Rheumatoid Arthritis: Autoimmune Inflammation of the Joints

Rheumatoid arthritis is a long term autoimmune disease that causes persistent inflammation within joints. It often affects several small joints on both sides of the body and can also cause fatigue or inflammation outside the joints. Early disease modifying treatment can suppress inflammation and prevent permanent damage.

What rheumatoid arthritis is Rheumatoid arthritis, usually called RA, is a long term inflammatory autoimmune disease. The immune system normally protects the body from infection. In RA, immune activity mistakenly targets tissues lining the joints. This lining is called the synovium. Persistent synovial inflammation causes pain, stiffness, warmth and soft swelling around affected joints. If inflammation remains active, it can damage cartilage, bone, tendons and ligaments. The resulting damage may reduce movement, weaken the joint or cause deformity. RA is a systemic disease. This means its effects can extend beyond the joints to the whole body. Rheumatoid arthritis is not simply joint wear RA is different from osteoarthritis, although one person can have both conditions. RA is driven primarily by immune mediated inflammation. Osteoarthritis is a structural joint disorder influenced by mechanical loading, previous injury, ageing, genetics and changes within cartilage and bone. Osteoarthritis pain is often related to using the affected joint. Morning stiffness is usually absent or settles within about 30 minutes. RA stiffness is often worse after waking or resting and commonly lasts longer than 30 minutes. Movement may gradually loosen the joints, although active inflammation can continue throughout the day. These patterns help guide assessment but are not absolute diagnostic rules. Osteoarthritis can produce swelling, and RA can sometimes affect joints asymmetrically or begin in one joint. The joints RA commonly affects RA often begins in the small joints of the hands, wrists or feet. Typical sites include the knuckles where the fingers meet the hand, the middle finger joints and the joints at the bases of the toes. The end finger joints nearest the nails are less typical sites for early RA. Osteoarthritis commonly affects those joints, but joint location alone cannot establish the diagnosis. RA can also affect the elbows, shoulders, knees, ankles, hips and the upper part of the neck. Several joints are often involved. The pattern may expand or fluctuate as the disease develops. Symmetry is common but not compulsory RA commonly affects matching joints on both sides of the body. Both wrists, both hands or both forefeet may become painful and swollen. This symmetrical pattern is characteristic and can help distinguish RA from some other conditions. However, early disease may be uneven. One hand may be more affected, or symptoms may begin on one side before the other. A person should not delay seeking care because their symptoms are not perfectly symmetrical. The inflammatory symptom pattern Persistent joint swelling is an important clue. Inflamed joints often feel soft or spongy rather than simply enlarged by hard bone. Pain and stiffness are usually worse in the morning and after periods of inactivity. Morning stiffness often lasts longer than 30 minutes and may continue for hours. The hands may be difficult to close fully. Tasks such as fastening buttons, turning keys, opening containers or walking after rest may become harder. Warmth can occur over inflamed joints. Marked redness is less typical and should raise concern about infection or crystal arthritis, particularly when one joint is acutely affected. Symptoms may develop gradually over weeks. In some people, several joints become inflamed over only a few days. General and systemic symptoms RA can cause profound tiredness that is not explained only by poor sleep or physical activity. Some people experience a low grade fever, sweating, reduced appetite, weight loss or a general feeling of illness. Anaemia may contribute to tiredness and breathlessness. Inflammation, medicine effects and other health conditions can all affect blood counts. Systemic symptoms are not specific to RA. Infection, cancer, thyroid disease and other inflammatory disorders can produce overlapping patterns. Flares and quieter periods RA activity can change over time. A flare means that pain, stiffness, swelling, fatigue or functional difficulty has increased. Flares may follow an infection, stress, treatment interruption or another trigger. Sometimes no trigger is identified. A flare does not always mean that the current medicine has permanently stopped working. The rheumatology team considers duration, severity, examination findings and disease activity measurements. New symptoms should not automatically be labelled as a flare. A hot joint, fever, breathlessness or neurological change may indicate infection or another complication. What happens within an inflamed joint The synovium normally produces a small amount of fluid that helps the joint move smoothly. In RA, immune cells and inflammatory chemical signals accumulate within the synovium. The lining becomes thickened and produces excess fluid. Persistent inflammation can form invasive tissue that damages cartilage and erodes adjacent bone. These erosions may be visible on later imaging. Tendons passing close to an inflamed joint can become weakened or damaged. Ligaments may stretch, reducing joint stability. Once structural damage has occurred, it may not be reversible. Suppressing inflammation early is therefore more effective than waiting for deformity to develop. Why rheumatoid arthritis develops There is no single known cause of RA. It develops through an interaction