Rheumatoid Arthritis PDF

Rheumatoid arthritis Dr Asma Mohamed Heima MBBS Arab Board Internal Medicine  Introduction Rheumatoid arthritis (RA) is a common form of inflammatory Arthritis , occurring throughout the world and In all ethnic groups. Annual incidence 3 cases per...

Rheumatoid arthritis Dr Asma Mohamed Heima MBBS Arab Board Internal Medicine  Introduction Rheumatoid arthritis (RA) is a common form of inflammatory Arthritis , occurring throughout the world and In all ethnic groups. Annual incidence 3 cases per 10,000 population. The peak age of onset is 35-50 years , female-to-male ratio of 3 : 1. It involves the synovium of joints , the inflamed synovium can cause damage to cartilage and bone. It is a chronic disease characterised by a clinical course of exacerbations and remissions. RA is a complex disease with both genetic and environmental components.  The importance of genetic factors is demonstrated by higher concordance of RA in monozygotic (12–15%) compared with dizygotic twins (3%), and an increased frequency of disease in first-degree relatives of patients.  It is currently believed that RA occurs when an environmental stimulus, such as infection, triggers autoimmunity in a genetically susceptible host by modifying host proteins through processes like citrullination so that they become immunogenic. However, no single specific pathogen has been identified as a cause. An important environmental risk factor is cigarette smoking, which is also associated with more severe disease and reduced responsiveness to treatment. Remission may occur during pregnancy and sometimes RA first presents post- partum. This is likely to be due to suppression of the immune response during pregnancy but hormonal changes may also play a role. Pathogenesis Synovial hyperplasia Hypercellularity Inflammatory cells (lymphocytes , plasma cells, dendritic cells and macrophages ) Joint effusion Panus (invasive synovium, erodes cartilage and bones , unique to RA) Clinical features  The typical presentation is with pain, joint swelling and stiffness affecting the small joints of the hands, feet and wrists in a symmetrical fashion. Large joint involvement, systemic symptoms and extra-articular features may also occur.  1. Inflammatory polyarthritis (joint swelling is the most common sign). a. Morning stiffness lasting >1 hour—improves as the day progresses. b. Joints commonly involved include joints of the hands (PIP, MCP) and wrists, knees, ankles , elbows, hips, and shoulders. DIP , Sacroiliac And Vertebral Joints Are Spared Except C1, C2 c. Characteristic hand deformities :  Ulnar deviation of the MCP joints.  Boutonnière deformities of the PIP joints (PIP flexed, DIP hyperextended).  Swan-neck contractures of the fingers (MCP flexed, PIP hyperextended, DIP flexed).  Examination typically reveals swelling and tenderness of the affected joints. Erythema is unusual and its presence suggests coexistent sepsis.  Characteristic deformities may develop with long-standing uncontrolled disease, although these have become less common over recent years with more aggressive management. d. other articular complications include Triggering of fingers because of nodules in the flexor tendon sheaths.  Subluxation of the MTP joints of the feet may result in ‘cock-up’ toe deformities.  loss of the longitudinal arch (flat foot) due to rupture of the tibialis posterior tendon  Popliteal (Baker’s) cysts may occur in patients with knee synovitis. Cock-up toes Popliteal bakers cyst  2. Constitutional symptoms can be prominent. a. Low-grade fever, Anorexia and weight loss. b. Fatigue can be prominent because this is a systemic disease.  3. Cervical spine involvement is common at C1-C2 (subluxation and instability). a. Instability of the cervical spine is a potentially life-threatening complication of RA. Most patients do not have neurologic involvement, but if they do, it can be progressive and fatal if not treated surgically. b. This is seen in 30% to 40% of patients. All patients with RA should have cervical spine radiographs before undergoing any surgery (due to risk of neurologic injury during intubation). However, disease-modifying antirheumatic drugs (DMARDs) have dramatically reduced the need for cervical spine surgery in RA patients.  Extraarticular features  Extra-articular features are most common in patients with long- standing seropositive erosive disease but may occasionally occur at presentation, especially in men.  Most are due to serositis, granuloma and nodule formation or vasculitis.  Rheumatoid Nodules occur almost exclusively in RF- or ACPA positive patients, usually in extensor tendons , also occur in visceral structures( lungs, pleura, pericardium ) Pathognomonic for RA. They are frequently asymptomatic but some may be complicated by ulceration and secondary infection.  