Rheumatoid Arthritis (RA) is an autoimmune disorder that usually damages the joints, but can affect almost every system in the body. The specific cause of this condition remains unknown. However, research suggests that genetic factors play an essential role.
This condition affects around 1% of the general population worldwide. First degree relatives (i.e., sons, daughters, and brothers) of persons with RA have an increased risk of suffering from this condition.
I am a medical doctor, and, in this article, I will carefully describe the symptoms, treatment, and implications of the disease. I will also explain the relationship between our genetic load and rheumatoid arthritis. Keep reading to obtain the most recent information about rheumatoid arthritis directly from the hands of an MD.
What is Rheumatoid Arthritis?
Rheumatoid Arthritis is an autoimmune disease that attacks the joints producing inflammatory arthritis. Rheumatoid arthritis is the perfect example of rheumatic disease, a group of autoimmune diseases that target joints, bones, muscle, and connective tissue. Examples of other rheumatic diseases include:
- Ankylosing spondylitis,
- Psoriatic arthritis
- Juvenile rheumatoid arthritis (also known as juvenile idiopathic arthritis).
In RA, the immune system mistakenly attacks the synovial membrane of the joint producing inflammation. Chronic inflammation eventually translates into permanent damage such as bone erosions and deformity. Although rheumatoid arthritis tends to target the joints, it can attack other tissues, including blood vessels, heart, skin, and lungs. This autoimmune disorder does not have a permanent cure, but medical treatment can improve symptoms and prevent physical disability.
You said autoimmune, an autoimmune disease, what does that mean?
An autoimmune disease is a condition in which the immune system mistakenly attacks healthy tissues in the body. In autoimmunity, the immune system mistakes normal body tissues for foreign invaders such as viruses and bacteria, thus activating a harmful immune response and the production of autoantibodies that attack healthy cells.
Some of the most common targets of autoimmune disease include the kidneys, the lungs, and the connective tissue. Some autoimmune disorders such as Type 1 Diabetes Mellitus attack a single organ (the pancreas), others such as Systemic Lupus Erythematosus attack the whole body. In rheumatoid arthritis, small joints are the preferred target, but in 40% of cases, other organs suffer damage as well.
What happens in a joint affected by rheumatoid arthritis?
RA is an inflammatory disease. It starts in the smaller joints, particularly the ones that attach our fingers to our hands. As the condition progresses, symptoms can spread to bigger joints such as wrists, elbows, and knees. The most common RA symptoms include joint swelling, pain, redness, and stiffness. These symptoms are reversible in the early stages of the disease. However, chronic inflammation will eventually lead to permanent damage with joint and tendon destruction and atrophy of hand muscles. In advanced stages, patients experience severe deformity and decreased range of motion. Similar symptoms are also seen in other kinds of arthritis. However, some features help distinguish rheumatoid arthritis from different types of arthritis.
RA affects multiple joints at the same time in a symmetrical manner, which means that it affects both hands at the same time. Many RA patients also experience other symptoms besides joint swelling, symptoms such as fever, fatigue, weight loss, difficulty sleeping, and loss of appetite. In about 40% percent cases, other organs can also suffer significant damage. Besides the joints, the heart, the lungs, and the skin tend to be the most common targets.
What are genes exactly, and what do you know about the genetics of RA?
The specific reason that causes the immune system to malfunction in RA remains unknown. However, research suggests that genetic factors may play a significant role along with environmental, hormonal, and immunologic factors. In fact, genetic factors account for 50% of the risk of developing RA. To have a better understanding of the genetic factors involved in RA, let’s take a quick look into some basic genetic concepts.
Our DNA is, simply put, a spiral ladder, each step of this ladder has two molecules known as nitrogen bases paired together. There are four kinds of bases, thymine (T), cytosine (C), adenine (A), and guanine (G). A gene is simply a string of these bases that occupies a specific segment of a chromosome called locus. The different combinations of A, C, G, and T compose each gene and determine its function. Each gene has two or more different versions called alleles, and we inherit two different alleles from each parent.
