How should I manage a patient who has been on prednisolone for over two months and now presents with a new maculopapular drug‑related rash?

Management of Maculopapular Rash After 2+ Months of Prednisolone

Stop the prednisolone immediately and evaluate for DRESS syndrome or delayed-type corticosteroid hypersensitivity, as this represents a paradoxical drug reaction requiring urgent assessment and alternative immunosuppression. 1, 2

Immediate Assessment Required

This clinical scenario is highly unusual and concerning—prednisolone itself is causing the rash after prolonged exposure. You must:

• Calculate the RegiSCAR score immediately to assess for DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), evaluating fever, lymphadenopathy, eosinophilia (>1,500/μL), atypical lymphocytes, extent of skin involvement, and organ involvement (liver, kidney). A score ≥2 indicates possible DRESS. 1

• Check complete blood count with differential focusing on eosinophil count and atypical lymphocytes, plus comprehensive metabolic panel for liver and kidney function within 24 hours. 1

• Assess the extent of the rash: document body surface area involved (<10% = grade 1,10-30% = grade 2, >30% = grade 3) and presence of systemic symptoms like fever, malaise, or lymphadenopathy. 3

Understanding the Paradox

While corticosteroids typically treat drug reactions, they can paradoxically cause delayed-type hypersensitivity reactions themselves:

• Delayed-type corticosteroid allergy is rare but well-documented, typically manifesting as maculopapular eruptions appearing hours to days after exposure in sensitized individuals. 2, 4, 5

• The 2+ month timeline suggests either: (1) delayed sensitization with recent manifestation, or (2) DRESS syndrome with its characteristic delayed onset (typically 2-8 weeks but can occur later). 1, 3

• Corticosteroids in Group A (including prednisolone, methylprednisolone, prednisone) commonly cross-react, so switching within this group will fail. 2, 4, 5

Immediate Management Steps

Discontinue prednisolone immediately—continuing the culprit drug risks progression to severe cutaneous adverse reactions or systemic involvement. 1, 3

If DRESS Syndrome is Suspected (RegiSCAR ≥2):

• Do NOT restart any corticosteroid initially—paradoxically, you need to clear the offending agent first. 1

• Provide supportive care with antihistamines for pruritus and emollients for skin barrier. 1

• Monitor closely for progression with repeat eosinophil count and liver enzymes in 3-5 days, and clinical reassessment within 48-72 hours. 1

• If systemic involvement worsens or skin progresses beyond grade 2, consider alternative immunosuppression such as intravenous immunoglobulin (IVIG) or cyclosporine rather than restarting corticosteroids. 1

If Simple Delayed Hypersensitivity (No DRESS Features):

• Switch to a non-cross-reactive corticosteroid from a different structural group. Hydrocortisone or dexamethasone may be tolerated if prednisolone caused the reaction, though patch testing would ideally guide this. 2, 4

• Direct switching to a non-cross-reactive agent results in only 3-6% recurrence rates, far superior to continuing the same agent. 3

• Never rechallenge with prednisolone—this can cause severe, rapid-onset reactions that are potentially fatal. 3

Diagnostic Confirmation

• Patch testing can confirm corticosteroid allergy once the acute reaction resolves (typically 4-6 weeks later), testing prednisolone and other corticosteroid groups to identify safe alternatives. 2, 4, 5

• Patch testing has 60-80% sensitivity, so negative results don't exclude the diagnosis. 3

• Document the specific reaction pattern, timing, and all treatments in the medical record for future reference. 3

Alternative Immunosuppression Strategy

Given the underlying condition requiring prednisolone for 2+ months, you need alternative immunosuppression:

• Steroid-sparing agents should be initiated based on the underlying condition (e.g., azathioprine, mycophenolate, methotrexate, or biologics depending on the disease). 1

• If corticosteroids are absolutely necessary, use hydrocortisone or a Group D corticosteroid (structurally distinct from prednisolone) after confirming tolerance through supervised challenge. 2, 4

Critical Pitfalls to Avoid

• Do not assume the rash is from the underlying disease—after 2+ months of stable prednisolone use, new rash onset strongly suggests drug reaction. 1, 3

• Do not increase the prednisolone dose thinking it will suppress the rash—this worsens drug-induced reactions. 2

• Do not use topical corticosteroids extensively if systemic corticosteroid allergy is confirmed, as cross-reactivity can occur. 2, 4

• Do not taper too quickly if DRESS is confirmed and alternative corticosteroids are eventually needed—DRESS requires prolonged treatment (weeks to months) with slow taper to prevent relapse and autoimmune sequelae. 1