Systemic Fever Weight loss Fatigue Susceptibility to infection  Musculoskeletal Muscle-wasting Tenosynovitis Bursitis Osteoporosis  Haematological Anaemia Thrombocytosis Eosinophilia  Lymphatic Felty’s syndrome (Triad of RA, neutropenia, and splenomegaly ) seropositive , thrombocytopenia ,NCNC anemia , recurrent infection  Ocular Episcleritis Scleritis Scleromalacia Keratoconjunctivitis sicca (most common )  Vasculitis Digital arteritis Ulcers Pyoderma gangrenosum Mononeuritis multiplex Visceral arteritis  Cardiac Pericarditis Myocarditis Endocarditis Conduction defects Coronary vasculitis Granulomatous aortitis  Pulmonary Nodules Pleural effusions Fibrosing alveolitis Bronchiolitis Caplan’s syndrome  Neurological Compression neuropathies (median nerve is most common) Cervical cord compression Peripheral neuropathy Mononeuritis multiplex  Amyloidosis (nephrotic syndrome) Investigation  The diagnosis of RA is essentially clinical but investigations are useful in confirming the diagnosis and assessing disease activity.  ACPA (Anticitrullinated peptide/protein antibodies) are positive in about 70% of cases and are highly specific for RA, occurring in many patients before clinical onset of the disease.  Rheumatoid factor Positive in 70% of cases but less specific than ACPA Helpful in determining prognosis. High titers → more severe disease.  Elevated ESR, C-reactive protein.  Anemia of chronic disease.  Radiographs  Not required for a diagnosis of RA but may have the following characteristic findings:  a. Loss of juxta-articular bone mass (periarticular osteoporosis).  b. Narrowing of the joint space (due to thinning of the articular cartilage) is usually seen late in the disease.  C. marginal joint erosions.  Atlanto-axial Disease Lateral X-rays Taken In Flexion And Extension  suspected Baker’s cyst ultrasound  Posteroanterior radiographs of the hand showing the typical pattern of involvement for (A) osteoarthritis (osteophytes, subchondral sclerosis, joint space narrowing) (arrows) and (B) rheumatoid arthritis (periarticular erosions, osteopenia) (arrows).  New criteria was released in 2010 from the American College of Rheumatology / EULAR for classification of RA  The ACR/EULAR classification system is a score-based algorithm for RA that incorporates 4 factors. Presence of synovitis in at least one joint Absence of an alternative diagnosis better explaining the synovitis  Score greater than 6/10 on: (definite RA ) 1 Number and site of involved joints (range 0–5) 2 Serological abnormality (range 0–3) 1987 ACR CRITERIA 3 Elevated acute-phase response (range 0–1) lacked the sensitivity to 4 Symptom duration (two levels; range 0–1) detect early RA  Disease activity measures ;  DAS28 is widely used to assess disease activity, response to treatment and need for biological therapy.  It involves counting the number of swollen and tender joints in the upper limbs and knees, and combining this with the ESR and the patient’s assessment of the activity of their arthritis on a visual analogue Scale.  The data is entered into a calculator to generate a numerical score. The higher the value, the more active the disease.  Principles of management  The therapeutic aims are: to educate patients about their disease to control pain, if present to optimize function to modify the disease process where this is possible to identify and treat comorbidity.  This involves a combination of pharmacological and non- pharmacological therapies. When RA occurs in women of child- bearing age, additional considerations need to be taken into account. Education Patients must always be informed about the nature of their condition and its investigation, treatment and prognosis, since education can improve outcome Exercise Aerobic fitness training can produce long-term reduction in pain and disability. Local strengthening exercise for muscles that act over compromised joints also reduces pain and disability, with improvements in the reduced muscle strength, proprioception, coordination and balance that associate with chronic arthritis. Physical and occupational therapy Local heat, ice packs , Splints and Orthoses Weight control Obesity aggravates pain at most sites through increased mechanical strain and is a risk factor for progression of joint damage.  Symptomatic treatment. NSAIDs are the drugs of choice for pain control. Corticosteroids Short-term treatment may be appropriate but avoid long-term use.  On first diagnosis, prednisolone should be started in a dose of 30 mg daily gradually reducing in 5 mg increments every 2 weeks until therapy is withdrawn after about 12 weeks.  