Triggers of histologically suspected drug-induced colitis

doi:10.3748/wjg.v25.i8.967

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World Journal of Gastroenterology

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Case Control Study

World J Gastroenterol. Feb 28, 2019; 25(8): 967-979
Published online Feb 28, 2019. doi: 10.3748/wjg.v25.i8.967

Table 1 Basic demographic characteristics n (%)

	Drug-induced colitis, n = 211	Non-inflammatory controls, n = 211	Inflammatory controls, n = 211
Basic characteristics
Age (yr)	62.3 ± 16.4	62.2 ± 16.3	61.8 ±15.7
Gender (male)	97 (46.0)	97 (46.0)	97 (46.0)
Height (cm)	168.9 ± 9.5	168.3 ± 12.4	170.0 ± 9.3
Body weight (kg)	76.9 ± 22.6	75.0 ± 20.3	72.9 ± 19.7
BMI (kg/m²)	26.9 ± 7.2^a¹^b	26.3 ± 6.8	25.0 ± 5.6^a³
ASA^b²
ASA 1	0 (0)	3 (1.4)	0 (0)
ASA 2	133 (63.0)	169 (80.1)	155 (73.5)
ASA 3	70 (33.2)	37 (17.5)	52 (24.6)
ASA 4	8 (3.8)	2 (0.9)	4 (1.9)
ECOG^b²,^b³
ECOG 0	0 (0)	1 (0.5)	2 (0.9)
ECOG 1	8 (3.8)	75 (35.5)	13 (6.2)
ECOG 2	149 (70.6)	104 (49.3)	147 (69.7)
ECOG 3	41 (19.4)	26 (12.3)	43 (20.4)
ECOG 4	13 (6.2)	5 (2.4)	6 (2.8)
Indication of colonoscopy^b¹,^a²
Diarrhoea	73 (34.6)	95 (45.0)	97 (46.0)
Constipation	6 (2.8)	5 (2.4)	1 (0.5)
Gastrointestinal bleeding	63 (29.9)	31 (14.6)	36 (17.1)
Abdominal pain	47 (22.3)	54 (25.6)	46 (21.8)
Weight loss	6 (2.8)	5 (2.4)	4 (1.9)
Scheduled survey	2 (0.9)	1 (0.5)	2 (0.9)
Miscellaneous	14 (6.6)	20 (9.5)	25 (11.8)

¹Drug-induced colitis vs inflammatory controls.

²Drug-induced colitis vs non-inflammatory controls.

³Non-inflammatory controls vs inflammatory controls.

^aP < 0.05.

^bP < 0.01. Statistical analysis was carried out with χ² test, ANOVA or t-test as appropriate. BMI: Body mass index.

Full Size Table

Table 2 Comorbidities n (%)

Comorbidity	Drug-induced colitis, n = 211	Non-inflammatory controls, n = 211	Inflammatory controls, n = 211
Pulmonary	39 (18.5)	31 (14.7)	37 (17.5)
Cardiac	110 (52.1)	93 (44.1)	87 (41.2)
Neurological	27 (12.8)	23 (10.9)	19 (9.0)
Psychiatric	10 (4.7)	9 (4.3)	10 (4.7)
Endocrine	47 (22.3)	44 (20.9)	30 (14.2)
Renal	28 (13.2)	18 (8.5)	21 (10.0)
Hepatic	11 (5.2)	13 (6.2)	11 (5.2)
Oncological	14 (6.6)	25 (11.8)	17 (8.1)
Other	19 (9.0)	15 (7.1)	16 (7.6)
Heart failure	35 (16.6)	16 (7.6)^b²	31 (14.7)^a³
Renal insufficiency	24 (11.4)	14 (6.6)	18 (8.5)
Atrial fibrillation	26 (12.3)	18 (8.5)	22 (10.4)
Coronary heart disease	47 (22.3)	28 (13.3)^a²	35 (16.6)
Peripheral arterial occlusive disease	7 (3.3)	10 (4.7)	11 (5.2)
Atherosclerosis	74 (35.1)^b¹	39 (18.5)^b²	40 (19.0)
Arterial hypertension	98 (46.4)	97 (46.0)	87 (41.2)
Diabetes mellitus	46 (21.8)	45 (21.3)	32 (15.2)
Hypercholesterinaemia	20 (9.5)	16 (7.6)	18 (8.5)
Hyperlipoproteinaemia	22 (10.4)^a¹	11 (5.2)^a²	9 (4.3)
Chronic obstructive lung disease	29 (13.7)	24 (11.4)	27 (12.8)
Stroke	14 (6.6)	9 (4.3)	11 (5.2)
Smoking	77 (36.7)	66 (31.3)	78 (37.0)
Surgery	9 (4.3)	1 (0.5)^a²	3 (1.4)
Intensive care therapy	9 (4.3)	2 (0.9)^a²	4 (3.1)

¹Drug-induced colitis vs inflammatory controls.

