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Cardiovascular Diseases and the Skin
Key Points
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Several systemic disorders can affect both the heart and the skin.
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Cutaneous findings may serve as a diagnostic clue for many of these conditions.
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Dermatologists and cardiologists must be aware of the multisystem aspects of such disorders in order to facilitate proper diagnosis and management.
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A number of cardiac therapies may cause cutaneous complications, and awareness of such potential complications is essential for the dermatologist.
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Recognition of cutaneous findings associated with an increased occurrence of heart disease places dermatologists in a unique role to help reduce cardiovascular risk in certain patient populations.
A number of multisystem disorders can affect both the heart and the skin, and cutaneous examination often provides diagnostic clues to such entities. Recognition of the multisystem aspects of these conditions by both dermatologists and cardiologists is imperative for proper diagnosis and management. Awareness of potential cutaneous complications of cardiac therapies is also essential for the dermatologist. Therapies directed at improvement of muscle function (e.g., digoxin) rarely result in cutaneous disease, while therapies seeking to achieve fluid reduction (diuretics), afterload reduction, and control of rhythmic disturbances can affect the skin. In addition, increasingly frequent use of potent immunosuppressive agents for autoimmune cardiovascular disease and cardiac transplantation may lead to a variety of dermatologic manifestations, including an increased risk of skin cancers, again emphasizing the need for interspecialty collaboration.
This text reviews several multisystem disorders with associated cardiovascular abnormalities. Table 37-1 lists cardiac abnormalities associated with these multisystem disorders, Table 37-2 lists common dermatological findings associated with primary cardiovascular disorders, and common cutaneous side effects of cardiac medications are described in Table 37-3 .
TABLE 37-1
Cardiac Manifestations in Multisystem Disorders with Prominent Cutaneous Features
| Disease | Cardiac Manifestation | Cutaneous Features | Comments |
|---|---|---|---|
| Primary systemic amyloidosis | Congestive heart failure, conduction disturbances, cardiomegaly | Pinch purpura, waxy translucent papules or diffuse waxy skin infiltration, enlarged tongue, hemorrhagic bullae | Due to immunoglobulin light chains; associated with nonprogressive plasma cell dyscrasia and myeloma, as well as renal and neurologic involvement |
| Behçet’s disease | Pericarditis, conduction abnormalities, valvular disease, coronary arteritis, myocarditis. Recurrent thromboses | Oral and genital aphthae, pathergy, pustular vasculitis, pyoderma gangrenosum-like lesions, sterile vesicopustules, erythema nodosum, superficial thrombophlebitis | Ocular involvement (leading cause of morbidity), arthritis, central nervous system (CNS) disease |
| Inflammatory bowel disease can share many features and should be excluded | |||
| Carcinoid syndrome | Endocardial plaque—tricuspid insufficiency, pulmonary stenosis, right-sided heart failure. | Flushing, telangiectases, sclerodermoid features may occur as a late manifestation | Serotonin-producing tumor, most commonly of the intestine. Usually metastatic to the liver prior to symptom onset |
| Left-sided cardiac manifestations exceedingly rare due to pulmonary deactivation of vasoactive substances | |||
| Cardiofaciocutaneous syndrome | Sparse, curly, woolly, or brittle hair, ichthyotic skin | Pulmonary stenosis, atrial septal defect, hypertrophic cardiomyopathy | Many other associated cutaneous findings such as keratosis pilaris, palmoplantar keratoderma, café-au-lait macules |
