What is the appropriate evaluation and management of a patient with forefoot or midfoot pain, potential risk factors for vascular disease, and no mention of Peripheral Arterial Disease (PAD) as a cause in UpToDate?

PAD as a Cause of Forefoot or Midfoot Pain

While UpToDate may not explicitly list PAD as a cause of forefoot or midfoot pain, peripheral arterial disease absolutely can and does cause pain in these locations, particularly in the context of critical limb-threatening ischemia (CLTI), and must be systematically evaluated in any patient with forefoot/midfoot pain who has vascular risk factors. 1

Why PAD Must Be Considered for Forefoot/Midfoot Pain

The 2024 ACC/AHA guidelines explicitly state that patients at increased risk for PAD should undergo comprehensive assessment for "lower extremity rest pain" and "lower extremity wounds or other ischemic skin changes"—both of which commonly manifest in the forefoot and midfoot regions. 1 Critical limb ischemia characteristically presents with ischemic rest pain localized to the lower leg or foot, with pain associated with the recumbent position. 1

The clinical reality is that distal ischemia from PAD frequently causes forefoot and midfoot pain through two mechanisms:

• Ischemic rest pain: Pain at rest localized to the foot, typically worse when supine and relieved by dependency (hanging the leg over the bed edge), indicating inadequate perfusion even at rest 1, 2
• Tissue ischemia with or without ulceration: Nonhealing wounds, gangrene, or pre-ulcerative ischemic changes in the forefoot/midfoot causing pain out of proportion to examination findings 1, 2

Structured Evaluation Algorithm

Step 1: Identify High-Risk Patients Requiring PAD Assessment

Evaluate for PAD in any patient with forefoot/midfoot pain who meets these criteria 1, 3:

• Age ≥65 years
• Age 50-64 years with atherosclerosis risk factors (diabetes, smoking history, hyperlipidemia, hypertension, chronic kidney disease)
• Age <50 years with diabetes plus one additional atherosclerosis risk factor
• Known atherosclerotic disease in another vascular bed (coronary, carotid, renal, mesenteric)

Step 2: Perform Targeted Vascular History

Document these specific features 1, 2:

• Pain character: Aching, burning, throbbing (ischemic) vs. sharp, shooting, tingling (neuropathic)
• Temporal pattern: Pain worse when supine and relieved by dependency strongly suggests critical limb ischemia 1, 2
• Exertional symptoms: Any walking impairment, claudication distance, time to relief with rest (typical claudication resolves in <10 minutes) 1
• Wound history: Any poorly healing or nonhealing lower extremity wounds 1
• Functional impact: Pain disturbing sleep is common in critical limb ischemia 2

Step 3: Conduct Comprehensive Vascular Examination

The 2024 ACC/AHA guidelines mandate these specific examination components 1:

• Pulse palpation: Assess and grade femoral, popliteal, dorsalis pedis, and posterior tibial pulses (0=absent, 1=diminished, 2=normal, 3=bounding) 1, 2
• Foot inspection: Remove shoes and socks to assess for color changes (pallor, rubor), temperature asymmetry, skin integrity, ulcerations, gangrene, distal hair loss, trophic skin changes, hypertrophic nails 1, 2
• Elevation pallor/dependent rubor: Elevation of the leg causing pallor and dependency causing rubor indicates severe ischemia 1
• Auscultation: Listen for femoral bruits 1, 2

Step 4: Obtain Diagnostic Testing

Any abnormal vascular history or physical examination finding requires immediate ABI testing 1, 3:

• Resting ABI: ABI ≤0.90 confirms PAD; ABI <0.40 or absolute ankle pressure ≤50 mmHg indicates critical limb ischemia requiring urgent vascular referral 1, 3, 2
• Toe-brachial index (TBI): Use when ABI >1.40 (suggesting noncompressible vessels from medial arterial calcification, common in diabetes); TBI <0.70 indicates PAD 1, 3
• Transcutaneous oxygen pressure (TcPO2): TcPO2 <30 mmHg indicates critical ischemia; values >50 mmHg generally predict wound healing capacity 1, 2

Step 5: Risk Stratification and Urgent Referral Criteria

Immediate vascular surgery referral is required for 1, 2:

• ABI <0.40 or absolute ankle pressure ≤50 mmHg
• Toe pressure <30 mmHg
• TcPO2 <30 mmHg
• Any forefoot/midfoot gangrene or nonhealing ulceration with abnormal vascular studies
• Ischemic rest pain with abnormal vascular studies

These findings represent critical limb-threatening ischemia, which leads to major amputation within 6 months if untreated. 2

Common Clinical Pitfalls

Do not assume bilateral presentation excludes vascular disease—bilateral PAD is common, and critical limb ischemia can present bilaterally. 2 The 2024 guidelines explicitly note that 40% of PAD patients have no leg symptoms at all, and only 10% present with classic claudication. 4, 1

Do not delay vascular assessment in diabetic patients with neuropathy—presentation may be subtle with absent pain despite severe ischemia due to sensory neuropathy masking ischemic pain. 2 These patients require TBI or TcPO2 measurement as ABI may be falsely elevated. 1, 3

Recognize that absence of palpable pulses is not required for diagnosis—diminished pulses (grade 1) with forefoot/midfoot pain still warrant urgent evaluation. 2 The physical examination findings must be confirmed with diagnostic testing. 1

Never miss infection in PAD patients—assess for local pain/tenderness, periwound erythema, edema, induration, discharge, or foul odor, as untreated infection with PAD confers nearly 3-fold higher amputation risk and requires immediate systemic antibiotics. 2

Management Framework Once PAD is Confirmed

If vascular studies confirm PAD as the cause of forefoot/midfoot pain 1, 2, 5:

• Critical limb ischemia (ABI <0.4): Urgent revascularization evaluation; narcotic analgesia is typically required as pain relief is temporary without revascularization 2
• Moderate PAD (ABI 0.6-0.9): Aggressive cardiovascular risk reduction with high-intensity statin (LDL <55 mg/dL), antiplatelet therapy, blood pressure control to <140/90 mmHg (or <130/80 mmHg if diabetic), smoking cessation, and supervised exercise therapy 1, 2, 5
• Diabetic patients: Daily foot inspection, appropriate footwear, topical moisturizing creams, chiropody/podiatric care, HbA1c <7% 1, 2

The evidence is unequivocal: PAD is a legitimate and important cause of forefoot and midfoot pain that demands systematic evaluation in at-risk patients, regardless of whether specific resources mention it explicitly in differential diagnosis lists.