My grandma has it, so does my mom and I feel like I too am destined to get it some day! Rheumatoid Arthritis, is arguably second most severe type of arthritis and a topic that is of an immense personal interest for me…
This is Chapter #2 of DawaiBox Arthritis Series.
Rheumatoid Arthritis (RA) is an inflammatory, systemic disease of autoimmune origin. It was first discovered by a French physician, Landré-Beauvais in 1800. He found this certain type of joint pain that is prevalent in poor and especially in women. He thought it was a type of gout, so he named it “Primary Asthenic Gout”. But it was a British physician, Archibald Garrod who coined the term “Rheumatoid Arthritis” later in his book Treatise on Rheumatism and Rheumatoid Arthritis.
The term, “Rheumatism” or “Rheumatic” is widely used to describe arthritic conditions. It is a term pertaining to diseases that cause joint pain. This term is interchangeably used for arthritis though it is not a valid medical term anymore!
Immune system is our body’s line of defense. When an external attacker (an infection or a foreign body) is detected withing the body, our immune system fights it and destroys it. But in certain cases, our body falsely recognizes a part of our own system as a foreign body and starts attacking it. This in nutshell is autoimmunity. Rheumatoid Arthritis is an autoimmune disease in which body starts attacking the synovial fluid membrane, which causes erosion of bone and cartilage. The swollen synovium causes swelling in the joints and bone erosion disrupts joint alignment, making fingers look crooked!
When a disease, though originates at a certain cite, affects more than one organ systems, it is called a systemic disease. Rheumatoid Arthritis is a systemic disease that affects not only joints but also eyes, heart, lungs, muscles, white blood cells, spleen etc. Some more classic examples of a systemic disease are Diabetes Mellitus, Hypothyroidism, Lupus and AIDS!
As we discussed RA is an autoimmune disease and what exactly triggers an autoimmune diseases is still pretty much a mystery. However there are some risk factors that has been identified. Some of those are-
It is largely speculated that certain infections like Epstein-Barr virus, parvoviruses, retroviruses and some bacteria and fungi can prime our immune system to mistakenly attack our joints! The research to support this hypothesis is still in it’s infancy though.
Research has established smoking and tobacco abuse being a risk factor in the development of RA. Recent investigative studies show that men and especially heavy smokers who are already RA positive are at an even greater risk of developing the disease. In females, smokers are 1.3X at higher risk for developing RA than non smokers! 
Next is a schematic representation of how smoking increases one’s chances of developing RA. This data is taken from a controlled study that recruited 1800 affected individuals and 1800 controls. HLA-DR gene is known to be responsible for many autoimmune conditions. Shared Epitope (SE) of HLA-DR is a prominent marker for development of RA. Study divides individuals in two subsets, 1 is people who are Rheumatoid Factor positive (jump to) and 2nd is RF negative. And then again both subsets are further divided in 3 groups of 1. people that have no SE HLA-DR genes, 2. people who have single copy of this gene, and 3. people that have 2 copies of this gene. Major point of consideration here is “Smoking” 
It has been long postulated that alteration in gut micro flora can have a role in causing RA. It is hypothesized that certain gut bacteria like Prevotella Copri, Collinsella aerofaciens, Eggerthella Lenta trigger immune system to cause an autoimmune reaction. Thought mechanisms are unknown, Dr. Veena Taneja at Mayo Clinic believes that such organisms can cause this effect by either proliferating exponentially and affecting the growth of other beneficial organisms in the gut. Some scientists believe that the toxins produced by these bacteria influences the development of Rheumatoid Arthritis, and others believe it happens because certain bacteria increase or decrease bio-availability of certain drugs.
Is Rheumatoid Arthritis hereditary? In simpler terms, the answer is NO! Inheriting a gene for RA from a parent and actually developing RA are two different things. Expression of RA genes is dependent on environmental factors like smoking, UV exposure, nutrition, overall health, infections etc. Some genes go unexpressed and the individual remains healthy. So what are the chances of someone inheriting a RA gene? Science does not have a definite answer to this. However we do have data from observational studies that tells us how your chances of developing RA increases based on who you share the genes with.
The more genes you share with someone who has RA, your chances of developing RA go that much up. For instance, if your sibling develops RA, your chances of developing it go up by ~5% and if that sibling is your maternal twin, then the number goes up to ~15%! 
Suggested Read, Can You Inherit Rheumatoid Arthritis?
The onset of disease may be earlier than one might notice and symptoms might go undetected for a period of time. In my mother’s case, now that we look back, it all started when she used to complain of pins and needles sensation every time she would walk. First we examined her foot, then changed her shoes, but she kept on complaining…and this went on for a long time before we decided it is time to go see a doctor! During early onset of Rheumatoid Arthritis, people usually complain of
- Pins and Needle Sensation
- Lumps under skin
- Minor joint swelling
- Loss of appetite
There is no definitive time line for the progression of Rheumatoid Arthritis. It all depends on how early the diagnosis was made and how well the symptoms are being managed. But even after tight management of health and symptoms, the disease gets worse progressively. There are four distinct stages of progression of Rheumatoid Arthritis.
Stage 1: Inflammation, minor swelling of joints, pain and stiffness of joints
Stage 2: Cartilage damage, loss of mobility
Stage 3: Inflammation has reached advanced stage. Cartilage, and bone destruction. Severe pain and swelling. Physical deformities.
Stage 4: Inflammation subsides, but the permanent damage is already done. Pain, swelling, lack of motion and disability persists.
