Which of the following medications, Calcium + Vitamin D, Omeprazole (proton pump inhibitor) or Prednisone (corticosteroid), is most likely to cause acute adverse drug reactions to the skin?

Prednisone is Most Likely to Cause Acute Adverse Skin Reactions

Among the three medications, prednisone (corticosteroid) is most likely to cause acute adverse drug reactions to the skin, followed by omeprazole, while calcium + vitamin D supplementation rarely causes cutaneous reactions.

Evidence from Drug Labels and Clinical Data

Prednisone (Corticosteroid)

Prednisone has extensive documented dermatologic adverse effects including acne, acneiform eruptions, allergic dermatitis, rash, urticaria, angioedema, and multiple other cutaneous manifestations. 1

• The FDA label specifically lists numerous dermatologic adverse reactions including: acne, acneiform eruptions, allergic dermatitis, alopecia, angioedema, erythema, facial edema, hirsutism, perineal irritation, purpura, rash, striae, urticaria, and telangiectasis 1
• Cosmetic skin changes occur in 80% of patients after 2 years of corticosteroid treatment 2
• Skin rash was documented as more common in prednisolone-treated patients compared to indomethacin in gout treatment trials 2
• In clinical practice, rash is a recognized complication requiring management with dose adjustment or temporary discontinuation 2

Omeprazole (Proton Pump Inhibitor)

Omeprazole has documented but less frequent cutaneous reactions compared to prednisone:

• Rash occurs in 2% of patients in clinical trials 3
• Severe skin reactions are rare but documented in post-marketing surveillance, including toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome, cutaneous lupus erythematosus, erythema multiforme, photosensitivity, urticaria, skin inflammation, and pruritus 3
• These severe reactions represent post-marketing reports from an uncertain population size, making true incidence difficult to establish 3

Calcium + Vitamin D Supplementation

• No significant acute cutaneous adverse reactions are documented in the clinical literature for calcium and vitamin D supplementation 2
• These supplements are routinely recommended for bone protection in patients taking corticosteroids without concern for skin reactions 2
• The primary concern with calcium is gastrointestinal absorption interactions with other medications, not dermatologic effects 2

Clinical Context and Severity Spectrum

Common vs. Severe Cutaneous Reactions

The distinction between common mild reactions and severe cutaneous adverse reactions (SCARs) is critical:

• Antibiotics, NSAIDs, and anticonvulsants are the most common causes of severe cutaneous adverse drug reactions overall, with antibiotics accounting for 88.1% of SCAR cases in one surveillance study 4
• Corticosteroids like prednisone cause frequent mild-to-moderate skin reactions (80% cosmetic changes) but can also trigger severe reactions 2, 1
• Morbilliform exanthemas are the most common CADR pattern (59.6%), followed by erythroderma, DRESS syndrome, and other severe patterns 5

Temporal Patterns

• Most cutaneous adverse drug reactions occur within 0-15 days (62.8% of cases) of drug initiation 5
• Anticonvulsants have statistically longer latency periods than other drug classes 5
• Prednisone's dermatologic effects can be both acute (rash, urticaria) and chronic (cosmetic changes over months to years) 2, 1

Clinical Pitfalls and Management Considerations

Key Diagnostic Considerations

• Any new rash in a patient on multiple medications requires systematic evaluation of all potential culprits, with particular attention to recently initiated drugs 6, 7
• Failure to improve after one week of antihistamines and topical steroids warrants dermatology referral for definitive diagnosis 7
• Rule out severe reactions (SJS, TEN, DRESS) by checking for systemic involvement, mucous membrane involvement, and fever 7, 4

Management Approach

When prednisone causes a rash:

• Mild-to-moderate reactions can be managed with topical therapies, antihistamines, or paradoxically, short courses of systemic steroids for severe drug-induced rashes from other medications 2
• Severe cases require interruption or dose reduction 2
• The irony is that prednisone itself is used to treat severe cutaneous drug reactions from other medications (1 mg/kg daily), but when prednisone is the culprit, dose reduction or discontinuation is necessary 2, 4

Cross-Reactivity and Future Prescribing

• Document any confirmed drug-induced rash as a drug allergy to prevent future exposure 6
• Patients who develop rash on one medication may not experience recurrence with structurally different alternatives 2
• Avoid using high-potency topical steroids in intertriginous areas due to increased risk of skin atrophy 6