²Drug-induced colitis vs non-inflammatory controls.

³Non-inflammatory controls vs inflammatory controls.

^aP < 0.05.

^bP < 0.01.

Statistical analysis was carried out with χ² test.

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Table 3 Histopathological reassessment n (%)

Parameter (n = 28)	Drug-induced colitis without atherosclerosis	Drug-induced colitis with atherosclerosis	Ischaemiccolitis
Oedema	2 (7.1)	2 (7.1)	4 (14.3)
Haemorrhage	1 (3.6)^a²	8 (28.6)^a¹	6 (21.4)
Lymphocytic infiltration	27 (96.4)	27 (96.4)	27 (96.4)
Granulocytic infiltration	27 (96.4)	26 (92.9)	28 (100.0)
Eosinophilic infiltration	12 (42.9)^b²	7 (25.0)	1 (3.6)^a³
Erosions	2 (7.1)^b²	9 (32.1)^a¹	10 (35.7)
Ulcerous lesions	4 (14.3)^b²	3 (10.7)	16 (57.1)^b³
Necrosis	1 (3.6)^b²	1 (3.6)	16 (57.1)^b³
Fibrin plaques on erosions	2 (7.1)	2 (7.1)	3 (10.7)
Fibrosis	3 (10.7)	3 (10.7)	7 (25.0)

¹Drug-induced colitis without atherosclerosis vs drug-induced colitis with atherosclerosis.

²Drug-induced colitis without atherosclerosis vs ischaemic colitis.

³Drug-induced colitis with atherosclerosis vs ischaemic colitis.

^aP < 0.05.

^bP < 0.01.

Statistical analysis was carried out with χ² test.

Full Size Table

Table 4 Drug assessment n (%)

Group	Drug-induced colitis, n = 211	Non-inflammatory controls, n = 211	Inflammatory controls, n = 211
Betablocker	97 (46.0)	78 (37.0)	83 (39.3)
ACE inhibitors	70 (33.2)	55 (26.1)	62 (29.4)
Angiotensin II inhibitors	20 (9.5)^b¹	24 (11.4)	6 (2.8)^b³
Non-Dihydropyridines	1 (0.5)^a¹	6 (2.8)	7 (3.3)
Dihydropyridines	34 (16.1)^a¹	27 (12.8)	20 (9.5)
Diuretics	55 (26.1)^b¹	29 (13.7)^b²	33 (15.7)
Benzothiazines	28 (13.3)	33 (15.6)	24 (11.4)
Aldosterone antagonists	13 (6.2)	13 (6.2)	12 (5.7)
Nitrates	7 (3.3)	13 (6.2)	5 (2.4)
Antiarrhythmic drugs	7 (3.3)	2 (0.9)	2 (0.9)
Glycosides	10 (4.7)	2 (0.9)^a²	8 (3.8)
ASS (100 mg to 300 mg)	67 (31.8)^b¹	47 (22.3)^a²	40 (19.0)
Platelet aggregation inhibitors	20 (9.5)^b¹	10 (4.7)	6 (2.8)
NSAIDs	35 (16.6)^b¹	21 (10.0)^a²	8 (3.8)^a³
Metamizole	21 (10.0)	16 (7.6)	21 (10.0)
Potassium	4 (1.9)	3 (1.4)	6 (2.8)
Vitman K antagonists/coumarin derivates	16 (7.6)	9 (4.3)	11 (5.2)
Direct thrombin inhibitors	6 (2.8)	2 (0.9)	4 (1.9)
Glucocorticosteroids	13 (6.2)^b¹	14 (6.6)	41 (19.4)^b³
Opioids	20 (9.5)	22 (10.4)	23 (10.9)
Metformin	8 (3.8)	16 (7.6)	4 (1.9)^b³
Insulin	17 (8.1)	15 (7.1)	17 (8.1)
Statins	56 (26.5)^a¹	42 (19.9)	38 (18.0)
Fibrates	7 (3.3)^a¹	1 (0.5)^a²	1 (0.5)
Levothyroxine	25 (11.8)	39 (18.5)	22 (10.4)^a³
Thyreostatics	3 (1.4)	3 (1.4)	1 (0.5)
Proton pump inhibitors	100 (47.4)	85 (40.3)	81 (38.4)
Penicillin derivates	0 (0.0)	2 (0.9)	2 (0.9)
Macrolides	0 (0.0)	1 (0.5)	1 (0.5)
Gyrase inhibitor	0 (0.0)	0 (0.0)	0 (0.0)
Carbapenems	1 (0.5)	0 (0.0)	0 (0.0)
Imidazoles	3 (1.4)	1 (0.5)	1 (0.5)
Cephalosporins	2 (0.9)	2 (0.9)	2 (0.9)
Antbiotics	4 (1.9)	5 (2.4)	3 (1.4)
SSRIs	14 (6.6)	5 (2.4)^a²	16 (7.6)^a³
Tricyclic antidepressants	7 (3.3)	10 (4.7)	7 (3.3)
Neuroleptics	5 (2.4)	8 (3.8)	6 (2.8)
Sedatives	16 (7.6)	16 (7.6)	16 (7.6)
Others	127 (60.2)^a¹	125 (59.2)	147 (69.7)^a³
Number of drugs^b	4.5 ± 2.8	3.9 ± 3.0^a²	3.9 ± 3.2

