DEFINITION OF RHEUMATOID ARTHRITIS
What is rheumatoid arthritis?
Rheumatoid arthrtitis (RA) is a form of Chronic Inflammatory Rheumatism (CIR). It is symmetrical (affects the same joint on the two sides of the body), destructive and crippling, and relates both to the small and large synovial joints (mobile joints) with a tendency to affect the joints in the hands, fingers and feet. It’s an autoimmune condition (activation of the individual’s immune system against its own body). It leads to various issues within the body and is accompanied by a diverse range of extra-articular manifestations. It’s development is seen through flare-ups, interspersed with periods of calm (decrease in symptoms of the condition) Without treatment, it worsens and tends to become debilitating. Diagnosis and early management are therefore necessary.
First, we notice inflammation of the synovial membrane called synovitis (this membrane corresponds to a thin layer of cells which lines the inside of the joint cavity), then multiplication of synovial cells and a thickening of the membrane. Synovial fluid is then released (liquid produced by the synovial membrane or synovium) within the joint, that leads to edema and pain, with damage to the cartilage, ligaments and muscles. Finally, there is erosion to the back, then destruction of the joint.
It can afect all joints: the most often being in the hands, fingers, knees and feet; but the cervical spine, shoulders, elbows and hips can also be affected. Finally we notice deformities characteristic of the fingers: mallet, swan-neck or buttonhole.
Is rheumatoid arthritis common?
This is the most common type of chronic inflammatory joint condition. It affects around 0.2 to 0.5% of the general population, which would represent around 200 000 patients in the UK and 21 million worldwide. It is 3 times more common in women (80% of patients suffering from rheumatoid arthritis), and the first symptoms generally emerge between ages 40 and 50.
Symptoms and complications of rheumatoid arthritis
The onset of the condition is pervasive: the intial symptoms have a benign appearance, yet in reality, they hide the severity of the condition.
The main symptoms are joint pain during rest (stronger at night and in the morning), an enlargement (swelling) and prolonged morning stiffness which fades after «morning stiffness» of joints (that is, after having mobilised and heated).
From the very onset of the condition, joint pathology is mainly located in the extremeties (notably those close to the hands). They are bilateral and symmetric (the same groupe of joints is affected by 2 sides of the body).
A significant fatigue and loss of appetite can also accompany the condition, related to its inflammatory and particularly autoimmune parts.
As a result, rheumatoid arthritis is characterised by persistant inflammation, gradual flare-ups, a deformity and gradual destruction of the joints, associated with extra-articular bone, visceral and infectious, complications, etc...
There are many extra-articular manifestations:
- systemic: anorexia, fatigue, weight loss, susceptability to infection;
- musculoskeletal: osteoporosis, muscular atrophy, tendonitis;
- neurological: spinal compression, peripheral neuropathy;
- cardiovascular: pericarditis, myocarditis, endocarditis, heart rythym disorders;
- pulmonary: alveolitis, bronchitis, nodules;
- haemotological: generalised adenopathy, anemia, thrombocytosis, eosinophilia, splenomegaly;
- cutaneous: sub-cutaneous nodules, cutaneous atrophy;
- ocular: scleritis, dry eye syndrome
- Gougerot-Sjögren syndrome, associated with ocular and oral dryness, can be noticed in patients affected by RA.
Causes and risk factors of rheumatoid arthritis
Rheumatoid arthritis is multifactorial:
- Genetic predispositions are observed: with the presence of HLA-DR4 genes (found with 60% of patients) and HLA-DR1 (in 30%) involved in the autoimmune response (in possessing a presenting function of antigens to immune cells). RA is two to three times more common within the family of affected individuals.
- There are also numerous environmental factors responsible: rheumatoid arthritis is the more common, more serious and responds less well to treatment in smokers. The condition is 3 times more common in women than in men. The peak occurrence of the condition is somewhere around 45 years old. Finally, there are geographical variations in the frequency of the condition (with for example a higher prevalence in the south west of France).
- Certain infectious agents have also been blamed such as the Epstein-Barr virus or P bacteria, gingivalis and A, actinomycetemcomitans, however their role is yet to be confirmed.
Diagnosis of rheumatoid arthritis
A diagnosis of rheumatoid arthritis should be made as early as possible in order to avoid the development of the condition with particularly severe and disabling joint damage. A diagnosis and early management also enable a more optimum response to be obtained.
