Association of extraintestinal manifestations of inflammatory bowel disease in a province of western Hungary with disease phenotype: Results of a 25-year follow-up study

Table 1 Clinical data of IBD patients

	Ulcerative colitis	Crohn’s disease
Number of patients	619	254
Male/female	317/302	125/129
Mean age at diagnosis	38.3 yrs (9-80 yrs)	32.5 yrs (12-80 yrs)
Location	Proctitis: 117	L1: 60
	Left sided colitis: 304	L2: 81
	Pancolitis: 198	L3: 113
Behaviour of CD	-	B1: 87
		B2: 62
		B3: 105

In Crohn’s disease (CD). Location: L1: Terminal ileum, L2: Colonic, L3: Ileocolonic, Behaviour: B1: Non stricturing-non penetrating, B2: Stricturing, B3: Penetrating.

Table 2 Prevalence of extraintestinal manifestations (EIM) in IBD

	Total n (%)	Disease duration
		≤ 10 yrs n (%)	> 10 yrs n (%)
IBD	873	511	352
Major EIMs	186 (21.3)	86 (16.8)	102 (30.0)
All EIM signs	547 (62.7)	278 (54.4)	269 (76.4)
Ulcerative colitis	619	357	262
Major EIMs	93 (15.0)	37 (10.4)	58 (22.1)
All EIM signs	360 (58.2)	167 (46.8)	193 (73.7)
Crohn’s disease	254	164	90
Major EIMs	93 (36.6)	49 (29.9)	44 (48.9)
All EIM signs	187 (73.6)	111 (67.7)	76 (84.4)

Table 3 Age at presentation and prevalence of major extraintestinal manifestations in patients with IBD

	A1 n (%)	A2 n (%)
UC (n: 619)	369	250
Joint	32 (8.7)	20 (8.0)
Hepatobiliary	49 (13.3)	28 (11.2)
Cutaneous	17 (4.6)	7 (2.8)
Ocular	11 (3.0)	8 (3.0)
CD (n: 254)	192	62
Joint	48 (25.0)	9 (14.5)
Hepatobiliary	48 (25.0)	9 (14.5)
Cutaneous	20 (10.4)	6 (9.7)
Ocular	5 (2.6)	3 (4.8)

A1: Age at presentation < 40 yrs, A2: Age at presentation ≥ 40 yrs.

Table 4 Familial IBD and association with extraintestinal manifestations

	Total	First degree relative	Second degree relative
Ulcerative colitis	24/619	18 (14 UC + 4 CD)	6 (5 UC + 1 CD)
	(3.9%)	(2.9%)	(1.0%)
Crohn’s disease	31/254	20 (3 UC + 17 CD)	11 (2 UC + 9 CD)
	(12.2%)	(7.9%)	(4.3%)

Table 5 Familial IBD and association with extraintestinal manifestations

	Ulcerative colitis	Familial IBD
Number of patients	619	24
Joint	52 (8.4%)	6 (25.0%)
Hepatobiliary	77 (12.4%)	3 (12.5%)
Cutaneous	24 (3.9%)	1 (4.2%)
Ocular	19 (3.0%)	2 (8.3%)
	Crohn’s disease	Familial IBD
Number of patients	254	31
Joint	57 (22.4%)	11 (35.5%)
Hepatobiliary	57 (22.4%)	4 (12.9%)
Cutaneous	26 (10.2%)	2 (6.5%)
Ocular	8 (3.1%)	0

Table 6 Prevalence of extraintestinal manifestations in ulcer-ative colitis and Crohn’s disease according to location and disease behaviour

	Joint n (%)	Hepatobiliary n (%)	Cutaneous n (%)	Ocular n (%)
Location	Ulcerative colitis
Proctitis (n = 117)	5 (4.3)	9 (7.7)	1 (0.9)	1 (0.9)
Left sided colitis (n = 304)	14 (4.6)	32 (15.7)	8 (2.6)	7 (2.3)
Pancolitis (n = 198)	33 (16.7)	36 (18.2)	15 (7.6)	12 (6.1)
Location	Crohn’s disease
L1 (n = 60)	11 (18.3)	14 (23.3)	6 (10.0)	2 (3.3)
L2 (n = 81)	17 (21.0)	17 (21.0)	10 (12.3)	3 (3.7)
L3 (n = 113)	29 (25.7)	26 (23.0)	10 (8.8)	3 (2.7)
Behaviour
B1 (n = 87)	13 (14.9)	22 (25.3)	11 (12.6)	1 (1.1)
B2 (n = 62)	16 (25.8)	11 (17.7)	5 (8.1)	0
B3 (n = 105)	28 (27.6)	24 (22.9)	10 (9.5)	7 (6.7)

