Rheumatoid Arthritis• The most common form, autoimmune inflammatory arthritis• Characterized by symmetric arthritis of the small joints of the hands and feet• Chronic erosive arthritis need early and aggressive management• Prevalence 0.5 – 1 %
Pathogenesis• Characterized by – synovial inflammation and hyperplasia (“swelling”), – autoantibody production (rheumatoid factor and anti–citrullinated protein antibody [ACPA]), – cartilage and bone destruction (“deformity”), – systemic features, including • cardiovascular, pulmonary, psychological, and skeletal disorders.
Criteria Diagnosis • At least 4 of these 7 criteria – criteria 1 to 4 must have been present for ≥6 weeks Morning stiffness Arthritis of 3 or more joint areas Arthritis of hands Symmetric arthritis Rheumatoid nodules Serum rheumatoid factor Radiographic changesArnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315-324.
American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) collaborative initiative 2010 rheumatoid arthritis classification criteria ScoreJoint involvement 1 large joint (shoulder, elbow, hip, knee, ankle) 0 2–10 large joints 1 1–3 small joints (MCP, PIP, Thumb IP, MTP, wrists) 2 4–10 small joints 3 >10 joints (at least 1 small joint) 5 Serology Negative RF and negative ACPA 0 Low-positive RF or low-positive anti-CCP antibodies 2 (3 times ULN) High-positive RF or high-positive anti-CCP antibodies 3 (>3 times ULN) Acute-phase Normal CRP and normal ESR 0 reactants Abnormal CRP or abnormal ESR 1 Duration of <6 weeks 0 symptoms 6 weeks 1
Extraarticular manifestations of rheumatoid arthritis
Management For Primary care PhysiciansEstablish Diagnosis of Rheumatoid Arthritis EarlyDocument Baseline Disease Activity and DamageEstimate Prognosis Start Treatment Patient Education Start DMARD(s) within 3 months Consider NSAIDs Consider Local / Low-dose Steroid Physical / Occupational Therapy Periodically Assess Disease Activity
Baseline Evaluation• Subjective – Degree of joint pain – Duration of morning stiffness – Duration of fatigue – Limitation of function• Physical examination – Actively inflamed joints (tender and swollen joint counts) – Mechanical joint problems: loss of motion, crepitus, instability, – malalignment, and/or deformity – Extraarticular manifestations
Baseline Evaluation• Laboratory – Erythrocyte sedimentation rate/C-reactive protein level – Rheumatoid factor – Complete blood cell count – Electrolyte levels and Creatinine level – Hepatic enzyme levels (AST, ALT, and albumin) – Urinalysis – Synovial fluid analysis – Stool guaiac• Radiography – Radiographs of selected involved joints• Other – Functional status or quality of life assessments using standardized
DMARDs Used for the Treatment of Rheumatoid Arthritis Other Common Drug Dosage Serious Toxicities Monitoring Side Effects Hydroxy 200–400 mg/d Irreversible retinal Nausea Funduscopicchloroquine orally damage Diarrhea and visual ( 6.5 mg/kg) Cardiotoxicity Headache field testing Blood dyscrasia Rash every 12 monthsSulfasalazine Initial: Granulocytopenia Nausea CBC every 2–4 500 mg orally Hemolytic anemia Diarrhea weeks for first twice daily (with G6PD deficiency) Headache 3 months, then Maintenance: every 3 1–1.5 g twice daily months
DMARDs Used for the Treatment of Rheumatoid Arthritis Other Common Drug Dosage Serious Toxicities Monitoring Side EffectsMethotrexate 10–25 mg/week Hepatotoxicity Nausea CBC, orally Myelosuppression Diarrhea creatinine, or SQ Infection Stomatitis/mouth LFTs every 2– Folic acid : Interstitial pneumonitis ulcers 3 months 1 mg/d to reduce Pregnancy category X Alopecia toxicities FatigueLeflunomide 10–20 mg/d Hepatotoxicity Alopecia CBC, Myelosuppression Diarrhea creatinine, Infection LFTs every 2– Pregnancy category X 3 months
approximate time to benefit of disease-modifying antirheumatic drugs used in the treatment of rheumatoid arthritis
Gout• Gout is a type of inflammatory arthritis induced by the deposition of monosodium urate crystals in synovial fluid and other tissues.• It is associated with hyperuricemia, which is defined as a serum urate level of 6.8 mg per deciliter or more.• In Population, 0.5% prevalence of gout overall
