Rheumatoid arthritis (RA) is a systemic, chronic inflammatory arthritis disease due to a breakdown in the self-tolerance of the immune system. This results in bone and cartilage destruction in the joints. The classic clinical presentation of RA includes symmetrical joint swelling for at least 6 weeks, morning stiffness of the affected joints for more than 1 hour, radiological deformities, and the presence of various biomarkers such as rheumatoid factor and anti-CCPs. Due to the systemic nature of the disease, there may be extraarticular manifestations such as lung involvement or vasculitis. The presentation of RA in patients varies. Patients may experience pain and stiffness that comes and goes while other patients may have constant pain and stiffness. Joints involved in RA can vary quite a bit as well with a number of joints having RA or only one or two joints having RA and the rest being fine. 

Figure 1: Metacarpophalangeal and proximal interphalangeal joint swelling characteristic of RA.

A 35 year old Caucasian female comes in for an initial visit with a rheumatologist. Her chief complaint is joint pain and stiffness which has been occurring intermittently for 3 years. When the symptoms initially began, they did not interfere with the patient's daily life. The pain and stiffness was less extreme and occurred only in the wrist. It gradually became worse and started affecting more joints. She has now reached the point she is having trouble performing simple tasks such as getting dressed. The pain and stiffness can present in any joints but seem to be the worst in the shoulder, elbow, and hand joints. The pain is the worst in the morning right after she wakes up. It can remain throughout the day, but some of the stiffness dissipates after physical activity. The patient does report a family history of RA. Physical exam reveals little swelling in the knee or foot joints and noticeable swelling in the hand joints. Elbow joints appear fine, but the patient has shoulder pain when asked to raise her hands/arms above her head. Measurements of serum rheumatoid factor (RF) and anti-CCP antibodies are ordered. Additionally, x-rays of the affected joints are ordered to look for damage. Vitals were all within normal range. 

The patient's x-ray showed an erosion on the proximal interphalangeal joint when compared to previous images. Additionally, high levels of RF and anti-CCP antibodies were detected in the patient's blood. 

The current diagnostic criteria for RA is in the figure above. A score of 6 or higher is required for diagnosis to be made. Based on the duration and character of the patient's joint symptoms as well as the blood tests, she is scored as a 7 and diagnosed with RA.

The patient is advised to take NSAIDs and methotrexate, a disease-modifying antirheumatic drug (DMARD), daily to slow the progession of the disease. 

For the last five years, I’ve had pain in my joints. My hands would ache in the morning when I got out of bed, but would feel better by the time I got to work. Over time, the pain has gotten worse, to the point where I cannot type as fast at work and had to stop tending my garden. When the pain first began, I thought it was just a part of getting older, but now when I look at my hands they are so twisted and deformed that I don’t recognize them. I first went to my doctor when my eyes became irritated and my vision became blurry. I was diagnosed with dry eye syndrome referred to a rheumatologist. After several tests, I was told I had rheumatoid arthritis and given medication. I don’t like the idea of taking pills for the rest of my life, but I am so tired of aching all the time. Although the pain has improved, I feel fatigued almost every day. I’m not sure if I should use my energy to deal with my aching joints or continue to sacrifice it for some small amount of relief.

This case study demonstrates the classic presentation of RA both in terms of symptomatology and demographic. Understanding the classic course RA runs and debilitating nature of the disease is critical.

Many details about the pathogenesis of RA are not fully understood, including the roles of anti-CCP and RF as well as the environmental and genetic triggers of the disease. However, there is a general concensus on the molecular mechanisms causing the chronic inflammation and joint damage. APCs activate synovial CD4+ T cells which in turn activate B cells. These B cells mature into autoantibody producing plasma cell. These antibodies form complexes in the joints, possbily with RF, triggering the complement pathway and causing more inflammation. 

There is currently no cure for rheumatoid arthritis. However, the progression of the disease can be controlled with physical therapy and anti-inflammatory drugs such as NSAIDs or a more powerful class of anti-inflammatory drugs known as anti-rheumatic drugs (DMARDS). In severe cases, other treatment options included joint aspiration, in which the fluid in the joint is drained or even surgical interventions such as joint replacement. Future treatments and research include the possible blockage of tumour necrosis factor-α (TNFα). Recent studies show this cytokine is overproduced in rheumatoid joints primarily by macrophages. Clinical studies based on the use of anti-TNFα antibodies or soluble receptors have suggested a potential beneficial effect of TNFα-blocking therapy in inducing amelioration of inflammatory parameters in patients with long-standing active disease.

Scott, I. C., Galloway, J. B., & Scott, D. L. (2015). Anti-Tumour Necrosis Factor-Alpha (TNF-α) Treatment. Inflammatory Arthritis in Clinical Practice, 119-135. doi:10.1007/978-1-4471-6648-1_8

Shah, Ankoor, and E. William St. Clair.. "Rheumatoid Arthritis." Harrison's Principles of Internal Medicine, 19e Eds. Dennis Kasper, et al. New York, NY: McGraw-Hill, 2014