Table 7 Joint manifestations in IBD patients

	Total n (%)	Axial arthritis n (%)	Type-1 arthritis n (%)	Type-2 arthritis n (%)
Ulcerative colitis
Total (n = 619)	52 (8.4)	20 (3.2)	17 (2.7)	13 (2.1)
Male (n = 317)	24 (7.6)	10 (3.2)	7 (2.2)	7 (2.2)
Female (n = 302)	28 (9.3)*	10 (3.4)	10 (3.3)	6 (2.0)
Crohn’s disease
Total (n = 254)	57 (22.4)	26 (10.2)	29 (11.4)	8 (3.1)
Male (n = 125)	23 (18.4)	11 (8.8)	12 (9.6)	3 (2.4)
Female (n = 129)	34 (26.4)	15 (11.6)	17 (13.2)	5 (3.9)

*Two female patients with ulcerative colitis had rheumatoid arthritis.

Table 8 Joint manifestations in IBD according to location and disease behaviour

	Total n (%)	Axial arthritis n (%)	Type-1 arthritis n (%)	Type-2 arthritis n (%)
Location		Ulcerative colitis
Proctitis (n = 117)	5 (4.3)*	1 (0.9)	2 (1.8)	1 (0.9)
Left sided colitis (n = 304)	14 (4.6)	4 (1.3)	5 (1.6)	5 (1.6)
Pancolitis (n = 198)	33 (16.7)*	15 (7.6)	10 (5.0)	7 (3.5)
Location		Crohn’s disease
L1 (n = 60)	11 (18.3)	5 (8.3)	4 (6.7)	2 (3.3)
L2 (n = 81)	17 (21.0)	7 (8.6)	10 (12.3)	3 (3.7)
L3 (n = 113)	29 (25.7)	14 (12.4)	15 (13.3)	3 (2.7)
Behaviour
B1 (n = 87)	13 (14.9)	8 (9.2)	5 (5.7)	2 (2.3)
B2 (n = 62)	16 (25.8)	8 (12.9)	6 (9.7)	3 (4.8)
B3 (n = 105)	28 (27.6)	10 (9.5)	18 (17.1)	3 (2.9)

*One patient with proctitis and one with pancolitis had rheu-matoid athritis.

Table 9 Hepatobiliary manifestations in IBD patients

	Total n (%)	PSC n (%)	Small duct PSC n (%)	NAFLD/NASH n (%)
Ulcerative colitis
Total (n = 619)	77* (12.4)	10 (1.6)	8 (1.3)	58 (9.4)
Male (n = 317)	39 (12.3)	3 (1.0)	6 (1.9)	30 (9.5)
Female (n = 302)	38* (12.6)	7 (2.3)	2 (0.7)	28 (9.3)
Crohn’s disease
Total (n = 254)	57 (22.4)	2 (0.8)	6 (2.4)	49 (19.3)
Male (n = 125)	27 (21.6)	2 (1.6)	6 (4.8)	19 (15.2)
Female (n = 129)	30 (23.3)	0	0	30 (23.3)

*One female patient had autoimmune hepatitis. NAFLD: Non-alcoholic fatty liver disease, NASH: Non-alcoholic steatohepatitis.

Table 10 Cutaneous manifestations in patients with ulcer-ative colitis (n = 619)

	Total n (%)	Male n (%)	Female n (%)
Erythema nodosum	8 (1.3)	2 (0.6)	6 (2.0)
Pyoderma gangrenosum	3 (0.5)	1 (0.3)	2 (0.6)
Chronic urticaria	6 (1.0)	2 (0.6)	4 (1.3)
Psoriasis	3 (0.5)	2 (0.6)	1 (0.3)
Aphthous stomatitis	3 (0.5)	1 (0.3)	2 (0.6)
Herpes zoster	2 (0.3)	1 (0.3)	1 (0.3)
Cellulitis	2 (0.3)	0	2 (0.6)
Recurrent dermatitis	2 (0.3)	1 (0.3)	1 (0.3)
Lichen ruber planus	1 (0.2)	1 (0.3)	0
Total	24 (3.9)	9 (2.8)	15 (5.0)

Table 11 Cutaneous manifestations in patients with Crohn’s disese (n = 254)

	Total n (%)	Male n (%)	Female n (%)
Erythema nodosum	14 (5.5)	4 (3.1)	10 (7.8)
Pyoderma gangrenosum	4 (1.6)	3 (2.4)	1 (0.8)
Erythema exsudativum	2 (0.8)	1 (0.8)	1 (0.8)
multiforme
Erythroderma	2 (0.8)	1 (0.8)	1 (0.8)
Stevens Johnson syndrome	1 (0.4)	0	1 (0.8)
Psoriasis	1 (0.4)	0	1 (0.8)
Eczema	1 (0.4)	0	1 (0.8)
Recurrent dermatitis	1 (0.4)	0	1 (0.8)
Total	26 (10.2)	9 (7.2)	17 (13.2)

