Non-allergic benign infantile proctocolitis: a neglected nosographic entity

Abstract

The presence of rectal bleeding in the first months of life is very often diagnosed as food protein-induced allergic proctocolitis (FPIAP). The symptoms typically start in infancy, and most cases resolve by age 12 months. Infants with FPIAP usually present bloody stools mixed with mucus, with or without reduced stool consistency. Most affected infants are generally healthy-appearing. We used the story of an infant with rectal bleeding as a reminder that there is also the possibility of a form of benign non-allergic proctocolitis that is not usually included in the differential diagnosis. In the absence of warning signs and in case of infant well-being, it should be the first clinical entity to suspect. Therefore, we suggest we should wait at least 2 months before starting to eliminate cow milk or other foods from the diet.

Background

During infancy, rectal bleeding is very often diagnosed as food protein-induced allergic proctocolitis (FPIAP), a transient inflammatory disease involving the distal colon. The symptomatology consists of emission of blood with the stool, with or without mucus and/or diarrhoea. Symptoms generally occur between 1 and 4 weeks of age in otherwise healthy infants and tend to resolve spontaneously within the first year of life. With the help of the story of an infant with rectal bleeding, we would suggest the possibility of a form of benign non-allergic proctocolitis that is not usually suspected in the differential diagnosis.

Case presentation

A Caucasian female infant, exclusively breast fed, at the age of 1 month and 8 days started presenting with rectal bleeding, sometimes mixed with mucus and stools. After 1 month, as the rectal bleeding persisted, her mother started a cow’s milk protein-free diet and the child’s mean haemoglobin level was measured (125 g/L). However, evacuation of stool mixed with blood and mucus continued and became more frequent (up to five times per day). At the age of 3 months and 18 days, the child made an outpatient examination to our allergy clinic. Prick tests for cow’s milk and soy were negative, and the ones for egg were positive. We suggested to reintroduce cow’s milk proteins in the mother’s diet and to eliminate egg and soy. The mother, who did not eat soy, eliminated the egg when the child was 3 months and 20 days old but, out of fear, did not reintroduce cow’s milk protein into her diet. The child continued to present with frequent evacuations of soft stools with mucus and blood, and once she presented an abundant bleeding 3 days after egg elimination from the mother’s diet (figure 1).

Figure 1.

Large amount of blood in the infant’s stool.

Investigation

She was admitted to the hospital where blood examinations showed mean haemoglobin level of 95 g/L and serum ferritin concentration of 18 ng/mL. Coagulation tests, C reactive protein, serologies and PCR for cytomegalovirus, stool culture and stool parasitology tests, faecal calprotectin, abdominal ultrasonography and intestinal scintigraphy were all negative or normal. A proctoscopy documented the presence of proctitis with small aphthae. Histological examination of the rectal mucosa showed a mild to moderate inflammatory lymphoplasmacytic infiltrate of the lamina propria with lymphoid and eosinophil aggregates (25 eosinophils/high-power field).

Outcome and follow-up

At 5 days after the elimination of the egg from the breastfeeding mother’s diet, and therefore at the age of 3 months and 25 days, the child stopped presenting with rectal bleeding. It was therefore suggested to reintroduce the egg, and there was a renewed suggestion to reintroduce cow’s milk in her maternal diet. The reintroduction started about 10 days after the disappearance of rectal bleeding, when the child was 4 months and 5 days old.

The rectal bleeding did not recur after the reintroduction of cow’s milk and egg in the mother’s diet and did not do so in the following 6 months. (table 1)

Table 1.

Summary of events

Age of infant	Event
1 month and 8 days	Occurrence of rectal bleeding
2 months and 8 days	Starting cow’s milk-free mother’s diet
3 months and 18 days	Outpatient visit, suggestion to eliminate egg from the maternal diet
3 months and 20 days	Starting egg-free and cow's milk-free mother's diet
3 months and 23 days	Abundant bleeding, hospital admission
3 months and 25 days	Disappearance of rectal bleeding
4 months and 5 days	Reintroduction of cow’s milk and egg into maternal diet
At least until the age of 11 months	No rectal bleeding

Discussion

The presence of rectal bleeding in early infancy is very often diagnosed as FPIAP.¹ Diagnosis is based on a history of rectal bleeding, exclusion of warning signs and disappearance of symptoms after the elimination of offending food from infant or breastfeeding mother’s diet. The trigger food most frequently involved in FPIAP are cow’s milk, egg and soy. Infants affected by FPIAP are usually breast fed, although exposure to cow’s milk protein can also occur in formula-fed infants.