between genetic susceptibility, immune regulation and environmental exposures. Having a relative with RA can increase risk, but most relatives do not develop the disease. RA is not inherited in a simple predictable pattern. Smoking is an important modifiable risk factor, particularly for antibody positive RA. Smoking can also worsen cardiovascular and lung risks after diagnosis. Hormonal and biological factors may contribute to the fact that RA is more common in women. RA can still affect people of any sex and at any adult age. RA is not caused by using the joints too much, cold weather, personal behaviour or one particular food. RA is not contagious RA is not an infection and cannot be passed between people. A person cannot acquire RA by touching, living with or sharing equipment with someone who has it. Some infections may trigger immune responses or temporarily worsen symptoms, but this does not make RA itself infectious. Early disease may be difficult to recognise Early RA does not always produce obvious deformity or dramatic swelling. The person may report only stiffness, difficulty making a fist, pain across the knuckles or tenderness when the forefoot is squeezed. Blood inflammatory markers can be normal. Rheumatoid factor and anti CCP antibodies can also be negative. An early X ray may show no erosions. Normal investigations therefore do not automatically exclude inflammatory arthritis. Clinical evidence of persistent synovitis is more important than waiting for every test to become abnormal. The window of opportunity The early months after persistent inflammatory symptoms begin are an important treatment opportunity. Active inflammation can start damaging cartilage and bone before deformity is visible. Starting an effective DMARD early improves the chance of controlling disease and preventing irreversible damage. NICE recommends offering a conventional DMARD as soon as possible after diagnosis and ideally within three months of persistent symptom onset. This does not mean treatment becomes useless after three months. People with established or longstanding RA still benefit substantially from appropriate disease control. The message is that persistent synovitis should not be managed for months with painkillers alone while specialist assessment is delayed. When referral should be urgent Any adult with suspected persistent synovitis of uncertain cause should be referred for specialist assessment. NICE advises urgent referral when the small joints of the hands or feet are affected, when more than one joint is involved or when symptoms began at least three months before medical advice was sought. Referral should proceed even when rheumatoid factor, anti CCP antibodies or inflammatory markers are negative or normal. Blood tests and X rays requested in primary care should not delay rheumatology referral. How clinicians assess the symptoms The clinician asks when stiffness, pain and swelling began and whether symptoms improve or worsen with movement. They ask how long morning stiffness lasts and which activities have become difficult. The effect on sleep, work, mobility, caring responsibilities and mood is relevant. Questions may cover psoriasis, bowel inflammation, eye inflammation, infections, recent travel, health problems in the family and symptoms of other autoimmune diseases. The clinician reviews smoking, pregnancy plans, other medicines, previous joint injuries and conditions that may affect treatment choices. Joint examination The clinician examines joints for soft swelling, warmth, tenderness, movement and function. They may assess whether the person can make a fist, grip objects, walk normally and move the wrists, shoulders, knees and feet. The number and distribution of tender and swollen joints contribute to estimates of disease activity. Hard bony enlargement, creaking and activity related pain may suggest osteoarthritis. These findings can coexist with inflammatory synovitis. A single intensely painful, hot or red joint requires urgent assessment for septic arthritis or crystal arthritis rather than being assumed to be RA. Rheumatoid factor Rheumatoid factor is an antibody found in many people with RA. A positive result supports the diagnosis when the clinical pattern is compatible. It does not prove RA by itself. Rheumatoid factor can occur in healthy people, other autoimmune disorders, chronic infections and some liver or lung diseases. Some people with confirmed RA never develop rheumatoid factor. This is one form of seronegative RA. Anti CCP antibodies Anti cyclic citrullinated peptide antibodies are usually called anti CCP antibodies. A positive anti CCP result strongly supports RA in the appropriate clinical setting. These antibodies can sometimes be detected before obvious arthritis develops. Anti CCP positivity can be associated with a greater risk of erosive progression. It does not predict a person's future function with certainty. A negative anti CCP test does not exclude RA. Inflammatory markers and other blood tests C reactive protein and erythrocyte sedimentation rate are blood markers that can rise during inflammation. They can support diagnosis and help monitor treatment, but neither test is specific to RA. Normal inflammatory markers do not exclude active synovitis. Infection, obesity, anaemia and other conditions can also affect these results. A full blood count can identify anaemia, high platelets or low blood cell counts. Kidney and liver tests provide baseline information before some treatments. Additional tests may be used to investigate alternative diagnoses or prepare safely for DMARD therapy. Imaging NICE recommends X rays of the hands and feet in adults with suspected RA and persistent