What is the diagnosis and treatment for a patient with bilateral skin tightness of the feet, potentially indicating an autoimmune condition such as scleroderma?

Bilateral Skin Tightness of the Feet: Diagnosis and Management

Diagnostic Considerations

Bilateral skin tightness isolated to the feet is an atypical presentation for systemic sclerosis and should prompt consideration of scleroderma mimics rather than classic systemic sclerosis. 1, 2

Key Distinguishing Features to Assess

• Absence of Raynaud's phenomenon, nailfold capillaroscopic abnormalities, or scleroderma-specific autoantibodies strongly suggests a scleroderma mimic rather than true systemic sclerosis 2
• Systemic sclerosis typically presents with symmetrical skin involvement that is NOT isolated to the feet alone—limited cutaneous SSc affects skin distal to elbows/knees (including hands prominently), while diffuse cutaneous SSc involves proximal areas and trunk 3, 4
• True SSc presents with Raynaud's phenomenon in >95% of cases, which would affect the hands and feet together, not feet in isolation 4

Differential Diagnosis for Isolated Bilateral Foot Skin Tightness

The following conditions should be prioritized over systemic sclerosis:

• Diabetic cheiroarthropathy (stiff-hand syndrome) can affect feet and presents with skin thickening without Raynaud's or SSc-specific antibodies 1, 5
• Scleredema causes skin thickening that can be bilateral and symmetric 1, 5
• Eosinophilic fasciitis is the most common mimic when Raynaud's, capillaroscopic changes, and antinuclear antibodies are absent 2
• Scleromyxedema presents with skin thickening and requires different treatment than SSc 1, 5
• Nephrogenic systemic fibrosis (in patients with renal disease and gadolinium exposure) 1, 2

Diagnostic Workup

Essential Laboratory Testing

• SSc-specific autoantibodies: anti-topoisomerase 1 (Scl-70), anti-centromere, anti-RNA polymerase III—if negative, strongly favors a scleroderma mimic 4, 2
• Antinuclear antibodies (ANA): absence makes SSc unlikely 2
• Complete blood count with eosinophil count: elevated eosinophils suggest eosinophilic fasciitis 2
• Serum protein electrophoresis: to detect paraproteins associated with scleromyxedema 2
• Fasting glucose and HbA1c: to evaluate for diabetes-related skin changes 1

Imaging and Specialized Testing

• Nailfold capillaroscopy: abnormalities are expected in SSc but absent in mimics 2
• Skin biopsy extending to fascia: essential to differentiate between conditions—look for eosinophil infiltration (eosinophilic fasciitis), increased mucin (scleromyxedema), or amyloid deposition 2
• MRI of affected areas: can assess fascial involvement in eosinophilic fasciitis 3

Treatment Approach

If Systemic Sclerosis is Confirmed (Unlikely with Isolated Foot Involvement)

For limited cutaneous SSc with skin involvement, mycophenolate mofetil is the most common first-line treatment, with methotrexate as an alternative 3

• Mycophenolate mofetil: 500-1000 mg/m² for pediatric patients 3 or standard adult dosing
• Methotrexate: commonly used as first-line or second-line after MMF 3
• Maintain treatment for at least 12 months before tapering once clinical remission is achieved 3

If Eosinophilic Fasciitis is Diagnosed

• Corticosteroids are the primary treatment 6
• Methotrexate can be used as a steroid-sparing agent 6

If Localized Scleroderma/Morphea is Diagnosed

• Methotrexate with corticosteroids is first-line for active disease 3
• Topical treatments (imiquimod) for isolated, non-progressive lesions 3
• UVA1 phototherapy as an alternative option 3

If Diabetic Cheiroarthropathy is Diagnosed

• Optimize glycemic control as primary intervention 1
• Physical therapy for joint mobility 5

Critical Pitfalls to Avoid

• Do not assume systemic sclerosis based solely on skin tightness—the absence of Raynaud's phenomenon, hand involvement, and SSc-specific antibodies makes this diagnosis unlikely 2
• Do not delay skin biopsy—this is essential for definitive diagnosis when clinical features are atypical 2
• Avoid treating empirically with immunosuppression before establishing the correct diagnosis, as different conditions require vastly different therapeutic approaches 2, 5
• Screen for underlying diabetes, renal disease, and paraproteinemias before attributing symptoms to autoimmune disease 1, 2