Prospective Assessment of Pediatrician-Diagnosed Food Protein-Induced Allergic Proctocolitis by Gross or Occult Blood

Abstract

To prospectively define the incidence of food protein–induced allergic proctocolitis (FPIAP) and identify risk factors.Newborn infants (n = 903) from a single suburban, private, primary pediatrics practice in Massachusetts from April 2014 to February 2017: Gastrointestinal Microbiome and Allergic Proctocolitis cohort.Infants were recruited at their initial newborn visit and managed prospectively at routine well-child checks and sick visits for a diagnosis of FPIAP. The primary outcome was pediatrician-diagnosed FPIAP, which was then confirmed by research staff by using prespecified inclusion criteria, including documentation of gross or occult blood in the stool.The recruited cohort was predominately male (54%), White (69%), term (89%), and delivered vaginally (68%). A cumulative incidence of 17% (n = 153) of infants met inclusion criteria for a FPIAP diagnosis. The median age at symptom onset was 26 days, and the median age at FPIAP diagnosis was 35 days. Of the FPIAP cases, 41% (n = 63) had gross blood, and 37% (n = 56) had mucus with microscopic blood in their stool. The median age of symptom resolution was 123 days. Risk factors for FPIAP included a first-degree relative with food allergy (odds ratio [OR]: 1.9; 95% confidence interval [CI]: 1.2 to 2.8; P = .005), eczema (OR: 1.5; 95% CI: 1.1 to 2.2; P = .02), and household pets at birth (OR: 1.5; 95% CI: 1.01 to 2.1; P = .043). Infants initially fed both breast milk and formula were 61% less likely to develop FPIAP, compared with infants exclusively formula fed (hazard ratio [HR]: 0.39; P = .005). Infants fed both breast milk and formula at any point during the first 4 months were 56% less likely than exclusively formula-fed infants and 38% less likely than exclusively breastfed infants to develop FPIAP (HR: 0.44 [P = .005]; HR: 0.62 [P =.0497].When diagnosed clinically by community pediatricians, without confirmatory oral challenge, the prospectively defined FPIAP incidence is markedly higher than previous published estimates.FPIAP is generally considered a mild, self-limited, non–immunoglobulin E–mediated food allergy (with cow’s milk protein the most common trigger) found in otherwise healthy infants. There is a lack of validated diagnostic criteria, but elimination diet and rechallenge have been proposed. Diagnosis based solely on occult blood is controversial. This prospective observational cohort study found an exceptionally high rate of diagnosis by using the criteria applied and is possibly biased by the single-center design. This is not a criticism! It raises many important questions about infants presenting with gross or occult fecal blood. Interestingly, many of the infants had associated gagging, vomiting, food refusal, reflux, and/or irritability. Are there alternative diagnoses among this cohort? Do we need firmer diagnostic criteria? These findings underscore the need for exploring this population with gross or occult blood in the stool to better understand diagnoses, causes, and treatments. A follow-up analysis of this cohort revealed that children with the FPIAP diagnosis had a twofold risk of developing immunoglobulin E–mediated food allergy, even when accounting for atopic dermatitis as a risk (Martin VM, Virkud YV, Phadke NA, et al. Increased IgE-mediated food allergy with food protein-induced allergic proctocolitis. Pediatrics. 2020;146[3]:e20200202). This could be explained by a shared pathophysiology, or the possibility that dietary elimination was a risk factor. Because symptoms of FPIAP are often not reproduced by reexposure, there may be an unnecessary risk imposed by presumptive dietary elimination. Although, in the study, the researchers raise fascinating questions, it is important to strongly consider confirming a food trigger. Earlier milk reintroduction attempts in infants with FPIAP are thus encouraged.