What is the cause of a flat red rash on the neck, trunk, and back in a patient with a recent history of pneumonia, currently being treated with azithromycin (a macrolide antibiotic)?

Flat Red Rash on Neck, Trunk, and Back During Azithromycin Treatment for Pneumonia

Most Likely Diagnosis: Drug Reaction to Azithromycin

This flat red rash is most likely a drug-induced hypersensitivity reaction to azithromycin, and you should discontinue the macrolide immediately and switch to an alternative antibiotic regimen. 1

Immediate Management Algorithm

Step 1: Discontinue Azithromycin Immediately

• Azithromycin can cause serious allergic reactions including dermatologic reactions, and despite initially successful symptomatic treatment, allergic symptoms may recur when symptomatic therapy is discontinued due to the drug's long tissue half-life 1
• The FDA explicitly warns that if an allergic reaction occurs, the drug should be discontinued and appropriate therapy instituted 1
• Physicians must be aware that reappearance of allergic symptoms may occur when symptomatic therapy is discontinued, related to azithromycin's prolonged tissue half-life 1

Step 2: Assess Rash Severity and Systemic Involvement

• Look specifically for: fever, mucosal involvement (eyes, mouth, genitals), blistering, skin sloughing, lymphadenopathy, eosinophilia, or organ dysfunction (liver, kidney) 1, 2
• If any of these features are present, this may represent Stevens-Johnson Syndrome, toxic epidermal necrolysis, or DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome—all potentially fatal conditions requiring immediate hospitalization 1, 2
• A simple maculopapular rash without systemic features is more common and less severe, but still requires drug discontinuation 1

Step 3: Switch to Alternative Antibiotic Regimen

For outpatient pneumonia with recent azithromycin exposure:

• Use a respiratory fluoroquinolone: levofloxacin 750 mg daily OR moxifloxacin 400 mg daily for 5-7 days 3, 4
• This provides coverage for both typical bacteria (S. pneumoniae, H. influenzae) and atypical pathogens (M. pneumoniae, C. pneumoniae) without macrolide exposure 3

Alternative if fluoroquinolones are contraindicated:

• High-dose amoxicillin 1 g three times daily PLUS doxycycline 100 mg twice daily for 5-7 days 3, 4
• This combination covers typical and atypical pathogens while avoiding both macrolides and fluoroquinolones 3

Step 4: Symptomatic Treatment

• Oral antihistamines (cetirizine 10 mg daily or diphenhydramine 25-50 mg every 6 hours) for pruritus
• Topical corticosteroids (triamcinolone 0.1% cream) for localized rash
• Do NOT restart azithromycin or any other macrolide (clarithromycin, erythromycin) due to cross-reactivity risk 1

Critical Pitfalls to Avoid

Never Continue Azithromycin Despite Rash

• Even if the rash appears mild, continuing the drug risks progression to severe cutaneous adverse reactions 1
• The long tissue half-life of azithromycin means symptoms may persist or recur even after discontinuation 1

Do Not Switch to Another Macrolide

• Cross-reactivity between macrolides is common—avoid clarithromycin and erythromycin 3, 5
• Erythromycin has the same mechanism of action and similar allergenic potential 3, 5

Avoid Premature Reassurance

• Patients require prolonged observation because allergic symptoms can recur when symptomatic therapy is discontinued 1
• Document the reaction clearly in the medical record as "azithromycin allergy" to prevent future exposure 1

When to Hospitalize

Admit immediately if any of the following develop:

• Mucosal involvement (conjunctivitis, oral ulcers, genital lesions) 1
• Blistering or skin detachment (>10% body surface area) 1
• Fever >38.5°C with rash 2
• Facial or tongue swelling (angioedema) 1
• Respiratory distress or wheezing (anaphylaxis) 1
• Elevated liver enzymes, eosinophilia >1500/μL, or acute kidney injury (DRESS syndrome) 2

Follow-Up

• Reassess in 48-72 hours to confirm rash resolution and pneumonia improvement on new antibiotic regimen 3, 4
• If rash persists beyond 7 days or worsens, refer to dermatology for possible skin biopsy 2
• Complete full course of alternative antibiotic (5-7 days total) to ensure pneumonia cure 3, 4