However, as early as 2006, Arvola et al² reported, in what has remained the only randomised controlled trial on this subject, that the duration and/or severity of rectal bleeding is not affected by the elimination of trigger food from the diet. Moreover, Nowak-Węgrzyn³ had reported that there was the disappearance of rectal bleeding in up to 20% of breastfed infants without the elimination of any food from breastfeeding mother’s diet.

Thus, what diagnosis is possible for the child we described? We did not observe recurrence of rectal bleeding after the reintroduction of the suspected food, so it should not be an FPIAP. It is theoretically possible that the child has acquired the tolerance in coincidence with the elimination of the egg from the mother’s diet, that is, at less than 4 months of age. But it is very unlikely. In fact, Nowak-Węgrzyn³ had reported that rechallenge within the first 6 months usually induces recurrence of bleeding within 72 hours, and that infants with proctocolitis become tolerant to the trigger food by 1–3 years of age and the majority achieves clinical tolerance by 12 months. It is true that Elizur et al⁴ reported that 11–20 infants tolerated the reintroduction of cow’s milk at a mean age of 5.3±2.1 months. However, none of these infants had been challenged a few days after the resolution of rectal bleeding for diagnostic confirmation. Thus, we cannot be sure that the children described by Elizur et al⁴ all had FPIAP. The diagnosis of FPIAP presumes, as the name of this disease implies, the demonstration of a causal relationship between the ingestion of a food and the presence of rectal bleeding. FPIAP is, by definition, induced by food proteins.^{1 3 5} However, in the case of our little patient, the elimination of cow’s milk from the maternal diet was not followed by disappearance of rectal bleeding, and the reintroduction of egg was not followed by its reappearance. Therefore, we cannot make a diagnosis of FPIAP for her.

None of the diseases that some authors list for differential diagnosis with FPIAP^{1 3 6} is compatible with the history of our patient; in all these, there are other symptoms or signs; none presents only with rectal bleeding. Therefore, our patient’s case report does not seem nosographically well settled. However, Leonard⁶ reports that some studies have questioned whether allergic proctocolitis may be overestimated as a cause of bloody stools in infants. Leonard⁶ mentions some studies in which some infants’ rectal bleeding resolved without dietary changes or did not reappear following reintroduction of the suspected food. Jang et al⁷ named this condition as idiopathic neonatal transient colitis and found it in 14 (87.5%) of 16 infants they studied.

Then, we believe that our patient had benign non-allergic proctocolitis. To adjust the name to the more typical age and benignity of the clinical condition, we change the name adopted by Jang et al⁷ and propose non-allergic benign infantile proctocolitis. This condition should be part of the differential diagnosis of any infant with rectal bleeding. It should be the first clinical entity to suspect if (a) an infant is less than 6 months old; (b) rectal bleeding has been going on for less than 2 months, is brilliant and not abundant; (c) no anal fissures are visible; and (d) there is the absence of warning signs and the infant is healthy. Today, we would modify the algorithm⁸ we proposed in 2018 for infants with rectal bleeding. If the above criteria were met, we would wait at least 2 months before starting to eliminate cow’s milk or other foods from the diet. In addition, we would proceed to further investigation only if warning signs¹ appeared or if rectal bleeding persisted beyond 1 year of age.

Learning points.

• Rectal bleeding in generally healthy-appearing infants is often diagnosed as food protein-induced allergic proctocolitis, due to non-IgE-mediated reaction to food proteins.

• Diagnosis is based on a good response to allergen-free diet and on the recurrence of symptoms following the reintroduction of the offending food.

• We think there is also a form of benign non-allergic proctocolitis that should be suspected in infants with bloody stools.

• We suggest waiting at least 2 months before starting an elimination diet.

Ethics statements

Patient consent for publication

Consent obtained from parent(s)/guardian(s).