CoMiSS Tracks Elimination Diet Response in Infants with Milk-Related Proctocolitis

A study showed that the Cow’s Milk Protein Related Symptom Score (CoMiSS) significantly reduced after the 4-week elimination diet among infants with Cow’s Milk Protein Associated Proctocolitis.1

A cow’s milk protein allergy remains the most common food allergy in the first year of life, impacting 2.5 percent of children < 3 years.2 A milk allergy can either be immunoglobulin E-mediated, non-IgE-mediated, or mixed type.

Food protein-induced allergic proctocolitis is classified as a non-IgE-mediated cow’s milk protein allergy. With no identified biomarker that can diagnose Cow’s Milk Protein Associated Proctocolitis, CoMiSS was developed as a diagnostic tool to monitor symptom improvement in infants with cow’s milk protein allergy.

However, no studies have evaluated the effectiveness of CoMiSS in monitoring elimination diet response in Cow’s Milk Protein Associated Proctocolitis.1 Investigators from Türkiye, led by Menşure Nur Çelik from Ondokuz Mayis University, sought to assess the efficacy of CoMiSS on elimination diet response in infants diagnosed with Cow’s Milk Protein Associated Proctocolitis compared with healthy controls.

“In clinical practice, CoMiSS can be a useful tool for monitoring dietary response, especially when tracking symptoms over time,” investigators wrote.1

Çelik and colleagues conducted a case-control study between August 2020 and March 2022 with 13 infants with Cow’s Milk Protein Associated Proctocolitis and 22 healthy controls, aged 17 – 26 weeks. Infants received diagnoses at 0 – 6 months if they presented with bloody stools, but bloody stools resolved within 48 - 72 hours after removing cow’s milk from the mother's or infant’s diet and then returned within 48 – 72 hours after introducing cow’s milk into the diet. Eligibility criteria included being 17 – 26 weeks, breastfed, gestational age of 37 – 42 weeks, singleton birth, birth weight ≥ 2500 g and ≤ 4500 g, and healthy term infants.

Infants followed the elimination diet until they turned 9 months; milk was slowly reintroduced and completely back at 1 year old. Visits took place at ages 6, 7, 9, and 12 months.

The mean age at Cow’s Milk Protein Associated Proctocolitis onset was 9.3 ± 6.9 weeks, and the mean age at diagnosis was 12.6 ± 6.1 weeks.

CoMiSS significantly decreased after 4 weeks of the elimination diet (P < .05). Visit 2 showed no difference in total symptom scores between groups (P > .05). When infants reintroduced to milk by visit 3, total symptom scores increased in both groups, but scores were greater in infants with Cow’s Milk Protein Associated Proctocolitis than in controls (P < .05).

Infants with Cow’s Milk Protein Associated Proctocolitis had greater median crying scores at visits 1 and 3 compared with healthy infants (P < .05). At visit 2, the crying score median value reduced for both groups, with no significant difference between groups (P > .05).

“Although we did not use fecal calprotectin or a similar parameter to support this, we think that crying may indirectly indicate inflammation in the gastrointestinal tract in CMPAP,” investigators wrote.1 “Thus, although these infants with CMPAP did not produce bloody or mucous stool when their elimination diet was stopped at one year of age to check the development of tolerance, they again showed a significant increase in crying scores compared to healthy controls, indicating that they may still not have fully developed tolerance to cow’s milk.”

Ultimately, among infants with Cow’s Milk Protein Associated Proctocolitis, CoMiSS scores reduced significantly from baseline to visit 1 (P = .013) and visit 2 (P = .03). The CoMiSS decrease from baseline to visit 3 was not statistically significant (P = .075). The analysis revealed significant score decreases between visits 1 and 2 (P = .0006), followed by increases from visit 2 to visit 3 (P = .018). Among controls, CoMiSS reduced significantly from baseline to visit 2 (P = .005) and from baseline to visit 3 (P = .035).

“While there are no universally established thresholds for CoMiSS scores, we believe that significant changes in symptom scores, particularly those indicating a reduction in crying or defecation abnormalities, could guide clinicians in adjusting the diet.,” investigators wrote.1 “CoMiSS can also be helpful for long-term management of CMPA on and response to diet…while CoMiSS is valuable for short-term monitoring, further studies with longer follow-up periods are needed to assess its long-term applicability in CMPAP management.”

References

1. Çelik MN, Köksal E, Terece SP, Köken G, Karagöl HİE, Bakirtas A. Evaluating the effectiveness of elimination diet in infants with CMP-induced allergic proctocolitis using CoMiSS. Pediatr Res. Published online May 13, 2025. doi:10.1038/s41390-025-04117-7.

2. Common Allergens. Food Allergy Research & Education. https://www.foodallergy.org/living-food-allergies/food-allergy-essentials/common-allergens#:~:text=Allergy%20to%20cow's%20milk%20is,their%20first%20year%20of%20life. Accessed May 14, 2025.