| Carney complex (including NAME and LAMB syndromes) | Atrial myxoma | Cutaneous myxomas and lentigines | Carney’s includes endocrine neoplasia of the adrenal, pituitary, and/or testes. Mutations in the PRKRA1A gene have been identified in many patients with familial cardiac myxomas |
| Cushing’s syndrome | Hypertension | Atrophy and striae, ecchymoses, acne, telangiectases | Due to overproduction of cortisol, commonly iatrogenic |
| Cutis laxa | Aortic dilation and rupture, pulmonary artery stenosis, right-sided heart failure | Looseness of the skin, premature aging appearance. Skin findings may be present from birth | Dominant (OMIM#123700), recessive (OMIM#219100), and X-linked (OMIM#304150) forms exist. Acquired forms also exist |
| Dermatomyositis | Cardiac arrhythmias, including atrial fibrillation/flutter, congestive heart failure, coronary artery disease | Gottron’s papules, heliotrope rash, photodistributed poikiloderma, nail fold capillary changes | Clinically evident cardiac involvement is a poor prognostic sign |
| Diabetes mellitus | Coronary artery and peripheral vascular disease | See Chapter 24 | — |
| Down syndrome | Septal defects, patent ductus arteriosus, tetralogy of Fallot | Palmoplantar hyperkeratosis, alopecia areata, cutis marmorata, fissured tongue | Characteristic dysmorphic features such as upslanting palpebral fissures, epicanthic folds, transverse palmar crease |
| Ehlers–Danlos syndrome | Aortic and pulmonary artery dilation, mitral and tricuspid valve prolapse, arterial rupture | Hyperelasticity of the skin, “cigarette paper” scars, ecchymoses | Cardiac diseases is limited to classic (OMIM#130000), hypermobility (OMIM#130020) and vascular (OMIM#130050) types |
| Endocarditis—bacterial or fungal | Vegetation and dysfunction of the valves, can lead to myocardial abscess and heart failure | Purpura, splinter hemorrhages (linear purpura in nail beds), Janeway lesions (nontender macules on palms and soles), Osler’s nodules (tender subcutaneous nodules usually on distal digits) | Fever. |
| Roth’s spots (retinal hemorrhages). | |||
| May simulate vasculitis | |||
| Exfoliative erythroderma | High-output cardiac failure | Exfoliative diffuse dermatitis | The eruption may be due to eczematous or atopic dermatitis, psoriasis, cutaneous T-cell lymphoma, drug eruption or other causes |
| Fabry’s disease | Mitral valve prolapse, conduction defects, congestive heart failure, myocardial infarction, cerebrovascular accidents | Angiokeratoma corporis diffusum, which may be an early feature and lead to diagnosis | Alpha-galactosidase A deficiency, X-linked (OMIM#301500), gene map locus Xq22. Renal failure is the usual cause of death |
| Hemochromatosis | Congestive heart failure, supraventricular arrhythmias | Generalized bronze hyperpigmentation | Diabetes, cirrhosis |
| Hyperlipidemias | Coronary artery disease | Xanthomas of all types | __ |
| Kawasaki disease (mucocutaneous lymph node syndrome) | Coronary artery aneurysms are the major complication, coronary arteritis, valvular insufficiency, pericardial effusion may also occur | Glossitis and cheilitis, acral edema, desquamative erythema of the perineum, diffuse morbilliform eruption, conjunctival injection | High fever, lymphadenopathy, treatment with intravenous immune globulin can be beneficial. |
| Infants <1 year old have highest risk of cardiac disease | |||
| Multiple lentigines (LEOPARD) syndrome | Electrocardiogram abnormalities, hypertrophic cardiomyopathy | Multiple lentigines | |
| Loeys–Dietz syndrome | Arterial tortuosity and aneurysm | Velvety or translucent skin in some patients | Described in 2005. Caused by heterozygous mutations in genes encoding transforming growth factor-β receptors 1 and 2; other features include hypertelorism, and bifid uvula or cleft palate. Shares features with Marfan’s syndrome and vascular-type Ehlers–Danlos syndrome, but Loeys–Dietz patients lack joint hypermobility and can often be successfully treated with vascular surgery |
| Lyme disease | Heart block, myopericarditis | Erythema migrans, borrelial lymphocytoma in some cases in Europe | Multisystem disease divided into stages: early localized, early disseminated, and late |
