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History of Rheumatoid Arthritis

Posted on March 31, 2021
See how 1718 members reacted on this article
Medically reviewed by
Ariel D. Teitel, M.D., M.B.A.
Article written by
Annie Keller

Rheumatoid arthritis (RA) has likely been observed and described for centuries, despite it being known as a relatively new disease. The condition may have first been described in the 300s B.C. by the Greek physician Hippocrates, who noted an arthritic condition that usually began in people in their early to mid-30s, starting in the hands hands and feet progressing to the elbows and knees. An Indian medical text from 123 A.D. also described abnormalities that are consistent with RA. Furthermore, skeletal remains have been found from ancient Egypt with evidence of RA-affected joints.

Rheumatoid arthritis is an inflammatory autoimmune condition in which the body’s immune system attacks the joints, resulting in pain, swelling, and deformity. Human understanding of the condition has evolved significantly since those initial early observations. Here’s a history of its modern progress.

Rheumatoid Arthritis Is Given Its Name

The first studies that discussed people with RA were written in 1800 by a French medical student named Augustin-Jacob Landre-Beauvais. He noted that many of his patients’ symptoms were distinct from osteoarthritis and other conditions that caused joint disease and joint damage. He also noted several risk factors: More patients were female than male, and the poor were more affected than the well-to-do. The disease appeared to be a previously undescribed condition, which he dubbed “primary asthenic gout.”

Gout is a variation of inflammatory arthritis that is caused by urate crystals made from uric acid, and it builds up in the joints. However, gout is not connected to RA. Despite Landre-Beauvais’ inaccurate classification of RA, he was correct in labeling it as its own condition, under the general umbrella of rheumatism.

RA was further classified in 1859. Alfred Garrod, a British physician, discovered the cause of gout through blood tests. In those who had gout, he found the characteristic urate crystals in their blood. However, he didn’t find them in the blood of people with other forms of arthritis — including RA. He proceeded to call RA “rheumatic gout” and distinguished it as a separate condition from both gout and osteoarthritis. In 1890, his son, Archibald Garrod, gave it the name “rheumatoid arthritis,” which stuck after more than a dozen other proposed names did not.

20th Century Developments

Years later, in 1934, the American College of Rheumatology was founded with the stated mission of “improving the care of patients with rheumatic disease and advancing the rheumatology subspecialty.” The group advocates for rheumatologists, rheumatology research, and people with RA and related conditions.

In 1940, RA was further distinguished as a condition when the rheumatoid factor was discovered. Rheumatoid factors are proteins found in the body that attack healthy tissue. This discovery led to new tests for diagnosing RA and predicting the disease’s progression. The discovery of the rheumatoid factor also distinguished RA further from a similar condition, ankylosing spondylitis (AS), and it led to RA being classified as an autoimmune disease. Later research showed that the autoantibodies produced by the body can cause autoimmunity responses and could be used to further measure autoimmune activity.

A more recent test for RA measures one such autoantibody, called anti-cyclic citrullinated peptide (anti-CCP). The anti-CCP test may be more accurate than the rheumatoid factor test, which cannot distinguish RA from various other autoimmune conditions, such as systemic lupus erythematosus and Sjogren's syndrome. The test looks for the anti-CCP autoantibody in specific human leukocyte antigens normally present in the blood. A positive test is also a good early predictor of how severe a person’s case will be.

Today, an estimated 1 percent of the world’s human population is living with RA. The condition is believed to be partly genetic, although various environmental factors can increase susceptibility.

History of Treatment for Rheumatoid Arthritis

The first advance in treating RA was discovered in 1897, a short seven years after the condition was named. Felix Hoffman, who worked for the German company Bayer, modified salicylic acid to create the basis for what we know as aspirin. It was found to reduce pain and inflammation. Aspirin began to be prescribed for symptom relief in RA and is still one of the nonsteroidal anti-inflammatory drugs that is used as a first-line treatment of RA.

In 1929, a doctor at the Mayo Clinic named Philip S. Hench discovered that one of his RA patient’s symptoms mysteriously vanished when they developed jaundice. Upon further study, he found out that pregnancy and recent surgery also seemed to have an antirheumatic effect — that is, to alleviate rheumatism. Suspecting a hormone was responsible, Hench began work to isolate hormones from adrenal glands. He dubbed these hormones adrenocorticosteroids, and one in particular — which he called cortisone — was eventually synthesized to become the first commonly used corticosteroid. Corticosteroid drugs are still used to reduce inflammation and slow joint damage from rheumatoid arthritis.

