Rheumatoid Arthritis Update (Kremer - 8/16/23)

 A recording of this presentation can be viewed HERE.

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Renoir's Jardin du peintre à Essoyes

Many many thanks to our veteran SMGR Rheumatologist, Dr. Lisa Kremer for a compelling, artsy, and moving Grand Rounds presentation this week on Rheumatoid Arthritis (RA). Immediately after Dr. Kremer's presentation, a fellow primary care physician remarked to me, "I am not sure I have ever heard a specialist say so loudly and so clearly how important the social determinants are on the health of our patients."

Truth. And gratitude. From a primary care perspective, even one who is practicing almost entirely in the hospital these days, so much of health comes down to our social support and our community. Thanks, Dr. Kremer, for highlighting that.

RA is an autoimmune condition that developed in industrial society. Rarely seen before the 1600s, RA has some genetic susceptibilities (e.g. HLA DR4) and is precipitated by infections, environmental toxins (smoking doubles the risk), social and physical stresses, and hormonal triggers. 

RA is characterized by symmetrical polyarticular swelling of the small and medium joints on more than one occasion, over more than six weeks, supported by lab and/or xray and absence of other diagnosis. The back is not a small joint and is not involved in RA. 

photo source: https://www.nyp.org/healthlibrary/multimedia/

Classic x-ray findings (seen in above image) include loss of alignment of our normally beautiful joints, ulnar deviation, erosion of the MCP and PIP joints, but sparing of the DIP joints.

Exact causes of RA are unknown. There are a myriad of triggers.

• 1% of the the adult world has RA (1.5 million people in the US)-- the most common chronic inflammatory arthritis
• 4:1 female to male
• Peak age onset 40-60 years (but anytime after puberty is possible)
• All races and geographic areas are affected
• Specific populations with higher incidence (Native Americans, particularly: up to 10% of Sioux, Algonquian, Pima, Yakima, and Inuit peoples)

• 

  Renoir's Young Girls at the Piano
  

While Dr. Kremer presented us with a ton of medical information, she also presented the case of artist Pierre Aguste-Renoir (1841-1919), a French painter in the impressionist movement. She described him as a joyous and radical young man, struck by RA around age 50. His RA seems to have been precipitated by a fall from a bicycle and a resulting arm fracture. A trauma from which he never really recovered. And yet Renoir continued to paint long into his illness-- even designing his own wheelchair and equipment to be able to reach up to his large canvas painting surface. 

We live in a modern environment of autoimmunity

• lung exposures: tobacco, silica, textile dust
• chronic gingivitis
• GI tract microbiome patterns, diet (processed foods, e.g. cheese whiz and bologna)
• extreme and prolonged social stressors: war, jail, victims of abuse

Laboratory testing in RA is helpful but pretest probability determines the benefit of the test. 

• Rheumatoid factor (RF) is not specific
• Anti-CCP is more specific (can actually be positive a few years prior to onset of symptoms, but not always)
• ANA can be positive
• ESR and CRP really convey inflammatory cascade



(these are used more for research than for clinical application)

Sometimes it can be surprisingly hard to distinguish RA from osteoarthritis (OA). 

RA vs. OA (from PPM here): 

Extra-articular complications of RA only occur only in seropositive patients (i.e. +RF, +CCP ):

• fever and weight loss (can look like cancer)
• nodules (can be anywhere: eyes, heart, etc)
• interstitial lung disease
• pleuro-pericarditis
• CAD
• malignancy (specifically lymphoma)
• infections (like pneumonia)
• a variety of hematologic abnormalities (anemia, thrombocytopenia)
• osteoporosis

Prognosis and Disability:
Untreated, RA shortens life by 5-10 years. Aggressive RA therapy decreased mortality due to CV disease, lung, alanto-axial subluxation, and drug toxicity (e.g. steroids, NSAIDs). Treatment reduces the need for joint replacements by 50%.

In 1975, 50% of people with RA were disabled within 3 years; current estimates that 33% of people will be disabled (i.e. leave the workforce) within 5 years. Fatigue and unpredictable joint symptoms are frequently the most disabling issues. We should feel comfortable and confident filling out paperwork for our patients with RA. Their symptoms will wax and wane unpredictably.

Auto Amplifying loops

RA, like many autoimmune disease, consists of auto amplifying loops. Destruction of cartilage--> thickened synovium--> unstable tendons--> immune complexes--> extreme fatigue

Source: https://www.sciencedirect.com/science/article/pii/S1074761317300419

Treatment

Our current therapeutics have been created in direct response to this immunology. Treatments for RA are named for their immune targets. Note that methotrexate is still mainstay treatment for RA and steroids should only ever be given for short-term management. The combination of methotrexate and TNF inhibitors can actually stop all disease progression!

• Antimetabolites: Methotrexate (worldwide, best treatment for RA), Leflunomide
• TNF: Adalimumab, Etanercept, Infliximab
• IL-6: Tocilizumab
• Co-stimulation (CD28-CD80/86): Abatacept
• B cell depletion (anti-CD20): Rituximab
• JAK inhibitors: Tofacitinib, Baricitinib
• IL-1: Anakinra

Lifestyle matters!

This was perhaps the most compelling part of Dr. Kremer's talk. It turns out that these wonderful, effective meds are less effective if not used in combination with attention to a patient's life. 

• diet, exercise weight management
• tobacco cessation and limited alcohol
• stress management
• community and social support are key

And finally, Dr. Kremer's pearls of wisdom:

• Deformity does not equal disability
• RA does NOT cause back pain
• Never order tests if you don't know what you are looking for
• Low SES is associated with onset and severity of RA
• Smoking DOUBLES the risk and worsens the progression
• RA is "soft and spongy" (not hard and bony like osteoarthritis)
• A positive RF is not diagnostic, it should prompt you to keep looking for a diagnosis
• DIP joints are almost always spared
• If after careful exam and lab testing, you suspect RA, refer early to rheum for treatment!