Definition

Rheumatoid arthritis (RA) is also called "arthritis". Sometimes arthritis is confused with osteoarthritis ("osteoarthritis"), psoriatic arthritis, gout and rheumatic pain syndroms like Fibromyalgia.

• Symptoms of Arthritis are Chronic Arthritis (Arthritis) in several joints at the same time (polyarthritis) and one feels sick

The joint swellings are quite soft to feel, usually easy to distinguish from normal joints and from osteoarthritis which has severe thickening. Blood tests show typical changes (see below). Not everyone has strengths joint pain, but stiffness of joints is common, often before the swellings appear.

• Early diagnosis and treatment are essential to avoid permanent joint damage

Occurrence and causes of illness

About one in 0,5% -1.0% of the population has RA (prevalence), and new cases (incidence) appear to be diminishing (reference: Gabriel SE, 2009)

• In childhood there are different forms of childhood arthritis (juvenile arthritis) that differs from RA in adults. Probably the causes are also different. In Norway a special department and national competence center (NAKBUR) for children with childhood arthritis are located at Rikshospitalet, Oslo
• The disease can start in all age groups with a peak around the age of 60X. RA occurs worldwide. The incidence is not particularly high in Norway
• Among adults, RA occurs three times more commonly in women.
  • The disease starts a little more often in the weeks following a born birth. A risk factor is probably reduced hormoneproduction from hypothalamic-pituitary-ovarian
  • Increased disease risk is also present in treatment with hormones (GnRH antagonists), as well as at anti-estrogen treatment (used by some forms of breast cancer)
• RA is triggered in part by hereditary disposition, but most people do not have RA in the immediate family
• Treatment of cancer with immunological checkpoint inhibitors can rarely trigger RA-like disease (reference: Belkhir R, 2017)

Climate and arthritis

Climate with changes in temperature, humidity and air pressure is claimed to affect the symptoms: "Weather change, cold and humidity are bad, hot, dry air is good for arthritis"

• Research has been done that shows increased pain in arthritis when the humidity is high. Studies also show that people with arthritis benefit most from rehabilitation in hot climates. However, changes in temperature and air pressure have not been shown to affect rheumatic pain, and the use of air-conditioned rooms and suitable clothing seems protective anyway. The studies show small results, but do not exclude that some are more affected by climate than others (references: Smedslund G, 2011, Patberg WR, 2004)

Symptoms of arthritis

Without known cause, multiple joints become stiff and sore at the onset of disease. The joints are somewhat hot and swollen (Arthritis) upon examination

• Typical are persistent, swelling of the wrists, finger joints ("knuckles") and in forefeet (feeling of "walking on cushions")
• Also knees, ankles, elbows, shoulders, fever and neck are often attacked. The extremities of the fingers (closest to the nails) are not attacked by the thumbs
• Typically, the same joints on both sides of the body are attacked, but not necessarily at the same time (symmetrical joint manifestations)
• Many people have a "flu feeling" in their body
• About. 7% get “Rheumatic nodes"Later in the process. They are harmless, hard knots beneath the skin, often over the strech side of elbows or fingers
• Symptoms of rheumatoid arthritis that have been on for more than two weeks should be referred to the rheumatologist
• In the event of suspicion of rheumatoid arthritis, rheumatological examination should be performed within six weeks of symptom onset

Diagnosis

The diagnosis must be made by a doctor, preferably a specialist in rheumatology

• General practitioner / physician assesses symptoms, takes current blood tests and refers to the nearest rheumatology department or to a practicing rheumatologist
• Special examinations of joints to confirm the diagnosis may include examinations with:
  • Ultrasound
  • MRI (magnetic resonance imaging)
  • Radiographs
• Blood tests are important. Almost everyone has elevated CRP and "erythrocyte sedimentation rate" (ESR). Most also have the more typical anti-CCP (ACPA), and rheumatoid factor (RF) even before the disease breaks out
• In research, special criteria are used to make arthritis diagnosis
  • The newest of these have been developed by the European Rheumatology Organization EULAR
• When the diagnosis is made, the rheumatologist will register for later comparison:
  • Number of joints that are painful and sore
  • Which joints (and numbers) that are swollen
  • Often, the patient (and doctor) evaluates the disease activity (subjectively) on a scale from 0-10
• When treating RA, it is important to start early. The treatment effect is then greatest

Complications

Serious joint damage

• Occurs within a few years if the disease is not adequately treated with appropriate medication

blood

The number of a group of white blood cells (granulocytes) may become too low and the spleen size increases. This may be a sign of Felty's syndrome or LGL syndrome

