Genetic Susceptibility to Periprosthetic Joint Infections

Surgical site infections (SSI), and more specifically periprosthetic joint infections (PJI), have plagued the orthopaedic surgeon since the introduction of total joint arthroplasty (TJA) procedures of the hip or knee in the mid twentieth century. It is estimated that the economic burden of PJI in the United States will approach 1.62 billion USD by 2020. Though methods of infection control have improved, the rate of PJI appears to have plateaued in the last several decades. Early rates of PJI in the first two decades of THA have been reported between 1 - 9%. Since the 1980's studies have reported rates between 1% - 3%. It has been suggested that as orthopaedic surgeons, doctors should not be satisfied with deep infection rates greater than 1%. Therefore, more must be done in order to prevent, or diminish the frequency, of PJI and its devastating effects on this patient population.

In hopes of allowing for early targeted prevention in potentially high-risk patients, risk calculators have been developed to identify patients at greater risk for developing infection following TJA. However, some investigators suggest that these scoring systems may not be ready for primetime use. Thus, further research is needed to improve the ability to accurately identify individuals at high risk for infection. Unfortunately, the ability to perform large scale longitudinal cohort studies needed to create and test these risk calculators isn't feasible. Thus, other methods of early identification are needed.

Genetic susceptibility testing for identifying patients at risk for disease is becoming more popular and may be a means by which patients at high-risk for PJI can be identified. A recent dermatological study on genetic risk factors for infection suggest that host attributes may play a role in the ability of the individual to be infected. When evaluating the risk of subsequent different site infection in patients with multiple TJA's, investigators suggest that some patients may be at greater risk for infection due to possible subclinical immune deficiencies. In 2013, one investigator reported familial susceptibility to surgical site infections (SSI), including but not isolated to PJI, through a large population based study. Further, a recent publication from this investigating institution demonstrated familial clustering in patients who suffered a PJI, showing an increased risk of PJI following TJA in relatives of patients who have experienced PJI. These families demonstrated infection rates of 9 - 17%. After performing a systematic review on the genetic susceptibility to PJI, the investigators concluded that though evidence exists supporting a genetic role in PJI, no definitive conclusions can be made given the relatively small amount of data available in the existing literature. The investigators further emphasize the need for prospective studies to validate previous findings and the relationship between genetic factors and PJI.

Given the evidence in the literature, the investigators hypothesize that a large familial study will provide greater evidence of a genetic susceptibility. The results of this study could validate previous research with smaller sample sizes and allow for early identification of high-risk patients via genetic susceptibility testing.

Inclusion criteria

• Families/pedigrees which demonstrate a high-risk for PJI
• Unaffected family members, up to 3rd degree

Exclusion criteria

• None