It is first based on questions and the clinical exam of the patient. It is made when less than 4 criteria of the following list are seen, for at least 6 weeks:
- Morning stiffness (>1H);
- Arthritis in 3 joints or more;
- Arthritis in the joints of the hand;
- Symmetrical arthritis
- Rheumatoid nodules (corresponding to hard and painless bumps, located under the skin): rather rare.
X-ray examinations (radiographs) can be asked forin order to confirm the clinical exam. The regions that are generally affted are the hands, fingers and feet (however, radiographs are often normal at the beginning of the condition). Further examinations such as osteoarticular or IRM can also be carried out in order to observe inflammation of the synovial membrane or the first signs of a bone erosion.
Finally, a blood test can be ordered in order to look for biological markers of inflammation such as the C-reactive protein (CRP) and the assessment of the sedimentation rate (sed rate), which corresponds to the rate to which red blood cells fall in a tube of blood positioned vertically. An assessment of the rate of CRP in the blood (>6mg/L) or of the sedimentation rate (greater than 20 minutes in young patients and greater than 35 minutes for patients over 65) shown through inflammation.
The presence of rheumatoid factor (present in 80% of RA but often negative in early forms), anti-citrullinated protein antibodies (ACPA or anti-CCP, very useful antibodies for early diagnosis of RA because they have a greater specificity at 95%) and antinuclear antibodies (directed against the nuclei of its own cells and present in ⅓ of RA cases) is also researched. ACPA or anti-CCP have both a role in diagnosis but also in prognosis of the condition (their presence is associated with a greater severity in development with greater erosions).
At the same time, measurement systems have been put in place to evaluate the activity of the condition, and therefore assess the efficacy of its treatment (slowing down and stabilisation of joint damage):
- The DAS 28 score (Disease Activity Score) takes into account 28 joint locations. It measures the number of synovials and swollen and painful joints on palpation, overall assessment of the condition from the patient on a visual analogue scale or VAS (scale of 0 to 100) as well as the SR or the CRP. Therefore, according to activity criteria and response to EULAR (European League Against Rheumatism), RA activity shows DAS 28 scores as follows:
DAS 28 <2.6: remission
2.6≤ DAS 28 ≤3.2: low RA activity
3.2 ≤ DAS 28 ≤ 5.1: moderate RA activity
DAS 28 > 5.1: strong RA activity
- The SDAI index (Simplified Disease Activity Index): the calculation is made by adding the number of synovials (out of 28) + the number of painful joints to the pressure (out of 28) + overall assessment of the activity of the patient + that of the doctor (VAS from 0 to 10cm) + CRP (in mg/dl):
SDAI score ≤ 3,3 : remission
SDAI score ≤ 11 : weak level of activity
SDAI score ≤ 26 : average level of activity
SDAI score > 26 : strong level of activity
- The CDAI index (Clinical Disease Activity Index): the calculation is made by adding the number of synovials (out of 28) + the number of painful joints to the pressure (out of 28) + overall assessment of the activity of the patient + that of the doctor (VAS from 0 to 10cm):
score SDAI ≤ 2,8 : remission
score SDAI ≤ 10 : low level of activity
score SDAI > 10 : average level of activity
- Finally, the RA Specific Functional Disability Tool: HAQ (Health Assessment Questionnaire) assesses eight areas or categories of daily activities (getting dressed, getting up, eating, walking or washing) ove the past weeks. 4 types of responses are possible:
0 without any difficulty
1 with some difficulty
2 with a lot of difficulty
3 unable to do it
An overall score of 0 corresponds to the absence of a disability and a score of 3 corresponds to maximum disability to carry out this task of everyday life.
Treatments for rheumatoid arthritis
There are multiple treatment objectives of rheumatoid arthritis. On the one hand, symptomatic treatment lowers pain and inflammation and then improves the patient's quality of life. On the other hand, the basic treatment slows down the development of the condition and thus prevents the onset of the appearance of complications (articular or extra-articular). Today, this treatment can result in prolonged remission.
Symptomatic treatment of pain
The teatment of pain is based primarily on the use of paracetamol (Doliprane®, Dafalgan®, Efferalgan®) but more powerful pain relief can also be used (codeine, tramadol). Even so, these last painkillers present more undesirable effects (in particular significant substance dependence). It is therefore necessary to regulate their prescription. The use of opiods is not used routinely.
