Rheumatoid Arthritis

Essentials

• If rheumatoid arthritis (RA) is suspected, the patient should be referred without delay to a rheumatology outpatient clinic.
  • RA as an immunological disorder may begin several years before the appearance of symptoms, which may, at first, be unspecific, making it impossible to distinguish incipient RA from other types of arthritis.
  • If there is inflammation in several, particularly small, joints, and rheumatoid factor and/or citrullinated peptide antibodies in blood, the patient probably has RA. Seronegative polyarthritis differs from seropositive polyarthritis as regards genetics and its more favourable prognosis, and it may prove in follow-up to be psoriatic arthropathy, for example.
  • ESR and CRP may be normal.
  • Systemic glucocorticoids interfere with the diagnosis and should therefore not be started in primary health care, but a glucocorticoid can be injected as first aid into inflamed joints.
  • New patients with symptoms of arthritis need to see a rheumatologist unless the diagnosis is evident and treatment can be provided on the primary care level, as is often the case with gout or reactive arthritis.
• RA is a progressive, debilitating disease but effective medication started early can make more than half of newly diagnosed patients asymptomatic within six months.
• The basic medication consists of a combination of methotrexate, sulfasalazine and hydroxychloroquine. Low glucocorticoid doses should be added to the regimen for at least a few months.
• Inflamed joints should be treated with glucocorticoid injections.
• RA not responding to combination drug therapy should be treated with biologicals biologicals or with a janus kinase (JAK) inhibitor.
• Physical exercise will improve the patient's functional ability and reduce the risk of cardiovascular disease.

Epidemiology

• About 40 adults per 100 000 per year develop RA.
• The age at onset is most commonly 65-70 years but two in three of those developing the disease are younger than 65 years old.
• Two in three patients are women.
• Some people are genetically susceptible to RA.
• Smoking doubles the risk of the disease.

Symptoms

• The onset of RA is usually insidious.
• Morning stiffness, tender and swollen joints are typical.
• Proximal interphalangeal and metacarpophalangeal joints, wrists, and balls of the feet are most commonly affected but basically any joint may become inflamed.
• Fatigue, malaise and mild fever may occur as systemic symptoms.

Investigations in primary care

• See the article Clinical examination of patients with joint inflammation in primary health care Clinical Examination of Patients with Joint Inflammation in Primary Health Care.
• Palpation can be used to find out whether a patient with joint symptoms has arthritis.
• An inflamed joint is characterized by soft swelling, tenderness, pain on movement and a limited range of motion.
  • Fist closure is often limited in patients with inflammation of small finger joints or with flexor tenosynovitis.
  • Tenderness on lateral squeezing of the knuckles or balls of the feet suggests arthritis.
  • It may be difficult to distinguish arthritis from osteoarthritis. In fingers, osteoarthritis occurs in the distal or proximal interphalangeal joints, RA in proximal interphalangeal and metacarpophalangeal joints. Patients with osteoarthritis may develop rheumatoid arthritis.
• Laboratory tests: ESR, CRP, basic blood count with platelets, RF, anti-CCP antibodies
  • ALT, ALP, creatinine, urate, Borrelia antibodies, chemical screening of urine, ANAs, antibodies to diagnose reactive arthritis, as considered necessary (see Reactive arthritis > Diagnosis Reactive Arthritis).
• If intra-articular injections are given, a synovial fluid sample should be taken at the same time for examination (synovial fluid leucocytes + differential count from synovial fluid, bacterial culture, possibly synovial fluid crystals), if fluid can be aspirated; see the article Investigation of Synovial Fluid.
  • In patients with arthritis, synovial fluid is cloudy, with a leucocyte count exceeding 2 000 × 10⁶ /l.
  • Highly cloudy synovial fluid suggests bacterial arthritis, usually monoarthritis.
• Imaging of patients with arthritis should mainly be performed at a rheumatology outpatient clinic.

Principles of drug treatment

• RA should be diagnosed and medication begun at a rheumatology outpatient clinic.

The efficacy of medication should be assessed by a rheumatologist after 3 and 6 months. Before the visits, the following should be tested: basic blood count (complete blood count with differential), creatinine (eGFR, calculator Gfr Calculator), ALT, ALP, ESR, CRP, chemical screening of urine.

Comorbidities , Bisphosphonates for Steroid Induced Osteoporosis

• Rheumatic inflammation is an independent risk factor for atherosclerosis.
  • Effective inhibition of inflammation is the most important means of preventing atherosclerosis.
  • Lipid tests to assess the risk of cardiovascular disease should be done when acute inflammation has subsided, i.e. after 3 months of antirheumatic medication, for example.
  • The target lipid levels are the same as in other high-risk patients.
  • Smoking cessation may also have positive effects on the results of treatment of RA.
• Higher doses of glucocorticoids impair glucose tolerance.
• Rheumatic inflammation, reduced functional ability and higher glucocorticoid doses make patients susceptible to osteoporosis.
  • In addition, glucocorticoids directly increase the risk of fractures.
  • All patients should be prescribed 1 g calcium + 800 IU vitamin D daily for osteoporosis prophylaxis.
  • At doses of prednisolone exceeding 7.5 mg, bone densitometry and osteoporosis medication should be considered.
  • See the article Osteoporosis Osteoporosis.
• About one patient in three will develop secondary Sjögren's syndrome.
• Glucocorticoids precipitate the development of cataracts.

