"Allergic to Everything"

John M Kelso, MD, professor in the division of allergy, asthma, and immunology at the Scripps Clinic, in San Diego, CA, opened his presentation "Allergic to Everything," at the 2025 ACP Internal Medicine Meeting, April 3-5, in New Orleans, with a series of clinical pearls for primary care clinicians.

John Kelso, MD

Food allergies typically present with characteristic patterns that can guide diagnostic and management decisions. Kelso emphasized that true IgE-mediated food allergies typically manifest within minutes to an hour after ingestion, with symptoms characteristic of mast cell degranulation – primarily cutaneous (hives, angioedema), respiratory, gastrointestinal, or cardiovascular symptoms.

The most common food allergens remain milk, eggs, nuts, fish/shellfish, and legumes (particularly peanuts and soy). However, Kelso stressed that "virtually any food can cause an allergic reaction," with the most severe reactions, including fatal ones, predominantly associated with these common allergens.

A critical diagnostic concept, Kelso said, is that sensitization (development of IgE antibody) requires prior exposure, either through ingestion or skin exposure in childhood. Subsequent uneventful ingestion largely excludes allergy, which makes careful history-taking essential.

The appropriate testing approach emphasizes specificity rather than broad screening, Kelso reminded the audience. "Test only for suspect foods and not for foods the patient eats uneventfully," he advised. "There are no clinical circumstances where evaluating specific IgE to a panel of common food allergens is appropriate."

He further clarified that chronic symptoms including gastrointestinal issues, brain fog, or fatigue are not consistent with IgE-mediated food allergy, making testing and dietary elimination inappropriate in these contexts.

For management, Kelso presented a nuanced approach to treatment decisions:

• For reactions limited to hives or a single episode of emesis: antihistamine and close observation
• Any respiratory or cardiovascular symptoms: epinephrine and close observation
• If response to epinephrine isn't prompt and complete: emergency department evaluation

"...chronic symptoms including gastrointestinal issues, brain fog, or fatigue are not consistent with IgE-mediated food allergy, making testing and dietary elimination inappropriate in these contexts."

Kelso highlighted the relatively recent FDA approval of epinephrine nasal spray for anaphylaxis in patients weighing 30 kg or more, the labeling for which is based on pharmacokinetic and pharmacodynamic studies showing comparable efficacy to injectable forms. The nasal administration may be beneficial for patients who are needle phobic or are unable to administer using an autoinjector.

Penicillin Allergy: The Case for "Delabeling"

Perhaps the portion of the presentation with the greatest potential to change clinical practice focused on penicillin allergy, where approximately 10% of patients report an allergy, but only about 5% of those demonstrate positive skin tests.

The consequences of inaccurate penicillin allergy labeling include "suboptimal treatment, more side effects (eg, Clostridium difficile), higher costs, and promotion of antibiotic resistance," according to Kelso.

He advocated for a systematic approach to "delabeling" appropriate candidates – essentially, almost anyone with penicillin allergy on their chart who doesn't have a history of severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis, DRESS, or AGEP.

The detailed history should explore:

• Timing of the reaction (recent reactions more concerning)
• Specific medication involved
• Duration of medication use before reaction
• Nature of symptoms
• Prior medication exposure
• Subsequent medication exposure

Kelso provided practical guidance for conducting oral amoxicillin challenges (250 mg single dose) in office settings for appropriate candidates. He noted that "the chance of either immediate or delayed reaction is less than 5% each" with "the vast majority of immediate reactions being hives easily treated with antihistamine."

Tips he offered for pursuing penicillin allergy delabeling included being completely transparent with patients about the low probability of reaction, arranging appropriate observation without creating anxiety, and providing clear documentation on whether delabeling was successful.

Environmental Allergies: Diagnostic and Treatment Updates

In the final segment of “Allergic to Everything,” Kelso addressed discussed what he considers the most high-value approach for diagnosing patients with an environmental allergy. He reviewed the classic presentation of allergic rhinitis: nasal symptoms (rhinorrhea, congestion, sneezing, itching), eye symptoms, and itching of the palate or ear canals – differentiating from cough, which suggests asthma. He reviewed the 3 purposes served by testing for aeroallergens: 1. Confirming IgE-mediated mechanisms; 2. Identifying allergens amenable to environmental control; and, 3. Determining allergens for potential immunotherapy.

Kelso provided practical guidance on antihistamine selection, noting relative effectiveness (cetirizine = fexofenadine > loratadine) and potential drowsiness (cetirizine > loratadine > fexofenadine). He questioned the value of newer "-des" and "levo-" formulations, citing: "Desloratadine would be expected to produce results similar to loratadine. There is no clinical advantage to switching a patient from loratadine to desloratadine."

For nasal corticosteroid sprays, Kelso stressed that all are equally effective, with standard dosing of 2 sprays per nostril daily (or 1 spray twice daily). For patients with inadequate response, combining with nasal antihistamine sprays may provide additional benefit.

Finally, he compared subcutaneous immunotherapy (SCIT, "allergy shots") with sublingual immunotherapy (SLIT), noting that SCIT has shown greater efficacy in comparative studies and can address multiple allergens simultaneously, while SLIT is limited to single allergens (grass, ragweed, dust mite).

Dr. Kelso concluded with several evidence-based practice changes:

• Order specific IgE testing for foods only with history consistent with IgE-mediated allergy
• Avoid food panels; test only for specific suspect foods
• For patients reporting penicillin allergy, assess reaction details:
• If SCAR: avoid
• If history of first-dose urticaria or anaphylaxis: refer to allergy
• For all others (the majority): perform amoxicillin challenge
• For rhinitis symptoms: assess for eye symptoms, seasonality, triggers, and family history
• Consider nasal corticosteroids for chronic symptoms

Sources

Sampson HA, Aceves S, Bock SA, et al. Food allergy: a practice parameter update-2014. *J Allergy Clin Immunol* 2014;134:1016-25.

Khan DA, Banerji A, Blumenthal KG, et al. Drug allergy: A 2022 practice parameter update. *Journal of Allergy and Clinical Immunology* 2022; 150:1333-93.

Dykewicz MS, Wallace DV, et al. Rhinitis 2020: A practice parameter update. *J Allergy Clin Immunol*. 2020 Oct;146(4):721-767.