In order to reduce inflammation, anti-inflammatories are used. Among them, we find non-steroidal anti-inflammatory drugs (NSAIDs) and steroidal anti-inflammatory drugs (or corticosteroids) such as prednisone (Cortancyl®) and prednisolone (Solupred®) used orally or methylprednisolone used for flare-ups intravenously via bolus route).
Physical treatment can also minimise pain and deformities: there can be use of orthotics (splint to minimise deformities), occupational therapy (to understand ways to avoid painful movements) and rehabilitation (to build muscle tone and joint mobility).
Finally, local treatment can be looked at when joint inflammation persists despite medicinal treatment: corticosteroid injections in the joint (or more rarely synovectomy, which refers to injections of radioactive substances within the joint permitting a stop in the development of inflammatory synovial cells).
Also, surgical treatrment of joint lesions enable pain to be relieved or normal function to return of a destroyed joint, even when resorting to treatment has become more and more rare as a result of current treatments in allowing for a minimised development of the condition.
Basic treatment should be started as quickly as possible in order to treat long term inflammation and to then avoid or reduce the number of damaged joints.
Among the conventionnal synthetic basic treatments for rheumatoid arthritis, methotrexate (Novatrex®, Metoject®) immunosuppressant is the standard treatment, (that is to say it lowers the body's immune defense systems) prescribed as a first line of treatment. It is administered once a week orally, intramuscular or subcutaneous. In case of drug interactions or undesirable effects with methotrexate, leflunomide (Arava®) or sulfasalazine (Salazopyrine®) can be prescribed.
As with other basic treatments, while used much more rarely, we can note hydroxychloroquine (Plaquenil®, synthetic anti-malarial drugs that need a cardiac and eye surveillance) or even azathioprine (Imurel®).
For approximately twenty years, new basic treatments have been used in the event of an inadequate response to basic conventional treatments: this is known as biotherapies (treatments made by the body or substances originating from the body). Among them, we find anticytokines (anti-TNFα and anti IL-6), cellular biotherapies (activity of T or B lymphocytes). More recently however, small synthetic molecules called anti-JAK/STAT such as baricitinib (Olumiant®) and tofacitinib (Xeljanz®) may be offered in the same way as biotherapies. Some biosimilars (notably for anti-TNFα such as Idacio®, Hulio® and Benepali®, and anti-CD20s such as Remsima® and Inflectra®) are also available.
Anti-TNFα biotherapies are predominantly made up of infliximab (Remicade®), adalimumab (Humira®), golimumab (Simponi®), etanercept (Enbrel®) and certolizumab (Cimzia®). Guidance over these drugs is made increasingly early, despite their rise in cost. The combination with methotrexate is recommended and it has a rapid effect. The appearance of neutralising antibodies is commonly observed (such as anti-infliximab) but more than 70% of patients are responders. However, different undesirable effects can be noticed: particularly an increased risk of infection and drug-induced lupus. Clinical, biological and radiological observation is therefore necessary. Treatment failure (the body's tolerance to a treatment) may also appear during the use of a biotherapy and requires a change of molecule.
Other targeted biological treatments than anti-TNFs exist such as anti-CD20 antibodies with rituximab (Mabthera®), anti-CD28 antibodies with abatacept (Orencia®), as well as interleukin-1 receptor inhibitors with anakinra (Kineret®) and interleukin-6 receptor inhibitors with tocilizumab (Roactemra®) or sarilumab (Kevzara®). Common drug interactions to all of these treatments are active infection and live-attenuated vaccines.
Finally, among targeted synthetic treatments, JAK inhibitors, of which baricitinib (Olumiant®) and tofacitinib (Xeljanz®) are recommended for refractory forms of RA to anti-TNFa.
Living with rhematoid arthritis
Follow-up of RA activity until control of the condition
Regular follow-up, set out by the doctor and the rheumatologist, is necessary for optimal support of rheumatoid arthritis. Therefore, a review should be carried out every 3 to 6 months when the condition is stabilised and every month in case of acute exacerbation or modification of basic treatment. Occassionally, observation of undesirable effects and biological exam results (hematological, kidney, liver) allows for treatment to be adjusted for each patient.
Furthermore, an assessment of the progression of joint damage, through radiological examinations, must be made every 6 months for the first year, then every year at a minimum during the first 3 to 5 years and in case of a change in treatment. Finally, 5 years after the diagnosis of RA, the assessment of the condition's development may be done further apart.
