Changes in inflammatory bowel disease subtype during follow-up and over time in 44,302 patients.

AIM: To investigate inflammatory bowel disease (IBD) register-based subtype classifications over a patient's disease course and over time. METHODS: We examined International Classification of Diseases coding in patients with ≥2 IBD diagnostic listings in the National Patient Register 2002-2014 (n = 44,302). RESULTS: 18% of the patients changed diagnosis (17% of adults, 29% of children) during a median follow-up of 3.8 years. Of visits with diagnoses of Crohn's disease (CD) or ulcerative colitis (UC), 97% were followed by the same diagnosis, whereas 67% of visits with diagnosis IBD-unclassified (IBD-U) were followed by another IBD-U diagnosis. Patients with any diagnostic change changed mostly once (47%) or twice (31%), 39% from UC to CD, 33% from CD to UC and 30% to or from IBD-U. Using a classification algorithm based on the first two diagnoses ('incident classification'), suited for prospective cohort studies, the proportion adult patients with CD, UC, and IBD-U 2002-2014 were 29%, 62%, and 10% (43%, 45%, and 12% in children). A classification model incorporating additional information from surgeries and giving weight to the last 5 years of visits ('prevalent classification'), suited for description of a study population at end of follow-up, classified 31% of adult cases as CD, 58% as UC and 11% as IBD-U (44%, 38%, and 18% in children). CONCLUSIONS: IBD subtype changed in 18% during follow-up. The proportion with CD increased and UC decreased from definition at start to end of follow-up. IBD-U was more common in children.

Birth outcomes in women with inflammatory bowel disease: effects of disease activity and drug exposure.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) have been associated with increased risks of adverse birth outcomes. Disease activity and drug exposure may contribute to the association. METHODS: A cohort from the Swedish health registers including 470,110 singleton births in Sweden from July 2006 to December 2010; 1833 to women with UC and 1220 to women with CD. Birth outcomes for women with UC and CD were compared with outcomes among those without disease. Diseased women were categorized by drug exposure, need of surgery, and hospital admissions as (1) no disease activity and (2) stable or (3) flaring disease. Logistic regression was used to calculate odds ratios with adjustments (aOR) for maternal age, parity, smoking status, body mass index, and comorbidity. RESULTS: There were increased risks of preterm birth for both UC (aOR, 1.78; 95% confidence interval [CI], 1.49-2.13) and CD (aOR, 1.65; 95% CI, 1.33-2.06). Risks were more pronounced in women with flaring disease during pregnancy. Risks of small for gestational age, low Apgar score, and hypoglycemia were also increased. The risk of stillbirth was elevated in women with CD, particularly among those with flaring disease (aOR, 4.48; 95% CI, 1.67-11.90). Thiopurine exposure increased risks for preterm birth, both in women with stable (aOR, 2.41; 95% CI, 1.05-5.51) and with flaring disease (aOR, 4.90; 95% CI, 2.76-8.69). CONCLUSIONS: Women with UC and CD are at increased risk of adverse birth outcomes, such as stillbirth, growth restriction, and preterm birth, particularly when they suffer from flares throughout pregnancy. Thiopurine exposure seems to further increase risks, independently of disease activity.

Increased risk of arthropathies and joint replacement surgery in patients with genetic hemochromatosis: a study of 3,531 patients and their 11,794 first-degree relatives.

OBJECTIVE: Genetic hemochromatosis (GH) is an autosomal recessive disease in individuals of Northern and Western European descent. Heterozygosity for the C282Y mutation is common (6-20%). Arthropathy is one of the few complications of GH suggested not to be associated with iron body stores; synovial iron deposition remains in iron-depleted patients. Previous studies suggest an elevated prevalence of clinical and radiographic signs of arthropathy in patients with GH, and 2 smaller studies suggest a possibly elevated risk of joint replacement surgery, but more mixed results are shown regarding risks with HFE genotype. We therefore assessed the risks of arthropathy and joint replacement surgery in patients with GH and in their first-degree relatives (FDRs). METHODS: We performed a population-based cohort study of 3,531 patients with GH and of their 11,794 FDRs (assumed to be heterozygous for the C282Y mutation) using nationwide Swedish population-based health and census registers. Hazard ratios (HRs) of arthropathies and joint replacement surgeries among patients and their FDRs (versus the general population) were assessed using Cox regression. RESULTS: Between 1997 and 2005, 406 of 3,531 patients were reported/hospitalized with any noninfectious arthropathies, including osteoarthritis, corresponding to an HR of 2.38 (95% confidence interval [95% CI] 2.14-2.64). Patients were also at increased risk of hip replacement (HR 2.77, 95% CI 2.27-3.38) and knee replacement (HR 2.14, 95% CI 1.58-2.88) surgery. Among the 11,794 FDRs (patients excluded), we found no increased risk of any of the joint morbidities. CONCLUSION: Patients with GH, but not their FDRs, are at increased risk of arthropathies, including the need for joint replacement surgery.

