The relationship between infections and musculoskeletal and rheumatic conditions is complex and multifaceted. Multiple factors are believed to contribute to the development of rheumatic diseases, including genetic predisposition, hormonal milieu, and environmental influences including microorganisms. Indeed, infections can mimic, initiate, or propagate rheumatic disorders, ranging from arthritis to vasculitis. This issue highlights the multiple dimensions in the interrelationships between infections and musculoskeletal and rheumatic conditions.
The relationship between rheumatoid arthritis and autoimmunity to citrullinated peptides is now well established. The potential for periodontitis and the unique enzymatic properties of the periodontal pathogen Porphyromonas gingivalis to contribute to this key series of events has recently emerged. The impact of such a localized infection on the initiation and propagation of an immune-mediated systemic inflammatory disease in genetically susceptible hosts emphasizes the interdependent relationship between infections and the immune system. Similarly, interactions between human leukocyte antigen (HLA) B27 subtypes and bacterial antigens predispose certain individuals to seronegative spondyloarthropathy, again highlighting the complex interactions between genetics and environment in a distinct clinical setting, with different genetic factors and immune manifestations.
Infections with many viral and bacterial pathogens can also lead directly to arthritic disease. This can range from pyogenic septic arthritis to immune-mediated reactive arthritis. The need for diagnostic inclusion of septic arthritis, and consideration of background factors in the identification of likely organisms, is a clinical maxim that remains true. Arthropod vectors such as ticks and mosquitoes transmit a number of arthritis-causing pathogens, and these diseases spread further with the increase in the global distribution of these vectors. The presentation of septic arthritis may differ depending on etiology, perhaps leading to diagnostic delays, significant morbidity, and even mortality.
Human immunodeficiency virus (HIV) infection is associated with persistent and prolonged immune dysregulation, which can lead to autoimmune phenomena such as serological abnormalities and other rheumatological symptoms. Even in immune-competent hosts, infections can play a causative role in a number of different types of vasculitis. Some examples include the association between hepatitis B infection and polyarteritis nodosa (HBV-PAN) and hepatitis C-associated (cryoglobulinemic) vasculitis (HCV-CV). Conversely, patients with vasculitis may develop infections, which sometimes mimic relapse. Clinical identification of vial-induced vasculitis is essential in order to avoid inappropriate immunosuppression in the subset of patients in whom only antiviral therapy is required.
The treatment of rheumatologic disorders often entails the use of immunosuppressive agents, with the potential of an increased risk of infections. This risk is even higher with the rapidly expanding armamentarium of biologic therapies such as tumor necrosis factor (TNF) inhibitors, B-cell-depleting agents, and co-stimulation blockers. The infections observed include new infections, opportunistic infections, as well as reactivated underlying latent infections. The correct diagnosis and management of these infections are crucial, as diagnostic and therapeutic delays could result in a detrimental effect on the patient. Registry data provide much of our understanding of infection risk for these drugs, and ongoing analysis of such data for newer drugs is vital, as the circumstances of randomized trials may not reveal all risks of a certain product. Particular caution in relation to the high prevalence of endemic infections such as viral hepatitis and mycobacterial infection is required.
Targeted strategies for reducing the increased risk of infection in such patients include vaccinations as well as antimicrobial treatment of latent infections or antibiotic prophylaxis in selected groups. However, the immunogenicity, efficacy, and safety of vaccines in patients receiving immunosuppressive therapies remain unresolved issues, especially as newer infectious risks (such as herpes zoster) emerge in our patients and newer vaccinations for these diseases enter the market. Similarly, the risk of opportunistic infections and selection of patients for antibiotic prophylaxis remain debatable.