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

• PallorCyanosisRedness

CONDITIONS ASSOCIATED WITH RAYNAUD'S PHENOMENONImmune 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 exposureAmmunition workers (outside work)

 Obstructive vascular disease   Atherosclerosis

Thromboangiitis obliterans (50%)Diabetic microangiopathyThoracic outlet syndrome (e.g. cervical rib)

 Drug induced   β-blockers (particularly non-selective)

Antimigraine compoundsSulfasalazineCytotoxic drugsCocaine abuse

 Metabolic disorders   Hypothyroidism

Carcinoid syndrome Infections  Chronic viral liver diseases (hepatitis B and C)

CytomegalovirusParvovirus B19

 Miscellaneous   Neoplasm

Complex regional pain syndrome type 1PolycythemiaArteriovenous fistulaFibromyalgia syndrome

% values are percentage of patients with disease who have Raynaud's phenomenon

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

Blood Cells• Platelets aggregate, Tx A2, TGF beta• RBCs stiff• WBCs produce ROS

• Inflammatory/immune TNF, lymphotoxin, IC abnormalities seen

Definite• Repeated episodes• Biphasic color changes on cold exposure

Possible• Uniphasic change plus numbness or paresthesia

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

FEATURES SUGGESTIVE OF PROGRESSION OF RAYNAUD'S PHENOMENON TO CTD

ClinicalOlder age at onset (>35 years)Vasospasm all year roundAsymmetric attacksSclerodactylyDigital ulcerationFinger pulp pitting scars

LaboratoryIncreased inflammatory markersDetection of autoantibodiesIncreased Von Willebrand factor antigen

Nailfold microscopy  Abnormal vessels

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

BetaBlockers Vasoconstrictors

• Clonidine, sympathomimetics, narcotics, ergotomines, serotonin agonists

Chemotherapy agents• Bleomycin, cisplatin/carboplatin,

vinblastine/vincristine Other

• Cyclosporin, interferons, estrogens Exposures

• Nicotine, cocaine, polyvinyl chloride

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,

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

heat

Nifedipine, amlodipine, ditiazem, others

XR nifedipine preferred• 30-180 mg/day

XR amlodipine second choice• 5-20mg/day

Verapamil ineffective

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

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

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

Medical emergencyhospitalization 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

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

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

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

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

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

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

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

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

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