From the pages of AllergyWatch

For this installment of From the Pages of Allergy Watch, I have selected articles from the July to August issue. The first, reviewed by Dr Lee, suggests that pretreatment with H₁ and H₂ antihistamines and montelukast can reduce the risk for reaction to coronavirus disease 2019 (COVID-19) vaccination. The second, reviewed by Dr Hernandez-Trujillo, reports data suggesting that alpha-gal allergy can be a problem even in areas not endemic for the lone star tick. The final article, reviewed by Dr Joshi, presented data suggesting that children with more severe atopic dermatitis are more likely to have learning disabilities.

Stanley Fineman, MD, Editor-in-Chief, AllergyWatch.

Coronavirus Disease 2019 Vaccine in Mast Cell Disorders

In patients with mastocytosis, vaccination has been reported to cause exacerbation of the symptoms of mast cell (MC) activation, including anaphylaxis. Anaphylactic reactions to the Pfizer-BioNTech messenger RNA (mRNA) COVID-19 vaccine have been reported. An approach to the safe administration of COVID-19 mRNA vaccine in 2 patients with mastocytosis and MC activation symptoms is described. The patients were 2 female nurses with cutaneous and systemic mastocytosis, both of whom had direct contact with patients having COVID-19. One patient with indolent systemic mastocytosis presented with severe MC mediator-related symptoms including abdominal pain and bloating, diarrhea, pruritus and lesion flare-up, and osteopenia. Before the first dose of the Pfizer-BioNTech mRNA vaccine, she was treated with H₁ and H₂ antihistamines (1 hour before) and montelukast 10 mg (1 and 24 hours before). Vaccination was carried out with no adverse effects. The second patient had indolent systemic mastocytosis with a history of anaphylactic reactions to multiple drugs and MC mediator-related symptoms including migraines, pruritus, gastroesophageal reflux, and osteopenia. She received the same premedication regimen before her first dose of COVID-19 mRNA vaccine, with myalgias as her only symptom. The authors suggest that their premedication regimen may enable safe and successful administration of the COVID-19 mRNA vaccine in patients with MC activation disorders. They emphasize that the procedure should be carried out under medical observation in a hospital setting with intensive care unit availability.

Comments from Gerald B. Lee, MD: This letter to the editor describes successful mRNA COVID-19 vaccination in 2 patients with systemic or cutaneous mastocytosis. The authors recommend pretreatment with H₁ and H₂ antihistamines and montelukast given 1 and 24 hours before vaccination.

Rama TA, Moreira A, Castells M. mRNA COVID-19 vaccine is well tolerated in patients with cutaneous and systemic mastocytosis with mast cell activation symptoms and anaphylaxis. J Allergy Clin Immunol. 2021;147(3):877-878.

Is Alpha-Gal Really a Problem in Patients With Food Allergy?

Patients with immunoglobulin E (IgE)-mediated allergy to galactose-alpha-1,3- galactose (alpha-gal) have delayed-onset allergic reactions after ingestion of mammalian meat. The true burden and geographic distribution of this emerging alpha-gal syndrome are unknown. This study analyzed recent US trends in alpha-gal IgE testing and diagnosis of the alpha-gal syndrome. The retrospective analysis included 122,068 specimens from 105,674 patients tested for alpha-gal antibodies from 2010 through 2018. The study used deidentified data provided to the Centers for Disease Control and Prevention by the test manufacturer. At least 1 positive result for alpha-gal IgE was reported for 32.4% of patients. Positive results were more common in men than women, 43.3% vs 26.0%, and increased with age. The number of tests performed increased during the study period, whereas the rate of positive results declined—in 2018, the positivity rate was 29.8% in a total of 26,148 tests. Positive results were more likely to occur in the summer and fall months. More than two-thirds (67.5%) of positive specimens came from the southern US census region. The positivity rate ranged from 30.0% to 34.8% in the Midwest, Northeast, and South, but was only 1.8% in the West. States with the highest rate of positive alpha-gal tests (2.35 per 100,000 population or higher) were Arkansas, Virginia, Kentucky, Oklahoma, and Missouri. In nearly 80% of cases, the alpha-gal IgE value on the first positive test was at least 0.35 kU/L. From 2010 to 2018, more than 34,000 US patients received positive test results for IgE antibodies to alpha-gal. Alpha-gal syndrome seems to be an increasingly recognized public health problem, with a geographic distribution consistent with exposure to Amblyomma americanum ticks. Clinicians must be aware of the possibility of this diagnosis, even in areas not endemic for the lone star tick.

Comments from Vivian Hernandez-Trujillo, MD: This study reports an increasing number of patients with positive IgE to alpha-gal. Almost one-third of patients received positive test results and the numbers of positive tests increased over the years. A high index of clinical suspicion in patients without a known cause of anaphylaxis is essential. As more patients are tested, we will likely learn more on the true prevalence of this form of food allergy, especially its geographic distribution throughout the United States and the world.

Binder AM, Commins SP, Alrtich ML, et al. Diagnostic testing for galactose-alpha-1,3 galactose, United States, 2010 to 2018. Ann Allergy Asthma Immunol. 2021;126(4):411-416.e1.

Atopic Dermatitis Severity Linked to Learning Disability in Children

Population-based studies have reported that children with atopic dermatitis (AD) are more likely to be diagnosed as having a learning disability. The association between AD severity and learning disability was evaluated in a large cohort of children. The analysis included 2074 children with AD, drawn from the Pediatric Eczema Elective Registry. Patients with a median age of 16 years completed 10 years of follow-up. The severity of AD, assessed using the Patient-Oriented Eczema Measure (POEM), was evaluated for association with patient-reported diagnosis of a learning disability. At follow-up, AD was rated very severe in 0.6% of children, severe in 4.2%, moderate in 17.9%, and mild in 24.4%, with 52.2% of patients having clear or almost clear skin. The rate of reported learning disabilities was 8.2%. The median total POEM score was 5 in children with a learning disability vs 2 in those without a learning disability. Based on both POEM score and patient self-rating, children with learning disabilities were more likely to have worse AD severity. On multivariable analysis, patients with more severe AD were more likely to report a learning disability, with an odds ratio of 1.72 for those with mild AD, 2.09 with moderate AD, and 3.10 for severe or very severe AD (compared with patients with clear to almost clear skin). Pediatric patients with more severe AD are more likely to report being diagnosed as having learning disability, independent of socioeconomic status, age at AD onset, and comorbid conditions. Pending further studies to confirm and evaluate the mechanism of this association, the authors recommend screening for learning disorders in children with more severe AD.

Comments from Shyam Joshi, MD: This cross-sectional study revealed that more severe forms of AD are associated with learning disability, even after accounting for common confounders such as socioeconomic status and comorbid neuropsychiatric disease. Although the study cannot determine the underlying etiology of this association, the authors postulate that itch and sleep disturbances may lead to poor learning ability. The role of shared neuroinflammatory signaling also needs further investigation.

Wan J, Mitra N, Hooper SR, Hoffstad OJ, Margolis DJ. Association of atopic dermatitis severity with learning disability in children. JAMA Dermatol. 2021;157(6):1-7.