Rheumatoid Arthritis PDF

RHEUMATOID ARTHRITIS DR.ISTABRAQ SATAM MBCHB ,F.I.B.M.S RHEUM.&MED. REHAB. WHAT IS RA?  RA is a chronic, systemic, inflammatory disorder of joints that is characterized by symmetrical pattern of joint involvement, and in the majority of cases, serum elevations of autoantibodies that inclu...

RHEUMATOID ARTHRITIS DR.ISTABRAQ SATAM MBCHB ,F.I.B.M.S RHEUM.&MED. REHAB. WHAT IS RA?  RA is a chronic, systemic, inflammatory disorder of joints that is characterized by symmetrical pattern of joint involvement, and in the majority of cases, serum elevations of autoantibodies that include rheumatoid factor (RF) and antibodies to citrullinated protein/peptide antigens (ACPA). The primary site of pathology is the synovium of the joints. EPIDEMIOLOGY Race—worldwide, all races. Native Americans have higher prevalence. Sex distribution—females > males 2–3:1. Age—the average age of onset of RA in women is 40 to 60 years, men are older. Occurs in about 1% of adults. PATHOPHYSIOLOGY ETIOLOGY  The exact cause of RA remains unknown, but it is likely multifactorial  Genetic factors:concordance of RA in monozygotic (12–15%) compared with dizygotic twins (3%), and an increased frequency of disease in first-degree relatives of patients. The strongest association is with variants in the HLA region.  Environmental factors: Smoking bacteria in the microbiomes of mucosal sites (e.g., mouth, lung, gut) Viruses :Epstein–Barr virus [EBV], parvovirus B19 PATHOPHYSIOLOGY  Hormonal factors symptoms improve during pregnancy.  Autoantibodies including RF and antibodies to modified protein antigens (AMPAs). AMPAs include antibodies to citrullinated and carbamylated proteins. PATHOPHYSIOLOGY PATHOPHYSIOLOGY PATHOPHYSIOLOGY Initiation of clinical disease  It is hypothesized that ACPAs could target citrullinated proteins in the joint. In addition, certain immune complexes can deposit in synovial postcapillary venules inciting inflammation through complement activation. Tissue inflammation can increase vascular permeability with the influx of more inflammatory cells and antibodies (including ACPAs).  The primary site of pathology is the synovium of the joints. The synovial tissues become inflamed and proliferate, forming pannus that invades bone, cartilage, and ligaments and leads to damage and deformities. PATTERNS OF ONSET a) Typical patterns of onset (90% of patients) Insidious (55%–65%): over weeks to months. Subacute (15%–20%): Similar to insidious onset but more systemic symptoms. Acute (10%):over days, Severe onset, some have fever. b) Variant patterns of onset (10% of patients) Palindromic (episodic) pattern: Usually involves less than five joints and resolves within several days. After an asymptomatic period, a flare in the same or another joint(s) occurs. Over time, 33% to 50% evolve into RA involving more joints persistently. Seropositive patients and those with elevated acute-phase reactants are more likely to progress to RA. Insidious onset of elderly (>65 years): Present with severe pain and stiffness of limb girdle joints often with diffuse swelling of hands, wrists, and forearms. May be difficult to differentiate from polymyalgia rheumatica. CLINICAL FEATURES  The hallmark feature of the disease is persistent symmetric polyarthritis (synovitis) that affects the hands and feet, although any joint lined by a synovial membrane may be involved.  Other symptoms: Fatigue - Stiffness - Weakness - Flu-like symptoms - Muscle pain - Loss of appetite - Depression WHICH JOINTS ARE COMMONLY AFFECTED IN RA? RA OA CERVICAL SPINES INVOLVEMENT  Historically, the cervical spine is involved in 30% to 50% of RA patients, with C1–C2 the most commonly involved level.  It is important to note that cervical spine disease often parallels peripheral joint disease.  The earliest and most frequent symptom of subluxation is pain radiating to the occiput. Pain, neurologic involvement, and death are the main concerns with subluxation PHYSICAL SIGNS PHYSICAL SIGNS PHYSICAL SIGNS EXTRARTICULAR MANIFESTATIONS EXTRARTICULAR MANIFESTATIONS EXTRARTICULAR MANIFESTATIONS WHICH PATIENTS WITH RA ARE MOST LIKELY TO GET EXTRAARTICULAR MANIFESTATIONS?  