injury (e.g. frozen-food packers) Polyvinyl chloride exposure Ammunition workers (outside work) Obstructive vascular disease   Atherosclerosis Thromboangiitisobliterans (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. Pathophysiology • 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. Pathophysiology • Blood Cells • Platelets aggregate, Tx A2, TGF beta • RBCs stiff • WBCs produce ROS • Inflammatory/immune • TNF, lymphotoxin, IC abnormalities seen

8. Clinical Features: Raynaud’s • Definite • Repeated episodes • Biphasic color changes on cold exposure • Possible • Uniphasic change plus numbness or paresthesia

9. Raynaud’s Phenomenon • 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

11. Asymmetric Raynaud’s

12. Digital Pitting

13. Not a good sport for Raynaud’s patients

14. Evaluation • 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 • Apropriateserologies

15. Nailfold Capillaries

16. Medications reported to worsen Raynaud’s phenomenon • BetaBlockers • Vasoconstrictors • Clonidine, sympathomimetics, narcotics, ergotomines, serotonin agonists • Chemotherapy agents • Bleomycin, cisplatin/carboplatin, vinblastine/vincristine • Other • Cyclosporin, interferons, estrogens • Exposures • Nicotine, cocaine, polyvinyl chloride

17. Treatment

18. Overview • Raynaud’s phenomenon • Avoid cold exposure, layer clothing • Stop smoking • Vasodilator therapy • Nifedipine>Diltiazem>prazosin • Topical nitroglycerin paste • Other agents • Ischemic lesions • IV PGE1 or PGI2 • Sympathetic blocks, amputation • Bosentan, sildenafil, SSRIs,

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

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

22. OtherAgents • 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. Sildenafil (Viagra) • 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. Prostaglandins • 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. Critical digital ischemia 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. Sympathectomy • 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. Chilblain (pernio) • 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

30. Chilblain

31. Chilblain • 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

32. Chilblain SLE

33. Frostbite • 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. Classification • 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

35. Superficial Frostbite

36. Deep Frostbite

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

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

39. PrehospitalTreatment 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. HospitalTreatment • 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

41. Questions?