JAAD CME

Aug 2023
J E F F WA N G R 4
SEPT 8 2023
Part I: Cutaneous manifestations of cardiovascular
disease
∙ Discuss the overlap between cutaneous and cardiovascular disease; identify the
cutaneous manifestations of common cardiovascular disorders:
Infective endocarditis, acute rheumatic fever, Kawasaki disease, cholesterol embolization
syndrome, lipid disorders, cardiac amyloidosis, and cardiac myxomas

∙ Understand how to diagnosis underlying cardiovascular disorders in order to

expedite early intervention.
Overview
∙ In this part 1 of a 2-part continuing medical education series, we review the
epidemiology and pathophysiology of cardiovascular disease, its association with
cutaneous symptoms, and the diagnosis and evaluation of cutaneous features of
cardiovascular syndromes, including infective endocarditis, acute rheumatic fever,
Kawasaki disease, cholesterol embolization syndrome, lipid disorders, cardiac
amyloidosis, and cardiac myxomas. As the incidence and prevalence of
cardiovascular diseases increase, dermatologists play an essential role in recognizing
the cutaneous manifestations of cardiovascular diseases in order to appropriately
connect patients with follow-up care.
Overview
∙ Dermatologists are exposed to diverse skin findings secondary to pathologies
associated with underlying cardiac diseases.
∙ Dermatologists may require increased awareness of these cutaneous manifestations
to appropriately refer cardiac patients.
∙ This section will provide an overview of cutaneous manifestations of classic
cardiovascular diseases, with a focus on distinguishing symptoms to diagnose and
appropriately refer patients.
Context
∙ Cardiovascular disease: leading cause of death in US and worldwide
∙ Lifetime risk CAD at age 40: 49% in men, 32% in women
∙ CVD has classical cutaneous manifestations: edema, cyanosis
∙ Recognizing skin signs can lead to accurate diagnosis, timely referral, appropriate
treatment
∙ Acronyms
Cardiovascular disease (CVD), coronary artery disease (CAD), congenital heart disease
(CHD), ischemic cardiomyopathy (ICM), congestive heart failure (CHF), pulmonary
hypertension (pHTN), arteriovenous malformation (AVM), peripheral vascular disease (PVD)
Clinical Signs (I)
∙ Edema: excess fluid in interstitial ∙ Clubbing: bulbous uniform swelling of
space soft tissue at terminal phalanx with loss of
Right-sided dz, pulm HTN, ICM, pHTN nailbed angle

∙ Cyanosis: abnormal blueish ∙ Cyanotic CHD, cor pulmonale, secondary

polycythemia, chronic CHF, chronic
discoloration of mucocutaneous
pulmonary disease
surfaces from decreased blood
oxygenation, reduce blood flow, ∙ Diagonal earlobe crease (Frank’s sign):
diagonal crease in earlobe from tragus to
anemia
rear auricle at angle of 45 with varying
Right-to-left shunt in CHD, AVM, reduced
depth
CO (LV failure, cardiogenic shock)
∙ CAD, PVD
Clinical Signs (II)
∙ Quincke pulse: visible pulsation of
nailbed or lip capillaries synchronous
with pulse
∙ Severe aortic valve insufficiency
∙ Xanthomas and corneal arcus: nodular
dermal lesions (many types); lipid
deposits on outer corneal rim
∙ Hyperlipidemia
Clinical Signs (III) – Infective Endocarditis
∙ Infective endocarditis: inflammation of
endocardial heart lining or bio/prosthetic
material from bacterial/fungal bloodstream
infection (Staph, strep, enterococcus)
∙ Splinter hemorrhage, Osler nodes, Janeway
lesions, Roth spots, conjunctival/palatal
petechiae
∙ Erythroderma, cellulitis, purpura,
hemorrhage, purpura fulminans, skin necrosis
∙ New-onset regurg murmur, cardiac emboli,
valvular damage, CHF,
∙ Duke Criteria
∙ Major: positive BCx or ECG with
endocardial involvement
∙ Minor: predisposing CVD, IVDU,
fever, vascular phenomena (Osler
nodes, Roth spots), immunologic
phenomena, serological evidence of
active infection (WBC, CRP, etc.)
∙ Diagnosis of IE requires 1 major+3
minor OR 5 minor
∙ Fig 4
A and B, Janewa
y lesions, osler
nodes, and
splinter
hemorrhages.
Janeway lesions,
osler nodes, and
splinter
hemorrhages on
the hands seen in
infective
endocarditis.
Clinical Signs (IV) – Rheumatic Fever
∙ Rheumatic fever: post-infectious ∙ Subcutaneous nodules: firm, painless, mobile,
sequelae from strep pharyngitis and <2cm on elbows, wrists, knees, ankles

