Variable outcome in infantile-onset inflammatory bowel disease in an Asian cohort

Table 1 Phenotypic characteristics, disease behavior, therapy and outcome in six Asian children with infantile-onset inflammatory bowel disease

Patients’ initials	No. 1	No. 2	No. 3	No. 4	No. 5	No. 6
Sex	Male	Male	Male	Male	Female	Female
Ethnicity	Chinese	Chinese	Malay	Chinese	Indian	Malay
Consanguinity	No	No	No	No	No	No
Breast feeding (duration)	No	No	No	Yes (3 mo)	Yes (2 mo)	Yes (4 mo)
Age at onset	First week	12 mo	7 mo	2 mo	6 mo	4 mo
Disease phenotype	EC→UC	UC	CD	CD	CD	IBD-U
Major symptoms at presentation	Bloody diarrhea and PR bleeding	Bloody diarrhea, anemia	Oral ulcers, bloody diarrhea, abdominal pain	Bloody diarrhea, abdominal pain	Bloody diarrhea, growth faltering	Bloody diarrhea
Perianal disease	Nil	Nil	Abscess and fistula	Abscess and fistula	Nil	Abscess and fistula
Other medical or autoimmune conditions	Nil	Nil	Nil	Nil	Nil	Nil
Recurrent infections	Nil	Nil	Congenital CMV infection,	Nil	Nil	Nil
Disease location1	E4S1	E4	L3L4a	L3L4a	L3	L2
Disease behavior/severity1	S1	S1	B2B3p	B2B3p	B1	B1p
Histopathology	Dense lymphoplasmacytic and eosinophilic infiltration of the lamina propria involving the gastric mucosa, duodenum and colonic mucosa.	Colonic mucosa showed mild degenerative atypia, cryptitis and crypt abscesses. Lamina propria showed increase in neutrophilic and lymphoplasmacytic infiltration.	Lymphocytic infiltration of lamina propria. No granuloma or crypt abscess seen. The duodenum showed chronic inflammation.	Lymphocytic infiltration of lamina propria. No granuloma or crypt abscess seen	Mild inflammation in the lamina propria with lymphocytes and plasma cells. No granuloma or crypt abscess	First biopsy: transmural inflammation involving all layers of bowel wall, including the skeletal muscle with dense lymphoplasmacytic infiltration. No crypt abscess seen.
						Second biopsy: colonic mucosa inflammed but the architecture was preserved. Significant lymphoplasmacytic and neutrophilic infiltration mainly confined to the lamina propria
Other associated diseases	Nil	Nil	Developmental regression at 6 yr age	Nil	Nil	Nil
Mutational analysis	Not done	Not done	Not detected	Not detected	Not detected	Not detected
Medical therapy	CS, CsA, enteral nutrition	CS, Aza	CS, Aza, IFX × 24 doses	EN, CS, Aza, IFX × 14 doses	Aza, IFX × 3 doses	Nil
Surgery	Total colectomy at 18 mo	Nil	Ileostomy at 6 yr of age	Nil	Nil	Ileostomy; closure at 18 mo of age
Age at last follow up	21 yr	6 yr	9 yr	6 yr	13 yr	3 yr
Final clinical status	Alive, deafness due to aminoglycosides. in remission, off therapy for 18 yr	Alive, in remission; on Aza	Alive, persistent disease, on CS, Aza. Developmentally delayed.	Alive, persistent disease, on CS, Aza and IFX. Parents refused surgery	Alive, in remission; off therapy for 2 yr	Alive, in remission; no therapy

¹According to Levine et al[24]. Aza: Azathioprine; CD: Crohn’s disease; CMV: Cytomegalovirus; CS: Corticosteroid; CsA: Cyclosporin; EC: Eosinophilic colitis; EN: Enteral nutrition; IFX: Infliximab; PR: Per rectal; UC: Ulcerative colitis.

Table 2 Comparison of disease characteristics, management and final outcome of infantile-onset inflammatory bowel disease and children with onset of disease after 12 mo of age

	Onset before 1 year, n (%)	Onset after 1 year, n (%)	P value
n	6	41
Median age at diagnosis (yr)	0.44	8.34
Duration of follow-up (yr), median (range)	6.1 (1.4-19.6)	8.3 (1.0-16.6)
Male	4	22
Female	2	19
Crohn’s disease	3	22
Ulcerative colitis	2	19
IBD-unclassified	1	0
Initial presentation, n (%)
Bloody diarrhea	6 (100)	23 (55)	0.039
Perianal disease	3 (50)	8 (19)	0.11
Extraintestinal involvement
Autoimmune liver disease	0 (0)	8 (19)	0.31
Therapy
Biologics-infliximab	3 (50)	15 (36)	0.40
Surgery	3 (50)	12 (29)	0.27
Disease status at final review
Inactive disease or in clinical remission	3 (50)	27 (66)	0.40
Discontinuation of immunosuppression
Yes	3 (50)	5 (12)	0.053
No	3 (50)	36 (88)

IBD: Inflammatory bowel disease.

Table 3 Clinical characteristics, management and outcome of infantile-onset inflammatory bowel disease in selected series

	Ref.	Patients in all age group), n (%)	Nature of patients, n (%)	Age of patients at onset of disease	Duration of follow-up (yr), median (range)	Medical therapies	Surgery, n (%)	Disease status: remission of survivors at final review, n (%)	Deaths
1	Ruemmele et al[8]	10 (2.5)	CD = 4 (40)	First 12 mo	2.5 (2.5-8)	Bowel rest, PN, CS, Aza, CsA	3 (30);	10 (100);	None
			UC = 2 (20)				2 colectomy, 1 ileostomy	off therapy, 2 (20);
			IC = 4 (40)					ongoing therapy, 8 (80)
2	Cannioto et al[9]	16 (8.6)	CD = 6 (37.5)	First 2 yr	6 (4-22)	Aggressive multi-drug therapy, Aza, IFX, thalidomide, CsA	3 (19);	11 (100);	5 (mortality rate 31%)1
			UC = 8 (50)				2 colectomy, 1 ileostomy	off therapy, 4 (25);
			Indeterminate = 2 (12.5)					ongoing therapy, 6 (38),
								after BMT, 1 (6)
3	Begue et al[15]	13 (-)	All had pancolitis, 6 had small bowel involvement2	First 12 mo	-	-	4 (31)	All required immuno-suppressive therapy. Final disease status not described	Not described
4	Present study, Malaysia, 2016	6 (13)	CD = 4 (67)	First 12 mo	5 (1.5-20)	Bowel rest, steroids, Aza, CsA, INF	3 (33);	4 (67);	None
			UC = 2 (33)				1 colectomy, 2 ileostomies	off therapy, 3 (50);
								ongoing therapy, 1 (17);
								not in remission, 2 (33)

The authors included IBD and IBD-mimicking enterocolitis;

¹Two deaths were related to infections; one death each for interstitial pneumonia, post-BMT, and giant cell hepatitis progressing to liver failure;

²The authors did not classify the patients into either Crohn’s disease (CD), ulcerative colitis (UC) or indeterminate colitis (IC). Aza: Azathioprine; BMT: Bone marrow transplantation; CS: Corticosteroid; CsA: Cyclosporin; IBD: Inflammatory bowel disease; IFX: Infliximab; PN: Parenteral nutrition.