Rheumatoid Arthritis: Causes, Risk Factors, Symptoms, Treatment and More

Rheumatoid arthritis is a progressive disease. Therefore, it starts slow and then keeps attacking more joints, making the person almost handicapped due to the extreme pain on movement. This disease becomes so severe in the end stages that it destroys the joint, the bone, and its adjoining structures.

Scientists have classified Rheumatoid arthritis as early and established based on the duration of symptoms experienced. Those who come with complaints for less than six months are said to have ‘Early Rheumatoid Arthritis,’ whereas those presenting with symptoms of more than six months are defined as ‘Established Rheumatoid Arthritis.’

What causes Rheumatoid Arthritis?

The leading cause that causes Rheumatoid Arthritis has yet been a mystery. However, what science could gather is that it is an autoimmune disorder, and many factors can play a role in the attribution of this disease.

One of the main links has been found to exist between the patient’s genes and the environment that can cause this condition to develop. Moreover, many external factors can also come into play triggering this pathology. Cigarette smoking and the occurrence of rheumatoid arthritis have been greatly discussed by researchers. Certain individuals are positive for a specific ACPA protein in their body. These individuals have a direct relationship between cigarette smoking and Rheumatoid Arthritis. Therefore, it is evident that social factors are also linked to the prevalence of this disease.

Another cause seen to be causing increased incidences of rheumatoid arthritis is the changes in the intestinal flora. All those individuals who suffer from this disease have a disturbed gut biome. Therefore, it can also be a contributing factor to this disease. This change in the gut microbiome has been linked to the severity of the disease.

Epidemiology

The incidence of Rheumatoid Arthritis is seen to exist in about 40 out of 100,000 individuals. It has been seen to develop more in females than in females. Females are twice at a higher risk of developing rheumatoid arthritis than men. The peak incidence of this disease is in the late sixties. It is a disease of old age, and the ones susceptible to it usually present with signs of this disease in their fifties.

⇒ Now, let’s discuss rheumatoid arthritis risk factors, Symptoms, diagnoses & treatment options .

Risk factors

There are a few modifiable risk factors that can contribute to the development of Rheumatoid Arthritis. They have been listed down below;

1. Smoking-As mentioned below, cigarette smoking has been strongly linked to the development of rheumatoid arthritis. The many toxins present in cigarette smoke can end up causing the production of many free radicals. These free radicals can easily attach to the genetic model and create mutations. These mutations can trigger the autoimmune reaction responsible for the development of Rheumatoid Arthritis.
2. Diet and Nutrition-It is a well-established fact that all we consume eventually is responsible for making our entire body function. Therefore, the ones who consume a lot of fatty food with high caloric and low fiber diet have an increased risk of developing Rheumatoid Arthritis. Moreover, people seen to consume the good fats (long-chain omega 3 polyunsaturated fats) are associated with a decreased risk of developing Rheumatoid Arthritis in their older age.
3. Obesity– Studies have shown that individuals with a BMI of 30 kg/m^2 or more have an increased risk of developing Rheumatoid Arthritis. The inflammatory processes increase in an obese individual, which can directly influence the incidence of this disease in such people.

What happens in the body of an individual with Rheumatoid Arthritis?

A) Autoimmune Type

Autoimmune conditions are those in which certain antibodies have been produced that attack the healthy cells of the body. This is usually due to a defect in the genetic machinery of the body, which codes for these ‘autoimmune antibodies,’ making the body suffer. Since it is the body’s cells that are against the normal functioning cells, it gets very hard to get rid of these antibodies out, as the system keeps producing more of them. The specific antibodies that are created in the case of Rheumatoid Arthritis are against the citrullinated proteins.

Citrulline is an amino acid that works as a building block of the body. Each amino acid is incorporated into the body by attaching, forming a big protein complex. The antibodies produced in individuals suffering from Rheumatoid Arthritis end up producing antibodies against these amino acid molecules. These antibodies see citrulline molecules as a foreign body and attack them, to destroy them. These antibodies are called ACPA (anti-citrullinated protein antibodies). As soon as ACPA molecules get attached to the molecules of citrulline, the complement system gets activated. This in turn triggers the entire inflammatory pathway. This way the body thinks it is under some form of threat, destroying the normal cells of the body even more.

