Allergic Proctocolitis: Literature Review and Proposal of a Diagnostic–Therapeutic Algorithm

Abstract

Allergic proctocolitis (AP) is a benign condition, frequent in childhood, that is classified as a non-IgE-mediated food allergy. The prevalence is unknown; however, its frequency appears to be increasing, especially in exclusively breastfed infants. Clinical manifestations typically begin in the first few months of life with the appearance of bright red blood (hematochezia), with or without mucus, in the stool of apparently healthy, thriving infants. Most cases of AP are caused by cow’s milk proteins; however, other allergens, such as soy, egg, corn, and wheat, may be potential triggers. Diagnosis is based on the patient’s clinical history and on the resolution of signs and symptoms with the elimination of the suspected food antigen from the diet and their reappearance when the food is reintroduced into the diet. The treatment of AP is based on an elimination diet of the trigger food, with resolution of the symptoms within 72–96 h from the beginning of the diet. The prognosis of AP is good; it is a self-limiting condition, because most children can tolerate the trigger food within one year of life, with an excellent long-term prognosis. The purpose of this review is to provide an update on the current knowledge and recommendations in epidemiological, diagnostic, and therapeutic terms to the pediatricians, allergists, and gastroenterologists who may find themselves managing a patient with AP.

To Diet or Not to Diet This Is the Question in Food-Protein-Induced Allergic Proctocolitis (FPIAP)—A Comprehensive Review of Current Recommendations

“…The pathogenesis of FPIAP is still not fully understood, although non-IgE-mediated and cellular immune responses to food proteins involving T cells and eosinophils are generally described [ 2 , 3 , 4 , 5 , 11 , 12 , 13 , 14 ]. Eosinophilic infiltration of the rectal mucosa is reported in many patients submitted to endoscopic investigation, with the number of eosinophils at histology ranging from 6 to more than 20 per 40× high-power field [ 2 ].…”

“…In particular, a decreased expression of transforming growth factor β (TGF-β), produced by regulatory cells, and an increased level of proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α) would alter the epithelial barrier, increase the permeability of tight junctions, and stimulate intestinal inflammation. Nevertheless, a different intestinal microbiota composition (with decreased number of bifidobacteria and lactobacilli) associated with an abnormal innate immune response to food antigens could contribute to impaired oral tolerance to cow’s milk protein or, less frequently, to soy, egg, and corn in infants with FPIAP [ 3 , 4 , 7 , 15 ]. Moreover, a genetic predisposition with a positive family history of atopy has been observed in 20–40% of patients [ 2 , 3 , 4 , 5 , 15 ].…”

“…Nevertheless, a different intestinal microbiota composition (with decreased number of bifidobacteria and lactobacilli) associated with an abnormal innate immune response to food antigens could contribute to impaired oral tolerance to cow’s milk protein or, less frequently, to soy, egg, and corn in infants with FPIAP [ 3 , 4 , 7 , 15 ]. Moreover, a genetic predisposition with a positive family history of atopy has been observed in 20–40% of patients [ 2 , 3 , 4 , 5 , 15 ]. In one study, virus particles were detected in the microvillus layer of the colon epithelium in 8 infants with rectal bleeding by electron microscopy but not in the stool samples [ 15 ].…”

“…One prospective study enrolled 40 infants (mean age: 2.7 months) with overt rectal bleeding who were randomized to continue or eliminate CMP for 1 month. Overall, 8 (20%) infants had spontaneous resolution of hematochezia, whereas 32 (80%) infants manifested bloody stools during the follow-up (mean [range]: 2.1 [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ] per day) with a mean number of 6 days of rectal bleeding that was not affected by CMP elimination diet. At colonoscopy, the mucosa appeared normal in less than half of the patients, and histology frequently revealed typical inflammatory findings.…”

“…Food-protein-induced allergic proctocolitis (FPIAP) is a transient, non-IgE-mediated allergic colitis manifesting with rectal bleeding and often associated mucus-streaked stools (with possible diarrhea) in well-appearing and thriving infants, with negative tests for pathogens [ 1 , 2 , 3 , 4 , 5 ]. Disappearance of blood in the stool usually occurs within 72–96 h from eliminating food allergen (most frequently cow’s milk protein, CMP), although it may take weeks and a more restricted diet in some patients.…”