Cox’s Conference: Chronic Urticaria, Penicillin Allergy, and Allergy Pearls

During this week’s Cox’s Conference, we had a special presentation from two of our Allergy/Immunology fellows, Dr. Daniel Har and Dr. Shyam Joshi, with expert discussant Dr. David Khan. They presented had two cases, one of chronic urticaria and another of pneumonia in the setting of reported penicillin and cephalosporin allergy.

Chronic Urticaria:

  • Definition: urticaria that has been continuously or intermittently present for at least six weeks
  • Pathophysiology: unknown. Possibly secondary to auto-allergy mediated IgE activation of mast cells
  • History: blanching wheals that last less than 24 hours, are not painful or burning. Triggers of wheals include pressure, heat, water.
  • Physical Exam:
    • Chronic urticaria
    • Dermatographism
  • Testing:
    • Choosing Wisely:Don’t routinely do diagnostic testing in patients with chronic urticaria.In the overwhelming majority of patients with chronic urticaria, a definite etiology is not identified. Limited laboratory testing may be warranted to exclude underlying causes. Targeted laboratory testing based on clinical suspicion is appropriate. Routine extensive testing is neither cost effective nor associated with improved clinical outcomes. Skin or serum-specific IgE testing for inhalants or foods is not indicated, unless there is a clear history implicating an allergen as a provoking or perpetuating factor for urticaria.
    • Skin Biopsy: neutrophils and eosinophils, but NOT leukocytoclasis or fibrinoid necrosis (vasculitis)
  • Differential Diagnosis:
    • Urticaric vasculitis: these lesions are nonblanching, spanning several days and often followed by residual hyperpigmented changes. Biopsy shows leukocytoclasis or fibrinoid necrosis (vasculitis)
  • Management:
    • CU management
      Note: After Step 3, steps 4 through 7 are interchangeable and depends on the experience and preference of provider. Omalizumab has shown remarkable success for remission in several patients

Antibiotic/Drug Allergy Pearls:

  • History of Penicillin Allergy

    • What do you do?
      • Confirm reaction. Oftentimes, these reactions are misdiagnosed, mislabeled, or have waning allergy. 10% of the population endorse a history of penicillin allergy; of these patients, 90% not allergic to penicillins and are able to take these antibiotics safely. If the reaction is not consistent with a mast-cell mediated reaction, the allergy is likely not real.
      • Penicillin Skin Testing:
        • Can be done as an inpatient and outpatient
        • Excellent negative predictive value for excluding penicillin allergy
        • Two-step process: First, PRE-PEN test (benzylpenicilloyl polylysine) and PCN-G test. Then, if negative, amoxicillin 500 mg challenge.
        • Note: Penicillin is the only antibiotic for which there is validated skin testing outcomes. Other skin tests exist but lack rigor in validation
    • What if you want to use a cephalosporin?
      • Medical Myth: 10% of patients with penicillin allergy have a cephalosporin allergy. This was perpetuated by early in vitro studies as well as studies using cephalosporins contaminated with penicillin
      • Facts:
        • The cross-allergy with 2nd, 3rd, and 4th generation cephalosporins in patients with penicillin allergy is negligible. 
        • The cross-allergy with 1st generation cephalosporins is approximately 1%.
  •  Drug Allergies:

    • If you want to determine if a drug is safe to administer in a patient with a reported allergy but has a low pre-test probability actual allergy, refer for a graded challenge.
      • This is purely diagnostic. It does not change tolerance to drug
      • Involves successive exposure to increasingly less dilute doses of the drug in question. The interval between exposures depends on the type of reported reaction

Other High-Value Allergy Pearls:

  • Choosing Wisely:  Don’t perform food IgE testing without a history consistent with potential IgE-mediated food allergy.
    • Testing individuals without a consistent history yields a high rate of false-positive or clinically irrelevant results that waste healthcare resources and lead to unwarranted patient lifestyle restrictions and anxiety.
    • Reactions that are IgE mediated are rapid (minutes to two hours), unless mediated by alpha-gal allergy in meats, with symptoms that can involve the skin, gastrointestinal tract, or cardiovascular system.


  • Diagnosis of anaphylaxisdiagnosis of anaphylaxis


  • Choosing Wisely:  Don’t diagnose or manage asthma without spirometry.


  • Choosing Wisely: Don’t routinely order low- or iso-osmolar radiocontrast media or pretreat with corticosteroids and antihistamines for patients with a history of seafood allergy, who require radiocontrast media.
    • The risk of allergic reaction to IV contrast to patients with shellfish allergy is similar to that of patients who have any form of atopy