by Diana Swift
Contributing Writer, MedPage Today
A family history of arthritis-related conditions, such as osteoarthritis (OA) or unspecified arthralgia, was not markedly predictive of developing rheumatoid arthritis (RA), according to a Swedish study.
“Although statistically significant familial co-aggregation was found for RA to every non-RA arthritis-related disease group — interestingly with no pronounced difference between seropositive and seronegative RA — there was no clinically meaningful association between relatives’ arthralgias or osteoarthritis and an individual’s risk of RA,” wrote Thomas Frisell, PhD, of the Karolinska Institute in Solna, and colleagues.
Furthermore, in individuals with an existing family history of RA, a family history of arthritis-related conditions conferred little or no additional RA risk.
“In other words, while a family history of lupus is informative, there is no additional information if the patient is already known to have a family history of RA,” they wrote in the Annals of the Rheumatic Diseases.
Familial aggregation of arthritis-related conditions often emerges during the clinical workup of RA since having a first-degree relative with RA confers a twofold to five-fold increased risk. Co-aggregation is also indicative of the genetic overlap between multiple immune-related inflammatory diseases.
Using Sweden’s National Patient Register, the nested case-control study identified people with RA and nine other arthritis-related diseases and used the Swedish Multi-Generation Register to identify the first-degree relatives of index RA patients.
Co-aggregation was assessed separately for seropositive and seronegative disease. After calculating familial risk via conditional logistic regression, the researchers used the Swedish Rheumatology Association’s Rheumatology Quality register to replicate their results.
They identified 54, 515 people with RA and 203,141 first-degree relatives. Familial conditions studied included other inflammatory arthritis, juvenile idiopathic arthritis (JIA), spondyloarthropathies, psoriasis/psoriatic arthritis, lupus, connective tissue diseases, arthralgias, and OA.
Overall, the co-aggregation pattern of arthritis-related diseases was very similar for seropositive and seronegative RA. “The difference between seropositive and seronegative RA was significant for only two of the non-RA diseases: spondyloarthropathies and psoriasis/psoriatic arthritis,” the authors wrote.
Some familial conditions were more strongly associated with RA and might be predictive. For example, a family history of JIA or a first-degree relative with lupus or connective tissue disease. There were no marked differences in familial risk by type of first-degree relative (siblings, parents, offspring).
Although with each disease there was familial co-aggregation with RA, the magnitude of the odds for arthritis-related diseases in first-degree relatives associated with the index patients’ RA varied widely from JIA (stronger) to arthralgia and OA (weakest).
With JIA, the odds ratio for association with seropositive RA was 3.98 (95% CI, 3.01-5.26) while for seronegative RA, the OR was 5.70 (95% CI 3.47-9.36). With OA, the OR for seropositive RA was 1.03 (95% 1.00-1.06); for seronegative RA, the OR was 1.05 (95% CI 1.00–1.09).
However, the authors proposed that even a slight association might be useful in distinguishing between those with seronegative RA and psoriatic arthritis. “We think these weak associations send an important clinical message, for example, regarding which patients should be referred early to arthritis clinic,” they wrote.
The authors acknowledged that their patient registries lacked measurements of anti-citrullinated protein antibodies (ACPAs), possibly allowing misclassification of seropositivity and seronegativity. But they pointed out that they found almost no differences between seropositive and seronegative RA in terms of familial co-aggregation, which would tend to rule out any large misclassification.
“An important task is now to investigate ‘seronegative’ RA in more detail, in particular, the extent to which ‘seronegative’ RA is made up of individuals positive to specific ACPAs or antibodies against similar epitopes, and thus potentially driven by pathophysiological mechanisms similar to those for seropositive RA,” they wrote.
The study was supported by the Swedish Foundation for Strategic Research, The COMBINE public-private research program, Swedish Research Council, ALF, the Strategic Research Programme for Epidemiology, and EU-IMI BTCure.
Frisell and co-authors disclosed no relevant relationships with industry.
Primary Source
Annals of the Rheumatic Diseases
Source Reference: Frisell T, et al “Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: a register-based case-control study from Sweden,” Ann Rheum Dis 2014; DOI: 10.1136/annrheumdis-2014-206133.