What are the potential side effects of high dose systemic steroids, such as prednisone (corticosteroid), in patients with a history of hypertension, diabetes, or cardiovascular disease?

Side Effects of High-Dose Systemic Steroids

High-dose systemic corticosteroids cause serious dose-dependent metabolic, cardiovascular, and immunosuppressive complications that are particularly dangerous in patients with pre-existing hypertension, diabetes, or cardiovascular disease, with mortality documented from cardiac arrest, infection, and congestive heart failure in high-risk populations. 1

Immediate and Short-Term Side Effects (Days to Weeks)

Metabolic Complications

• Hyperglycemia and worsening diabetes occur commonly with prednisone, requiring blood glucose monitoring even during short courses 2, 3, 4
• Increased appetite and rapid weight gain develop within the first few weeks of therapy 2
• Fluid retention with sodium retention and potassium loss necessitates caution in patients with congestive heart failure, hypertension, or renal insufficiency 4

Cardiovascular Effects

• Hypertension can develop or worsen quickly, with elevation of blood pressure occurring as a direct effect of corticosteroids 2, 4
• Salt and water retention exacerbates pre-existing heart failure 4
• Literature reports suggest an association between corticosteroid use and left ventricular free wall rupture after recent myocardial infarction, requiring extreme caution in this population 4

Gastrointestinal Effects

• Gastric irritation occurs in 21-32% of patients, which can be ameliorated with H2-receptor antagonists 1, 2
• Increased risk of peptic ulcer formation and gastrointestinal perforation, with signs of peritoneal irritation potentially minimal or absent 4

Neuropsychiatric Effects

• Insomnia, restlessness, and nervousness occur in more than 30% of patients 2, 3
• Mood disturbances ranging from euphoria and hypomania to depression develop commonly 2
• Behavioral changes including irritability, fussiness, and personality changes occur in up to 29% of patients 1

Long-Term and Severe Complications (Weeks to Months)

Musculoskeletal Toxicity

• Osteoporosis and increased fracture risk are among the most serious complications, with vertebral compression fractures occurring in up to 27% of patients requiring treatment withdrawal 2
• Aseptic necrosis of femoral and humeral heads can develop even at moderate doses 2
• Steroid myopathy affecting diaphragmatic and intercostal muscles may occur 2
• Corticosteroids decrease bone formation and increase bone resorption through effects on calcium regulation and inhibition of osteoblast function 4

Endocrine Dysfunction

• Hypothalamic-pituitary-adrenal (HPA) axis suppression occurs with potential for adrenal insufficiency after withdrawal 4
• This relative insufficiency may persist for up to 12 months after discontinuation of therapy 4
• Growth suppression occurs in pediatric patients even at low systemic doses and in the absence of laboratory evidence of HPA axis suppression 4

Ophthalmologic Complications

• Posterior subcapsular cataracts develop with prolonged use 1, 2, 3
• Increased intraocular pressure and glaucoma can occur, requiring regular ophthalmologic evaluation 1, 2, 3

Immunosuppression and Infection Risk

• Increased risk of both opportunistic and non-opportunistic infections, including pneumonia, skin infections, and sepsis 2, 4
• Rare cases of Pneumocystis carinii pneumonia have been reported, with some experts advocating prophylaxis with trimethoprim-sulfamethoxazole 1
• Consider Pneumocystis jirovecii pneumonia prophylaxis for patients taking ≥20 mg prednisone for ≥4 weeks 2
• Reduced B- and T-lymphocyte counts and poor response to vaccines 1
• Reactivation of latent tuberculosis may occur, requiring close monitoring and chemoprophylaxis during prolonged therapy 4

Cosmetic and Dermatologic Effects

• Redistribution of body fat with truncal obesity, moon facies, and buffalo hump occurs in 80% of patients after two years of therapy 2
• Facial rounding can begin even during short-term use 2
• Striae (stretch marks), skin atrophy, and telangiectasia develop with prolonged use 2, 3

Cardiovascular Disease Risk

• Observational studies indicate long-term use of higher doses (≥5 mg prednisone) in rheumatoid arthritis patients is associated with higher cardiovascular event risk 2
• Dyslipidemia occurs with long-term use, increasing cardiovascular disease risk 2

