What are the side effects and monitoring requirements for oral corticosteroids, such as prednisone (corticosteroid), and how can their use be optimized to minimize risks?

Oral Corticosteroid Side Effects, Monitoring, and Risk Optimization

Oral corticosteroids cause significant dose- and duration-dependent adverse effects that require systematic monitoring and preventive strategies, with osteoporosis, infection risk, metabolic disturbances, and neuropsychiatric symptoms being the most clinically important complications requiring proactive management.

Major Side Effects by System

Musculoskeletal Complications

• Osteoporosis and fractures represent the most serious long-term complication, with vertebral compression fractures occurring in up to 27% of patients and potentially requiring treatment withdrawal 1, 2
• Avascular necrosis of the femoral and humeral heads can develop even at moderate doses during long-term therapy 1, 2
• Corticosteroid-induced myopathy affecting proximal muscles, including diaphragmatic and intercostal muscles, may complicate disease assessment 1
• Bone loss occurs through decreased calcium absorption, increased calcium excretion, and direct inhibition of osteoblast function 3

Metabolic and Endocrine Effects

• Hyperglycemia and new-onset or worsening diabetes mellitus are common, particularly with prednisone, requiring blood glucose monitoring 2
• Weight gain, fluid retention, and redistribution of body fat with truncal obesity, moon facies, and buffalo hump occur in 80% of patients after two years of therapy 2
• Hypertension can develop or worsen rapidly, even during short-term use 2
• Dyslipidemia increases cardiovascular disease risk with long-term use 2
• HPA axis suppression can persist for up to 12 months after discontinuation following prolonged high-dose therapy 3

Infectious Complications

• Increased risk of both opportunistic and non-opportunistic infections, including pneumonia, skin infections, bacteremia, and sepsis, with risk increasing proportionally with dose 1, 2, 3
• Live vaccines are contraindicated in patients already taking immunosuppressants, though patients on <20 mg prednisone daily may receive shingles vaccine per CDC guidelines 1
• Reactivation of latent tuberculosis, hepatitis B, amebiasis, and Strongyloides can occur 3
• Varicella and measles can have serious or fatal courses in non-immune patients taking corticosteroids 3

Neuropsychiatric Effects

• Mood disturbances ranging from euphoria and hypomania to severe depression and psychosis are dose-dependent and typically occur in the first few weeks of therapy 2, 3, 4
• Insomnia, restlessness, and nervousness occur in >30% of patients 2
• Cognitive decline affecting declarative and working memory is reported during therapy 4
• Symptoms are similar to bipolar disorder and are reversible with dose reduction or discontinuation 4

Ophthalmologic Complications

• Posterior subcapsular cataracts develop with prolonged use 1, 2, 3
• Increased intraocular pressure and glaucoma can occur, requiring monitoring if therapy continues >6 weeks 2, 3

Gastrointestinal Effects

• Increased risk of peptic ulcer formation and gastrointestinal perforation, particularly when combined with NSAIDs 1, 3
• Signs of peritoneal irritation may be minimal or absent in patients receiving corticosteroids 3

Critical Monitoring Requirements

Baseline Assessment Before Initiating Therapy

• Assess all comorbidities that increase risk of steroid-related side effects: hypertension, diabetes, glucose intolerance, cardiovascular disease, dyslipidemia, peptic ulcer, osteoporosis (particularly recent fractures), cataracts, glaucoma risk factors, and chronic/recurrent infections 1
• Screen for hepatitis B infection before initiating immunosuppressive treatment 3
• Rule out latent tuberculosis or tuberculin reactivity; provide chemoprophylaxis if positive during prolonged therapy 3
• Rule out latent amebiasis in patients who have spent time in the tropics or have unexplained diarrhea 3
• Obtain baseline bone mineral density via DEXA scan for all patients anticipated to receive ≥5 mg prednisone for ≥3 months 3
• Document baseline weight, blood pressure, glucose, lipid profile, and electrolytes 5

