Microscopic colitis and its associations with complications observed in classic inflammatory bowel disease: a systematic review

Figures & data

Figure 1. Search strategy microscopic colitis.

Figure 2. PRISMA 2009 flow diagram.

Table 1. Study characteristics.

Study	Country	Study design	Concomitant disease	Inclusion criteria	Sample size	Results	Conclusion
Wickbom et al. [17]	Sweden	Case-control study	Rheumatism	CC and LC: histologically diagnosed, shown clinical symptoms	115 CC patients	(Only significant results) Cutaneous disease: CC patients = 6 (5%), CC controls = 3 (1%), OR (95%CI) = 6.0 (1.4–26), p = .027, Rheumatic disease: CC patients = 22 (19%), CC controls = 32 (13%), OR (95%CI) = 1.9 (1.0–3.5), p = .042	There is a statistically significant association between CC and rheumatic or cutaneous diseases. However, the same results in the LC cohort is not significant. There is no statistically significant association between MC and malignancy, eye disease, anemia, and thromboembolism
			Cutaneous disease		263 CC controls
			Eye disease		97 LC patients
			Anemia		224 LC controls
			Thromboembolism
			Malignancy
Kao et al. [18]	USA	Retrospective cohort study	Malignancy	MC: histologically diagnosed, no ulcerations, erythema or other visible abnormalities	171 CC patients	(Only significant results) RA: CC = p < .001, LC = p < .01 Raynaud/CREST syndrome: CC = p < .01, LC = p < .01 Fibromyalgia: LC = p < .01 Giant cell/temporal arteritis: LC = p < .025 SLE: LC = p < .025	There is a significant association between MC and RA, and Raynaud/CREST syndrome. Additionally, there is a significant association between LC and fibromyalgia, SLE, and giant cell/temporal arteritis. No association between MC and colorectal malignancy could be found
			Rheumatism		171 CC controls
					376 LC patients
					376 LC controls
Yen et al. [19]	USA	Case-control study	Malignancy	MC: histologically diagnosed, clinical history of diarrhea available, no active colitis or ulceration	647 MC patients	Risk of colorectal cancer in MC versus control: AOR (95%CI) = 0.34 (0.16–0.73), p = .006	There is a significant negative association between MC and colorectal neoplasia
					647 controls	Risk of colorectal adenoma in MC versus control: AOR (95%CI) = 0.52 (0.39–0.69), p < .0001
Roth et al. [20]	Sweden	Case-cohort study	Malignancy	MC: age ≤73, histologically diagnosed, female gender, no celiac disease, no gastroenteritis	131 MC patients	RA: MC = 31 (23.7%), control = 27 (3.7%), AOR (95% CI) = 7.21 (3.81–13.64), Malignancy: MC = 11 (8.4%), control = 42 (5.7%), AOR (95% CI) = 1.14 (0.53–2.47)	A statistical association between MC and RA is established. However, there is no data whether there is a causality involved. There is no statistically significant association between MC and malignancy
			Rheumatism		737 controls
Tontini et al. [21]	Italy	Cohort study	Malignancy	MC: CNBD of unknown origin, endoscopically and histologically diagnosed non-MC: CNBD of unknown origin with MC excluded	43 MC patients	Neoplastic colorectal lesions: MC = 2 (4.6%), non-MC = 36 (17.9%), OR (95%CI) = 0.22 (0.05–0.97), p = .035	There is a significant negative association between MC and colorectal neoplasia in MC patients compared to MC-negative CNBD subjects
					201 non-MC patients
Sonnenberg et al. [22]	USA	Retrospective cohort study	Malignancy	MC: histologically diagnosed, no known history of MC	11,176 MC patients	Hyperplastic polyp: AOR (95%CI) for MC = 0.46 (0.43–0.49), AOR (95%CI) for IBD = 0.18 (0.15–0.21), Serrated adenoma: AOR (95%CI) for MC = 0.24 (0.19–0.30), AOR (95%CI) for IBD = 0.24 (0.16–0.35), Tubular adenoma: AOR (95%CI) for MC = 0.35 (0.33–0.38), AOR (95%CI) for IBD = 0.18 (0.15–0.21)	There is a significant negative association between MC and colonic neoplasia. Additionally, there is a significant negative association between IBD and colonic neoplasia as well. The same statistical association is found in different age groups
				IBD: histologically diagnosed, no know history of IBD	4435 IBD patients
					97,593 controls
Levy et al. [23]	USA	Retrospective case-cohort study	Malignancy	MC: histologically, clinically, and endoscopically confirmed diagnosis for MC	221 MC patients	Tubular adenoma: MC = 31%, control = 31.4%, Serrated adenoma: MC = 4%, control = 7.2%, Villous adenoma: MC = 1%, control = 1%, SIR (95% CI) between MC cohort and SEER population: Men = 1.59 (0.27–5.24), Women = 1.97 (0.86–3.89)	MC is not associated with an increased risk of colonic or extra-colonic malignancies or neoplasms
					306 control - GIDER
					SEER database
Gu et al. [24]	China	Cohort study	Rheumatism	MC: histologically, clinically, and endoscopically confirmed diagnosis for MC	87 MC patients	MC = 13 (14.9%), controls = 3 (3.2%), p=.022	MC is associated with an increased risk of rheumatoid arthritis
				Diarrhea controls: patients with diarrhea but without MC	90 diarrhea controls
Lorinczy et al. [25]	Hungary	Case-control study	Osteoporosis	MC: earlier diagnosed, asymptomatic, 6 weeks medication free	14 MC patients	Osteoporosis: MC = 1 (7%), CD = 5 (17.8%), control = 0, Osteopenia: MC = 7 (50%), CD = 12 (42%), control = 3 (10.7%)	Similarly decreased BMD in MC and CD. Uncoupled bone remodeling in MC similar to changes observed in CD
				CD: earlier diagnosed, CDAI  <  150, 1 year steroid free, azathioprine ≤2.5 mg/kg/day, mesalazine ≤4 g/day	28 CD patients
					28 controls
Wildt et al. [26]	Denmark	Case-control study	Osteoporosis	MC: age ≥18, histologically diagnosed, disease activity in the last 2 years, no prednisolone treatment in the last 6 months, no pregnancy, no malignancy	50 MC patients	Osteoporosis: MC = 7 (14%), control = 4 (8%), Osteopenia: MC = 22 (44%), control = 15 (31%)	Risk of low BMD was not increased in patients with MC. Both disease duration and cumulative amount of budesonide was associated with lower BMD
					49 controls
Guagnozzi et al. [27]	Spain	Cohort study	Anemia	MC: histologically, clinically and endoscopically confirmed diagnoses	32 MC patients	MC = 0, controls = 13 (5.2%), p = .21	No association between anemia and MC
				Diarrhea controls: patients with diarrhea but without MC	253 Diarrhea controls

AOR: adjusted OR; BMD: bone mass density; CI: confidence interval; CC: collagenous colitis; CNBD: chronic non-bloody diarrhea; IBD: inflammatory bowel disease; LC: lymphocytic colitis; MC: microscopic colitis; OR: Odds ratio; RA: rheumatic arthritis; SIR: standardized incidence ratio; SLE: systemic lupus erythematosus.

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