Diagnosis and management of functional symptoms in inflammatory bowel disease in remission

Table 1 Summary of studies that have determined prevalence of irritable bowel syndrome-like symptoms in quiescent inflammatory bowel disease

Ref.	Type	Sample size (CD/UC)	Criteria used to define IBD remission	Exclusions (IBD characteristics or previous surgery)	Criteria used to define IBS	IBD-IBS prevalencen (%)
Isgar et al[1]	Case-control	98 (0/98)	Endoscopic remission, steroid-free	Not further specified	Manning	UC: 33 (33.7)
		98 non-IBD controls
Simrén et al[2]	Cross-sectional	83 (40/43)	CD: Physician global assessment, endoscopic/radiological remission and normal inflammatory markers (Hb, ESR, CRP, platelets, albumin) UC: Endoscopic remission, no blood nor mucus, normal CRP	Stenotic CD	Gastrointestinal symptom questionnaire validated	37 (44.6)
				CD patients with > 2 surgeries		CD: 23 (57)
						UC: 14 (33)
				Significant comorbidities
Zaman et al[43]	Cross-sectional	55 (30/25)	Stable symptoms, no changes in medication for 3 mo	Not available	Rome II	35 (63.6)
						CD: 20 (66.7)
						UC: 15 (60)
Minderhoud et al[44]	Case-control	107 (34/73)	CD: CDAI < 150	Significant comorbidities	Manning	Manning: 33 (30.8)
		66 non-IBD controls	UC: CAIUC < 10		Rome II	CD: 8 (23.5)
						UC: 25 (34.2)
						Rome II: 37 (34.6)
						CD: 14 (41.7)
						UC: 23 (31.5)
Farrokhyar et al[45]	Cross-sectional	149 (105/44)	No changes/addition of medication nor change dosage in the last year	Not further specified	Rome II	31 (20.8)
						CD: 27 (26)
						UC: 4 (9.1)
Ansari et al[46]	Case-control	50 (0/50)	Mayo score ≤ 2 (bleeding score = 0, endoscopic score 0-1)	Not further specified	Rome II	UC: 23 (46)
		100 non-IBD controls
Keohane et al[33]	Cross-sectional	106 (62/44)	CD: CDAI < 150	Not further specified	Rome II	54 (50.9)
			UC: UCAI ≤ 3			CD: 37 (59.7)
			For both: physician’s global assessment, CRP < 10 mg/L, no use of steroids or biological agents in previous 6 mo			UC: 17 (38.6)
Piche et al[48]	Cross-sectional	92 (92/0)	CDAI < 150 for > 6 mo, endoscopic/radiologic remission (CDEIS < 6), normal inflammatory markers (CRP, Hb, ESR, platelets, albumin)	Stenosis	Rome III	CD: 42 (45.7)
				CD patients with previous surgery
				Recent corticoid use
Barratt et al[3]	Case-control	276 (110/166)	CD: HBI < 5	Not further specified	Rome II	31 (11.2)
		348 non-IBD controls	UC: SCCAI < 5			CD: 14 (12)
						UC: 17 (9)
Bryant et al[4]	Cross-sectional	93 (47/43)1	Physician’s global assessment using inflammatory markers, histological and endoscopic activity and clinical data	Not further specified	Rome III	12 (12.9) (no CD/UC differentiation)
Jelsness-Jørgensen et al[49]	Cross-sectional	89 (28/61)	CD: SCDAI < 4	Not further specified	Rome II	Rome II: 21 (23.6)
			UC: SCCAI < 3		Rome III	CD: 6 (21.4)
			No current steroid treatment			UC: 15 (24.6)
						Rome III: 30 (33.7)
						CD: 8 (28.6)
						UC: 22 (36.1)
Kim et al[50]	Cross-sectional	226 (107/119)	No changes on therapy in last year, normal limits of CRP, hemoglobin, no blood or mucus in stools for UC	CD with stenotic/penetrating phenotype	Rome III	82 (36.3)
						CD: 50 (46.7)
				Previous surgery		UC: 32 (26.9)
Berrill et al[5]	Cross-sectional	97 (40/57)	CD: HBI < 5, CRP < 10 mg/L	Ileostomy, colostomy or total colectomy	Rome III	31 (32)
			UC: SCCAI < 3, CRP < 10 mg/L			CD: 13 (32.5)
						UC: 18 (31.6)
Jonefjäll et al[35]	Pro-spective	94 (0/94)	Mayo ≤ 2 (endoscopic < 1)	Significant comorbidities	Rome II	UC: 25 (27)
			No relapse during 3 mo before inclusion
Vivinus-Nébot et al[51]	Cross-sectional	49 (31/18)	CD: CDAI < 150,CDEIS ≤ 4	Stenotic or complicated CD	Rome III	18 (36.7)
			UC: UCAI ≤ 3, Mayo = 0			CD: 11 (35.4)
			For both: physician’s global assessment, CRP < 10 mg/L, no use of steroids over the last year	Significant comorbidities		UC: 7 (38)
Fukuba et al[52]	Case control	172 (0/172)	CAI ≤ 4, CRP < 5 mg/L	Colectomy	Rome III	UC: 46 (26.7)
		330 non-IBD controls
Total	-	1836 (726/1107)1	-	-	-	Total: 567 (30.9)
						CD: 259 (38.1)2
						UC: 296 (27.8)2