Depression

Rheumatoid arthritis often results in pain, reduced nighttime sleep, fatigue, rheumatic inflammation / inflammation and reduced physical function. These are the factors they have at their disposal to develop depression. Studies show that about 15% with RA have depression. Early attention to the problem and the implementation of relevant measures is important (reference: Engelbrecht M, 2019)

Heart

"Pericardial fluid" (pericarditis) occurs (reference: Carmona L, 2003)

Lungs

The lungs are attacked in about 4 - 10%, usually after several years of disease (Reference Kelly C, 2014)

• "Fluid in the lungs" (pleurisy)
• Risk factors are
  • Serious disease course with elevated CCP test (please see above)
  • Smoking
  • Men are attacked more frequently than women
  • High age
  • Some medicines can rarely cause side effects from the lungs (Methotrexate, Leflunomide (Arava), TNF inhibitors
• More about rheumatic diseases and lungs; please read here

Rheumatoid nodules (nodules)

Revma nodules are harmless hard spheres, most often on the stretch side (extensor) of the elbows and over the fingers. They can also occur in lung tissue

Vasculitis diseases

Es may occur Rheumatoid vasculitis; Please read more here

Eye symptoms

• You can read more about the Eye at RA here

Incorrect diagnosis? (Similar diseases / differential diagnoses)

• Differential diagnoses at RA are found here

Treatment av rheumatoid arthritis

Before starting treatment, it is important to be informed about the disease, what the target is, and any side effects that may occur. Blood tests to rule out signs of liver, kidney, blood disease and infection, as well as X-rays of the lungs are common. Need for vaccines against influenza and pneumococcus (pneumonia) are considered.

• Treatment goals are to stop the disease completely, that is, obtain remission. Unfortunately, there is no treatment to cure the disease.

Data indicate that the need for hip prostheses was 3 times higher and knee prostheses 14 times higher before more extensive use of disease-reducing treatment (most Methotrexate og Biological drugs) began (1996 versus 2011 in Denmark, Reference Cordtz RL, 2018)

However, adequate physical activity makes sense diet, non-smoking and aids for a simpler everyday life still important measures in Rheumatoid arthritis (Arthritis).

Painkillers

Paracetamol (Paracet, Pinex, Pamol and others) is the first choice because the risk of serious side effects is generally relatively small

• NSAIDs is an alternative to Paracetamol, but generally at greater risk of side effects
• Potentially addictive drugs (Piex forte, Paralgin forte, Tramadol, Nobligan, Oxyconitin and more) are avoided because there is often a need for long-term treatment and habituation and other side effects occur in the long run.

Cortisone Injections

Swollen joints can be drained and injected with cortisone which has a good effect. Nevertheless, the symptoms will return after weeks - months (recurrence). Cortisone injections are therefore only a supplement to disease-reducing treatment.

Cortisone / Prednisolone

Over the first 6-8 weeks stays Prednisone (cortisone) often used, but in fairly low doses (5 - 15 mg / day in a tapering dose). The effect comes quickly (within a few days). Later the dose is reduced.

• Some recommend a slightly higher initial dose of prednisolone (15-30mg / day) with gradual termination of termination within six months. It requires initiation of methotrexate (see below) concomitantly with Prednisolone

Methotrexate

To reduce the side effects of cortisone in the long term and to reduce joint damage, supplementation with Methotrexate in the form of tablets one day a week or weekly an injection (Metex) . Treatment should begin as early as possible when the diagnosis is made and the risk of serious side effects is excluded as far as possible. The dose is often 15-20mg / week. The effect of Methotrexate is felt after 6-8 weeks of treatment. If doses above 15-20 mg / week are required, subcutaneous / intramuscular injections are considered instead of syringes because these are better absorbed and the effect is therefore better.

• Methotrexate has contributed to people with arthritis now having less aggressive disease and causing less damage to the joints
• 25-40% have a good effect of methotrexate alone and combined with prednisolone achieve almost 50% low disease activity or remission in early RA
• Together with biological drugs, methotrexate increases the treatment effect
• Methotrexate reduces the development of neutralizing antibodies through the use of biological drugs (see below)

Other effective drugs

There are a number of other drugs that, like Methotrexate, have effects on both symptoms and the course of the disease

• Such medications are (in alphabetical order) Arava (Lefunomid) Enbrel (Etanercept), Humira (Adalimumab), Cimcia (Certolizumab) Kineret (Anakinra), MabThera (Rituximab), Metex (Methotrexate), Orensia (abatacept),  Remicade (Infliximab), RoActemra (tocilizumab), Salazopyrin (sulfasalazine).