downstream immune inflammatory ∙ Erythema marginatum: Serpiginous rings with

response red raised margins and central clearing on
torso, arms, legs, never face (5% of patients)
∙ Incidence 5/100000 in developed
∙ Arthritis: painful red swollen joints in lower
countries, cases in children 5-15 y.o. extremity migrating to upper, common and
∙ Carditis (MV 65%, AV 25%), found in 75% of patients

regurgitation ∙ Cardiac: pancarditis, valvulitis, CHF

∙ Regurgitation of AV/MV
∙ Sydenham chorea
Clinical Signs (V) – Kawasaki disease
∙ Idiopathic multisystem inflammatory
disorder of children, possibly
infectious
∙ Immune mediated vasculitis,
prolonged fever, acute inflammation
∙ 1/80 Japanese children develop KD by
age 5, with cardiac sequelae incl.
coronary artery abnormalities
∙ Diffuse generalized exanthem with
morbilliform, targetoid, scarlatiniform
morphologies
∙ Coronary artery aneurysm/dilation
(common), pericarditis, sudden death/MI
∙ Bilateral nonexudative conjunctivitis,
periungual and groin desquamation,
mucous membrane redness dryness
bleeding, strawberry tongue, peripheral
extremity edema, unilateral non-tender
cervical adenopathy
∙ Fig 5 Nonexudative bulbar
conjunctival injection seen
in Kawasaki disease.
Nonexudative bulbar
conjunctival injection with a
rim of sparing immediately
around the iris. Adapted
from Pride et al17
∙ with permission from
Science Direct.
∙ Fig 6 Desquamation seen in
Kawasaki disease. Fine
desquamation beginning in
the periungual area as a late
finding of Kawasaki disease.
Adapted from Pride et al17
∙ with permission from
Science Direct.
∙ Fig 7 Cracked lips seen in
Kawasaki disease. Kawasaki
disease with red, cracked
lips and conjunctival
injection. Adapted from
Pride et al17
∙ with permission from
Science Direct.
Clinical Signs (VI) – Chronic cardiac disease
∙ Cholesterol embolization syndrome
Atherosclerotic occlusion of arterial
vessels, often post invasive procedure
(I: 34%) Blue toe syndrome, livedo,
erythematous lesions, petechiae,
ecchymoses, splinter lesions, cyanosis,
ulcerations, retiform purpura
Workup: biopsy, CT angio, MR angio
Treatment: supportive, cardiovascular risk
management, anticoagulation/thrombolytic
(controversial)
∙ Lipid disorders
Xanthomas (tendinous, tuberous, plantar,
eruptive), depositions of fat
DDx: NXG, JXG, seb. Hyperplasia,
syringona, nBCC, xanthoma diffusum
planum
Workup: lipid panel (primary DLP: familial
hyperlipoproteinemia, Bolognia ch. 92;
secondary DLP: CKD, nephrotic syndrome,
hypothyroid, DM, obstr. Liver dz, drugs-
retinoid, CS, HIV-protease inhibitors, CsA)
Clinical Signs (VII) – Chronic cardiac disease
∙ Cardiac amyloidosis
Amyloid light chain (AL) amyloidosis
infiltration from plasma cell dyscrasia
causing diastolic heart failure 2* to
restrictive CM (Bolognia Ch. 47)
(I: 40%) Ecchymoses, periorbital pinch
purpura, waxy papules, macroglossia, nail
dystrophy, cutis laxa
Workup: skin/fat biopsy + Congo red, echo
∙ Cardiac myxomas
Secondary to tumor-related thrombi, embolic
fragments. DDx: papillary fibroelastoma,
rhabdomyoma, right atrial mass, valvular veg,
metastatic tumors, angiosarcomas
a/w Carney complex: NAME (nevi, atrial
myxoma, myxoid neurofibroma, ephelides)
LAMB (lentigines, atrial myxoma, blue nevi)
(I: 30-50%): Clubbing, red macules/papules on
extremities, blue nevi, lentigines, serpiginous
lesions, livedo reticularis, petechiae, splinter
lesions, hemorrhages, Raynauds
Workup: echo, CT, MR
Part I – CME Quiz
Part I – CME Quiz
Part II: Cutaneous manifestations of peripheral
vascular disease
∙ Discuss the overlap of cutaneous and vascular disease; identify the cutaneous
manifestations of common vascular disorders:
chronic venous insufficiency, peripheral artery disease, superficial and deep vein thrombosis,
lymphedema, acrocyanosis, pernio, livedo reticularis and livedo racemosa, erythromelalgia,
and Raynaud’s
Understand how to diagnosis underlying peripheral vascular disorders in order to expedite
early intervention.
Overview
∙ In this Part 2 of a 2-part continuing medical education series, we review the
epidemiology of peripheral vascular disease, its association with cutaneous
symptoms, and the diagnosis and evaluation of cutaneous features of vascular
disorders. As peripheral vascular disease becomes more prevalent globally, it is
essential for dermatologists to become competent at accurately recognizing and
diagnosing cutaneous manifestations and directing individuals to receive appropriate
care and treatment.
Context
∙ PVD: vasculopathy and inflammation of arteries, veins, and capillaries.
∙ Vasculopathy is characterized by intravascular thrombosis, and vasculitis refers to
inflammation directed toward vessel walls.
∙ Cutaneous manifestations can facilitate early diagnosis by dermatologists
∙ Acronyms
Ankle brachial index (ABI), chronic venous disease (CVD), chronic venous insufficiency
(CVI), deep vein thrombosis (DVT), erythromelalgia (EM), livedo reticularis (LR), livedo
racemose (LRC), peripheral artery disease (PAD), venous thromboembolism (VTE)
Vasculopathy vs vasculitis
∙ Vasculopathy
Intravascular thrombosis, +/- association
with other inflammatory conditions
Pauci-inflammatory (DIC, warfarin-
induced skin necrosis, HIT), inflammatory
(arthropod bite, calciphylaxis)
Diagnosis: Skin biopsy (+DIF), ANCAs,
anti-cardiolipin, coagulation studies,
complement levels, cryoglubulins,
cryofibrinogen, D-dimer
E.g. livedoid vasculopathy
∙ Vasculitis
Inflammation directed towards vessel wall
resulting in endothelial damage, fibrinoid
necrosis, and erythrocyte extravasation
Primary (small/medium/large vessels),
secondary (CTD, drugs, malignancy,
infection, serum sickness)
Diagnosis: biopsy, ANCAs, coagulation
studies, complement levels, D-dimer,
heparin-platelet factor 4
E.g. nodular vasculitis
Cutaneous symptoms of PVD
∙ Edema ∙ Gangrene
Visible swelling from extravascular fluid, pitting and non- Tissue necrosis from lack of blood supply and nutrients,
pitting, tx compression wet/dry

