Should a patient on chronic low‑dose prednisolone (≤5 mg daily) have the dose doubled during an acute illness or physiological stress?

Should Patients on Chronic Low-Dose Prednisolone Double Their Dose During Acute Illness?

Yes, patients on chronic low-dose prednisolone (≤5 mg daily) should double their dose during acute illness to prevent adrenal crisis, particularly during infections with fever or other significant physiological stressors.

Understanding the Risk of Adrenal Suppression

Patients taking prednisolone ≥5 mg daily for longer than one month develop hypothalamic-pituitary-adrenal (HPA) axis suppression in a substantial proportion of cases. 1 Even at doses as low as 5 mg daily, approximately 33-50% of patients fail to mount an adequate cortisol response on stimulation testing, indicating insufficient adrenal reserve. 1

The critical point: HPA axis suppression should be anticipated in any patient receiving more than 7.5 mg of prednisolone equivalent daily for more than 3 weeks, though the risk exists even at lower doses. 2

When to Double the Dose

Specific Triggers Requiring Dose Escalation

• Infections, particularly respiratory infections with fever, precipitate approximately 50% of adrenal crises in individuals with adrenal insufficiency and represent the most common indication for stress dosing. 1

• Other physiological stressors include gastroenteritis with vomiting or diarrhea, trauma, surgical procedures, or any acute illness causing significant systemic symptoms. 2

The Doubling Protocol

For patients on ≤5 mg prednisolone daily: Double the usual dose for the duration of the acute illness, typically 2-3 days for minor illnesses, and continue until symptoms resolve. 2, 3

For patients on 5-16 mg prednisolone daily: The same doubling principle applies, with the doubled dose maintained for 48 hours minimum for uncomplicated illness, or up to one week for more severe illness before tapering back to maintenance. 3

Evidence Supporting This Approach

The EULAR guidelines explicitly recommend adequate glucocorticoid replacement in acute situations for patients on chronic glucocorticoid treatment, pragmatically suggesting increasing the dosage for 3 days depending on the clinical situation. 2

A randomized controlled trial in nephrotic syndrome patients demonstrated that doubling alternate-day prednisolone during viral upper respiratory tract infections reduced relapse rates from 48% to 18% (p=0.014), providing direct evidence that dose escalation during acute illness prevents adverse outcomes. 4

The guideline consensus is clear: When uncertainty exists about the necessity of additional glucocorticoids, clinicians should administer them ("if in doubt, give"), as short-term glucocorticoid administration has no long-term adverse consequences. 3

Consequences of Failing to Increase the Dose

Omission or under-dosing of glucocorticoids during acute illness is a recognized precipitant of adrenal crisis. 1 In a prospective 2-year follow-up of 423 patients with adrenal insufficiency, two deaths occurred during adrenal crises, highlighting the potentially fatal outcome of inadequate stress-dose coverage. 1

Clinical case evidence: A patient on 7 mg prednisolone daily who appropriately doubled the dose during the first pneumonia episode but failed to do so during a second episode subsequently developed adrenal crisis, demonstrating the very high likelihood that omitting stress-dose steroids contributed to this life-threatening complication. 1

Practical Implementation

Dosing Algorithm

1. At first sign of acute illness (fever, significant respiratory symptoms, gastroenteritis): Double the usual prednisolone dose immediately. 3, 1

2. Continue doubled dose for minimum 48 hours for minor illness, or until clinical stability is achieved for more severe illness. 3

3. Return to maintenance dose once symptoms resolve, without need for gradual taper after short-term doubling. 4

4. Seek medical attention if unable to take oral medications (vomiting), if symptoms worsen despite doubled dose, or if severe illness develops. 1

Patient Education Essentials

Patients must understand that their adrenal glands cannot respond adequately to stress while on chronic prednisolone. 2 They should be instructed to:

• Keep extra prednisolone tablets readily available at home. 1
• Double the dose at the first sign of illness without waiting for medical consultation. 3, 1
• Wear medical alert identification indicating adrenal insufficiency. 1
• Have emergency injectable hydrocortisone available if vomiting prevents oral intake. 1

Common Pitfalls to Avoid

Do not wait for laboratory confirmation or medical consultation before doubling the dose during acute illness—the risk of adrenal crisis outweighs any concern about short-term glucocorticoid excess. 3, 1

Do not assume that low doses (<5 mg daily) are safe without stress dosing—even these doses can suppress the HPA axis sufficiently to cause crisis during physiological stress. 1

Do not taper the doubled dose after brief (2-3 day) stress dosing for minor illness—patients can return directly to their maintenance dose once symptoms resolve. 4

Ward staff may overlook early warning signs of glucocorticoid under-replacement in hospitalized patients, so explicit orders for stress dosing must be written. 1