Late-onset Crohn's disease resembles ulcerative colitis

Last Updated: 2018-06-14

By Will Boggs MD

NEW YORK (Reuters Health) - Crohn's disease (CD) diagnosed at age 55 years or later resembles ulcerative colitis (UC) and should be considered a distinct subgroup of inflammatory bowel disease (IBD), researchers report.

"Late-onset CD is a different subgroup from both etiological and clinical perspectives," Dr. Dermot P. B. McGovern from Cedars-Sinai Medical Center, in Los Angeles, told Reuters Health by email. "UC-like characteristics of this specific subgroup indicate that there might be shared underlying mechanisms between UC and late-onset CD."

Earlier studies have suggested that clinical presentations and natural history of CD might differ according to age at diagnosis, but findings have been inconsistent.

Dr. McGovern and colleagues examined the distribution of genetic factors based on 172 CD loci across ages of diagnosis in 2,344 Caucasian CD patients (Cedars-Sinai cohort) and replicated the results in an independent group of more than 13,000 CD patients (International IBD Genetic Consortium (IIBDGC) cohort).

The researchers employed a polygenetic risk score (PRS) that represented a weighted sum of the number of risk alleles carried by each individual at known CD loci. The PRS was normalized to have a mean of 0 and standard deviation of 1.

Overall, 4.5% of the Cedars-Sinai cohort and 6.5% of the IIBDGC cohort had been diagnosed after age 55.

The PRS was significantly lower in the late-onset group (0.15 in Cedars-Sinai and 0.25 in IIBDGC) than in the group diagnosed at age 5-55 years (0.55 and 0.48, respectively), the researchers report in Inflammatory Bowel Diseases, online May 30.

The only known CD-associated SNP associated with late-onset CD, compared with intermediate-onset CD) was a NOD2 frameshift mutation, which showed an inverse direction of its reported association with CD.

In multivariable models, late-onset CD in the Cedars-Sinai cohort was independently associated with ex-smoking, antinuclear cytoplasmic antibody (ANCA) positivity and lower CD PRS. Late-onset CD in the IIBDGC cohort was independently associated with ex-smoking, lower CD PRS, less penetrating (B3) disease and colon-only (L2) location.

"With more colon-only affection, UC-like smoking behaviors (more ex-smokers, fewer current smokers), and UC-like serological patterns (high ANCA and low ASCA), the late-onset group is likely a distinct subgroup of CD with UC-like characteristics in both clinical presentation and disease etiology," the researchers conclude. "This is also supported by the strong correlation of single-SNP signals in late-onset versus intermediate and CD vs. UC comparisons. These findings further illustrate the heterogeneous nature of CD and the need for more personalized treatment strategies in clinical practice."

"Late-onset CD patients may warrant a distinct clinical intervention strategy, especially as some of our medications have higher risk of adverse events in these populations," Dr. McGovern said. "Further work is definitely needed here."

Dr. Jason Ken Hou from Baylor College of Medicine, in Houston, Texas, who has studied elderly-onset IBD, told Reuters Health by email, "Late-onset CD appears less likely to be associated with genes previously identified to be associated with CD. This not surprising, as it makes sense that patients with more genetic risk factors are diagnosed at a younger age."

"This may also be biased in that most studies are done in patients that are younger, so perhaps we just have not described the late-onset genes as well," said Dr. Hou, who was not involved in the study. "This also may suggest that late-onset CD is more likely to occur from non-genetic causes, such as environmental exposures."

"Late-onset CD can be difficult to define," he added. "The authors use 55 years of age and older; however, the literature has used other definitions, (>60, >65). Also, patients with late-onset CD can be difficult to define, as many patients may have had inflammation or even symptoms for many years and may not have sought out medical attention. This may also influence the findings that late-onset CD may also be less severe, as patients with more severe symptoms obtained medical attention earlier."

SOURCE: https://bit.ly/2sWAlNT

Inflamm Bowel Dis 2018.