Biological drugs

Medications such as Remicade, Enbrel, Humira, Cimzia, MabThera, RoActemra are often called “Biological”. They are designed to block specific parts of the immune system, thereby reducing the activity of the disease. (Reference: Smolen JS, 2015)

If the effect has not been sufficient on methotrexate or other similar disease-suppressing agents (DMARDs) within 6 months and signs of persistent inflammation are found, treatment with biological drugs / bioequivalents (bDMARDs) is considered. 

• Most commonly used are TNF inhibitors (Remicade / Remsima (infliximab), Enbrel / Benepali (etanercept), Humira (adalimumab), Cimzia (certolozumab) and others, but also B-cell inhibitors MabThera (rituximab), IL-6 inhibitors RoActemra (tocilizumab), IL-1 inhibitors Kineret (anakinra) and the T-cell co-stimulator Orencia (abatacept) are in use
• Bio-similar drugs ("Biosimilars") are almost identical to the biological ones (see above), but are usually less expensive. Surveys (Nor-Switch study) indicate that the effect is as good and the incidence of adverse reactions does not differ from the original preparations

JAK inhibitors

JAK inhibitors are a relatively new group of disease-suppressing drugs in the form of tablets for rheumatoid arthritis. They reduce rheumatic inflammation and the immune system by inhibiting the janus kinase enzymes JAK1, JAK2, JAK3 and to a lesser extent TyK2. This weakens the interleukins (IL-2, -4, -6, -7, -9, -15, -21) and interferon I and II. JAK inhibitors are alternatives to biological drugs (see above). Used alone or in combination with methotrexate (MTX).

• Tofacitini (Xeljans) tablets are usually dosed 5mg twice daily
• Baricitnib (Olumiant tablets are dosed 4mg once daily)
• Upadacitinib (Rinvoq) 15mg once daily
• Jyseleca (filotinib) 200mg once daily

Follow-up during treatment

When using disease-reducing drugs such as methotrexate, biological drugs or JAK inhibitors, regular check-ups should include assessment of blood tests at least every 1-3. month.

• Recommendations are described in a separate chapter

Hormones

Medicines that inhibit the release of ovarian hormones (GnRH antagonists) has shown promising, rapid onset in research studies led by the Norwegian doctor Anita Kåss (reference: Kåss A, 2015). It remains (per 2019) to see if such drugs become available for approved use except in research studies

Other therapeutic measures

Most rheumatology departments work closely with physiotherapists, occupational therapists, social workers and specialty nurses.

• Physiotherapists can, among other things, examine joints, muscle strength and physical function. They can set up a plan for individual activity and exercises to maintain mobility and strength
• Occupational therapists see the need for aids to master everyday life and special tasks in the best possible way when joints and muscles fail.
• Social workers can, among other things, inform about rights and benefits
• Nurses with a good knowledge of rheumatic diseases can provide supplementary information, follow up after treatment and be coordinating

Rheumatoid arthritis (RA) and diet

Arthritis (RA) Usually have better medical prognosis / living expectations now than before today's medications were available. Nevertheless, the disease can lead to reduced health. Symptoms are weight loss and fatigue. Blood tests may show low protein (albumin), iron deficiency, vitamins and other trace elements. Protein rich energy drinks, small, but frequent meals (every 2. hour by malnutrition, otherwise every 3-4 hour), and intake of vitamins and minerals are recommended. Meals may consist of fruit, yogurt, oily fish, peanut butter, pasta, egg and chicken. Avoid much sugar. Regular medical checkup with blood tests to measure albumin, iron, folic acid, B12, other vitamins, salts and trace elements is recommended. Measures against osteoporosis is recommended (see above).

Arthritis (RA) contributes to increased risk Atherosclerosis (atherosclerosis) (reference: Dessein PH, 2015). In the process, heart attack and stroke may occur. In arthritis, optimal drug treatment is important, but also risk factors must be reduced as high cholesterol (via diet and drugs), smoking, poorly regulated diabetes (diabetes) and obesity. High intake of multi-unsaturated fatty acids via "Mediterranean diet" reduces the risk of atherosclerosis. Treatment with biological drugs probably has a beneficial effect on atherosclerosis in arthritis (reference: Provan SA, 2015).

A combination of several immunosuppressive drugs (for example, different combinations of Prednisolone, Methotrexate, MabThera, Remicade / Remsima / Inflectra) increases the risk of infection. Avoid foods that may contain bacteria. This can be raw meat, raw fish (sushi), raw eggs, unpasteurized cheese, milk or unwashed vegetables.