| Multicentric reticulohistiocytosis | Pericarditis, myocarditis, congestive heart failure | Erythematous nodules of the hands and occasionally the face | Deforming arthritis is frequent |
| Neonatal lupus erythematosus (NLE) | Congenital heart block | Transient, photosensitive, nonscarring lesions of lupus erythematosus (SCLE-like), predilection for face and periorbital skin. May be first noted after phototherapy for neonatal jaundice. Resolve with dyspigmentation | Presumed to be due to transplacental passage of autoantibodies, most commonly Ro (SS-A). May have transient cytopenias, hepatitis. Mothers may be asymptomatic. Hydroxychloroquine may help prevent against NLE in subsequent pregnancies, but data are limited |
| Neurofibromatosis | Hypertension due to pheochromocytoma | Café-au-lait macules, neurofibromas, axillary freckling | — |
| Pseudoxanthoma elasticum | Premature atherosclerotic vascular disease, hypertension | Yellow papules on intertriginous surfaces, redundant lax skin | Upper or lower gastrointestinal hemorrhage. Angioid streaks in the eye, uterine hemorrhage. Autosomal dominant and recessive variants (OMIM#264800 and #177850) |
| Psoriasis | Increased risk of myocardial infarction and coronary artery disease | Well-demarcated erythematous plaques with micaceous scale, often involving knees, elbows, umbilicus, gluteal cleft, scalp | Associated with metabolic syndrome, obesity, diabetes mellitus, hyperlipidemia, smoking |
| Relapsing polychondritis | Aortic insufficiency, dissecting aortic aneurysm, valvular disease, arrhythmias | Beefy, red ears or other cartilaginous areas. Late cauliflower-ear deformity or other cartilaginous destruction | Arthritis, tracheal collapse. Dapsone may be helpful. Corticosteroids and/or other immunosuppressive therapies may also be beneficial |
| Rheumatic fever | Pancarditis in the acute phase. Late manifestations include mitral and/or aortic valve dysfunction | Erythema marginatum, subcutaneous nodules | Rare in United States. Follows pharyngitis due to group A β-hemolytic streptococcal infection. Polyarthritis, chorea, fever |
| Sarcoidosis | Conduction defects, congestive heart failure | Granulomatous papules, nodules, and plaques, often with a predilection for scars or tattoos. Subcutaneous nodules may also occur. Nonspecific lesions such as erythema nodosum may occur; erythema nodosum associated with better prognosis | Pulmonary disease, hypercalcemia, lymphadenopathy, hepatic, neurologic, and ocular involvement. Cardiac involvement denotes a poor prognosis and can lead to sudden death. Electrocardiogram recommended at diagnosis in all patients, echocardiogram and 24-h Holter monitor in patients with palpitations |
| Scleroderma | Conduction defects, pulmonary hypertension, pericarditis | Cutaneous sclerosis, Raynaud’s phenomenon | Cardiac involvement denotes a poor prognosis |
| Syphilis | Aortitis, especially of the ascending aorta | Multiple potential skin lesions including genital chancre in primary disease, diffuse papulosquamous eruption involving the palms and soles, alopecia, condyloma lata, mucous patches in secondary disease | |
| Systemic lupus erythematosus | Verrucous endocarditis, pericarditis, coronary artery disease | Malar erythema, photosensitivity, lupus-specific skin lesions such as discoid and subacute cutaneous lupus | Anticardiolipin antibody may play a role in cardiac disease. Corticosteroid therapy may predispose to coronary artery disease |
| Tuberous sclerosis | Cardiac rhabdomyomas | Adenoma sebaceum, periungual and subungual fibromas, ash leaf macule, shagreen patch, fibrous forehead plaque | Renal and retinal hamartomas, CNS tumors, mental retardation, seizures, pulmonary lymphangioleiomyomatosis |
| Turner syndrome (gonadal dysgenesis) | Aortic coarctation | Alopecia of frontal scalp, webbed neck, short stature, koilonychia, numerous nevi | Despite multiple nevi, melanoma risk appears low. |
| Increased risk of thyroid disease. | |||
| May also be associated with increased incidence of alopecia areata and halo nevi | |||