High-Risk Mortality Data

In a study of eight patients with severe disease treated with very high-dose intravenous methylprednisolone (1 g daily or 15 mg/kg daily for 3 days), seven had significant medical comorbidity. One patient died within 1 week, and three died between 1 and 4.5 months following treatment. The causes of death were cardiac arrest, infection, and congestive cardiac failure. 1

Critical Monitoring Requirements

For All Patients on High-Dose Steroids

• Regular blood pressure monitoring 2, 3
• Blood glucose monitoring, particularly in diabetic patients 2, 3
• Weight monitoring to detect rapid fluid retention 2

For Long-Term Therapy (>3 months)

• Baseline and annual bone mineral density testing with DEXA scans 2, 3
• Regular ophthalmologic examination for cataracts and glaucoma 2, 3
• Lipid profile monitoring 2
• Assessment for vertebral compression fractures 2

Risk Mitigation Strategies

Dosing Principles

• Use the lowest possible dose for the shortest duration to control the condition 4, 5
• Doses exceeding 10 mg daily for more than 18 months significantly increase risk of severe complications 2
• Duration of treatment longer than 6 weeks significantly increases risk of adverse effects 2
• Consider alternate-day therapy when appropriate to reduce adrenal suppression 2

Bone Protection (Essential for All Patients)

• Initiate calcium and vitamin D supplementation for all patients anticipated to receive at least the equivalent of 5 mg prednisone for at least 3 months 2, 3, 4
• Consider bisphosphonate therapy (alendronate, risedronate) if bone mineral density is below normal 4
• Encourage weight-bearing exercise for 30-60 minutes daily 4
• Lifestyle modification including smoking cessation and limitation of alcohol consumption 4

Infection Prevention

• Update all vaccines before starting immunosuppressive therapy 2
• Avoid live vaccines in patients already taking immunosuppressants 2
• Educate patients about signs of infection and when to seek medical attention 2
• In corticosteroid-treated patients exposed to varicella, prophylaxis with varicella zoster immune globulin may be indicated 4

Steroid-Sparing Approaches

• Consider steroid-sparing agents when long-term therapy is anticipated to reduce corticosteroid-related complications 2
• Add alternative immunosuppressive therapy rather than increasing steroid dose when disease control is inadequate 1

Special Population Considerations

Patients with Diabetes

• Particularly high risk for hyperglycemia requiring intensive glucose monitoring 2, 3
• May require adjustment of antidiabetic medications 2

Patients with Cardiovascular Disease

• Extreme caution required due to risk of left ventricular rupture post-myocardial infarction 4
• Higher cardiovascular event risk with long-term use 2
• Monitor closely for fluid retention and hypertension 4

Patients with Hypertension

• Sodium retention and blood pressure elevation are predictable effects 4
• May require adjustment of antihypertensive medications 2
• Dietary salt restriction may be necessary 4

Elderly Patients

• Require more careful monitoring and often lower doses due to increased risk of complications 2
• Increased risk of diabetes mellitus, fluid retention, and hypertension 4
• Dose selection should be cautious, usually starting at the low end of the dosing range 4

Pediatric Patients

• Growth velocity may be a more sensitive indicator of systemic corticosteroid exposure than tests of HPA axis function 4
• Linear growth should be monitored and patients titrated to the lowest effective dose 4
• Almost all children experience "catch-up" growth after completion of therapy 1

Critical Contraindications

• Presence of superficial or deep infection 6
• Recent myocardial infarction (relative contraindication requiring extreme caution) 4
• Active or latent peptic ulcers (relative contraindication) 4

Common Pitfalls to Avoid

• Underestimating the impact of sleep disturbances and mood changes on quality of life 2
• Failing to recognize that increasing the dose in poorly responsive patients confers little additional benefit and is significantly more toxic 1
• Not providing stress-dose steroids for surgical patients on long-term therapy 3
• Abrupt discontinuation leading to adrenal crisis 4
• Inadequate patient education about infection risk and when to seek care 2, 4