Table 12 Ocular manifestations in IBD patients

	Total n (%)	Anterior uveitis n (%)	Conjunctivitis n (%)	Scleritis n (%)
Ulcerative colitis
Total (n = 619)	20* (3.2)	6 (1.0)	9 (1.5)	4 (0.7)
Male (n = 317)	4 (1.3)	1 (0.3)	3 (1.0)	1 (0.3)
Female (n = 302)	16 (5.3)	5 (1.7)	6 (2.0)	3 (1.0)
Crohn’s disease
Total (n = 254)	8 (3.1)	4 (1.6)	4 (1.6)	1 (0.4)
Male (n = 125)	2 (1.6)	1 (0.8)	0	1 (0.8)
Female (n = 129)	6 (4.7)	3 (2.3)	4 (3.1)	0

*One orbital pseudotumor was observed in a young female UC patient.

Table 13 Hematological manifestations in patients with ulcerative colitis

	Total n (%)	Male n (%)	Female n (%)
Iron deficieny anaemia	159 (25.9)	62 (19.6)	97 (32.1)
Chronic anaemia	59 (9.6)	34 (10.7)	25 (8.3)
Macrocytic anaemia	24 (3.9)	15 (4.7)	9 (3.0)
AIHA	4 (0.6)	2 (0.6)	2 (0.6)
Non-Hodgkin lymphoma	1 (0.2)	1 (0.3)	0
CML	1 (0.2)	1 (0.3)	0
Chronic myeloproliferative disease	1 (0.2)	0	1 (0.3)
Leukemoid reaction	1 (0.2)	0	1 (0.3)
Methaemoglobinaemia	1 (0.2)	0	1 (0.3)
Total	260 (42.0)	90 (28.4)	170 (56.3)

AIHA: Autoimmune hemolytic anaemia, CML: Chronic myeloid leukaemia.

Table 14 Hematological manifestations in patients with Crohn’s disease

	Total n (%)	Male n (%)	Female n (%)
Iron deficieny anaemia	91 (35.8)	40 (32.0)	51 (39.5)
Chronic anaemia	45 (17.7)	23 (18.4)	22 (17.1)
Macrocytic anaemia	11 (4.3)	6 (4.8)	5 (3.9)
Chronic myeloproliferative disease	1 (0.4)	0	1 (0.8)
Leukopenia	1 (0.4)	0	1 (0.8)
ITP	1 (0.4)	0	1 (0.8)
Total	150 (59.1)	69 (55.2)	81 (62.8)

ITP: Immune thrombocytopenic purpura

Table 15 Association between hematological complications and location and disease behaviour in Crohn’s disease patients

	Iron deficieny anaemia n (%)	Chronic anaemia n (%)	Macrocytic anaemia n (%)
Location
L1 (n = 60)	17 (28.3)	9 (15.0)	3 (5.0)
L2 (n = 81)	22 (27.2)	9 (11.1)	2 (2.5)
L3 (n = 113)	42 (37.2)	27 (23.9)	6 (5.3)
Behaviour
B1 (n = 87)	27 (31.0)	10 (11.4)	2 (2.3)
B2 (n = 62)	23 (37.1)	12 (19.4)	3 (4.8)
B3 (n = 105)	41 (39.0)	23 (21.9)	6 (5.7)

Table 16 Thromboembolic complications in patients with IBD

	Ulcerative colitis	Crohn’s disease
Number of patients (%)	11/619 (1.8)	8/254 (3.1)
Male/female	9/2	2/6
Location	Proctitis: 0	L1: 3
	Left sided colitis: 6	L2: 1
	Pancolitis: 5	L3: 4
Behaviour of CD	-	B1: 0
		B2: 2
		B3: 6
Place of thromboembolism
Lower extremity thrombosis	8	4
Pulmonary embolism	1	0
Lower extremity thrombosis	2	3
complicated by
pulmonary embolism
Splenic vein thrombosis	0	1

Table 17 Prevalence of multiple extraintestinal diseases

	Total n	Ulcerative colitis n	Crohn’s disease n
Two	27	14	13
Three	14	5	9
Four	1	0	1
Total	42/873 (4.5%)	19/619 (3.1%)	23/254 (9.3%)

Table 18 Extraintestinal manifestations in IBD affecting other organ systems

	Total n (%)	Ulcerative colitis n (%)	Crohn’s disease n (%)
Glomerulonephritis	3 (0.4)	1 (0.2)	2 (0.8)
Asthma bronchiale	7 (0.8)	4 (0.6)	3 (1.2)
Chronic pancreatitis	4 (0.5)	3 (0.5)	1 (0.4)
Acute pancreatitis	2 (0.2)	1 (0.2)	1 (0.4)
Celiac disease	2 (0.2)	1 (0.2)	1 (0.4)
Thyreoiditis	2 (0.2)	2 (0.3)	0
SLE	2 (0.2)	1 (0.2)	1 (0.4)

SLE: Systemic lupus erythematodes.