| Thyroid disorders | Arrhythmias, palpitations, cardiomyopathy | Myxedema, ocular proptosis in Grave’s disease, pruritus | |
| Vasculitis | Coronary artery vasculitis | Palpable purpura, nodules, livedo reticularis, ulcerations | Arthritis, gastrointestinal colic or bleeding, cardiac involvement is uncommon |
| Werner’s syndrome | Premature atherosclerosis | Premature graying, alopecia, sclerodermoid changes, loss of subcutaneous fat, ankle ulcerations | Myocardial infarction is usually responsible for death by the fifth decade. Autosomal recessive (OMIM#277700, gene map locus 8p12-p11.2). Other features include cataracts, malignancy |
TABLE 37-2
Cutaneous Findings Observed in Association with Primary Cardiac Abnormalities
| Cutaneous Changes | Cardiac Disorders |
|---|---|
| Diagonal earlobe crease, androgenetic alopecia, thoracic hairiness | Coronary artery disease/atherosclerosis |
| Dependent edema, ascites | Congestive heart failure |
| Increased risk of skin cancers (some data suggest higher risk than renal transplant) Increased risk of herpes simplex and varicella zoster |
Cardiac transplantation from any cause |
| Stasis dermatitis, peripheral edema, lipodermatosclerosis, lower leg ulcerations (often adjacent to the medial malleolus) | Hypertension—venous |
| Palpable purpura, livedo reticularis, ulcerations | Embolic phenomenon (i.e., due to cholesterol emboli [often follows an invasive procedure, such as catheterization or angiography], left atrial myxoma, subacute bacterial endocarditis) |
| Osler’s nodes, Janeway’s lesions, petechiae, purpuric pustules, splinter hemorrhages, leukocytoclastic vasculitis | Endocarditis—bacterial, fungal, or vegetative |
| Xanthelasma, plane xanthomas, tendon xanthomas | Hyperlipidemia |
| Eruptive xanthomas, tuberous xanthomas | Hypertriglyceridemia |
| Cyanosis | Cyanotic heart disease, circulating methemoglobin or sulfhemoglobin, arterial or venous obstruction, arteriolar vasoconstriction (i.e., Raynaud’s phenomenon) |
| Clubbing | Cyanotic heart disease, pulmonary disease may also be associated with clubbing |
TABLE 37-3
Common Cutaneous Side Effects of Cardiac Medications
| Cutaneous Changes | Medication/Procedure |
|---|---|
| Photosensitivity, resultant slate blue-gray pigmentation | Amiodarone |
| Angioedema, drug-induced subacute cutaneous lupus erythematosus | ACE inhibitors |
| Flare of psoriasis, worsening of Raynaud’s | β-Adrenergic blockers |
| Hypertrichosis | Minoxidil |
| Petechiae (thrombocytopenia), photosensitivity | Quinidine |
| Drug-induced systemic lupus erythematosus | Procainamide hydrochloride |
| Photosensitivity, drug-induced subacute cutaneous lupus erythematosus | Thiazide diuretics, calcium channel blockers, ACE inhibitors |
| Gynecomastia | Spironolactone |
| Xerosis | Statins |
| Pedal edema | Calcium channel blockers |
| Petechiae from heparin-induced thrombocytopenia, retiform purpura or noninflammatory necrosis from heparin-induced necrosis | Heparin |
| Painful, well-demarcated erythema that rapidly becomes necrotic due to warfarin necrosis, more common in fatty areas | Warfarin |
| Radiation burns | Prolonged angioplasty and radiation exposure |
Antiphospholipid Antibody Syndrome/Antiphospholipid Syndrome
Antiphospholipid antibodies (i.e., anticardiolipin, lupus anticoagulant, and anti-β2-glycoprotein-1) are associated with antiphospholipid syndrome (APS), a multisystem disorder that can affect both the heart and the skin. The disorder may be primary or secondary to an associated autoimmune disease, the most common of which is systemic lupus erythematosus. Symptoms result from antibody-driven arterial or venous thrombogenesis, and most commonly include cutaneous findings, deep vein thrombosis, pulmonary embolism, cerebrovascular accidents, and/or recurrent fetal loss. Thrombocytopenia is often seen and, importantly, does not influence the risk of thrombosis. The most common skin finding is livedo reticularis or racemosa ( Fig. 37-1 ). Leg ulcerations, retiform purpura, livedoid vasculopathy, or superficial thrombophlebitis may also occur. Myocardial infarction and cardiac valvular disease, including