synovitis. X rays can establish whether erosions or other structural changes are already present. Early RA may produce a normal X ray. Ultrasound can demonstrate synovial thickening, fluid and increased blood flow. It may help when examination findings are uncertain. MRI is more sensitive for some early inflammatory changes but is not required for every person. Imaging supports clinical assessment. It does not replace what the person describes, the examination or specialist interpretation. Classification is not identical to diagnosis Specialists may use classification criteria combining joint involvement, symptom duration, inflammatory markers and antibodies. These criteria help create consistent groups for research and can support clinical reasoning. A person can have clinically important early inflammatory arthritis without yet meeting every classification threshold. Treatment and referral decisions should therefore not rely on a score used in isolation. Treat to target care Modern RA care uses a treat to target strategy. The agreed target is usually remission, meaning little or no active inflammatory disease. Low disease activity may be used when remission cannot be achieved safely or realistically. Disease activity is measured repeatedly using symptoms, joint examination, inflammatory markers and functional impact. Treatment is adjusted when the target is not reached. This is called tight control rather than waiting indefinitely on an ineffective regimen. Reaching a target reduces pain and fatigue while also lowering the risk of joint damage and systemic complications. DMARDs are the main treatment Disease modifying anti rheumatic drugs are called DMARDs. DMARDs suppress the inflammatory disease process. Their purpose is not merely to mask pain. Effective DMARD treatment can reduce swollen joints, improve function, prevent erosions and lower the risk of disability. Because DMARDs may take weeks or months to reach full effect, treatment begins before permanent damage is allowed to accumulate. A person may need dose escalation, combination treatment or a change of drug to reach the agreed target. Conventional synthetic DMARDs Common conventional DMARDs include methotrexate, leflunomide, sulfasalazine and hydroxychloroquine. NICE recommends oral methotrexate, leflunomide or sulfasalazine as first line monotherapy for newly diagnosed active RA. Hydroxychloroquine may be considered for mild or palindromic disease. Methotrexate is a common first choice and remains a central treatment internationally. In RA it is usually taken once each week, not daily. Folic acid is commonly prescribed on a different day to reduce some methotrexate adverse effects. The choice depends on disease activity, pregnancy plans, kidney and liver health, lung disease, alcohol intake, infection risk, other medicines and patient preference. Methotrexate safety Methotrexate used for RA is normally taken weekly on an agreed day. Accidental daily dosing can cause severe and potentially fatal toxicity. A person should seek urgent clinical or pharmacy advice after taking more than the prescribed weekly dose, even if they initially feel well. Blood tests monitor blood cell counts, liver function and kidney function. The monitoring interval changes according to treatment stage and individual risk. A sore mouth, unusual bruising, severe diarrhoea, jaundice, fever or new breathlessness requires prompt advice. Trimethoprim and co trimoxazole can interact dangerously with methotrexate. All prescribers and pharmacists should know that methotrexate is being taken. Bridging glucocorticoids Glucocorticoids, often called steroids, can reduce inflammation quickly while a DMARD takes effect. They may be given as tablets, an injection into a joint or an injection into a muscle. This is called bridging treatment because it covers the delay before the DMARD controls disease. Steroids are not a substitute for an effective long term DMARD strategy. Prolonged exposure increases risks including infection, osteoporosis, diabetes, cataracts and adrenal suppression. Steroids should not be stopped suddenly after prolonged use unless a clinician gives an appropriate withdrawal plan. Pain relief and anti inflammatory medicines Paracetamol, some opioid containing medicines or non steroidal anti inflammatory drugs may reduce pain. NSAIDs can also reduce stiffness and inflammation temporarily. They do not prevent RA from damaging joints. NSAIDs can cause stomach bleeding, kidney injury, fluid retention and cardiovascular complications. The risks differ according to age, dose, other medicines and past health problems. A stomach protecting medicine may be prescribed with an oral NSAID. Pain relief should support function while disease modifying treatment controls the underlying inflammation. Biological DMARDs Biological DMARDs are medicines designed to block particular immune pathways. Examples include tumour necrosis factor inhibitors, interleukin 6 inhibitors, abatacept and rituximab. They are generally considered when active disease has not responded adequately to conventional DMARD treatment or when another clinical indication exists. Most biological medicines are given by injection or infusion. They may be combined with methotrexate or another conventional DMARD. Biological treatment can be highly effective but may increase susceptibility to particular infections. Screening and vaccination planning are therefore important. Targeted synthetic DMARDs Janus kinase inhibitors, usually called JAK inhibitors, are targeted synthetic DMARDs taken by mouth. They block signalling pathways involved in immune inflammation. They may be options for moderate or severe RA under specialist care when