Can a fever of hyperthermia be related to discontinuation of prednisolone (corticosteroid) in a 1.5-year-old child with a history of erythema multiforme who was treated with prednisolone for 2 days and had a good response?

Fever After Prednisolone Discontinuation in Erythema Multiforme

The fever of 104°F is unlikely to be directly caused by prednisolone discontinuation after only 2 days of treatment, and you should urgently evaluate this child for an infectious process or underlying systemic inflammatory condition.

Understanding the Clinical Context

After such a brief corticosteroid course (2 days), several key physiologic principles apply:

• Adrenal suppression does not occur with 2-day prednisolone courses – the hypothalamic-pituitary-adrenal axis requires prolonged exposure (typically >2 weeks) before suppression becomes clinically significant 1
• Rebound inflammation is extremely unlikely after such short-duration therapy, as this phenomenon typically occurs with abrupt cessation after prolonged courses (>7-10 days) 2
• Steroid withdrawal fever is not a recognized entity in pediatric literature following brief therapeutic courses 3, 1

What This Fever Likely Represents

The temporal association between stopping prednisolone and developing high fever suggests three more probable scenarios:

1. Underlying Infectious Trigger (Most Likely)

• Erythema multiforme in children is most commonly triggered by infections, particularly herpes simplex virus or Mycoplasma pneumoniae 4
• The fever may represent the underlying infectious process that initially triggered the erythema multiforme, which was masked by the anti-inflammatory effects of prednisolone 2
• High fever (104°F/40°C) is more consistent with active infection than drug reaction 5

2. Progression to Stevens-Johnson Syndrome or More Severe Disease

• While erythema multiforme typically has minimal mucosal involvement, progression can occur 4
• Urgent evaluation for mucosal involvement, extensive skin detachment, or systemic symptoms is critical to differentiate from Stevens-Johnson syndrome 6
• The American College of Rheumatology emphasizes that persistent fever with ongoing end-organ involvement requires escalation of therapy 5

3. Concurrent Illness Unrelated to Steroid Withdrawal

• A 1.5-year-old child may have acquired a new infection coincidentally 4
• Common pediatric infections (viral syndromes, otitis media, urinary tract infection) should be systematically excluded

Immediate Clinical Actions Required

Perform urgent assessment for:

• Infectious workup: Complete blood count with differential, blood cultures, urinalysis and culture, chest radiograph if respiratory symptoms present 5
• Mucosal examination: Carefully inspect oral mucosa, conjunctivae, and genital areas for erosions or bullae that would suggest progression to Stevens-Johnson syndrome 6, 4
• Skin assessment: Evaluate for new bullae formation, epidermal sloughing, or increased body surface area involvement 1
• Inflammatory markers: C-reactive protein and erythrocyte sedimentation rate to assess systemic inflammation 5

Treatment Decision Algorithm

If infection is identified:

• Treat the specific pathogen appropriately 4
• Consider restarting prednisolone 1 mg/kg/day only if skin lesions are worsening despite antimicrobial therapy 1, 6

If no infection found but skin disease is progressing:

• Restart prednisolone at 1-2 mg/kg/day as a single morning dose (maximum 60 mg/day) 1
• For severe progression with >30% body surface area involvement, consider dermatology consultation same-day 1
• If truly refractory, escalation to methylprednisolone 1-2 mg/kg/day IV may be warranted 3

If fever persists without clear source:

• Consider atypical infections (Mycoplasma, viral triggers) that commonly precipitate erythema multiforme 4
• Empiric acyclovir may be considered if herpes simplex is suspected as the trigger 4

Critical Pitfalls to Avoid

• Do not assume the fever is "steroid withdrawal" – this is not a recognized phenomenon after 2-day courses and may delay diagnosis of serious infection 3, 1
• Do not restart steroids empirically without ruling out infection – corticosteroids will mask fever and blunt the immune response, potentially allowing infections to progress unchecked 2
• Do not discharge without identifying fever source – 104°F in an 18-month-old warrants thorough evaluation regardless of recent medication changes 5
• Do not overlook drug-induced causes – if the child received any new medications (including the antihistamines mentioned), these could be triggering worsening disease 6, 4