Additionally, an assessment of the functional impact of disability (everyday tasks, transport, studies, work) can be assessmed at least once per year.
It is also required to research and address the other cardiovascular risk factors: quitting smoking, decrease in cholesterol level, fall in blood pressure, managing diabetes, loss of weight if obese and gradual decrease of corticosteroid therapy if necessary.
Therapeutic patient education
Management of rheumatoid arthritis is multidisciplinary: general practitioner, rheumatologist, physiotherapist, occupational therapist, podiatrist and eventually psychological follow-up from a psychiatrist or psychologist.
All of these health providers contribute to therapeutic patient education and allows them to obtain a good understanding of the condition and its treatments (medicinal or non-medicinal). This allows them to anticipate the appearance of new flare-ups (new painful inflammatory episodes) and to prevent and act when facing undesirable effects from treatments.
Lastly, beyond treatments, non-medicinal care also provides an improved quality of life with this disease: better arrangement of living space and finding out practices to adopt in order to prevent joint deformities with the help of an occupational therapist and to therefore be able to carry out more tasks by themselves, being advised by the podiatrist to wear suitable shoes, attend balneotherapy sessions in order to relieve pain and stiffness and therefore improve the ability to move around, etc.
In order to improve the exchange between the doctor and the management, it is also possible to write down in a diary, the date when flare-ups occurred, their duration and the intensity of pain, as well as tratment taken and their effectiveness or not.
Accessible housing for disabled people is also available to inform, support and advise people suffering from RA and their support network.
In addition, the practice of physical activites (to avoid stimulating the affected joints during periods of inflammatory flare-ups) should be considered alongside medicinal treatment. This ensures a reduced amount of fatigue, stress and anxiety and supports the maintenance of bones (lowering the risk of osteoporosis) and of joints, the increase of muscule capacity and the reduction of cardiovascular risk factors. Levels of anti-inflammatory drugs and of necessary corticosteroids can also be reduced through PA (physical activity).
It is important to adapt physical activity their physical activity to the state of their joints (swimming is particularly well-suited to relax the joints, but cycling and walking are also beneficial) and it is important to avoid carry heavy loads.
Lastly, a balanced diet keeps you healthy and reduces the development of the condition. It is particularly important to be vigilant with the intake of corticosteroids: they allow you to manage pain and inflammation but promote bone destruction, the reabsorption of salt, poorer absorption of proteins and a more significant storage of sugar and fats promoting weight gain. Therefore, calcium-rich food (dairy products: milk, yogurts, cheeses), in proteins (meats, fish, eggs), low in salt, sugars and fats is recommended. It is important to be vigilant with diets that exclude certain foods and that can lead to deficiencies.
Professional life and rheumatoid arthritis
Rheumatoid arthritis can have various impacts on professional life. It is advised to discuss them with the medical team, and in particular with their own doctor, to assess their abilities in carry out tasks requested according to their profession and eventually setting up their workplace.
Rheumatology can inform and document the different affected joints, the intensity of pain, of fatigue as well as the different prescribed treatments in a letter addressed to the doctor.
Lastly, stopping work may be issued by their own doctor. During a visit to the workplace, the company doctor should evaluate the abilities to maintain the job, provide accommodation, and perhaps even consider professional redeployment if necessary.
Pregnancy and rheumatoid arthritis
It is important to note that certain treatments for rheumatoid arthritis are not suitable for use during pregnancy or breastfeeding (methotrexate, leflunomide and JAK inhibitors). In fact, they can be toxic and lead to abnormalities in the fetus (teratogenic effect). This is because women of reproductive age who undergo treatment for RA must use effective contraception.
However, after making an appointment with the company doctor and the stopping of treatment for RA (before contraceptive treatment), it is possible to consider pregnancy. It is even quite common to notice a reduction in signs of inflammation and RA recovery in pregnant women.
Finally, rheumatoid arthritis is not considered as a hereditary illness: the risk of transmission to the child is very low.
To conclude, rheumatoid arthritis is a chronic inflammatory rheumatism able to affect a number of joints but also other organs and lead to certain disability. Yet there are many treatments and types of mutlifactorial support making it possible to improve its development.
Published 2 Sep 2019 • Updated 31 May 2021