What are the potential side effects and management strategies for an adult patient with a chronic inflammatory condition, such as rheumatoid arthritis (RA) or asthma, taking low-dose prednisone (5-10 mg per day) long-term?

Side Effects of Chronic Low-Dose Prednisone

Chronic low-dose prednisone (5-10 mg daily) carries significant risks that require systematic monitoring and prevention, with osteoporosis being the most critical concern requiring universal prophylaxis with calcium and vitamin D supplementation. 1

Major Side Effects by Frequency

High-Priority Adverse Events (Require Active Prevention)

Osteoporosis is the most significant concern with chronic low-dose glucocorticoid therapy:

• Incidence: 16 events per 100 patient-years with medium-dose therapy (compared to 3 per 100 patient-years in glucocorticoid-naive patients) 1
• All patients on prednisone >7.5 mg daily for more than 3 months must receive calcium (800-1,000 mg/day) and vitamin D (400-800 units/day) supplementation 1, 2
• Bisphosphonate therapy should be based on bone mineral density measurement and individual risk factors 1

Adrenal Insufficiency develops predictably:

• Hypothalamic-pituitary-adrenal axis suppression should be anticipated in any patient receiving >7.5 mg daily for >3 weeks 1, 3
• Patients remain at risk and require stress-dose glucocorticoids during acute illness, surgery, or physiologic stress 1
• For patients on 10 mg prednisone daily during acute stress, increase to hydrocortisone 50 mg twice daily for 3 days 3
• Risk persists for up to 12 months after discontinuation 3

Moderate-Frequency Adverse Events

Cardiovascular Effects:

• Hypertension: 3-28 events per 100 patient-years (compared to 0-19 in controls) 1
• Monitor blood pressure at every visit 1
• Cardiovascular disease risk may be influenced by both the inflammatory disease itself and glucocorticoid therapy 1

Metabolic Complications:

• Diabetes/glucose intolerance: 0-3 events per 100 patient-years (compared to 0-1 in controls) 1
• Chronic treatment with 10 mg prednisone daily generally does not lead to higher glucose levels in most patients, but individual variation exists 1
• Monitor fasting blood glucose at baseline and periodically during therapy 1

Gastrointestinal Effects:

• Peptic ulcer disease: 1-4 events per 100 patient-years (compared to 0-2 in controls) 1
• Risk increases substantially when combined with NSAIDs 1
• Patients on glucocorticoids with concomitant NSAIDs should receive proton pump inhibitors or misoprostol, or switch to COX-2 selective inhibitors 1

Lower-Frequency but Clinically Important Effects

Infections:

• Serious infections: 14 events in glucocorticoid users versus 4 in matched controls in one cohort 4
• Glucocorticoid therapy increases infection risk in patients with rheumatoid arthritis based on cohort and case-control studies 1

Ocular Complications:

• Cataracts: 17 events in glucocorticoid users versus 5 in matched controls 4
• Glaucoma: approximately 18 patients need to be screened to detect one case per year 1
• Monitor ocular pressure depending on individual risk factors 1

Musculoskeletal Effects:

• Fractures: 21 events in glucocorticoid users versus 8 in matched controls 4
• This risk is directly related to glucocorticoid-induced osteoporosis 1

Dermatologic Effects:

• Skin thinning and bruising are the most common adverse effects, particularly with long-term use 5
• These effects appear primarily cosmetic rather than medically serious 5

Dose-Response Relationship

A clear dose-dependent relationship exists for adverse events:

• Prednisone 10-15 mg/day: Odds ratio 32.3 for developing adverse events (95% CI 4.6-220) 4
• Prednisone 5-10 mg/day: Odds ratio 4.5 for developing adverse events (95% CI 2.1-9.6) 4
• Prednisone <5 mg/day: Appears to have an acceptable risk profile with primarily bruising and skin-thinning as adverse effects 5

Essential Monitoring Protocol

Baseline Assessment (Before Starting Therapy):

• Body weight, blood pressure, peripheral edema 1
• Fasting blood glucose 1
• Serum lipids 1
• Risk factors for glaucoma 1
• Bone mineral density measurement 1
• Screen for cardiovascular disease, peptic ulcer disease, recurrent infections, and osteoporosis risk factors 1

Ongoing Monitoring:

• Standard care monitoring does NOT need to be extended for patients on low-dose glucocorticoid therapy, except for osteoporosis management 1
• Monitor body weight, blood pressure, peripheral edema, and glucose at regular intervals based on individual risk 1
• Systematic evaluation of glucocorticoid-related adverse effects should occur at follow-up visits 6

Critical Management Principles

Prevention Strategies:

• Initiate calcium and vitamin D supplementation immediately when starting prednisone >7.5 mg daily 1, 2
• Consider bisphosphonates based on bone density and fracture risk 1
• Add gastroprotection if using concomitant NSAIDs 1
• Educate patients about stress-dose requirements during illness or surgery 1, 3

Common Pitfalls to Avoid:

• Failing to provide calcium and vitamin D supplementation universally 1
• Not educating patients about adrenal insufficiency risk during stress 1, 3
• Combining glucocorticoids with NSAIDs without gastroprotection 1
• Abrupt discontinuation without tapering after >3 weeks of therapy 1, 7
• Using doses >10 mg daily when lower doses would suffice 2, 8

Special Populations:

• Children require regular monitoring for linear growth and consideration of growth hormone replacement if growth impairment occurs 1
• Pregnancy: Glucocorticoids have no additional risk for mother and child at therapeutic doses 1
• Female patients may have higher risk of glucocorticoid side effects 1, 9