The titers of ACPA can stay in the body and can be tested in the blood for up to 10 years before the clinical symptoms of Rheumatoid Arthritis appear. The body takes time to increase the concentration of both ACPA and cytokine levels, which becomes a determining factor for the diagnosis of this disease in the later stages.

The cells of the joints are the main target of ACPA, therefore the fluid present between the joints (synovium) is filled with inflammatory cells and their debris. Chronic inflammatory cells also invade this space and the number of chemokines and tumor necrosis factors also increases considerably. The connective tissue of the joint capsule made up of fibroblast works with the inflammatory cells to erode the bone. This erosion of bone is the hallmark of the development of Rheumatoid Arthritis.

B) Environment triggered Rheumatoid Arthritis

 

It has been studied through years and years of research that environmentally triggered Rheumatoid Arthritis is due to the continuous activation of the innate immune system.

The biggest link between cigarette smoking and the development of Rheumatoid Arthritis comes from the theory that it induces the alveolar macrophages to convert a different amino acid; arginine into citrulline. This again triggers the immune response to form the ACPAs in the body, which starts by damaging the normal cells all over again.

What are the signs and symptoms of Rheumatoid Arthritis?

A person with Rheumatoid Arthritis can start getting symptoms at least ten years before having extreme joint stiffness and pain. It is a slow process of joint destruction, therefore unless the damage is significant, people don’t realize they could be suffering from this disease.

The most common symptom is noted to be joint pain and stiffness. This joint stiffness is usually experienced in the morning, which is one of the important features of this disease. Some individuals feel pain throughout the day, however, some have an episodic pattern of pain.

Almost all cases of Rheumatoid Arthritis complain of pain in the small joints of the body, including; fingers and toes.

When individuals attend a doctor’s clinic, pressure is applied to their painful joints and checked for a gritty feeling while palpating. Most people also mimic symptoms of carpal tunnel syndrome whenever their wrist joint is involved. In later stages of the disease, the presenting symptoms differ, with their hand deviated more towards the ulnar side, subluxation of the finger joints, and swan neck deformity of the fingers of the hand. There are also nodules and ulcerations noted on the surface of the skin attached directly on top of the bone; such as the olecranon.

Diagnosis

The diagnosis of Rheumatoid Arthritis is most often sufficient based on history and physical examination. However, X-rays and other invasive tests give great clues about the prognosis and the stage of this disease.

The disease starts with vague symptoms and hence takes time for exact diagnosis early on in the disease. There is no single diagnostic test to confirm Rheumatoid Arthritis, therefore, there are many features tested to determine whether the person has this disease or some other joint issue. Some of the tests that are carried out are mentioned below;

A) Blood Tests

1. 1. Levels of C-reactive Protein- The levels of C-reactive protein always increase when inflammatory processes are happening inside the body. Therefore, increased markers represent that the person could be suffering from Rheumatoid Arthritis.
   2. Rheumatoid Factor- The most important determinant of Rheumatoid Arthritis is the rheumatoid factor, which rises slowly, and is detected a little later in the stages of the disease.
   3. Erythrocyte Sedimentation Rate- The ESR levels raise due to the amount of inflammation happening inside the body.
   4. Anti-Citrulline Antibodies- These are specific biomarkers for the distinction of Rheumatoid Disease as opposed to any other joint disease.

B) Imaging Studies

1. 1. X-ray- X-rays give the biggest clues regarding the development of Rheumatoid Arthritis. It shows the significant narrowing of the joint spaces. This is what gives the biggest clues to the diagnosis of the disease.
   2. MRI- An MRI is done to confirm the diagnosis and establish the extent of damage to the other adjoining structures.

Stages of Rheumatoid Arthritis

There are 4 stages as clinically established by researchers. These stages largely define the prognosis of the disease. All of them have a distinguishing feature to look for in an X-ray.