appropriate previous treatment has been ineffective or unsuitable. JAK inhibitors require careful assessment of infection, cardiovascular, cancer and blood clot risks. The balance differs between individuals. These medicines should not be started, stopped or exchanged without specialist advice. Treatment monitoring DMARD monitoring is designed to identify toxicity early while allowing effective treatment to continue. Before starting treatment, clinicians assess blood counts, kidney and liver function and relevant infection risks. Some medicines require additional tests. The BSR recommends risk based monitoring. People at higher risk need more frequent blood tests, while stable low risk patients may eventually have longer intervals. Monitoring responsibilities may be shared between rheumatology and general practice through an agreed protocol. Normal previous results do not remove the need to report new symptoms or adverse effects. Infection screening and vaccination Immune modifying treatment can alter the risk or presentation of infection. Screening may include hepatitis B, hepatitis C, HIV and tuberculosis according to the medicine and the person's risk factors. Vaccination status should be reviewed before significant immune suppression begins where possible. Seasonal influenza and pneumococcal vaccination are commonly advised. Eligibility for COVID 19 and shingles vaccination depends on current national guidance and immune status. Some live vaccines are unsuitable during particular immunosuppressive treatments. Vaccine advice should be obtained from the rheumatology team, GP or vaccination service. Infection while taking a DMARD Fever, shaking chills, severe sore throat, breathlessness, painful urination or a rapidly spreading skin infection requires prompt clinical advice. Some DMARDs may need temporary interruption during a severe infection. This decision depends on the drug, infection and disease activity. A person should not routinely stop every RA medicine for a minor illness without checking the agreed plan. Steroids must be considered separately because abrupt withdrawal can be dangerous. Pregnancy, contraception and reproductive planning RA and its treatment should be reviewed before trying to conceive. Some medicines are compatible with pregnancy, while others must be stopped in advance or require a drug elimination procedure. Methotrexate must not be used during pregnancy and requires pre conception planning. Leflunomide also requires specialist advice because it remains in the body for a long time. Sulfasalazine, hydroxychloroquine and selected biological medicines may be used in appropriate circumstances under specialist guidance. Do not stop effective treatment independently after discovering a pregnancy. Contact rheumatology and maternity services promptly so risks from the medicine and uncontrolled disease can both be considered. Physical activity and exercise Appropriate physical activity does not wear away an inflamed joint simply because RA is present. Exercise supports muscle strength, cardiovascular health, balance, bone health and confidence with movement. During a severe flare, activities may need temporary modification. Complete prolonged inactivity can increase stiffness, weakness and loss of function. A physiotherapist can create strengthening, stretching and aerobic plans suited to disease activity and existing damage. Hand exercise programmes can improve function for some people with hand or wrist difficulties. Occupational therapy and joint protection Occupational therapists help people manage work, household tasks and self care. They may recommend pacing, altered techniques, splints or equipment that reduces strain during daily activities. Joint protection does not mean avoiding all use. It means distributing load, using stronger joints where possible and reducing repeated force during active inflammation. Workplace adjustments may help maintain employment and independence. Foot care RA commonly affects the forefoot, ankles and toe joints. Pain, deformity, pressure areas or difficulty finding footwear can reduce mobility. Podiatry assessment may include footwear advice, insoles, skin and nail care and referral for further treatment. A red, ulcerated or infected foot requires prompt assessment, particularly when immune suppression or diabetes is present. Smoking and cardiovascular health RA is associated with an increased risk of heart attack and stroke. Persistent systemic inflammation contributes to this risk. Smoking, high blood pressure, diabetes and cholesterol remain important additional factors. Stopping smoking supports cardiovascular and lung health and may improve the response to some RA treatments. Annual review should include attention to cardiovascular risk, weight, blood pressure and other relevant conditions. Bone health RA, reduced mobility and glucocorticoid treatment can increase osteoporosis risk. Clinicians assess fracture risk according to age, steroid exposure, previous fractures and other factors. Weight bearing activity, adequate nutrition, smoking cessation and appropriate vitamin D contribute to bone health. Some people need a bone density scan or medicine to reduce fracture risk. Rheumatoid nodules and skin changes Rheumatoid nodules are firm lumps that can develop beneath the skin, often near pressure points such as the elbows or fingers. They are more common in some antibody positive forms of RA. Many nodules are painless. Skin ulcers, painful nodules, colour changes or areas of poor circulation require assessment for infection, pressure damage or vasculitis. Not every lump in a person with RA is a rheumatoid nodule. Eye involvement RA can be associated with dry eyes through