¹Drug-induced colitis vs inflammatory controls.

²Drug-induced colitis vs non-inflammatory controls.

³Non-inflammatory controls vs inflammatory controls.

^aP < 0.05.

^bP < 0.01.

Statistical analysis was carried out with χ² test (a) or t-test (b). NSAIDs : Nonsteroidal anti-inflammatory drugs; SSRIs: Selective serotonin reuptake inhibitors; ACE: Angiotensin-converting enzyme.

Full Size Table

Table 5 Echocardiographic parameters n (%)

Parameter	Drug-induced colitis, n = 54 of 211 (25.6)	Non-inflammatory controls, n = 34 of 211 (16.1)	Inflammatory controls, n = 24 of 211 (11.4)
Dilated right atrium	4 (7.4)^a¹	4 (11.4)	5 (23.8)
Dilated left ventricle	8 (14.8)	0 (0.0)	6 (26.1)^b³
Hypokinesia	10 (18.5)	5 (14.3)	3 (13.0)
Right heart failure	5 (9.3)	4 (11.4)	2 (8.7)
Diastolic dysfunction	22 (43.1)	16 (48.5)	7 (30.4)
LV Function^b²,^b³
Normal (> 50%)	39 (72.2)	29 (85.3)	17 (73.9)
Slightly decreased (40%-50%)	4 (7.4)	5 (14.7)	1 (4.3)
Moderately decreased (30%-40%)	5 (9.3)	0 (0.0)	2 (8.7)
Severely decreased (< 30%)	6 (11.1)	0 (0.0)	3 (13.0)

¹Drug-induced colitis vs inflammatory controls.

²Drug-induced colitis vs non-inflammatory controls.

³Non-inflammatory controls vs inflammatory controls.

^aP < 0.05.

^bP < 0.01.

Statistical analysis was carried out with χ² test. LV : Left ventricular.

Full Size Table

Table 6 Binary logistic regression analysis

Parameter	Drug-induced colitis vs inflammatory controls OR (95%CI)	Drug-induced colitis vs non-inflammatory controls OR (95%CI)
Heart failure	0.6 (0.3-1.1)	1.3 (0.6-2.8)
Atherosclerosis	2.1 (1.2-3.7)^b	1.7 (0.9-3.1)
Dihydropyridines	1.3 (0.7-2.5)	1.0 (0.5-1.8)
Diuretics	1.5 (0.8-2.6)	1.7 (1.0-3.0)
Digitalis glycosides	1.1 (0.4-3.1)	3.7 (0.8-17.9)
Low-dose ASS	1.7 (1.0-2.8)	1.1 (0.7-1.9)
Platelet aggregation inhibitors	2.0 (0.7-5.7)	1.4 (0.6-3.3)
NSAIDs	6.7 (3.0-15.1)^b	2.2 (1.2-4.0)^a
Statins	1.1 (0.6-1.9)	0.9 (0.6-1.6)
Fibrates	9.1 (1.1-74.3)^a	8.9 (1.1-74.2)^a

^aP < 0.05.

^bP < 0.01.

NSAIDs: Nonsteroidal anti-inflammatory drugs.

Full Size Table

Citation: Brechmann T, Günther K, Neid M, Schmiegel W, Tannapfel A. Triggers of histologically suspected drug-induced colitis. World J Gastroenterol 2019; 25(8): 967-979
URL: https://www.wjgnet.com/1007-9327/full/v25/i8/967.htm
DOI: https://dx.doi.org/10.3748/wjg.v25.i8.967