• Stage 1- No pathological changes are visible on the X-ray.
• Stage 2- There is some bone damage seen in the surface between the joints, but there is no joint deformity appreciated on the X-ray.
• Stage 3- There is clear evidence of bone and cartilage damage along with joint deformity on the X-ray.
• Stage 4- All the features of stage 3 are markedly appreciated along with the unification of the joint surfaces on the X-ray film.

Treatment

The treatment of Rheumatoid Arthritis is more of managing the pain and the worsening condition, as there is no cure for completely treating the person. There are a few medications that help in decreasing the severity of pain, whereas others work by decreasing the rates of inflammation. These drugs help in modifying the disease and decrease the chances of exacerbations. The list of those drugs are as follows;

1. NSAIDs- These are given to help the patients with the pain that they suffer from throughout the day.
2. Steroids- Steroids are given to decrease the extent of the inflammation and to modify the pattern of the disease.
3. DMARDs- These are specific ‘Disease-Modifying Anti-Rheumatic Drugs,’ which are given to stop the disease from progression. These include methotrexate, hydroxychloroquine, and sulfasalazine.
4. Biologic Response Modifiers- These are paired with DMARDs to get the best therapeutic outcome. They have recently been introduced in the treatment of this disease. The drugs used are abatacept, adalimumab, and anakinra.

What are the complications that can develop due to Rheumatoid Arthritis?

Rheumatoid Arthritis requires extensive treatment of drugs that often come with a lot of side effects. Therefore, apart from slowing the progression of the disease, they also present with a lot of complications. These complications have been listed down below;

1. Osteoporosis- The continuous steroid therapy for decreasing the rates of inflammation also causes the bones to weaken and hence there is early onset of osteoporosis in these individuals.
2. Osteopenia- This refers to the loss of bone mass, which also happens due to the high doses of glucocorticoids.
3. Pulmonary diseases- The increased use of methotrexate and TNF blockers result in the development of pleuritis, bronchiolitis, as well as interstitial fibrosis.
4. Thromboembolic disease- Many individuals with Rheumatoid Arthritis suffer from some form of vascular disorder, and are at an increased risk of Coronary Heart Disease and Stroke.
5. Depression- Lack of physical exercise and inability to move around makes the person extremely depressed.
6. Anemia- With the persistence of any chronic disease, anemia always develops, as iron stores get depleted and the person feels more fatigued.

Prognosis

Rheumatoid Arthritis is a condition that has many options of management but has no cure. One can limit the disease from progressing at a fast pace but it cannot completely block the pathways causing the production of ACPAs.

Every individual suffering from this disease experiences exacerbations throughout their life. The ones who get diagnosed late end up with increased disability and mortality.

It has been seen that individuals who get treatment started within six months of their appearance of symptoms have a better outcome at dealing with this illness as compared to the ones who come after six months.

It comes as no surprise that patients who suffer from Rheumatoid Arthritis have their illness significantly affecting their work life. This makes them completely bedridden at the age of their late fifties, where their joints become so stiff that it is unable for them to move around.

The risk of early death also increases in these patients as cardiovascular diseases, lung diseases and malignancies rise in such individuals.

What are some of the other diseases that can present as Rheumatoid Arthritis but be something else?

Several diseases mimic the condition of Rheumatoid Arthritis, but with proper investigation, they turn out to be something else. Below is a list of those conditions;

1. Systemic Lupus Erythematosus (SLE)- This is also an autoimmune condition that involves multiple organ systems including the joints.
2. Lyme disease- This condition is due to an organism gaining entry inside the body, which can be treated with the use of antibiotics.
3. Sarcoidosis- This condition is often misdiagnosed with Rheumatoid Arthritis, due to similar manifestations, however, it can be due to any causative organism rather than just the body’s immune system.
4. Osteoarthritis- This is also a debilitating disorder, but it is due to infection of Staph. Aureus, which can be treated with the use of antibiotics.
5. Psoriatic arthritis- This is also an autoimmune disorder, in which almost all joints are severely affected. The main distinguishing feature against Rheumatoid Arthritis is the changes in nails in a person suffering from Psoriatic Arthritis.