A Rheumatologist will diagnose Rheumatoid Arthritis. For that he will do physical assessment, take family history, run blood and urine tests, take X-rays.
Medical History: your medical history, your family’s medical history, records of all tests and labs done so far, and all the drugs that you are on or have taken so far!
Physical Exam: Physician will examine each joint and check for inflammation, swelling, range of motion. He will also check for nodules underneath the skin.
Blood Tests: Apart from Complete Blood Count and Comprehensive Metabolic Panel, your rheumatologist might order additional tests like RA factor and CCP
RA factor: RA factor is a protein, it is an antibody that is found in almost 80% of Rheumatoid Arthritis patients. It’s presence in the blood (>14 IU/mL) is indicative of Rheumatoid Arthritis. RA factor however is also found in the blood of patients with Lupus, Sjögren’s syndrome, infectious hepatitis etc.
CCP: Cyclic Citrullinated Peptide, CCPs are used to detect Anti-Citrullinated Protein, a type of antibodies that are present in most RA patients. Normal value – < 20 EU/mL
presence of both RA factor and CCP in the blood are strong indicators of Rheumatoid Arthritis.
Markers of Inflammation
Underline inflammation is a classic tell-tale sign of an autoimmune condition. There are certain labs or tests that indicate the level of inflammation in one’s body. ESR are CRP are two such prominent markers of inflammation.
ESR: Erythrocyte Sedimentation Rate, ESR is a test that has been used to measure inflammation for years now. In case of inflammation, levels of fibrinogen (a glycoprotein) are increased in the blood which causes faster sedimentation of Erythrocytes (red blood cells). Normal values for women are 0-22 mm/hr and for men it is 0-29 mm/hr.
CRP: C-Reactive Protein is an acute phase protein produced by liver in response to an inflammation. Acute phase means that levels of CRP will rise or drop in accordance with inflammation. Which is what makes CRP such a sensitive and accurate marker of inflammation. Normal range: Should be Zero! CRP is present only when there is an inflammation going on, and in any healthy person, the value should be close to nil.
Imaging tests like X-ray, Ultrasound, and Magnetic Resonance Imaging are deployed in case your physician wants to examine the extent of joint deformation.
Seropositive: patients have anti-cyclic citrullinated peptides (ACPAs) in their blood.
Seronegative: Patients who test negative for ACPAs
RA positive: Patients that are tested positive for RA factor
RA negative: Patients that are tested negative for RA factor
Juvenile Rheumatoid Arthritis: In children under 17, Rheumatoid Arthritis is called as Juvenile Rheumatoid Arthritis or Juvenile Idiopathic Arthritis. In younger patients RA can hamper their growth and development. For majority of these patients, the disease continues for rest of their lives. Diagnosis and management of disease is the same as adult onset RA.
Rheumatoid Arthritis has traditionally been managed with the help of pain relievers and anti-inflammatory drugs.
NSAIDS: Nonsteroidal anti-inflammatory drugs are used for pain management. Some of the common and well known ones are ibuprofen, naproxen sodium, ketoprofen. These can be taken orally or applied topically.
Steroids: Corticosteroidal drugs like prednisone reduce and manage inflammation. They also help reduce swelling and pain. These are mostly used for duration just to control a flare up, as they have many side effects like weight gain, diabetes, bone loss etc.
DMARDs: Disease-Modifying Antirheumatic Drugs are capable of slowing down the progression of the disease and saving the joint altogether. Common ones are Methotrexate and hydroxychloroquine. There are subtypes in DMARDS as well
- Biologics: These are drugs that produce target specific anti-inflammatory responses and they are faster in action than traditional DMARDS. These are highly effective in slowing down the progression of the disease. Best known biologics are Humira, Lantus, Avastin and Avonex.
- JAK inhibitors: Very specific in action, these block the Janus Kinase (JAK) pathway of immune system. Examples, Jakvinus, Jakavi etc.
Surgery: In advance cases of joint deformity or disability, surgery is the patient’s best bet. Read more about Surgery types here.
Sick with having to take half a dozen of drugs every day and their side effects, many patients tend to turn to alternative therapeutic options. My mother herself turned to Ayurvedic Panchkarma, and leech therapy. People also opt out for Yoga, acupuncture, Weights and magnets etc. Here is a great article detailing all of those. Just know that all these alternative therapies may work for pain relief for a certain period of time but none of them really “cures” or reverses the disease. And alternative medications may adversely react with your medications. So do consult with your Rheumatologist before trying anything on your own.
Stem Cell Transplant
Stem cell therapy is not a new treatment option. Earlier this kind of therapy was under a lot of scrutiny due to use of embryonic stem cells, but now a newer option, induced pluripotent stem cells is available in which stem cells are obtained from a person’s own fat/blood/bone marrow. Proponents of stem cell transplant believe that if a stem cell is introduced into an affected joint it adapts to the surrounding and forms new cartilage cells and bone cells, and heals the joint. Studies have shown mixed results for the efficacy for Steam Cell Transplant and it is still not an approved treatment. More research is going on and we need to look out for new developments. 
Human Monoclonal Antibodies
Certain human monoclonal antibodies are shown to have positive effect on treatment of Rheumatoid Arthritis. Sarilumab, Tocilizumab, Sirukumab are all such antibodies against Interleukin-6 receptor, a cytokine that plays very important role in immune response. First two of them are approved by US FDA but Sirukumab is not approved due to lack of data associated with safety. 
That was everything about Rheumatoid Arthritis. Concluding this chapter with this lovely and useful article,
Next up in DawaiBox Arthritis Series is Arthritis Diet Article,