In the 1930s, a new treatment, injection of gold, became popular. Gold injections work in a similar way to disease-modifying antirheumatic drugs (DMARDs) — by blocking inflammation in the joints it is injected into. Like aspirin, gold is still used today, although usually only in early rheumatoid arthritis when other treatments have proven ineffective. It can be injected or taken in tablet form. Another DMARD, hydroxychloroquine — which was originally developed for malaria — was found to be similarly effective for RA in the 1940s.

In 1949, a folate inhibitor called methotrexate was found to be an effective treatment for acute lymphocytic leukemia in children. Since folate inhibitors had been studied alongside cortisone for anti-inflammatory effects, some researchers thought methotrexate might inhibit symptoms in a similar manner to cortisone. A 1951 paper showed that methotrexate could help control symptoms in rheumatic diseases such as RA and psoriasis.

However, at the time, rheumatologists saw RA as being essentially benign and were reluctant to treat it with a drug like methotrexate, which can cause serious side effects — especially at higher doses. It wasn’t until 1983 that a long-term study was published showing 78 patients with RA improved significantly in a quicker time period with low-dose methotrexate, compared to using injectable gold and some steroids. The U.S. Food and Drug Administration approved methotrexate to treat RA in 1988.

The 1990s brought a new form of treatment for RA: targeted biological therapies, also known as biologics. Biologics target certain biomarkers and cytokines, such as interleukin or tumor necrosis factor (TNF), which can cause symptoms of RA. The specificity of these drugs can mean fewer side effects from treatment, as they don’t target other body systems. In 1999, a clinical trial showed people with RA who received etanercept (a TNF inhibitor) and methotrexate improved more rapidly than those given methotrexate alone. A study in 2005 found that another biologic, infliximab, worked just as effectively.

There is still no cure for RA, but advancement in treatments means people living with RA can better manage their symptoms and limit the condition’s impact on their quality of life.

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References
  1. A Brief History of Rheumatoid Arthritis — Arthritis National Research Foundation
  2. Why Did Rheumatoid Arthritis Begin in 1800? — The Rheumatologist
  3. Historical Perspective on the Etiology of Rheumatoid Arthritis — Hand Clinics
  4. Gout — Mayo Clinic
  5. The Story of Aspirin — International Aspirin Foundation
  6. Gold Treatment — University of Washington Orthopaedics and Sports Medicine, Seattle
  7. On the Occurrence of a Factor in Human Serum Activating the Specific Agglutination of Sheep Blood Corpuscles — Acta Pathologica Microbiologica Scandinavica
  8. Rheumatoid Factor — Mayo Clinic
  9. DMARDs — Arthritis Foundation
  10. Discovery of the Wonder Drug: From Cows to Cortisone — Clinical Chemistry
  11. Rheumatoid Arthritis — Mayo Clinic
  12. Treatment of Solid Tumor Cancers with the Chemotherapy Drug Methotrexate — National Cancer Institute
  13. Landmark Papers on the Discovery of Methotrexate for the Treatment of Rheumatoid Arthritis and Other Systemic Inflammatory Rheumatic Diseases: A Fascinating Story — International Journal of Rheumatic Diseases
  14. Methotrexate Therapy in Rheumatoid Arthritis: 15 Years Experience — American Journal of Medicine
  15. Historical Research — Arthritis Foundation
  16. About Us — American College of Rheumatology
  17. A Trial of Etanercept, a Recombinant Tumor Necrosis Factor Receptor: Fc Fusion Protein, in Patients with Rheumatoid Arthritis Receiving Methotrexate — The New England Journal of Medicine
  18. Infliximab for the Treatment of Early Rheumatoid Arthritis — Expert Opinion on Biological Therapy
  19. Autoantibodies Targeting Intracellular and Extracellular Proteins in Autoimmunity — Frontiers in Immunology
  20. RA Facts: What Are the Latest Statistics on Rheumatoid Arthritis? — Rheumatoid Arthritis Support Network
  21. RA and Anti-CCP: What Is the Purpose of an Anti-CCP Test? — Rheumatoid Arthritis Support Network
Ariel D. Teitel, M.D., M.B.A. is the clinical associate professor of medicine at the NYU Langone Medical Center in New York. Review provided by VeriMed Healthcare Network. Learn more about him here.
Annie Keller specializes in writing about medicine, medical devices, and biotech. Learn more about her here.

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