secondary Sjögren disease. It can also cause episcleritis or scleritis. Scleritis produces significant eye pain and may threaten vision. A painful red eye, sensitivity to light or reduced vision requires urgent same day eye assessment. Dry, gritty eyes without pain are less urgent but still deserve review and appropriate treatment. Lung involvement RA can inflame the lung lining, producing pleuritic chest pain. It can also cause interstitial lung disease with inflammation and scarring within the lungs. Possible symptoms include persistent dry cough and increasing breathlessness. Infection and medicine toxicity can cause similar symptoms. New respiratory symptoms must not automatically be attributed to RA. Sudden or severe breathlessness requires emergency assessment. Persistent cough or gradual breathlessness needs prompt clinical review. Heart and blood vessels Inflammation can affect the sac surrounding the heart, causing pericarditis and chest pain. Rarely, RA can cause vasculitis, meaning inflammation and damage within blood vessel walls. Vasculitis may affect skin, nerves or internal organs. Possible features include painful ulcers, purple skin changes, new numbness or weakness. Any new chest pain, neurological deficit or evidence of poor circulation requires urgent assessment for common emergencies as well as RA related disease. Nerve problems and carpal tunnel syndrome Inflammation around the wrist can compress the median nerve within the carpal tunnel. This can cause tingling, numbness, pain or weakness affecting the thumb and nearby fingers. Persistent weakness, dropping objects or muscle wasting requires assessment because prolonged nerve compression can cause lasting damage. Numbness can also result from neck disease, diabetes, medicine effects or another neurological condition. The cervical spine Longstanding or severe RA can affect joints and ligaments in the upper neck. Instability may rarely compress the spinal cord. Warning features include new limb weakness, numbness, unsteady walking, loss of hand coordination or bladder and bowel disturbance. These symptoms require urgent imaging and specialist assessment. A person with significant cervical RA should tell anaesthetic and surgical teams before procedures because neck positioning may require special care. Joint infection is an emergency RA and immune modifying treatment can increase the risk of septic arthritis. Septic arthritis usually causes severe pain, rapid swelling and loss of movement in one joint. Fever may be absent, particularly during immune suppression. A prosthetic joint can also become infected. A suddenly hot, swollen and very painful joint requires same day emergency assessment. It should not be treated as an ordinary flare without excluding infection. Joint damage and surgery Effective early treatment has reduced the frequency of severe deformity, but some people still develop established joint damage. Surgery may be considered for persistent pain, loss of function, tendon rupture, nerve compression or progressive deformity despite optimal medical care. Procedures can include tendon repair, joint fusion or joint replacement. Surgery treats structural consequences. Ongoing inflammatory disease still requires medical control. Emotional and social effects Pain, fatigue and unpredictable flares can affect sleep, relationships, employment and mood. Reduced activity may lead to isolation or loss of confidence. These effects are part of the disease burden and deserve attention. Psychological support, social advice and workplace adjustments may complement medical treatment. Depression or anxiety should not be assumed to explain inflammatory symptoms, but both can coexist and require appropriate care. Diet and complementary approaches There is no single diet proven to cure RA or replace DMARD treatment. A balanced dietary pattern similar to a Mediterranean diet can support cardiovascular health and general wellbeing. Complementary treatments may provide temporary symptom relief for some people. Evidence for preventing joint damage is limited. Supplements and herbal products can interact with prescribed medicines or affect the liver, kidneys and bleeding risk. Discuss complementary products with a pharmacist or clinician and do not replace disease modifying treatment with them. Ongoing review RA requires long term follow up even after remission or low disease activity is reached. Reviews assess disease activity, function, medicine safety, joint damage and complications involving the eyes, lungs, cervical spine or blood vessels. Annual review also considers cardiovascular disease, osteoporosis, depression, vaccination and the effect of RA on daily life. People should know how to obtain rapid specialist advice during a flare or suspected treatment complication. What this lesson should not be used for This lesson cannot diagnose RA from morning stiffness, symmetrical pain or one antibody result. It cannot safely distinguish an RA flare from joint infection, crystal arthritis or another emergency. Do not use it to start, stop or change a DMARD, steroid, biological medicine or JAK inhibitor. Seek medical assessment for persistent joint swelling and prolonged morning stiffness because early specialist treatment can prevent irreversible damage.

Rheumatoid arthritis is an autoimmune inflammatory disease, not simply mechanical joint wear. Persistent synovitis often affects several small joints and causes prolonged morning stiffness, but the pattern is not always perfectly symmetrical and blood tests may be normal. Early treat to target DMARD therapy suppresses disease and prevents damage, while painkillers and short steroid courses mainly provide symptom control.