DMARDs Methotrexate  Can reduce morbidity and mortality (by nearly 30%)—by limiting is the complications, slowing progression of disease, and preserving joint mainstay of therapy in RA. function  Should be initiated early (at the time of diagnosis)  They have a slow onset of action (6 weeks or longer for effect to be seen), so begin treating RA while waiting for the disease-modifying therapy to take effect. Gradually taper and discontinue NSAIDs and corticosteroids once effects are evident.  Methotrexate—best initial DMARD  Initial improvement is seen in 4 to 6 weeks.  Side effects include GI upset, oral ulcers (stomatitis), mild alopecia, bone marrow suppression (co-administer with folic acid), hepatocellular injury, and idiosyncratic interstitial pneumonitis, which may lead to pulmonary fibrosis. It increases liver enzymes in some patients.  Closely monitor liver and renal function  Supplement with folate.  If the patient fails to respond adequately or dose-limiting toxicity occurs, then an additional DMARD should be commenced in combination with MTX. The most common combination is triple therapy, in which methotrexate, sulfasalazine and hydroxychloroquine are combined.  Other DMARDs can be substituted or added, along with a low- dose glucocorticoid such as prednisolone (5–10 mg daily) if the patient fails to respond fully.  If disease activity remains high (DAS28 > 5.1) despite triple therapy, however, it is usual to progress to biologic therapy. The main adverse  ‘biologic’ refers to a group of medications that includes effect of the biologics monoclonal antibodies, fusion proteins and decoy receptors, used which are used in the treatment of several inflammatory in rheumatic diseases. They are targeted towards specific cytokines, inflammatory diseases is receptors and other cell-surface molecules regulating the immune an increased response risk of infections  The most commonly used first-line biologics in RA are TNF inhibitors (etanercept , infliximab…) although several other options are available (abatacept, rituximab).  When the patient has been stabilized on biologic treatment for 12 months or more, a reduction in dose should be considered.  The JAK inhibitors( tofacitinib and baricitinib) have efficacy in patients who fail to respond adequately to other DMARDs and provide an alternative to biologic therapies.  Transient flares can be dealt with by intra-articular glucocorticoid injections or a short course of oral glucocorticoids, but if a sustained flare occurs, a change in systemic DMARD and/or biologic therapy may need to be considered.  Surgery  Synovectomy can be helpful in joints that have failed to respond adequately to systemic therapy and intra- articular injections. Joint replacement surgery may be required but the need for this has diminished over recent years, presumably as the result of more aggressive medical management.  Other surgical procedures that can be helpful are excision of the metatarsal heads in patients with subluxation of the MTP joints; neurosurgery in patients with atlanto-axial subluxation; and fusion or the wrist or ankle in patients with joint damage.  Predicting the long-term course of an individual case of RA at the outset remains difficult, though the following all correlate with an unfavorable prognosis in terms of joint damage and disability:  HLA-DRB1*04/04 genotype  High serum titer of autoantibodies (eg, RF and ACPA)  Extra-articular manifestations  Large number of involved joints  Age younger than 30 years  Female sex  Insidious onset  Rheumatoid arthritis and pregnancy  Immunological changes in pregnancy: many patients with rheumatoid arthritis go into remission during pregnancy.  Conception: methotrexate should be discontinued for at least 3 months and leflunomide discontinued for at least 24 months before trying to conceive.  Paracetamol: the oral analgesic of choice during pregnancy.  Oral non-steroidal anti-inflammatory drugs and selective cyclo- oxygenase 2 (COX-2) inhibitors: can be used from implantation to 20 weeks’ gestation.  Glucocorticoids: may be used to control disease flares; the main maternal risks are hypertension, glucose intolerance and osteoporosis.  Disease-modifying antirheumatic drugs (DMARDs) that may be used: sulfasalazine, hydroxychloroquine and azathioprine if required to control inflammation.  DMARDs that must be avoided: methotrexate, leflunomide, cyclophosphamide, mycophenolate and gold.  Biologic therapies: experience is limited but they may be relatively safe during pregnancy. The main theoretical risk is immunosuppression in the neonate, except for certolizumab, which does cross the placenta in negligible amounts.  Breastfeeding: methotrexate, leflunomide and cyclophosphamide are contraindicated. Thank you