nonbacterial vegetations, have been described, potentially predisposing the patient to bacterial endocarditis. Cutaneous manifestations are often the presenting feature of APS, placing the dermatologist in an important role for diagnosing this potentially morbid condition. The presence of livedo racemosa in particular in patients with APS has been associated with an increased risk for arterial thrombosis, cerebral thrombosis, and heart valve abnormalities, and should alert dermatologists to these potential complications. Recently updated diagnostic criteria require antiphospholipid antibody positivity on two serologic tests separated by 12 weeks, along with evidence of objectively confirmed thrombosis or pregnancy morbidity. Therapy is dependent upon the history of thromboembolic events, and includes anticoagulants and platelet inhibitors, as well as approaches aimed at lowering antibody levels. Hydroxychloroquine may also help prevent thrombosis, particularly in those with systemic lupus erythematosus, although a convincing body of evidence is lacking. Whether therapy has an effect on cardiac involvement remains unknown, although low-dose aspirin or anticoagulation is frequently recommended in this setting.
Carcinoid Syndrome
Carcinoid syndrome refers to a constellation of symptoms caused by the release of neuroendocrine vasoactive substances, primarily serotonin, from a carcinoid tumor. Paroxysmal flushing of the face, neck, and chest, along with intermittent diarrhea, bronchospasm, and hypotension, are the characteristic findings. Symptoms typically occur with liver metastasis or with tumors originating in the stomach or lung. Telangiectases and sclerodermoid changes may occur with continued disease. Right-sided heart failure, tricuspid insufficiency, and pulmonic stenosis are the most common cardiac manifestations. Cardiac involvement is present in approximately 50% of symptomatic patients and contributes to a poor prognosis, emphasizing the need for early diagnosis and intervention. Dermatologists may facilitate diagnosis by suspecting carcinoid syndrome in patients with unexplained paroxysmal flushing. Other causes of similar flushing include physiologic events, pheochromocytoma, VIPoma, systemic mast cell disease, rosacea, alcohol, and certain medications (i.e., niacin).
Malignant Atrophic Papulosis (Degos Disease)
Malignant atrophic papulosis is a rare, idiopathic arteriopathy characterized by pale-red papules with central necrosis that evolve into atrophic, ivory-porcelain white scars with telangiectatic rims. Similar lesions may occur in the gastrointestinal tract or central nervous system (CNS), and, less commonly, the ophthalmologic, pulmonary, or cardiovascular systems. Pericarditis and/or pericardial effusions are the typical cardiac manifestations. Systemic involvement may result in death from ischemic complications or uncontrolled hemorrhage; intestinal perforation is the most common cause of death. Skin lesions may precede systemic involvement by months to years, placing the dermatologist in a unique role to identify early systemic disease.
Earlobe Creases
An increased prevalence of the diagonal earlobe crease occurs with age. The cutaneous change is characterized by a crease extending from the tragus to the posterior pinna, involving at least one-third of the distance. While data have been somewhat conflicting, most studies correlate a diagonal earlobe crease with an increased risk of coronary artery disease (CAD), and limited data have linked the diagonal earlobe crease to carotid artery atherosclerosis. Moreover, incorporating the diagonal earlobe crease into a CAD risk algorithm (the Diamond–Forrester algorithm) was recently shown to improve predictive ability for CAD. As such, thorough cardiac risk assessment has been suggested in patients with a diagonal earlobe crease. Two hypotheses link the diagonal earlobe crease to CAD: (1) end arteries with little collateral circulation supply both sites; and (2) a generalized loss of elastin and elastic fibers produces both conditions.
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