Patients who are RF- or ACPA-positive (dual-positivity may pose a higher risk)  HLA-DR4-positive  males are more likely to have extraarticular manifestations. ❖ It is important for clinicians to rule out other causes, such as infection, malignancy, and medications side effects, for an extraarticular manifestation especially if the patient is RF-negative. INVESTIGATIONS To establish diagnosis Erythrocyte sedimentation rate and C-reactive protein Ultrasound or magnetic resonance imaging Rheumatoid factor and anti-citrullinated peptide antibodies To monitor disease activity and drug efficacy  DAS28 score Erythrocyte sedimentation rate and C-reactive protein To monitor disease damage X-rays Functional assessment To monitor drug safety Urinalysis Full blood count Chest X-ray Urea and creatinine Liver function test THE RADIOGRAPHIC FEATURES OF RA The mnemonic ABCDE’S is a convenient way to remember these:  A—Alignment, abnormal  B—Bones—periarticular (juxtaarticular) osteoporosis; no periostitis or osteophytes  C—Cartilage—uniform (symmetric) joint space loss in weight-bearing joints; no cartilage or soft tissue calcification  D—Deformities (swan neck, ulnar deviation, boutonnière)  E—Erosions, marginal  S—Soft-tissue swelling; nodules without calcification DO ANY MARKERS HELP PREDICT IF AN RA PATIENT WILL HAVE SEVERE DISEASE AND A POOR PROGNOSIS? ❖ Long disease duration prior to treatment ❖ RF and ACPA positivity ❖ poor functional status at presentation Generalized polyarthritis involving both small and large joints (>13 total joints) Extraarticular disease, especially nodules and vasculitis Radiographic erosions within 2 years of disease onset HLA-DR4 genetic marker Low education level. COMPLICATIONS  Atherosclerosis  Sjogren Syndrome—Approximately 20% to 30% of RA patients develop secondary SS with dry eyes and dry mouth  Amyloidosis— This occurs in longstanding, poorly controlled RA and usually presents as nephrotic syndrome.  Osteoporosis—seen in the majority of RA patients and is related to disease activity, immobility, and medications.  Entrapment neuropathy—median nerve (carpal tunnel), posterior tibial nerve (tarsal tunnel)are most commonly involved.  Laryngeal manifestations—cricoarytenoid arthritis can present as pain, dysphagia, hoarseness, and rarely, stridor.  Ossicles of ear—tinnitus and decreased hearing.  Renal and gastrointestinal involvement—rare. Abnormalities are typically attributable to (NSAIDs) causing renal insufficiency or gastric ulcers with hemorrhage.  Felty’s syndrome FELTY’S SYNDROME WHAT ARE THE MOST IMPORTANT GOALS FOR THE TREATMENT OF RA? Treat early: the best results are seen when RA patients are started on therapy within 3–6 months of synovitis onset. This goal may be difficult to reach because of delay in presentation to primary care, delay in referral to rheumatology, and delays between referral and first visit with the rheumatologist. Treat to a target: aim for low disease activity or remission. NON-PHARMACOLOGIC TREATMENT FOR RA  Patient education  Rest, exercise, heat and cold, splints, weight loss PHARMACOLOGIC TREATMENT FOR RA  NSAIDs = used for pain but do NOT halt disease progression  Corticosteroids - symptomatic relief, and slows progress but not halt it. 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 conventional DMARDs (cDMARDs), biologic DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs). - reduce or prevent joint damage and preserve joint integrity - delayed onset of action CONVENTIONAL DMARDS (CDMARDS) Methotrexate has been the most effective drug used and can induce low disease activity as monotherapy  initial dose of 15 mg weekly, along with folic acid 5 mg weekly, and escalated up to a maximum of 25 mg weekly, depending on the response  Toxicities: hepatic, myelosuppression, pulmonary  SE: GIT upset  C/I in pregnancy Others = Lefluonomide, Sulphasalazine, Hydroxychloroquine BIOLOGIC DMARDS (B DMARDS)  TNF Inhibitors first line bDMARD in methotrexate non-responders due to long-term familiarity with their use, efficacy and safety profile. All the TNF inhibitors have comparable efficacy, with the choice of agent generally being dependent on patient preference for route of administration and frequency of treatment Toxicities of anti-TNF: Increased risk of infection Reactivating latent TB Neoplasia Multiple sclerosis Autoimmune Disease  Other biologics: Interleukin1 Ra (anakinra) B cell depleting (rituximab) T cell inhibitors (abatacept) Anti Interleukin-6 receptor Ab (Tocilizumab) TARGETED SYNTHETIC DMARDS (TS DMARDS).  JAK inhibitors (Tofacitinib). SURGERY  Synovectomy  Joint replacement  excision of the metatarsal heads in patients with subluxation of the MTP joints  neurosurgery in patients with atlanto-axial subluxation  fusion or the wrist or ankle in patients with joint damage WHAT CAUSES THE INCREASED MORTALITY IN RA PATIENTS?  CVD: frequency is increased 1.5 to 2-fold over the general population.  Infections: Pneumonia is especially common in patients with RA.  Cancer and lymphoproliferative malignancies: Lymphoma and leukemia are increased 2 to 3-fold. Lung cancer is increased 1.5 to 3.5-fold.  Others: Includes renal disease as a result of amyloidosis, gastrointestinal hemorrhage resulting from NSAIDs. 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