∙ Venous dilation ∙ “Overlying skin changes”

Dilated veins near skin surface or MM (telangiectasia,
reticular, varicose)
∙ Corona phlebectatica (ankle flare sign)
Fan shaped confluence of blue telangiectasias commonly
along malleoli
∙ Cyanosis
Blue skin from poor circulation or inadequate oxygenation,
central and peripheral patterns
Cool temp, hairless, shiny, nail changes
∙ Hemosiderin pigmentation
Red stippling progressing to brown confluence
∙ Lipodermatosclerosis
Firm tender red induration (inverted champagne bottle)
∙ Stasis dermatitis
Prurititic, scaly, fissured, crusted, bulla, plaques,

∙ Ulcers ∙ Acroangiodermatitis (pseudo-KS)

Full thickness skin breakdown from compromised blood flow Reactive angiodysplasia of cutaneous vessels in form of
+/- infection; venous arterial mixed violaceous macules, indurated plaques/nodules bilaterally
Chronic venous disease
∙ Abnormalities in venous system leading to
reflux or obstruction in normal blood flow
∙ Etiologies: idiopathic, congenital,
secondary (trauma, standing, hormonal,
thrombotic)
∙ Venous hypertension releases inflammatory
mediators triggering endothelial
dysfunction and wall permeability,
mediating symptoms of lower leg pain,
edema Fig 1. Skin changes secondary to long-term venous stasis. A,
e.g. Lipodermatosclerosis from TGF-b1 and Hyperpigmentation with leg edema. B, Pacemaker-induced
collagen/fibrosis venous stasis at thoracic outlet with collaterals present.
∙ Fig 3 Chronic lipodermatosclerosis.
Progressive fibrosis and atrophy of the
dermal and subcutaneous layers of the
extremities with a characteristic
concave appearance (“inverted
bowling pin” sign).
∙ Fig 4 Classic representation of diffuse
atrophie blanche scarring along the
distal portion of the calf with
associated white atrophic plaques and
superimposed capillary stippling
(C4b). A. Original photo. B, Courtesy
of Dr Dirk Elston.
Diagnostics of PVD
∙ ABI -> PAD
Ratio of SBP at ankles dorsalis
pedis/posterior tibial to SBP at upper arm
brachial artery [systolic toe pressure]
Normal (0.9-1.4), abnormal (<0.9, >1.4)
∙ Duplex ultrasound -> PAD, VTE, CVI
Evaluation of speed and flow through
vessels using traditional and Doppler u/s
∙ Capillary refill -> PAD
Compression of nailbed until white and time
to reperfuse (abnormal is >2s)
∙ Nuclear lymphoscintigraphy
Nuclear medicine scan of lymphatic system
to examine blockages a/w lymphedema
∙ Transcutaneous oximetry -> PAD
Non-invasive measure of tissue oxygenation
beneath skin and assessment of
microperfusion
Regular room vs hyperbaric chamber vs
supine
Abnormal (<40 mmHg, impaired would
healing)
Diagnosis and evaluation of vascular
disease
∙ History: hypercoagulable, VTE history,
oral contraceptive
∙ Exam: skin findings, acute and chronic
symptoms i.e. swelling, redness,
warmth, edema, discoloration,
engorgement,
∙ Diagnostics: venous duplex ultrasound,
ABI
∙ VTE and superficial vein thrombosis
Thrombus formation within vascular
system and includes both DVT/PE
Superficial vein thrombosis:
thrombophlebitis, inflammatory reaction
around superficial thrombosed vein
Etiologies: surgery, OCP, trauma,
immobility, obesity, cancer
Criteria: Well’s criteria >2, PERC, other
