Very Early Onset Inflammatory bowel disease (VEOIBD) is a growing concern in the paediatric population. This category of patients has certain peculiarities, among which are the single gene causation found in a good number of these patients and unusual course of the disease.¹

The patient was a 3-Year-Old girl who was initially brought for a General Paediatric assessment following concerns of new onset constipation. She was treated for 6 months with Movicol and sodium picosulfate with partial resolution. On further assessment however, she was noted to have perianal mucosal protrusions thought to be internal haemorrhoids and weight loss. She was referred for specialist assessment where she was found to have pancolitis on endoscopy. She also had an unusual finding of splenomegaly. She was started on infliximab infusions, azathioprine, and topical tacrolimus (for rectal lesions).

In view of her age and clinical findings, she had additional investigations as required for children with VEOIBD. She was found to have IL-27 serum auto-antibodies (IgG). She however showed normal response to IL-10 panel testing. She had additional immunological, genetic testing and glycogen storage disease screening done which were normal. She is currently on 4 weekly vedolizumab treatment, with steroids, following poor response to high dose infliximab and is being considered for colostomy and colectomy if current treatment fails.

Many literatures highlight the difficulty of diagnosing VEOIBD due to overlapping clinical features.^2,3The patient presented in this case was on long-term treatment for constipation and anal protrusions were initially thought to be mere complications of this, however incidental findings of pancolitis on endoscopy made the diagnosis apparent in this child. Such initial misdiagnosis is not uncommon.

The relationship between IL-27 and IL-10 have been described by some authors, but whereas there is documented cases of IL-10 signalling defects resulting in VEOIBD, data is lacking on IL-27 related disease.³ It would therefore be interesting to see if our patient would have any disease peculiarity as is the case with IL-10 related cases.

As highlighted above, our patient is currently on vedolizumab therapy, some authors suggest ‘considering anakinra, an IL-1 receptor antagonist, in patients with IL-10 signalling defects who are too ill to undergo transplant or while searching for a suitable donor, as this has led to marked clinical, endoscopic, and histologic improvement in some patients’.(Schwartz et al, 2022)⁴ It remains to be seen if our patient would respond to a particular type of treatment, in preference over another. Currently, the patient has failed repeated treatment with high dose infliximab. Response to further treatment will be closely monitored.

In conclusion, this case highlights a rare direct IL-27 association with VEOIBD. We hope that this case stimulates a search for similar genetic cases, and that observation of the course of the disease and response to current therapies provides useful insight into this rare entity.

References

1. Ouahed J, Spencer E, Kotlarz D, et al. Very early onset inflammatory bowel disease: a clinical approach with a focus on the role of genetics and underlying immune deficiencies. Inflamm Bowel Dis. 2020;26(6):820–842. doi: 10.1093/ibd/izz259. PMID: 31833544; PMCID: PMC7216773.

2. Snapper SB. Very-early-onset inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2015;11(8):554–6. PMID: 27118953; PMCID: PMC4843045.

3. Zhang H, Madi A, Yosef N, et al. An IL-27-driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets. Cell Rep. 2020;33(8):108433. doi: 10.1016/j.celrep.2020.108433.

4. Schwartz DA, Peyrin-Biroulet L, Lasch K, et al. Efficacy and safety of 2 vedolizumab intravenous regimens for perianal fistulizing crohn’s disease: ENTERPRISE study. Clinical Gastroenterology and Hepatology. 2022;20:1059–1067.