Ongoing Monitoring During Therapy

• Monitor blood pressure and blood glucose regularly, even during short courses 2
• Weight monitoring to detect rapid fluid retention 2
• Annual bone mineral density testing for patients on long-term therapy 2
• Regular assessment for vertebral compression fractures 2
• Intraocular pressure monitoring if therapy continues >6 weeks 3
• Regular ophthalmologic examinations for cataracts and glaucoma 2
• Monitor for signs of infection and educate patients to seek immediate medical attention 2
• Lipid profile monitoring for patients on long-term therapy 2

Risk Minimization Strategies

Dose and Duration Optimization

• Use the lowest possible effective dose for the shortest duration to control the condition 3
• Doses >20 mg prednisone daily for >18 months lead to severe adverse effects in approximately 15% of patients 2
• When dose reduction is possible, taper gradually to minimize adrenal insufficiency 3
• Consider alternate-day therapy when appropriate to reduce adrenal suppression 2

Bone Health Protection

• Initiate calcium and vitamin D supplementation for all patients anticipated to receive ≥5 mg prednisone for ≥3 months 1, 3
• Prescribe bisphosphonates (alendronate or risedronate) if bone mineral density is below normal or osteoporosis is evident 1, 3
• Encourage lifestyle modifications: smoking cessation, alcohol limitation, and weight-bearing exercise 30-60 minutes daily 3
• Consider sex hormone replacement therapy for hypogonadal patients (combined estrogen/progestin in women; testosterone in men) 3

Infection Prevention

• Update all vaccines before starting immunosuppressive therapy: pneumococcal, influenza (intramuscular), hepatitis B, recombinant HPV, and live attenuated herpes zoster 1
• Provide Pneumocystis jirovecii pneumonia prophylaxis (trimethoprim-sulfamethoxazole) for patients taking ≥20 mg prednisone for ≥4 weeks 1, 2
• Avoid live vaccines in patients already taking immunosuppressants 1
• If exposed to varicella, consider prophylaxis with varicella zoster immune globulin; if varicella develops, consider antiviral treatment 3
• If exposed to measles, consider prophylaxis with immunoglobulin 3

Steroid-Sparing Strategies

• Consider steroid-sparing agents (methotrexate, azathioprine, mycophenolate) when long-term therapy is anticipated to reduce cumulative corticosteroid exposure 1, 2
• For patients at high risk of side effects or relapse, add steroid-sparing agents early 1

Perioperative Management

• Prior to elective surgery, corticosteroids should be stopped or dose minimized wherever possible to reduce risk of postoperative infectious complications and anastomotic leaks 1
• Doses ≥20 mg prednisone are associated with significantly increased surgical complications 1
• Patients on corticosteroids at time of surgery should receive intravenous hydrocortisone in equivalent dosage until oral intake resumes (prednisolone 5 mg = hydrocortisone 20 mg) 1
• There is no value in increasing steroid dosage to cover perioperative stress 1

High-Risk Populations Requiring Enhanced Monitoring

• Elderly patients require more careful monitoring and often lower doses due to increased risk of complications 2
• Patients with diabetes, chronic liver disease, chronic kidney disease, or organ transplant have increased risk of infectious and metabolic complications 1, 2
• Female patients have higher baseline risk of glucocorticoid-related adverse events 1
• Children on long-term therapy require careful monitoring for growth suppression 1, 2, 3
• Postmenopausal women have particularly high risk of osteoporosis 3

Critical Patient Education Points

• Never discontinue corticosteroids abruptly or without medical supervision due to risk of adrenal insufficiency 3
• Advise patients taking corticosteroids to inform all medical providers of their medication 3
• Warn patients to avoid exposure to chickenpox and measles; seek immediate medical advice if exposed 3
• Educate about signs of infection and when to seek urgent medical attention 2
• Counsel about expected side effects including mood changes, insomnia, weight gain, and increased appetite 2
• Following prolonged therapy, withdrawal may cause myalgia, arthralgia, and malaise 3

Common Pitfalls to Avoid

• Underestimating the impact of sleep disturbances and mood changes on quality of life 2
• Failing to initiate bone protection measures at the start of therapy 1, 3
• Not screening for latent infections before initiating immunosuppressive therapy 3
• Inadequate baseline documentation before starting therapy 1
• Combining corticosteroids with NSAIDs, which significantly increases gastrointestinal bleeding risk 1
• Failing to provide stress-dose steroids during acute illness in patients with potential HPA axis suppression 3