Outcomes of Infants With Severe Refractory Food Protein-induced Allergic Proctocolitis Treated With Mesalamine

**Background:** Food protein-induced allergic proctocolitis (FPIAP) is a common, typically benign condition in infants, presenting with rectal bleeding, mucousy stools, and irritability. Severe cases may involve feeding intolerance, vomiting, and failure to thrive. Standard management includes elimination diets and elemental formulas, but evidence-based guidelines for refractory cases are lacking. Mesalamine, a locally active anti-inflammatory agent used in colitis, has limited data in infants with FPIAP. This study aimed to evaluate outcomes of a short course of mesalamine in infants with severe refractory FPIAP.

**Methods:** A retrospective chart review was conducted on patients diagnosed with FPIAP from January 2009 to December 2012 (total 580 patients). Inclusion criteria: age <12 months, no other comorbidities, treated with elemental formulas for >2 weeks, and persistent severe symptoms (defined as significant distress and routine disruption per parental report). Of 65 severe cases identified, all underwent esophagogastroduodenoscopy (EGD) and flexible sigmoidoscopy (FS). Forty-four infants received mesalamine (40-60 mg/kg/day for average 100 ± 50 days) and were compared to 21 severe cases not treated with mesalamine. Statistical analysis used Fisher exact test with significance at P <0.05.

**Key Results:** Among 65 severe FPIAP infants (mean age 2.98 ± 1.88 months, 58.46% male, 78.46% Caucasian), common symptoms included spitting up/vomiting (96.92%), fussiness (92.31%), stool changes (87.69%), and choking/gagging (73.85%). On FS, 53.84% had lymphonodular hyperplasia, 40% normal, 6% patchy colitis; all biopsies showed eosinophilic infiltration (5-45/hpf). On EGD, 36.92% had hiatal hernia, 58.46% normal; 75.38% had eosinophilic infiltration (9-40/hpf). Of 57 patients with pH study, 32% had gastroesophageal reflux. Mesalamine was started at mean age 3.5 months (range 22 days-7.5 months). Two patients required a second course; two discontinued (one black tongue, one cough). At 3 months, mesalamine-treated patients showed significant improvement vs. untreated: fussiness (73.17% vs. 10.52%, P=0.0001), spitting up/vomiting (72.72% vs. 9.5%, P=0.0001), stool consistency (52.27% vs. 5.2%, P=0.0005), decreased appetite (79.16% vs. 12.5%, P=0.0016), respiratory problems (88.46% vs. 40%, P=0.0062), choking/gagging (81.57% vs. 38.46%, P=0.0106), gassiness (51.72% vs. 0%, P=0.0121), and back arching (95.65% vs. 60%, P=0.0214). No significant differences for skin problems, blood/mucous in stool, hiccups, or sleep problems. Fecal occult blood test (FOBT) was positive in 79.54% before mesalamine; after treatment, 15 converted to negative, 2 remained positive, 11 not retested. Mesalamine group had lower failure to thrive (20.45% vs. 47.61%) and fewer problems after cow's milk (85% vs. 22%) or soy milk (42.3% vs. 22%) introduction at 15 and 14 months, respectively. Use of histamine H2 antagonists decreased from 84% to 57% and proton pump inhibitors from 53% to 25% after mesalamine.

**Clinical Implications:** This retrospective study suggests that a short course of mesalamine (40-60 mg/kg/day for ~100 days) is safe and effective in improving multiple severe symptoms of FPIAP in infants who fail elemental formulas. The treatment also reduced the need for acid-suppressing medications and was associated with lower failure to thrive rates and better tolerance to cow's milk and soy milk. However, the study is limited by its retrospective design, small sample size, lack of randomization, and potential selection bias. The authors note that FOBT should not be used as the sole monitoring tool, as 78% of severe cases had positive FOBT despite biopsy-proven proctocolitis. Further prospective studies are needed to confirm these findings and explore the pathophysiology and optimal management of severe FPIAP.