Does hemochromatosis predispose to celiac disease? A study of 29,096 celiac disease patients.

BACKGROUND AND AIM: Case reports suggest an association between hereditary hemochromatosis (HH) and celiac disease (CD), but estimates of association are lacking. We estimated the association between HH and CD in a population-based study. MATERIAL AND METHODS: Case-control study. We identified 29,096 individuals with biopsy-verified CD (equal to villous atrophy, Marsh stage III) through biopsy reports from all 28 pathology departments in Sweden. We then investigated the risk of a clinical diagnosis of HH in CD and in 144,522 controls matched for age, sex, county and calendar year. Conditional logistic regression was used to calculate odds ratios (ORs) for CD in patients with HH. RESULTS: HH was seen in 30 patients with CD and in 60 matched controls. HH was hence associated with an increased risk of CD (OR = 2.30; 95% CI = 1.53-3.45). Restricting HH to individuals with at least two records of HH, the OR for CD was 2.54 (95% CI = 1.57-4.11), with a similar risk estimate when we only looked at HH diagnosed before CD (and matched date in controls) (OR = 2.64; 95% CI = 1.24-5.60). CONCLUSION: HH seems to be associated with an increased risk of CD.

Complications from inflammatory bowel disease during pregnancy and delivery.

BACKGROUND & AIMS: Little is known about complications from ulcerative colitis (UC) or Crohn's disease (CD) during pregnancy and delivery. We assessed complications by using data from a large, population-based cohort. METHODS: We analyzed data from 1209 women with UC, 787 women with CD, and 10,773 women without these diseases (the comparison group) by using the Medical Birth, Patient, and Prescribed Drug Registers of all residents in Sweden. All the women included in the analysis gave birth to a single infant between October 2006 and December 2009. We used data on medical treatment, surgery, and hospital admissions to assess disease activity. Risks of pregnancy and delivery complications were determined from adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: The risk of venous thromboembolism was increased among women with UC (aOR, 3.78; 95% CI, 1.52-9.38), particularly for those with flaring disease. Women with CD had a higher risk of antepartum hemorrhage (aOR, 1.66; 95% CI, 1.12-2.45), with the highest risks among those with no disease activity. Risks of elective cesarean delivery were more than doubled among women with UC (aOR, 2.44; 95% CI, 2.06-2.88) or CD (aOR, 2.31; 95% CI, 1.89-2.83). Women with UC (aOR, 1.39; 95% CI, 1.13-1.70) or CD (aOR, 1.50; 95% CI, 1.17-1.92) had increased risk for emergency cesarean delivery. Women with an inactive UC or flaring CD had the highest risks of cesarean delivery. CONCLUSIONS: Women with UC or CD have more complications during pregnancy and delivery than women without these diseases. Disease activity affects mode of delivery, and thrombophilic events present differently in women with UC vs CD.

Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives.

BACKGROUND & AIMS: Iron overload may be carcinogenic. Patients with hereditary hemochromatosis (HH) are reportedly at a 20-200-fold risk of intrahepatic cancer, but the reported risks for nonhepatobiliary cancers are conflicting. The risk of cancer in heterozygous individuals (estimated allele frequency, 1/10 to 1/20) is unknown. This study aimed to better assess these risks. METHODS: We performed a population-based cohort study of 1847 Swedish patients with HH and 5973 of their first-degree relatives using nationwide, population-based health and census registers. We used standardized incidence ratios (SIRs) as relative risk. RESULTS: With 62 liver cancers and 128 nonhepatobiliary cancers, patients with HH were at a 20-fold risk of liver cancer (SIR, 21; 95% confidence interval [CI], 16-22) but an almost unaltered risk of all other cancers (SIR, 1.2; 95% CI, 1.0-1.4), including nonelevated risks for several gastrointestinal tract cancers. At 10 years of follow-up, the absolute risk of liver cancer was 6% among men and 1.5% among women. With 21 liver cancers and 508 nonhepatobiliary cancers, first-degree relatives were at an unaltered risk of extrahepatic cancer (SIR, 1.0; 95% CI, 0.9-1.1, including unelevated risks for gastrointestinal cancers) but at a modest and historic increased risk of hepatobiliary cancer (SIR, 1.5; 95% CI, 1.0-2.4), the histopathologic spectrum of which differed from the patients. CONCLUSIONS: Patients (particularly men) with HH are at increased risk for hepatocellular cancer, although the magnitude of the risk is lower than previous estimates. Overall cancer risk in first-degree relatives does not seem to be increased.