A gene is said to be polymorphic when there are several alleles at a specific locus in more than 1 % of the population. Polymorphism occurs, in part, thanks to a process known as genetic variation in which some of the nitrogen bases that form a gene sequence are interchanged or deleted. In the next section, we will explore how polymorphism in specific genes can affect the way our immune system works.
What is the relationship between your immune system and your genes?
There most polymorphic genes that are known to science so far are the Major Histocompatibility Genes that code Human Leukocyte Antigen (HLA) molecules. Every single one of the cells in our body has an HLA molecule on its surface. This HLA molecule is what allows the immune system to recognize the cell as part of the body. There are more than 800 different alleles for each HLA locus. Therefore different persons express different HLA molecules.
The immune system recognizes foreign HLA molecules as dangerous producing an inflammatory response. Decades ago, in the early days of organ transplantation, many transplants were rejected by the recipient because of an immune response caused by HLA incompatibility. Nowadays, doctors make sure the donor has a compatible HLA phenotype before performing the transplant.
Which genes are responsible for increasing the risk of rheumatoid arthritis?
Having specific HLA genes is the most significant genetic risk factor for RA. Particular variations on the HLA gene HLA-DR are heavily associated with RA. The expression of alleles HLA-DR1 and HLA-DR4 increase genetic susceptibility and disease risk.
Unfortunately, the MHC system isn’t the only genetic variant associated with RA; many other susceptibility genes like STAT4, PTPN22, TRAF1, and C5 are also associated with increased RA risk. Most of these genes are also related to the immune system and are responsible for things such as chronic inflammation and activation of the immune response.
Many of the genes associated with RA are also related to other autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus. Persons that suffer from one autoimmune disease have an increased risk of developing another autoimmune disorder throughout their lifetimes.
How much of the risk of developing rheumatoid arthritis is determined by my genes?
Genetic predisposition is not enough to produce the disease by itself. Genetic factors account for only 50 percent of the risk of having RA, and the rest is attributed to environmental factors (more on this later).
The fact that a genetic marker such as an HLA-DR4 gene increases the risk of having the disease doesn’t necessarily mean that every person with these alleles will have arthritis. Several studies suggest that 80% of RA patients express the HLA-DR4 alleles associated with the condition. However, there is also an important percentage of healthy individuals that express these alleles and will never have arthritis through their lifetimes.
What are the chances of developing RA if there is a family history?
First degree relatives of a person with arthritis have increased risk of developing the condition compared to the first degree relative of persons that don’t have arthritis. Some studies even suggest that the siblings and children of RA patients have three times more risk of suffering from arthritis at some point in their lives. Although a three-fold risk may sound like a lot, this statistic can be misleading. The general population has a 1% chance of suffering from RA, which means that the children of an RA patient have a 3% chance of developing the condition. In short, having susceptibility to RA is way more common than the disease itself.
What are the rheumatoid arthritis causes and risk factors?
Susceptibility is only the first step in the process of developing the condition. The combination of genetic predisposition and risk environmental factors is what actually causes the disease. The subject isn’t fully understood yet. However, there are modifiable and non-modifiable factors that have proven to increase the risk of developing the disease.
Smoking is the most important modifiable risk factor. Susceptible smokers are twice as likely to develop RA as their nonsmoking counterparts, probably due to increased inflammation, oxidative stress, and aberrant DNA methylation. Smoking is also in association with increased disease severity and a poorer response to treatment.
Exposure to certain substances such as silica and asbestos has shown to increase the risk of RA, although to a lesser extent than smoking. Construction or mine workers in constant contact with these substances have a higher risk of developing an autoimmune disorder than the general population. The exact reason remains unknown. Obese people also appear to have a higher risk of suffering from RA at some point in their lives.