Risk Factor• Hyperuricemia – thiazide diuretics, cyclosporine, and low-dose aspirin (<1 g per day)• Triggers for recurrent flares include – recent diuretic use, alcohol intake, hospitalization, and surgery.• Urate-lowering therapy – which reduces the risk of gout attacks in the long term, can trigger attacks in the early period after its initiation
Classification of Gout Clinical category Cause Metabolic defect Primary gout (90% of cases) Enzyme defects unknown (85%-90% - Overproduction of uric acid of primary gout) - Normal excretion (majority) - Increased excretion (minority) - Normal production of uric acid - Under-excretion Known enzyme defects, e.g. partial - Overproduction of uric acid HGPRT deficiencySecondary gout (10% of cases) Associated with increased nucleic - Over production of uric acid with acid turnover, e.g. leukemia increased urinary excretion Chronic renal failure - Reduced excretion of uric acid with normal production Inborn errors of metabolism, e.g. - Overproduction of uric acid with complete HGPRT deficiency (Lesh- increased urinary excretion Nyhan syndrome)
Diagnosis (Definite Dx)• synovial fluid or tophus aspiration with identification of • light microscopy ; needle shape crystal • compensated polarized light microscopy ; positive birefringence with negative elongation
Diagnosis (Presumptive Dx)• Medical Treatment with Colchicine improve within 12 - 24 hr• Criteria Diagnosis from American college of Rheumatology (6 in 12) – More than one attack of acute arthritis – Maximum inflammation developed within 1 day – Monoarthritis attack, redness observed over joints – First metatarsophalangeal joint painful or swollen – Unilateral first metatarsophalangeal joint attack – Unilateral tarsal joint attack – Tophus (confirmed or suspected) – Hyperuricaemia – Asymmetric swelling within a joint on x-ray film – Subcortical cyst without erosions on x-ray film – Joint culture negative for organism during attack.
Complication• Acute uric acid nephropathy – most commonly in patients treated with cytotoxic agents, especially for lymphoproliferative disorders and large tumour burdens• Chronic urate or gouty nephropathy – Accumulated in medullary interstitium induced inflammation process• Uric acid stone – Uric acid calculi constitute 10% of the renal stones
Management Acute gout attack• Aim of therapy for acute gout – rapid relief of pain and disability caused by intense inflammation.• Drug used – nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, glucocorticoids, and possibly corticotropin.• Adjunctive treatment include – applying ice to and resting the affected joint.• NSAIDs and colchicine are first-line agents for acute attacks
What if treatment fails in acute gout ?• If there is no improvement in symptoms after 2–3 days: – Review the diagnosis, check compliance with medication, and encourage self-care strategies. – Increase the dose of medication to maximum and add paracetamol, with or without codeine.• If there is still no improvement in symptoms, try an alternative drug or consider combining treatment, or seek specialist advice.
What follow up is recommended after an acute attack of gout?• Follow up the person 4–6 weeks after an acute attack of gout has resolved, and: – Check the serum uric acid level. – Measure their blood pressure and take blood for fasting glucose, renal function, and lipid profile. – Identify underlying conditions such as hypertension, diabetes, or renal impairment, and assess the persons overall cardiovascular risk. – Assess and provide advice on risk factors such as obesity, diet, excessive alcohol consumption, and exercise. – Consider the need to start prophylactic medication if the person is having two or more attacks of gout in a year.
Management Patient with Hyperuricemia• The purpose of lowering serum urate levels – To prevent acute flares and development of tophi• When treatment – Severity and frequency of flares, the presence of coexisting illnesses (including nephrolithiasis), and patient preference are additional considerations• Urate-lowering therapy – should not be initiated during acute attacks – started 2 to 4 weeks after flare resolution• The dose should be adjusted as necessary – maintain a serum urate level below 6 mg per deciliter which is associated with a reduced risk of recurrent attacks and tophi.
