What are the side effects of high-dose steroid (corticosteroid) therapy?

Side Effects of High-Dose Corticosteroid Therapy

High-dose corticosteroid therapy commonly causes significant side effects including cosmetic changes, metabolic disturbances, psychiatric symptoms, and increased infection risk, with 80% of patients experiencing adverse effects after 2 years of treatment. 1

Common Side Effects by Body System

Cosmetic and Musculoskeletal Effects

• Cosmetic changes (80% after 2 years) 1:

  • Facial rounding (moon face)
  • Dorsal hump formation
  • Striae
  • Weight gain
  • Acne
  • Alopecia
  • Facial hirsutism

• Musculoskeletal effects:

  • Osteoporosis and vertebral compression (27% of patients who discontinue due to side effects) 1
  • Decreased bone formation and increased bone resorption 2
  • Growth inhibition in pediatric patients 2
  • Muscle weakness 1, 2

Metabolic and Endocrine Effects

• Glucose metabolism:

  • Hyperglycemia (most common adverse effect, affecting 17.6% of patients on high-dose therapy) 3
  • Brittle diabetes (20% of patients who discontinue due to side effects) 1

• Other metabolic effects:

  • Fluid retention/bloating (most commonly reported symptom) 4
  • Hypertension 1, 2
  • Increased appetite 1

Neuropsychiatric Effects

• Psychiatric manifestations 2:

  • Euphoria
  • Insomnia (chief side effect in short-term treatment <2 weeks) 4
  • Mood swings
  • Personality changes
  • Severe depression
  • Psychosis (severe side effect with prolonged therapy) 1

• Neurological effects:

  • Acute myopathy (especially with neuromuscular disorders) 2
  • Increased seizure threshold when used with certain medications 2

Gastrointestinal Effects

• Gastric irritation 1
• Peptic ulcers (serious complication with high-dose therapy) 1
• Gastrointestinal perforations 1

Immune System Effects

• Increased susceptibility to infections 1, 2
• Lower resistance to infection 1
• Reactivation of latent infections (tuberculosis, hepatitis B) 5
• Risk of opportunistic infections (Pneumocystis jirovecii pneumonia) 5

Ophthalmic Effects

• Elevated intraocular pressure 2
• Cataracts or glaucoma with prolonged use 1
• Blurred vision 1

Risk Factors for Severe Side Effects

1. Dose and duration related factors:

   • Severe complications typically occur after >18 months of therapy 1
   • Doses above 20 mg daily of prednisone for prolonged periods 1
   • High-dose therapy (≥30 mg prednisone equivalent) for >4 weeks 5
   • Moderate doses (≥15 to <30 mg) for ≥8 weeks 5

2. Patient-specific factors:

   • Pre-existing cirrhosis (25% vs 8% complication rate) 1
   • Pre-existing bone or joint problems 1
   • Diabetes mellitus 2
   • Elderly patients (increased risk of diabetes, fluid retention, hypertension) 2

Prevention and Monitoring

Prevention Strategies

• Use the minimum effective dose for the shortest duration possible 2, 6
• Single morning dosing to minimize adrenal suppression 6
• Calcium and vitamin D supplementation for bone protection 2
• Consider bisphosphonate therapy for osteoporosis prevention 2
• Screening for tuberculosis, hepatitis B, and other infections before starting therapy 5
• Prophylaxis against Pneumocystis jirovecii pneumonia for high-risk patients 5

Monitoring Recommendations

• Regular blood pressure monitoring 2
• Blood glucose monitoring, especially in diabetic patients 2
• Bone mineral density testing 2
• Intraocular pressure monitoring if therapy continues >6 weeks 2
• Growth monitoring in pediatric patients 2
• Regular skin examinations for patients on long-term therapy 1

Special Considerations

Tapering

• Never discontinue high-dose corticosteroids abruptly 2
• Gradual tapering is essential to prevent adrenal insufficiency 2
• Withdrawal symptoms may include myalgia, arthralgia, and malaise 2

Drug Interactions

• Potassium-depleting agents (risk of hypokalemia) 2
• Anticoagulants (altered response to warfarin) 2
• Antidiabetic agents (may require dose adjustment) 2
• Fluoroquinolones (increased risk of tendon rupture) 2

Pregnancy and Nursing

• Potential risk to nursing infants - consider discontinuing nursing or medication 2
• Fetal risk includes prematurity, with infant mortality related to degree of prematurity 1

High-dose corticosteroid therapy requires careful patient selection, thorough education about risks, appropriate preventive measures, and regular monitoring to minimize potentially serious adverse effects while maximizing therapeutic benefits.