scores, imaging
Peripheral artery disease
∙ Atherosclerosis of lower extremity arteries
causing overlying skin change, dependent
rubor, ischemic ulcers, gangrene
∙ a/w smoking ,dyslipidemia, age >65
∙ Range of symptoms including chronic
changes (atrophy, cool, dry, shiny, hairless
skin, brittle discolored nails), intermittent
claudication, critical limb ischemia,
ulcers/gangrene
∙ Diagnosis: absent pulses, clinical findings,
ABI
Lymphedema
∙ Discussed in Dec 2017 JAAD CME
Raynaud’s phenomenon
∙ Pallor, cyanosis, and erythema in digits ∙ Diagnosis: features of cold sensitivity,
from transient vasospasm of arteries color change, workup for secondary
and arterioles lasting min to hours causes (CBC, ANA/ENA, RF, CK),
nailfold capillaroscopy
∙ Primary: no etiology, common and
benign, age 15-30 yrs, symmetric
∙ Secondary: CTD (SSc, APLS, SLE,
Sjogren’s), asymmetric and frequent
∙ Pathogenesis from alpha adrenergic
receptor sensitivity causing excessive
vasoconstriction
Acrocyanosis
∙ Painless blue discoloration of hands, face, ∙ Diagnosis: pulses, Doppler u/s, labs to
feet with symmetric distribution, long rule out other etiologies
duration, no pallor/pain
∙ Primary and secondary (CTD, Buerger’s
disease, MI, drug exposure, chronic arsenic
poisoning, cryoglobulimia, anorexia)
∙ a/w palmar, plantar hyperhidrosis, chronic
vasospasm of cutaneous arteries and
arterioles after cold exposure and
compensatory vasodilation of capillaries
and post capillary venules
Pernio/Chilblain’s
∙ Pruritic and/or burning purple ∙ Diagnosis: localized erythema and
discoloration of toes/fingers, acral swelling >24 hours, with at least
symmetric and lasting up to 1 week 1 of worsening in cooler season,
histopath findings of pernio and NO
∙ Chilblain lupus: requires evidence of
LE, responsive to warming
LE on skin lesions and response to
lupus therapy or negative cryoglobulin, ∙ Workup for LE, blood dyscrasias, AI-
cold agglutinin studies CTD
∙ Etiology: decreased blood flow
secondary to vascular changes and
hyperviscosity
Erythromelalgia
∙ Neurovascular syndrome of episodic
occlusion of blood vessels in hands/feet,
with redness, increased temperature,
burning pain of hands or feet in
intermittent episodes with varying
durations, numbness/ulcers
∙ Diagnosis: cutaneous symptoms, rule
out secondary causes (CBC, HIV,
ANA, RF, uric acid), EMG/NCS, gene
testing
∙ Skin biopsy not recommended

∙ Primary EM: AD neuropathy with

inherited mutation in voltage-gated Na
channels, allodynia
∙ Secondary EM: myeloproliferative d/o,
infx, autoimmune, gout, DM
Livedo reticularis and livedo racemosa
∙ LR: transient symmetric violaceous ∙ Diagnosis: skin biopsy from non-
net-like mottling, idiopathic, discolored skin in center of mottling
commonly in women 20-50 y.o may show vasculitis, calciphylaxis,
intravascular eosinophilic plugging,
∙ LRC: protracted asymmetric and
thrombosis, cholesterol clefting
irregular skin changes, secondary to
autoimmune, drug, hematologic dz, ∙ Rule out DVT, APLS
anorexia, livedoid vasculopathy
∙ Etiology: microvascular changes
leading to compromised blood flow,
arteriole vasospasm with reversible
changes in LR
Part II – CME Quiz