• A professional, comprehensive knowledge summary here (Haugen M et al., 1999)

"Difficult RA": When arthritis does not respond to treatment

Despite today's good drugs and other measures, the treatment is still not successful in everyone with RA. This is due to several different reasons listed below. Obviously, each individual case must be considered separately in order to achieve the best possible result (Reference: Roodenrijs NMT 2018)

• Resistance to DMARDs means that the disease modyfying drugs no longer work. Development of antibody by Biological treatment is an possibility.
• Side effects or intolerance cause few or no good drugs to be relevant
• Difficulties in taking the drugs
• Memory problems or reluctance to do the treatment
• Concomitant other diseases (comorbidity) that limit the range of drugs that can be used
  • Infections
  • Heart failure
  • Kidney failure
  • Severe lung disease
• Other conditions that cause persistent rheumatic symptoms despite treatment
  • Osteoarthritis
  • Fibromyalgia and other pain syndromes
  • Depression

Five non-drug measures against rheumatoid arthritis

1. Quit smoking
   • Smoking is a risk factor for the disease and for a bad prognosis
2. Ensure good dental status
   • Bad teeth can cause infections that may spread during immunosuppressive treatment
3. Avoid overweight
   • Obesity can increase inflammation and reduce the effect of biological drugs (see above)
4. Diet / Diet
   • No special diet or dietary allowance (vitamins, minerals, proteins, etc.) has proven benefit if there is no deficiency condition (which can be detected by a doctor's examination)
   • General advice on diet in rheumatic diseases is described on a separate page here
5. Be sure to be vaccinated
   • Annual flu vaccine
   • Pneumococcal vaccine against pneumonia
   • Other recommended vaccines (The Norwegian Public Health Institute)

Tips (keywords) for investigation, referral to specialist and journal writing in rheumatoid arthritis - Arthritis

 Please follow the link here

Prognosis

Rheumatoid arthritis varies. Also in the individual, the disease is characterized by good and bad phases. It is possible that a future immunological test will be able to predict flare-up of the disease 1-2 weeks before it occurs, but so far we lack such methods in practice (Orange DE, 2020)

The vast majority have the effect of Methotrexate, which is often perceived as the "gold standard" in treatment. In case of ongoing disease activity, treatment should start as soon as the diagnosis is given, at the latest within 3 months. Nevertheless, many will still have active disease that causes pain and reduces physical function in the long run. By adding a "biological" drug, usually a TNF inhibitor (for example Remicade, Enbrel, Humira) or a JAK inhibitor, achieves approx. 70% better treatment effect. Survival after 5 years with RA is now similar to the rest of the population. Smoking worsens the prognosis more in arthritis than expected.

Follow-up by a specialist for rheumatoid arthritis - Arthritis

Regular follow-up by a specialist in rheumatic diseases is internationally recommended for disease activity, progressive disease course or when treatment is given with disease-suppressing drugs (DMARDs, JAK inhibitors or biological drugs).

The role of the specialist is to assess disease activity and signs of side effects. One can not expect patients, GPs and other healthcare professionals to have sufficient competence:

• If the disease has resolved, it is a specialist task to assess whether the drug doses can be reduced or treatment terminated.
• The specialist can assess whether the drugs have lost their effect over time
• Younger patients may want to become pregnant. At the forefront, changes in medication are often required
• Older people often get other diseases and drugs that affect the anti-rheumatic drugs. Overdose or loss of action is then possible. The specialist is aware of this and may change the treatment
• When the disease is in a stable phase without special medication, there is no need for follow-up by a specialist
• Internationally approved recommendations for the follow-up have been prepared and published (EULAR recommendations; Smolen JS 2017)

RA disease develops very differently from person to person and the treatment response is also individual. Nevertheless, the course is generally much milder now than before methotrexate and the newer drugs came on the market. This is shown in the fact that the need for joint operations has been greatly reduced among persons with RA.

Pregnancy

• More about pregnancy in the rheumatic diseases; Please read here

EULAR recommendations

• Investigation, treatment and follow-up (reference: Smolen JS, 2017)

Guidelines, Criteria and Misc Links (EMEUNET)

Rights in rheumatoid arthritis (Norsk Revmatiker Forbund)

Treatment guidelines

• Treatment with DMARDS, EULAR: (Smolen JS, Ann Rheum Dis 2020)
• Early Arthritis EULAR: Combe B, 2016
• Cardiovascular risk EULAR; Agcar, 2016
• Nurse Recommendations EULAR; Bech B, 2019
• Physical activity EULAR: Rauch Osthoff, 2018

Norwegian Rheumatological Association / The Norwegian Medical Association

Literature

• Scott DL, 2010
• Grans Compendium in Rheumatology

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