The two most critical non-modifiable factors are age and sex. This condition is three times more frequent in women than in men, probably due to hormonal differences between the two sexes. Although RA can occur at any age is far more likely to start between the ages of 30 and 55.
What are the signs and symptoms of rheumatoid arthritis?
Rheumatoid arthritis starts slowly. They are usually beginning with non-specific symptoms such as weakness, fever, malaise, and joint pain, followed by minor joint inflammation. Only 10% of patients start with severe acute joint swelling and damage to other organs. Other common symptoms of early rheumatoid arthritis include:
- Morning stiffness (that can last a few hours)
- Numbness and tingling
- Weight loss
As the disease progresses, patients may notice a decrease in the range of motion of the affected joints. A typical RA patient is unable to bend or straighten some fingers completely. With time, the destruction of joints and tendons leads to permanent deformity. Swann-neck deformities and hammertoes deformities, named after the shape the finger takes, are some of the deformities classically in association with the condition. Besides joint inflammation some other common musculoskeletal manifestations include:
- Carpal tunnel syndrome
- Osteoporosis, which can be limited to the inflamed joints or generalized due to chronic systemic inflammation
- Tenosynovitis and tendon rupture due to inflammation
Up to 40% of patients also experience symptoms outside the joint, here is a list of the most common organs RA can affect:
- Skin: through the appearance of rheumatoid nodules, firm lumps that develop under the skin near affected joints.
- Heart: Increase the risk of heart attacks and pericardial effusions.
- Lungs: Pleural effusion, pulmonary fibrosis, and pulmonary nodules
- Hematologic: Anemia and increased platelets are a common finding on these patients
Can a test predict whether I will get rheumatoid arthritis?
So, far we have mentioned some genetic markers for RA, but genetic testing isn’t the only way to predict RA risk. The presence of specific autoantibodies can precede joint inflammation for many years. The first of these antibodies to be discovered is called rheumatoid factor (RF) and can be found in approximately 75% of RA patients.
However, RF is not specific for RA and can be positive in several other conditions such as other rheumatic diseases, infections, cancer, and healthy 50-year-olds. Thankfully RF is not the only biomarker doctors use to assess RA susceptibility. Anti- citric citrullinated antibodies (ACPAs) are very specific for RA; therefore, doctors consider it the best for achieving RA diagnosis.
Rheumatoid arthritis can be classified according to the presence or absence of these antibodies into seronegative and seropositive arthritis. Seropositive patients are more likely to suffer from severe rheumatoid arthritis than seronegative patients.
According to one study, in asymptomatic patients, RF by itself is not in association with the risk of RA. ACPAs have a link with a 5% risk of developing RA in the next five years, and the two together increase the risk to a 100%. ACPA positive individuals with a family history have a 69% chance of developing the condition in 5 years.
What sort of medication can help me deal with rheumatoid arthritis?
Rheumatoid arthritis medication aims to control disease activity, slow down joint destruction, and alleviate symptoms such as joint inflammation, pain, and stiffness. Rheumatologists achieve these targets through a combination of nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs). NSAIDs such as ibuprofen and diclofenac decrease pain and swelling but do not slow down joint damage nor prevent organ damage. DMARDS inhibit the immune system, slowing down the progression of RA. Here is a list of some DMARDs doctor commonly use in RA treatment:
- Gold Salts
What is the prognosis for a patient with rheumatoid arthritis?
There is currently no cure for RA, but modern medications can reduce symptoms and slow down RA progression. Thanks to advances in contemporary medicine, most patients can live a happy and active life with RA. Although in some cases, RA can reduce life expectancy by 15 or 10 years, many RA patients live through their 80s and 90s with treatment.
What can I do If I am having symptoms?
This tool is a rheumatoid arthritis symptoms checker. Its design includes risk factors and symptoms in association with rheumatoid arthritis. Therefore, it will help you to assess how likely it is that your symptoms are from this disease.