In a 38‑year‑old woman who develops acute pruritic generalized urticaria one day after starting oral penicillin V for streptococcal pharyngitis, what histologic finding is most likely on skin biopsy of the lesions?

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Histologic Finding in Acute Urticaria Following Penicillin V

The most likely finding on biopsy of these urticarial lesions is dermal edema (Option C).

Understanding the Clinical Presentation

This patient developed acute pruritic urticaria one day after starting penicillin V for confirmed streptococcal pharyngitis. The sudden onset of a pruritic rash following antibiotic initiation strongly suggests an IgE-mediated immediate hypersensitivity reaction 1.

  • Urticaria typically manifests as raised, erythematous, pruritic wheals that appear suddenly and can occur within hours to days of drug exposure 1.
  • The timing (one day after starting penicillin) is consistent with an immediate-type drug reaction, though delayed urticaria can occur up to several days into therapy 1.

Histopathologic Features of Urticaria

Dermal edema is the hallmark histologic finding in urticaria:

  • Urticarial lesions are characterized by dermal edema with separation of collagen bundles due to fluid accumulation in the superficial and mid-dermis 1.
  • There is typically a sparse perivascular lymphocytic infiltrate with occasional eosinophils, but the predominant feature is interstitial edema 1.
  • The epidermis remains intact without significant changes—no acantholysis, spongiosis, or dyskeratosis 1.

Why Other Options Are Incorrect

  • Acantholysis (Option A): Loss of intercellular connections between keratinocytes, seen in pemphigus and other blistering disorders—not characteristic of urticaria 1.
  • Acanthosis (Option B): Epidermal thickening seen in chronic conditions like psoriasis or lichen planus—not a feature of acute urticaria 1.
  • Dyskeratosis (Option D): Abnormal keratinization seen in conditions like actinic keratosis or squamous cell carcinoma—not present in urticaria 1.
  • Epidermal spongiosis (Option E): Intercellular edema within the epidermis characteristic of eczematous dermatitis—urticaria primarily affects the dermis, not the epidermis 1.

Clinical Management Considerations

This patient requires immediate discontinuation of penicillin V and alternative antibiotic therapy:

  • For patients with immediate hypersensitivity reactions to penicillin (urticaria, angioedema within hours to days), all β-lactam antibiotics including cephalosporins should be avoided due to up to 10% cross-reactivity risk 1, 2.
  • Clindamycin 300 mg orally three times daily for 10 days is the preferred alternative, with only ~1% resistance among Group A Streptococcus in the United States 2, 3.
  • Azithromycin 500 mg once daily for 5 days is acceptable but has 5-8% macrolide resistance rates 2, 3.

Symptomatic management of the urticaria:

  • Oral antihistamines (H1-blockers such as cetirizine or loratadine) should be initiated for pruritus control 1.
  • The urticaria typically resolves within 24-48 hours after discontinuing the offending drug, though recurrent hives may persist for 1-2 days 1.
  • Long-acting antihistamines may be continued for several days if needed 1.

Important Pitfall to Avoid

Do not rechallenge with any β-lactam antibiotic in this patient. The development of urticaria within 24 hours of starting penicillin V indicates immediate hypersensitivity, and future exposure to penicillins or cephalosporins carries significant risk of more severe reactions including anaphylaxis 1, 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Treatment of Streptococcal Infections in Patients with Penicillin Allergy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Clindamycin for Group A Streptococcal Infections in Elderly Patients

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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