Appendicitis, mesenteric lymphadenitis, and subsequent risk of ulcerative colitis: cohort studies in Sweden and Denmark

Abstract

Objective: To determine whether the repeatedly observed low risk of ulcerative colitis after appendicectomy is related to the appendicectomy itself or the underlying morbidity, notably appendicitis or mesenteric lymphadenitis.

Design: Nationwide cohort studies.

Setting: Sweden and Denmark.

Participants: 709 353 Swedish (1964-2004) and Danish (1977-2004) patients who had undergone appendicectomy were followed up for subsequent ulcerative colitis. The impact of appendicectomy on risk was also studied in 224 483 people whose parents or siblings had inflammatory bowel disease.

Main outcome measures: Standardised incidence ratios and rate ratios as measures of relative risk.

Results: During 11.1 million years of follow-up in the appendicectomy cohort, 1192 patients developed ulcerative colitis (10.8 per 100 000 person years). Appendicectomy without underlying inflammation was not associated with reduced risk (standardised incidence ratio 1.04, 95% confidence interval 0.95 to 1.15). Before the age of 20, however, appendicectomy for appendicitis (0.45, 0.39 to 0.53) or mesenteric lymphadenitis (0.65, 0.46 to 0.90) was associated with significant risk reduction. A similar pattern was seen in those with affected relatives, whose overall risk of ulcerative colitis was clearly higher than the background risk (1404 observed v 446 expected; standardised incidence ratio 3.15, 2.99 to 3.32). In this cohort, appendicectomy without underlying appendicitis did not modify risk (rate ratio 1.04, 0.66 to 1.55, v no appendicectomy), while risk after appendicectomy for appendicitis was halved (0.49, 0.31 to 0.74).

Conclusions: In individuals with or without a familial predisposition to inflammatory bowel disease, appendicitis and mesenteric lymphadenitis during childhood or adolescence are linked to a significantly reduced risk of ulcerative colitis in adulthood. Appendicectomy itself does not protect against ulcerative colitis.

Fig 1 Rate ratios with 95% confidence intervals for ulcerative colitis by age at appendicectomy (10 year age intervals) adjusted for country (Sweden v Denmark), sex, attained age (10 year intervals), calendar period (<1970, 1970-9, 1980-9, 1990-9, 2000-4), and time since appendicectomy (<0.5, 0.5-<1, 1-4, 5-9, 10-14, 15-19, ≥20 years). Reference rate was rate of ulcerative colitis among patients who underwent appendicectomy at age ≥50

Fig 2 Rate ratios for ulcerative colitis by time since appendicectomy in one year intervals for patients aged <20 or ≥20 at appendicectomy, adjusted as in fig 1. Reference rate was rate of ulcerative colitis five years after appendicectomy among those aged ≥20. P<0.001 reflects significance of effect of age at appendicectomy (<20 v ≥20) obtained in slightly reduced regression model with similar effect of time since appendicectomy in compared groups

Fig 3 Rate ratios for ulcerative colitis by time since appendicectomy in two year intervals according to underlying disease in patients aged <20 (P<0.001) or ≥20 (P=0.48) at appendicectomy. Rate ratios adjusted for country (Sweden v Denmark), sex, attained age (10 year intervals), calendar period (<1970, 1970-9, 1980-9, 1990-9, 2000-4), and age at appendicectomy. Reference rate was rate of ulcerative colitis four to five years after appendicectomy among patients with other disease. P values reflect significance of effect of underlying disease (appendicectomy or mesenteric lymphadenitis v other disease) obtained in slightly reduced regression models with similar effect of time since appendicectomy in compared groups