Withdrawal of medication during infections

• Conventional immunosuppressive antirheumatic drugs (methotrexate, leflunomide, azathioprine and ciclosporin) should be withdrawn for the duration of any infection requiring antimicrobial treatment.
• Biological agents should be withdrawn for the duration of any generalized infection until the infection has subsided and been confirmed not to be serious.
  • In prolonged bacterial infections, restarting of biological medication can be considered even during antimicrobial medication, as soon as the active infection has subsided.
  • In mild upper respiratory tract infections with no fever, there is no need to withdraw biological medication.
• Important: The interleukin 6 inhibitors tosilizumab and sarilumab may mask symptoms and findings associated with serious infection and prevent the elevation of CRP levels.

Withdrawal of medication for procedures

• "Conventional" antirheumatic drugs need not be withdrawn for elective surgery.
• Even though research results are contradictory, withdrawal of biological agents and JAK inhibitors for elective surgery is recommended, meaning that the agents should be withdrawn for at least 1-2 weeks before operation.
  • Medicines have different half-lives.
• In the case of endoscopic gastroenterological and gynaecological procedures and other small procedures, such as naevus resection, withdrawal of medication is unnecessary.
• After uncomplicated surgical procedures, biological medication and JAK inhibitors can usually be restarted when the wound has healed.
• Biological medication or JAK inhibitors need not be withdrawn for normal filling of dental cavities.
  • There are no guidelines available for procedures possibly causing bacteraemia, such as dental scaling. The procedure can be scheduled between two doses.
  • In the case of more extensive dental surgical procedures or root treatment, the same instructions for temporary withdrawal can be followed as for other types of surgery.

Rehabilitation , , Non-Pharmacological Interventions for Fatigue in Rheumatoid Arthritis, Occupational Therapy for Rheumatoid Arthritis, , , Balneotherapy for Rheumatoid Arthritis, , Psychological Therapies for the Management of Chronic Pain in Adults, , Dynamic Exercise Therapy for Rheumatoid Arthritis, Acupuncture and Electroacupuncture for the Treatment of Rheumatoid Arthritis, ,

• Physical activity recommendation is an important part of the treatment of RA. Physical exercise improves functional ability.
  • When visiting their doctor, patients should be encouraged to exercise.
  • Exercises may be guided by a physiotherapist, as necessary.
• Conventional recommendations for health-enhancing physical activity can be given in most cases.
  • At least 2.5 hours of aerobic exercise per week
  • Strength training at least twice weekly
  • Such exercising has no negative effects on disease activity, pain or radiologically observed joint damage.

Aids Assistive Technology for Rheumatoid Arthritis,

• If joint damage has developed, the patient's functional ability can be improved by using aids supplied by the place of treatment.
  • Wrist splints
  • Support insoles
  • Cervical orthosis
  • Mobility aids
• The expertise of occupational and physiotherapists should be utilized in matters associated with aids and appliances.

Surgery

• See article Rheumatoid arthritis surgery Rheumatoid Arthritis Surgery.
• With improved pharmacological treatment, the need for surgical treatment has considerably decreased.
• Patients with a long history of the disease may need joint fusion or joint replacement.
• Destructive rheumatoid arthrosis may be associated with changes in the cervical spine. Atlanto-axial subluxation, which must be borne in mind when administering general anaesthesia, can be seen in flexion radiography of the cervical spine.
  • Subluxation exceeding 10 mm, particularly if associated with neurological symptoms, may require surgical treatment.
• Disturbing rheumatic nodules and bursae can be removed.

Vaccinations in RA

• See national or local guidelines on vaccination of adults with rheumatic disease.
• Live vaccines must not be given during immunosuppressive medication.

Continuity of care Downtitration and Discontinuation Strategies of Tnf-Blocking Agents in Rheumatoid Arthritis

• If remission is stable, after 2 years follow-up can be transferred to primary health care, where the patient should visit a physician - primarily one familiar with rheumatic diseases - once a year.
• Patients on biological agents or JAK inhibitors should continue being monitored by a rheumatology unit. If remission is stable, annual visits can be paid alternately to a rheumatology nurse and to a rheumatologist.
• Antirheumatic medication is normally used for several years or several decades because the symptoms of RA usually recur if medication is withdrawn.
  • If, however, after gradual discontinuation of glucocorticoids the patient's remission is stable for a long time, reduction of medication should be considered.
  • However, total withdrawal of medication is rarely possible. 10-15% of patients with RA achieve long-term remission without medication.
  • If the disease is reactivated when medication is reduced, the medication that previously gave a good response should be resumed.
• Long-term glucocorticoid treatment may cause adrenocortical suppression Pharmacological Glucocorticoid Treatment.

Follow-up in primary care

• Cooperation is necessary between the rheumatology outpatient clinic and primary health care.
• Patients with RA should be followed up annually by a physician - preferably one very familiar with the treatment of the disease.
• At follow-up visits, the activity of RA should be assessed based on the indicators listed below.
  • Patient's overall assessment of the activity of RA (VAS)
  • Pain (VAS)
  • Functional ability (Health Assessment Questionnaire, HAQ, find out about locally available version)
  • Joints with symptoms
  • Need for analgesics
  • ESR, CRP
  • Joint status: swollen and tender joints, ranges of joint motion
• What to do if RA is activated
  • Glucocorticoid injections into individual inflamed joints
  • Increased dosage of conventional antirheumatic drugs
  • Low-dose (5-10 mg/day) systemic glucocorticoids, with the dosage later minimized
  • Follow-up to confirm that inflammation can be controlled
  • Consultation of a rheumatologist if the above measures do not correct the patient's status