Can steroid withdrawal cause fever?

Can Steroid Withdrawal Cause Fever?

Yes, steroid withdrawal can cause fever as part of a recognized glucocorticoid withdrawal syndrome, though this must be carefully distinguished from infection, which is far more common and dangerous in patients on chronic steroids. 1

Understanding Steroid Withdrawal Syndrome

Glucocorticoid withdrawal syndrome (GWS) develops after withdrawing from supraphysiological levels of corticosteroids and represents a distinct entity from adrenal insufficiency, though symptoms overlap. 2 The syndrome includes:

• Fever and constitutional symptoms that can mimic infection 3
• Fatigue, myalgias, arthralgias, and malaise 2
• Symptoms that are typically temporary but can significantly impair quality of life 2

Critical Clinical Context

In a documented case, high fever occurred five weeks after transsphenoidal hypophysectomy in a patient with inadequate corticosteroid replacement, where extensive workup revealed no infection and fever was attributed to steroid withdrawal. 3 This demonstrates that steroid withdrawal fever is a real phenomenon but remains a diagnosis of exclusion.

The Infection Imperative: Why This Matters Most

The most critical clinical point is that fever in steroid-treated patients is usually due to infection, not withdrawal, and misattributing infection to withdrawal can be fatal. 4

Evidence from SLE Patients

In a prospective study of 92 SLE patients on maintenance prednisone (median 10 mg), SLE-related fever was rare during steroid therapy. 4 When fever developed in steroid-treated patients:

• Infection was the predominant cause 4
• Three patients developed fatal sepsis when high-dose steroids were continued for presumed disease activity rather than infection 4
• Prednisone doses of 28 mg (range 20-40 mg) completely suppressed disease-related fever within 24 hours, whereas infection fever persisted despite prednisone 35-300 mg/day 4

Diagnostic Algorithm for Fever in Steroid-Treated Patients

When fever develops in a patient on chronic steroids, follow this approach:

1. Assume infection first – Obtain cultures (blood, urine, sputum as indicated), imaging, and inflammatory markers 1, 4

2. Assess steroid dose and timing:

   • If on maintenance doses (≥10 mg prednisone equivalent), withdrawal fever is unlikely 4
   • If recently tapered or stopped steroids, consider withdrawal but only after infection excluded 3, 2

3. Use fever response as a diagnostic tool:

   • If fever resolves within 24 hours of moderate-dose steroids (20-40 mg prednisone), this suggests inflammatory/withdrawal etiology 4
   • If fever persists despite adequate steroids, infection is highly likely and continuing high-dose steroids increases sepsis risk 4

4. Check adrenal function if withdrawal suspected:

   • Rapid ACTH stimulation test can assess HPA axis suppression 5
   • Biochemical HPA suppression can exist without symptoms (Type IV withdrawal syndrome) 5

Types of Steroid Withdrawal Syndromes

Four distinct patterns exist, which can occur in combination: 5

• Type I: Symptomatic with biochemical HPA suppression 5
• Type II: Recrudescence of underlying disease 5
• Type III: Physical or psychological dependence with normal HPA function and no disease recurrence 5
• Type IV: Biochemical HPA suppression without symptoms 5

Management of Confirmed Withdrawal Fever

If infection is definitively excluded and withdrawal syndrome confirmed:

• Temporarily increase glucocorticoid replacement to the previous well-tolerated dose 2
• Provide patient education and reassurance that symptoms are expected and typically temporary 2
• Resume tapering more gradually once symptoms resolve 2
• No consensus exists on optimal tapering strategy, but slower tapers do not necessarily prevent relapses 6, 2

Critical Pitfalls to Avoid

The most dangerous error is attributing fever to steroid withdrawal when infection is present, leading to continuation or escalation of immunosuppression. 4 This has resulted in fatal sepsis in documented cases. 4

Conversely, some patients develop true withdrawal symptoms that clinically suggest HPA suppression but have demonstrably normal adrenal function (Type III syndrome), representing physical or psychological dependence rather than true adrenal insufficiency. 5

Glucocorticoids blunt the febrile response to infection, making fever surveillance essential but also making the presence of fever particularly concerning. 7