¹In the original article the numbers given by the authors do not add up to the total of patients and they do not specify if the rest correspond to undetermined colitis;

²For the pooled prevalences in CD and UC, patients from study of Bryant et al have not been included as they do not state a differentiated IBS-IBD prevalence for CD and UC respectively. CD: Crohn’s disease; UC: Ulcerative colitis; IBD: Inflammatory bowel disease; IBS: Irritable bowel disease; CRP: C reactive protein; Hb: Haemoglobin; ESR: Erythrocyte sedimentation rate; CDAI: Crohn’s disease activity index; CAIUC: Clinical activity index for ulcerative colitis; UCAI: Ulcerative colitis activity index; CDEIS: Crohn’s disease endoscopic index of severity; HBI: Harvey-Bradshaw index; SCCAI: Simple clinical colitis activity index; SCDAI: Simple Crohn’s disease activity index; CAI: Colitis activity index.

Table 2 Irritable bowel syndrome Rome III criteria

Recurrent abdominal pain or discomfort at least 3 d per month in the last 3 mo (with onset at least 6 mo prior to diagnosis) associated with two or more of the following

Relieved with defecation

Onset associated with a change in frequency of stools

Onset associated with a change in form (appearance) of stools

Adapted from Longstreth et al[40].

Table 3 Studies that explore quality of life and anxiety in inflammatory bowel disease patients in remission with irritable bowel syndrome-like symptoms

Ref.	Sample size (CD/UC)	Questionnaires used	Results
Simrén et al[2]	83 (40/43)	GSRS	Higher anxiety and depression scores in IBD-IBS (worst in CD)
	37 IBD-IBS (23/14)	HADS
		STAI
		PGWB
Minderhoud et al[44]	107 (34/73)	IBDQ	Lower QoL scores in IBD-IBS
	37 IBD-IBS (14/23)
Farrokhyar et al[45]	149 (105/44)	sIBDQ	Occurence of any FGID taken in count (not only IBS-like)
	31 IBD-IBS (27/4)	EQ-5D	Lower QoL scores in CD patients with FGID
			Difference not significant for UC
Ansari et al[46]	50 (0/50)	SF-36	Lower QoL scores in IBD-IBS than in asymptomatic and similar to patients in flare
	IBD-IBS: 23 (0/23)
Keohane et al[33]	106 (62/44)	IBSQ	QoL scores only significantly lower in UC-IBS
	54 IBD-IBS (37/17)	HADS	Levels of anxiety and depression only significantly higher in UC-IBS
Piche et al[48]	92 (92/0)	French-validated IBS severity scoring system	Higher severity, impact, depression and fatigue scores in CD-IBS
	42 IBD-IBS (42/0)
		Likert scales	No significant differences in anxiety level
		FIS
		Short BDI
		HADS
Barratt et al[3]	276 (110/166)	SF-36	No differentiation between IBD patients in remission or in active phase
	31 IBD-IBS (14/17)	HADS	Lower QoL scores and higher anxiety, depression scores in IBD-IBS
Bryant et al[4]	93 (47/43)	sIBDQ	Occurrence of any FGID taken in count (not only IBS-like)
	12 IBD-IBS (no CD/UC differentiation)	HADS	Lower QoL scores and higher anxiety and depression scores in IBD patients with any FGID
		BDQ-6
			Lowest scores in IBS-like symptoms
Jelsness-Jørgensen et al[49]	89(28/61)	FQ	More fatigue scores in IBD-IBS (worst in UC)
	30 IBD-IBS (8/22)	RFIPC	More concerns in UC-IBD (difference non significant for CD)
Kim et al[50]	226 (107/119)	EQ-5D	Occurrence of any FGID taken in count (not only IBS-like)
	82 IBD-IBS (50/32)	HADS	Lower QoL scores and higher anxiety and depression scores in UC-IBS (difference non-significant for CD)
Berrill et al[5]	97 (40/57)	HADS	No differentiation between IBD patients in remission or in active phase
	31 IBD-IBS (13/18)		Higher anxiety and depression scores in IBD-IBS
Jonefjäll et al[35]	94 (0/94)	HADS	Lower QoL scores and higher anxiety scores in UC-IBS (difference in depression score non-significant)
	25 IBD-IBS (0/25)	SF-36
Vivinus-Nébot et al[51]	49 (31/18)	French-validated IBS severity scoring system	Higher severity and impact scores in IBD-IBS
	18 IBD-IBS (11/7)

IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohn’s disease; GSRS: Gastrointestinal symptom rating scale; HADS: Hospital anxiety and depression scale; STAI: Spielberger state trait anxiety inventory; PGWB: Psychological general well-being index; IBSQ: Inflammatory bowel disease questionnaire; QoL: Quality of life; sIBDQ: Inflammatory bowel disease questionnaire; EQ-5D: EuroQOL-5D; FGID: Functional gastrointestinal disorders; FIS: Fatigue impact scale; BDI: Becks depression inventory; BDQ-6: Bowel disease questionnaire-6; FQ: Fatigue questionnaire; RFIPC: Rating form of inflammatory bowel disease patients concerns.