Can prednisone or Imuran (azathioprine) cause reddish discoloration of the feet?

Can Prednisone or Imuran Cause Reddish Feet?

Neither prednisone nor Imuran (azathioprine) are recognized causes of isolated reddish discoloration of the feet in clinical practice or medical literature. The available evidence does not support a direct causal relationship between these medications and reddish feet as a primary adverse effect.

Evidence Review

Prednisone Side Effects

The documented dermatological side effects of prednisone are well-characterized and do not include reddish discoloration of the feet 1:

• Common cutaneous effects include cosmetic changes (weight gain, facial rounding, hirsutism), skin thinning, easy bruising, and impaired wound healing 1
• Systemic corticosteroid effects encompass diabetes, hypertension, osteoporosis, and emotional instability, but not localized erythema of the feet 1
• Topical corticosteroids can cause local skin atrophy and suppression of cell proliferation, but systemic prednisone does not typically cause localized redness 2

Azathioprine (Imuran) Side Effects

Azathioprine has a distinct side effect profile that does not include reddish feet 1:

• Early idiosyncratic reactions (occurring in ~5% of patients) manifest as arthralgias, fever, skin rash, or pancreatitis within days to weeks, requiring immediate discontinuation 1
• Common adverse effects include gastrointestinal disturbance, hepatotoxicity (documented in up to 25% of patients), and myelosuppression 1
• The skin rash associated with azathioprine hypersensitivity is generalized, not localized to the feet 1

Alternative Explanations to Consider

Chemotherapy-Induced Hand-Foot Syndrome

If the patient is on anticancer agents, palmar-plantar erythrodysesthesia (hand-foot syndrome) presents with redness, swelling, and tingling of palms and soles 1:

• Associated with cytotoxic chemotherapy agents (5-FU, capecitabine, doxorubicin) and VEGFR inhibitors (sorafenib, sunitinib) 1
• Develops within days to weeks after therapy initiation 1
• This is not caused by prednisone or azathioprine 1

Vasculitis or Underlying Disease

Reddish feet may represent the underlying condition being treated rather than medication side effects 3:

• Rheumatoid vasculitis can cause cutaneous manifestations including redness 3
• The combination of prednisone plus azathioprine is actually used to treat vasculitis-related skin changes, not cause them 3

Other Differential Considerations

• Infection: Secondary bacterial or fungal infections, particularly in immunosuppressed patients 1, 4
• Peripheral vascular disease: Erythema from venous insufficiency or arterial disease
• Contact dermatitis: Reaction to footwear or topical products
• Drug interactions: If the patient is on multiple medications, consider other agents

Clinical Approach

Immediate assessment should include 1, 4:

• Examination for warmth, tenderness, swelling, or discharge suggesting infection
• Assessment for systemic signs (fever, malaise) that might indicate drug hypersensitivity 1
• Review of all concurrent medications, not just prednisone and azathioprine
• Evaluation for signs of the underlying disease process

If infection is suspected, obtain bacterial/viral/fungal cultures before initiating antimicrobial therapy 1, 4.

If drug hypersensitivity is considered, azathioprine idiosyncratic reactions typically present with generalized rash, fever, and arthralgias—not isolated foot erythema 1.

Clinical Caveat

The absence of documented association between these medications and reddish feet in the medical literature strongly suggests an alternative etiology. Do not discontinue immunosuppressive therapy based solely on this symptom without thorough evaluation, as the underlying disease may pose greater risk than the medications themselves 3, 5, 6.