What are the side effects of prednisone (corticosteroid) and how can they be managed?

Prednisone Side Effects and Management

Prednisone causes numerous adverse effects affecting virtually every organ system, with up to 80% of patients experiencing side effects after two years of therapy, and severe effects occurring mainly at doses >20 mg/day for more than 18 months. 1, 2

Common Short-Term Side Effects (First Few Weeks to Months)

Metabolic and Physical Changes

• Weight gain, increased appetite, and fluid retention are among the most common early effects, often appearing within the first few weeks 1, 2, 3
• Facial rounding (moon face) can begin developing even during short-term use 1, 2
• Insomnia and sleep disturbances occur in >30% of patients and represent the chief complaint in those receiving short-term treatment (<2 weeks) 2, 4
• Hyperglycemia and worsening of diabetes are common, particularly requiring blood glucose monitoring 2, 3

Neuropsychiatric Effects

• Mood elevations (hypomania/mania) are more common than depression during prednisone therapy, with statistically significant increases in manic symptoms observed even at modest doses 5
• Emotional instability, euphoria, restlessness, and nervousness occur frequently 2, 3
• Patients with pre-existing depression may actually show improvement rather than worsening during prednisone therapy 5
• Important caveat: Patients with post-traumatic stress disorder may experience increases in depression and traumatic memories during therapy 5

Gastrointestinal Effects

• Gastric irritation and increased risk of peptic ulcer formation 3, 4
• Increased appetite leading to weight gain 2, 3

Cardiovascular

• Hypertension can develop or worsen quickly, even during short courses 2, 3
• Fluid retention and edema in susceptible patients 3

Long-Term Side Effects (Months to Years)

Musculoskeletal Complications

• Osteoporosis and increased fracture risk are among the most serious complications, with vertebral compression fractures occurring in up to 27% of patients 2, 3
• Aseptic necrosis of femoral and humeral heads can develop even at moderate doses 1, 2, 3
• Myopathy affecting proximal muscles, including diaphragmatic and intercostal muscles 1, 3
• Even low-dose prednisone (5 mg/day) significantly suppresses bone formation markers in postmenopausal women 6

Endocrine and Metabolic

• Hypothalamic-pituitary-adrenal (HPA) axis suppression with potential for adrenal insufficiency after withdrawal 3
• Development of cushingoid state with truncal obesity, moon facies, and buffalo hump in 80% after two years 2, 3
• New-onset diabetes or worsening of existing diabetes 2, 3

Ophthalmic

• Posterior subcapsular cataracts develop with prolonged use 2, 3
• Increased intraocular pressure and glaucoma requiring regular monitoring 2, 3

Dermatologic

• Skin atrophy, telangiectasia, striae, and purpura 2, 3
• Impaired wound healing and increased bruising 3
• Acne and hirsutism 1, 3

Infectious Complications

• Increased risk of both opportunistic and non-opportunistic infections, including pneumonia, skin infections, and sepsis 2, 3
• Reactivation of latent tuberculosis in susceptible patients 3
• Varicella and measles can have serious or fatal courses in non-immune patients 3
• Hepatitis B virus reactivation can occur 3

Dose and Duration-Related Risk Factors

Severe adverse effects occur mainly at doses >20 mg/day for more than 18 months, leading to treatment discontinuation in approximately 15% of patients 1

• Duration >6 weeks significantly increases risk of adverse effects 2
• Combination therapy with azathioprine is associated with much lower occurrence of corticosteroid-related adverse events compared to prednisone monotherapy (10% vs 44% in controlled trials) 1
• In autoimmune hepatitis studies, steroid side effects occurred in 51.5% with prednisone versus 26.0% with budesonide 1

Management Strategies

Prevention of Osteoporosis

• All patients on long-term corticosteroids should receive calcium (800-1000 mg/day) and vitamin D (800 IU/day) supplementation 2, 7
• Baseline and annual bone mineral density testing with DEXA scans 2
• Consider bisphosphonate therapy selectively 1

Infection Prevention

• Consider Pneumocystis jirovecii pneumonia prophylaxis for patients taking ≥20 mg prednisone for ≥4 weeks 2
• Update all vaccines before starting immunosuppressive therapy 2
• Avoid live vaccines in patients already taking immunosuppressants 2
• Screen for hepatitis B and tuberculosis before initiating prolonged therapy 3

Metabolic Monitoring

• Regular monitoring of blood pressure and blood glucose, even during short courses 2
• Weight monitoring to detect rapid fluid retention 2
• Consider lipid profile monitoring for long-term users 2

Dose Minimization Strategies

• Use the lowest effective dose for the shortest duration possible 2
• Consider alternate-day therapy when appropriate to reduce adrenal suppression 2
• In patients with severe steroid side effects, switching from prednisone to budesonide (6 mg/day) resulted in 40% reduction in steroid side effects 1
• Consider steroid-sparing agents (azathioprine, mycophenolate) when long-term therapy is anticipated 1, 2

Special Population Considerations

• Elderly patients require more careful monitoring and often lower doses due to increased risk of complications 2
• Children on long-term therapy are at risk for growth suppression 1, 2
• Patients with diabetes, chronic liver disease, or chronic kidney disease require close monitoring 2

Critical Pitfalls to Avoid

• Never abruptly discontinue prednisone after prolonged use - HPA axis suppression may persist for up to 12 months after discontinuation, requiring stress-dose coverage during illness or surgery 3
• Do not underestimate the impact of sleep disturbances and mood changes on quality of life 2
• Avoid concurrent IV magnesium in patients with myasthenia gravis as it can worsen neuromuscular weakness 8
• In non-immune patients, particular care must be taken to avoid exposure to varicella and measles - prophylaxis with immune globulin may be indicated if exposure occurs 3