What is the cause and treatment of bilateral lower extremity swelling, worse on the left, without pitting edema, in a patient with uncontrolled diabetes (A1c 8.0), normal renal function (GFR 94), and a history of prolonged standing, 5 weeks after ruling out deep vein thrombosis (DVT) with ultrasound?

Non-Pitting Bilateral Lower Extremity Swelling in a Diabetic Patient

The most likely diagnosis is diabetic myonecrosis or early Charcot neuro-osteoarthropathy, and treatment should focus on strict glycemic control, rest, analgesia, and urgent MRI to differentiate between these conditions and guide management.

Differential Diagnosis Based on Clinical Features

Most Likely: Diabetic Myonecrosis

• Diabetic myonecrosis presents with acute non-traumatic swelling and pain in the lower extremity, typically in patients with long-standing poorly controlled diabetes (A1c 11-15% in reported cases), which can mimic DVT 1, 2
• The absence of pitting edema is characteristic, as this condition involves muscle tissue rather than interstitial fluid accumulation 1, 2
• Patients typically have no fever, normal white blood cell count, mildly increased ESR, and elevated CRP in 50% of cases 2
• The unilateral predominance (left > right) is typical, as diabetic myonecrosis usually affects one extremity more than the other 1, 2
• Normal D-dimer levels and negative ultrasound Doppler help rule out DVT, which you have already done 2

Alternative Consideration: Charcot Neuro-Osteoarthropathy

• In diabetic patients with peripheral neuropathy presenting with unilateral red, warm, swollen foot with intact skin, always suspect active Charcot neuro-osteoarthropathy after excluding infection, gout, and DVT 3
• The condition presents with temperature asymmetry >2°C between limbs suggesting active inflammatory process 3, 4
• Charcot typically shows a "flattened" midfoot appearance on imaging and requires immobilization with total contact casting 5

Less Likely: Chronic Venous Insufficiency

• While prolonged standing is a risk factor, chronic venous insufficiency typically presents with pitting edema, aching, heaviness, cramping that worsens at day's end and improves with leg elevation 4
• The absence of pitting edema makes this diagnosis less likely 4

Immediate Diagnostic Workup

Essential Imaging

• MRI of both lower extremities is the diagnostic test of choice to differentiate diabetic myonecrosis from other conditions 1, 2
• MRI in diabetic myonecrosis shows a focus of non-enhancement in the gastrocnemius or other muscles along with increased enhancement of the rest of the muscle 1
• The typical MRI findings include lack of fascial enhancement or well-defined rim-enhancing collections that would be seen in necrotizing fasciitis and pyomyositis 2
• If Charcot is suspected, MRI demonstrates diffuse bone marrow edema within the navicular, cuneiforms, cuboid and metatarsal bases 5

Laboratory Evaluation

• Check CPK levels (typically normal in diabetic myonecrosis), ESR (mildly elevated), and CRP (elevated in 50% of cases) 2
• Verify inflammatory markers including white blood cell count (typically normal in diabetic myonecrosis) 2
• The patient's A1c of 8.0% indicates suboptimal glycemic control, which is a key risk factor 1, 2

Vascular Assessment

• Assess for arterial ischemia and venous insufficiency as recommended for all diabetic foot evaluations 5
• Determine ankle-brachial index (ABI) using sphygmomanometers and hand-held Doppler 5
• If ABI is >1.40 (suggesting arterial calcification common in diabetes), obtain toe-brachial index (TBI) or duplex ultrasound 5

Treatment Algorithm

For Diabetic Myonecrosis (Most Likely)

• Strict glycemic control is the cornerstone of treatment 1, 2
• Bed rest and analgesics for symptom management 2
• Antiplatelet therapy (aspirin) should be initiated 1
• NSAIDs for pain and inflammation control 1
• The clinical course is usually self-limiting with supportive medical therapy, with complete resolution typically occurring within months 2
• Avoid muscle biopsy or other invasive procedures, as the diagnosis can be made clinically and with MRI 2

For Charcot Neuro-Osteoarthropathy (If Confirmed)

• Immediate immobilization with total contact casting or DH Offloading Walker (removable knee-high offloading device) 5
• Complete non-weight bearing or protected weight bearing until acute phase resolves 5
• Serial imaging to monitor for resolution of bone marrow edema 5
• Optimal glycemic control to improve foot outcomes 5

Glycemic Control Optimization

• Target A1c reduction from current 8.0% to <7.0% through intensification of diabetes management 5
• Consider consultation with endocrinology for insulin therapy optimization 5
• Patient and family education on diabetes management 5

Critical Pitfalls to Avoid

• Do not perform muscle biopsy in suspected diabetic myonecrosis, as it can lead to complications and the diagnosis can be made non-invasively 2
• Do not treat empirically for cellulitis or necrotizing fasciitis without proper imaging, as diabetic myonecrosis lacks the radiologic signs of fascial enhancement seen in these conditions 2
• Do not assume venous insufficiency based solely on prolonged standing history when pitting edema is absent 4
• Do not delay MRI if symptoms persist or worsen, as this is essential for definitive diagnosis 1, 2
• In diabetic patients with neuropathy, always consider Charcot arthropathy when unilateral warmth and swelling are present 3

Follow-Up and Monitoring

• Regular reassessment of swelling and associated symptoms 6
• Monitor inflammatory markers (ESR, CRP) to assess treatment response 6
• Serial MRI if symptoms do not improve within 4-6 weeks 2
• Multidisciplinary approach involving endocrinology, podiatry, and potentially vascular surgery 5
• If diabetic myonecrosis is confirmed, counsel patient that recurrence in the contralateral limb can occur 2