Lower Extremity Discoloration: Causes and Clinical Approach

Primary Atherosclerotic Causes

The American College of Cardiology recommends that lower extremity discoloration should prompt immediate evaluation with ankle-brachial index (ABI) testing, particularly in patients with smoking history, diabetes, limited mobility, or age >50 years with risk factors 1, 2
Atherosclerosis is the major cause of lower extremity peripheral arterial disease (PAD), with risk factors including cigarette smoking, diabetes, dyslipidemia, hypertension, and hyperhomocysteinemia 1, 2, 3
Smoking is exceptionally powerful, affecting >80% of PAD patients and being 2-3 times more likely to cause PAD than coronary artery disease 3
Diabetes increases claudication risk by 3.5-fold in men and 8.6-fold in women, with diabetic PAD patients being 7-15 times more likely to require amputation 3

Trophic skin changes, such as thin, shiny, atrophic skin, are a manifestation of severe PAD 1, 2
Distal hair loss on the lower legs and feet is a sign of severe PAD 1, 2
Hypertrophic nails, or thickened, dystrophic toenails, are a manifestation of severe PAD 1, 2
Color changes, such as pallor with elevation and rubor with dependency, are a sign of severe PAD 1
Temperature changes, such as cool or cold extremities, are a manifestation of severe PAD 1
Presence of ulcerations, particularly at pressure points, is a sign of severe PAD 1, 2

The American Heart Association suggests that PAD has diverse etiologies beyond atherosclerosis that must be considered for accurate diagnosis and treatment 1, 4, 2
Thromboembolic disease, or acute arterial occlusion, is a non-atherosclerotic cause of PAD 4, 2, 5
Inflammatory vasculitis, such as Buerger disease in young smokers, is a non-atherosclerotic cause of PAD 5
Aneurysmal disease, such as atherosclerotic, hereditary, or trauma-related aneurysms, is a non-atherosclerotic cause of PAD 4, 2
Fibromuscular dysplasia, particularly in renal arteries, is a non-atherosclerotic cause of PAD 5, 4
Popliteal artery entrapment syndrome, which occurs in young adults with exercise-induced symptoms, is a non-atherosclerotic cause of PAD 5
Adventitial cysts or entrapment syndromes are non-atherosclerotic causes of PAD 4, 2
Trauma or dissection is a non-atherosclerotic cause of PAD 5, 4

The American College of Cardiology recommends that patients with high-risk features, such as age ≥50 years with atherosclerosis risk factors or age ≥70 years, should be evaluated for PAD 1, 4, 2
Smoking history is a high-risk feature for PAD 1, 2, 3
Diabetes mellitus is a high-risk feature for PAD 1, 2, 3
Limited mobility is a high-risk feature for both arterial and venous disease 6
Assessing pulse quality at femoral, popliteal, dorsalis pedis, and posterior tibial arteries is an important part of the diagnostic algorithm for PAD 1
Removing shoes and socks to inspect feet for color, temperature, skin integrity, and ulcerations is an important part of the diagnostic algorithm for PAD 1, 2
Looking for bilateral vs. unilateral changes can help differentiate between systemic/arterial causes and venous thrombosis or localized pathology 6
Assessing for edema, such as pitting edema with hyperpigmentation, can help diagnose venous insufficiency 6
Exercise ABI testing is useful when resting ABI is normal but symptoms suggest PAD 4, 2
Toe-brachial index or pulse volume recording should be used when ABI >1.30, which suggests arterial calcification, common in diabetes 4, 2, 3

Approximately 40% of PAD patients have no leg symptoms, and two-thirds of those with lower extremity disease are asymptomatic, highlighting the importance of screening high-risk patients 4, 2
Do not wait for symptoms to screen high-risk patients for PAD 4, 2
Arterial calcification in diabetes falsely elevates ABI, requiring alternative diagnostic approaches like toe-brachial index 3
Neuropathy masks ischemic pain, increasing the risk of foot ulceration and limb-threatening complications in diabetic patients 3
PAD patients have increased risk for MI, stroke, and death due to coexistent coronary and cerebrovascular disease 1, 4, 2
Cardiovascular ischemic events are more frequent than limb ischemic events in PAD cohorts 1, 2
All PAD patients require aggressive cardiovascular risk modification, including antiplatelet therapy, statins, smoking cessation, and blood pressure/diabetes control 1, 4, 2