Management Patient with Hyperuricemia• How long for used Urate – lowering therapy – Suggest patient can keep uric acid level below 6.0 mg/dl and no attack at least 4-5 years – In Chronic tophaceous stage should stop when tophaceous gout resolve and continue for 4-5 years after resolution
Management Patient with Hyperuricemia• Flare Prophylaxis during Initiation of Urate-Lowering Therapy – general recommendation for flare prophylaxis is to use colchicine at a dose of 0.6 mg once or twice daily, with dose adjustments as needed for renal impairment – Diarrhea was common, resulting in a once- daily regimen of colchicine for many patients
Calcium pyrophosphate deposition disease (CPPD)• metabolic arthropathy caused by the deposition of calcium pyrophosphate dihydrate in and around joints, – especially in articular cartilage and fibrocartilage.• Although CPDD is often asymptomatic, with only radiographic changes seen – (ie, chondrocalcinosis)• various clinical manifestations may occur, including – acute (pseudogout) and chronic arthritis
Risk Factor• Age is most important risk factor• Osteoarthritis (OA) - threefold increased risk if CPPD present• Previous joint trauma/injury• Joint surgery/lavage promotes crystal shedding4• Metabolic disease – Hemochromatosis, 1˚Hyperparathroidism, Hypomagnesemia, Malabsorption syndromes – Consider in age <50-60 yo, especially if polyarticular chondrocalcinosis (CC)• Familial predisposition to CPPD
Clinical Presentation• Associated with both acute and chronic arthritis• Acute CPP crystal arthritis – inflammatory arthritis of one or more joints. Knees, wrists, shoulders, ankles, elbows, or hands can be affected.• chronic form of CPP arthritis – mimics osteoarthritis or rheumatoid arthritis and is associated with variable degrees of inflammation.• Typically occurs in older patients but can occur in younger patients with associated metabolic conditions, such as hyperparathyroidism and haemochromatosis.
Most common presentations of CPDDType A. PseudogoutType B. Pseudorheumatoid arthritisType C and D. PseudoosteoarthritisType E. Lanthenic or asymptomaticType F. Pseudoneuropathic jointOther :• ankylosing spondylytis or diffuse idiopathic skeletal hyperostosis (DISH)• pseudotophaceous disease
Diagnostic Criteria (Definite & Probable)• I. Demonstration of CPP crystals in tissues or synovial fluid – IIA. Identification of CPP crystals by morphological analysis using compensated polarising light microscopy. – IIB. Typical calcifications on x-rays (cartilage calcification); heavy punctuate or linear calcifications in fibro-cartilage, articular (hyaline) cartilage, or joint capsules.
Diagnostic Criteria (Possible)• IIIA. Acute arthritis, especially of the knee or other large joints.• IIIB. Chronic arthritis of the knee, hip, wrist, elbow, shoulder, or MCPs, particularly if accompanied by acute exacerbations, and if characterised by: – Involvement of uncommon sites for primary osteoarthritis – Radiographical appearance, including severe patellofemoral involvement – Subchondral cyst formation – Severe progressive joint degeneration with bony collapse – Variable and inconsistent osteophyte formation – Tendon calcifications, particularly of the Achilles, triceps, and obturator tendons – Axial skeletal involvement with subchondral cysts, disc calcification, and vacuum disc phenomena, as well as sacroiliac joint involvement.
Management (Acute attack)Ice and RestJoint aspirationOral Non steroidal Anti-inflammatory DrugsColchicineIntraarticular glucocorticosteroids (GCS)IV/IM/PO corticosteroid
Case #1• A 72-year-old woman presents with polyarticular joint pain.• She has long-standing mild joint pain, but over the last 10 years notes increasing discomfort in her wrists, shoulders, knees, and ankles. She has had several recent episodes of severe pain in 1 or 2 joints, with swelling and warmth of the affected areas. These episodes often last 3 to 4 weeks.• Her examination shows severe bony changes consistent with osteoarthritis in many joints, and slight swelling, warmth, and tenderness without erythema in the second and third MCP joints, left shoulder, and the right wrist.
Case #2• A 52-year-old woman presents with a 2-month history of bilateral hand and wrist pain, and swelling in her fingers.• She has also recently noted similar pain in the balls of her feet. She finds it hard to get going in the morning and feels stiff for hours after waking up. She also complains of increasing fatigue and is unable to turn on and off taps or use a keyboard at work without a significant amount of pain in her hands.• She denies any infections before or since her symptoms started.
Case #3• A 54-year-old man complains of severe pain and swelling in his right first toe that developed overnight. He is limping because of the pain and states that this is the most severe pain he has ever had (even covering my foot with the bed sheet hurts). He has had no previous episodes. His only medication is hydrochlorothiazide for hypertension. He drinks 2 to 3 beers a day. On examination, he is obese. There is swelling, erythema, warmth, and tenderness of the right first toe. There is also tenderness and warmth with mild swelling over the mid foot.
