Infections are more common in RA patients and increase risk of dying
By K. Molnar-Kimber, Ph.D.


Rheumatoid arthritis patients get infections twice as often as the general public [1, 2].   Patients who smoked, used corticosteroid, or had a positive rheumatoid factor were more likely to go to the hospital for a serious infection. 

Some prescription medications such as corticosteroids, TNF inhibitors, and IL-1 inhibitors suppress the immune response and also increase the rate of infection.  Rheumatoid arthritis patients who have serious infections and go to the Intensive Care Unit have a higher mortality rate than non-RA patients [3]. 

In a 17 yr prospective study, RA patients died twice as often as people of their age. This higher death rate was associated with infection and sudden death [4] 

Infections may also be an underlying cause of RA or a trigger for flares.

Is your Rheumatoid Arthritis caused or aggravated by an infection?

Dr. Leirisalo-Repo concluded that about 20% of rheumatoid arthritis patients had an infection at the beginning of their disease, maybe you, too. [5]      

Some Native American and Mexican skeletons showed evidence of deformities similar to rheumatoid arthritis before 1550 A.D.   Many scientists and physicians have searched for a single infectious agent that causes rheumatoid arthritis in all patients. 

No single infectious bacteria, virus or mold causes RA symptoms in all patients.

How infections may cause and aggravate rheumatoid arthritis

Let’s pretend that you get infected, such as a cold sore on one of your lips.  Your immune system sees the infectious intruder. It recruits many cell types ― macrophages, NK cells, antibodies and killer T cells ―so it can clear the infection. 

Infections can affect the joints in at least these five ways:

First, some bacteria or viruses can leave the original site of infection and migrate to the joint capsule.  For example, the joint fluid of some patients with active RA contains DNA of Herpes Simplex virus and Epstein Bar virus but not several others [6].

Second,  part of your joint tissue such as the synovium may look very much like a part of the intruder to your immune system. Your immune system may attack that part of your joints that looks similar, or is cross-reactive to the intruder. 

This is called “molecular mimicry” because some of the molecules of your joints and the intruder look similar to your immune system. For example, several proteins of Proteus have similar amino acid sequences to parts of two host proteins in RA patients [7].   

Third, the intruder may alter some of your joint proteins.  For example, Porphorymonas gingivalis causes gum disease, makes citrullinated proteins, and may prime the immune systems of some people to induce RA [8, 9].  The citrullinated proteins are your human proteins that were altered.  Your immune system may begin targeting your altered proteins.  

Fourth, when an infection activates your immune system, sometimes tissues nearby get damaged (called bystander effect). If your body makes too few signals to turn off inflammation, it may continue to target those tissues that had originally been affected by the infection.

Fifth, even after your immune system has cleared or rid your body of the intruder, your immune system may be confused. It may keep attacking your proteins that look like the invader. 

Whether infections caused your rheumatoid arthritis or not is an academic issue. 

However, learning if you have an infection now that is triggering your rheumatoid arthritis to flare is really important.  This information can help you and your healthcare providers find the best therapies.

 

Signs and symptoms of an infection in a joint

The classic symptoms of an infection in your joint include:

  1. severe pain in the affected joint, especially when you move that joint,
  2.  warmth in the affected joint
  3.  swelling in the affected joint, and
  4.  usually fever and chills.  

Symptoms of joint infections are very similar to flares in joints of rheumatoid arthritis and may be difficult to distinguish, note several physicians.  

Various infectious agents—bacteria, mycoplasmas, viruses, yeasts and molds—have been found in higher levels in rheumatoid arthritis patients than osteoarthritis patients or healthy controls.

Tips that may help your body fight infections

First, let’s get plenty of sunshine on our arms, face and legs for 15-45 min each day, depending on where you live.  Sunshine converts cholesterol in your skin to vitamin D precursors which the liver and kidney then transformed into vitamin D.   Vitamin D is essential for strong bones and a healthy immune system.   

Several trace minerals including zinc and selenium aid in maintaining a healthy immune system.   

Eating plenty of colorful vegetables and fruits can provide many nutrients that help the immune system disarm the disease-causing bacteria, viruses and molds.  

As always, discuss any changes with your healthcare provider.   

Selected References

1. Franklin, J.P., M. Lunt, D. Bunn, et al. Risk and predictors of infection leading to hospitalisation in a large primary-care derived cohort of inflammatory polyarthritis. Ann. Rheum. Dis., 2006. 66(3): 308-12

2. Yoshinaga, Y., T. Kanamori, Y. Ota, et al. Clinical characteristics of Mycobacterium tuberculosis infection among rheumatoid arthritis patients. Mod Rheumatol, 2004. 14(2): 143-8.

3.  Janssen, N.M., D.R. Karnad,  K.K. Guntupalli Rheumatologic diseases in the intensive care unit: epidemiology, clinical approach, management, and outcome. Crit. Care Clin., 2002. 18(4): 729-48.

4.  Riise, T., B.K. Jacobsen, J.T. Gran, et al. Total mortality is increased in rheumatoid arthritis. A 17-year prospective study. Clin. Rheumatol., 2001. 20(2): 123-7.

5.  Leirisalo-Repo, M. Early arthritis and infection. Curr. Opin. Rheumatol., 2005. 17(4): 433-9.

6.  Burgos, R., G. Ordonez, J. Vazquez-Mellado, et al. Occasional presence of herpes viruses in synovial fluid and blood from patients with rheumatoid arthritis and axial spondyloarthritis. Clin. Rheumatol., 2015. 34(10): 1681-6.

7.  Rashid, T.,  A. Ebringer Autoimmunity in Rheumatic Diseases Is Induced by Microbial Infections via Crossreactivity or Molecular Mimicry. Autoimmune Dis, 2012. 2012: 539282.

8.  Quirke, A.M., B.A. Fisher, A.J. Kinloch, et al. Citrullination of autoantigens: upstream of TNFalpha in the pathogenesis of rheumatoid arthritis. FEBS Lett., 2011. 585(23): 3681-8.

9.  Bonfil, J.J., F.L. Dillier, P. Mercier, et al. A "case control" study on the role of HLA DR4 in severe periodontitis and rapidly progressive periodontitis. Identification of types and subtypes using molecular biology (PCR.SSO). J. Clin. Periodontol., 1999. 26(2): 77-84.