Reference• American College of Rheumatoogy Ad Iloe Committee on Clinical Guidelines. Guidelines for the initial evaluation of the adult patient with musculoskeletal symptoms, /Irth,.itis Rheum 1996; 39: 1-8.• Ellrodt AG. Cho M. Cush J el. af. An evidence-based medicine approach to the diagnosis and management of musculoskeletal complaints. lIm J Med 1997: 103(45 ): 3-6.• Ashok Kumar. ; Clinical Guide : Approach to Arthritis. Vol. 4 No.1, January-March 2002; p.51-54• William P. Arend AND George V. Lawry; Chapter 264 Approach to the Patient with Rheumatic Disease in Goldman’s Cecil medicine. Rev. ed. of: Cecil medicine. 23rd ed. c2008. p.1648-1651
Reference• Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J: Chapter 321. Rheumatoid Arthritis in Harrisons Principles of Internal Medicine, 18th edition: McGraw-Hill Companies,2012.• Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J: Chapter 331. Approach to Articular and Musculoskeletal Disorders in Harrisons Principles of Internal Medicine, 18th edition: McGraw-Hill Companies,2012.• Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J: Chapter 333. Gout and Other Crystal-Associated Arthropathies in Harrisons Principles of Internal Medicine, 18th edition: McGraw-Hill Companies,2012.• Tintinalli JE, Stapczynski JS, Ma OJ, Cline DM, Cydulka RK, Meckler GD: Chapter 281. Acute Disorders of the Joints and Bursae in Tintinallis Emergency Medicine : A Comprehensive Study Guide, 7th Edition. McGraw-Hill. 2010
Reference• Arnett FC, Edworthy SM, Block DA, et al. The ARA 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988, 31: 315- 24• American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis 2002 update. Arthritis Rheum 2002;46:328-46• Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569-2581• แนวทางเวชปฏิบัติโรคข้ออักเสบรูมาตอยด์ (rheumatoid arthritis) โดยสมาคมรูมาติสซั่มแห่งประเทศไทย. วารสาร โรคข้อและรูมาติสซั่ม, 2545;13:25-31
Reference• Iain B. McInnes, F.R.C.P., Ph.D., and Georg Schett, M.D. The Pathogenesis of Rheumatoid Arthritis. N Engl J Med 2011; 365:2205-2219• Tuhina Neogi, M.D., Ph.D. ;Clinical Practice : Gout. N Engl J Med 2011; 364:443-452February 3, 2011• Emilio B. Gonzalez ; An update on the pathology and clinical management of gouty arthritis.Clin Rheumatol (2012) 31:13–21• Newsome G. ;Guidelines for the management of rheumatoid arthritis: 2002 update.J Am Acad Nurse Pract. 2002 Oct;14(10):432-7.• C. Ferrone, R. Andracco, M.A. Cimmino ; Calcium pyrophosphate deposition disease: clinical manifestations.Reumatismo, 2011; 63 (4): 246-252
Reference• Iain B. McInnes, F.R.C.P., Ph.D., and Georg Schett, M.D. The Pathogenesis of Rheumatoid Arthritis. N Engl J Med 2011; 365:2205-2219• Tuhina Neogi, M.D., Ph.D. ;Clinical Practice : Gout. N Engl J Med 2011; 364:443- 452February 3, 2011• Emilio B. Gonzalez ; An update on the pathology and clinical management of gouty arthritis.Clin Rheumatol (2012) 31:13–21• Choi HK, Mount DB, Reginato AM. Pathogenesis of gout. Ann Intern Med. 2005;143:499-516.
Reference• Zhang W, Doherty M, Bardin T, et al. European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis. Ann Rheum Dis 2011; 70: 563-70.• Zhang W, Doherty M, Pascual E, et al. EULAR recommendations for calcium pyrophosphate deposition. Part II: management. Ann Rheum Dis 2011; 70: 571-75.• Rosenthal A, Ryan LM. Calcium pyrophosphate crystal deposition diseases, pseudogout, and articular chondrocalcinosis. In: Koopman WJ, Moreland LW, eds. Arthritis and allied conditions. 15th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004:2373-2396.• McCarty DJ. Crystal identification in human synovial fluids. Methods and interpretation. Rheum Dis Clin North Am 1988;14:253-67.