General Rheumatology 3: Osteoarthritis, Rheumatoid Arthritis, Adult Still's Disease PDF

Steven C Kimmel, MD, FACR, FACP, CTI, RhMSUS Disclosures (Grant Research Support) Roche Novartis Amgen Anesiva Genetech Wyeth Centacor Bionicare Searle Abbott GE Lunar Co...

Steven C Kimmel, MD, FACR, FACP, CTI, RhMSUS Disclosures (Grant Research Support) Roche Novartis Amgen Anesiva Genetech Wyeth Centacor Bionicare Searle Abbott GE Lunar Corp Meditrend Teragenix Pfizer Immunicon Purdue Pharma LP UAB Proctor and Gamble Lilly BMS  Osteoarthritis and Rheumatoid Arthritis Steven Kimmel, M.D. West Broward Rheumatology Associates (American Arthritis and Rheumatology Associates)  RA: Therapy Baseline Therapy: Same as for OA PT Analgesics NSAIDs Injections (steroids / No Hylans ) Surgery Other Options Steroids (oral) cDMARDs: (Conventional DMARDs) bDMARDs (Biologic DMARDs) Oral “Biologic” DMARDs: Protein Kinase inhibitors: JAK Kinase inhibitor  RA Linear Progression Early RA Intermediate Late Inflammation Radiographs Severity (Arbitrary Units) Disability Late Intervention Early Intervention 0 5 10 15 20 25 30 Duration of Disease (years) Graph: Adapted from: Kirwan JR. J Rheumatol. 2001;28:881-886. Photo: Copyright © American College of Rheumatology.  RA: Therapy Biologic Steroids NSAIDs cDMARDs DMARDs Oral COX-2 Specific Anti-Malarials Anti TNF < 20 mg/day or Selective SQ injection High doses Sulfasalazine Anti T-Cell IV if needed Low dose as MTX Anti B-Cell adjunct for pain Leflunomide Intra-articular Azathioprine Anti IL-6 Cyclosporine MMF JAK kinase inh Disease Will Progress Prevent Disease Progression Decrease Life Expectancy Improve Life Expectancy  NSAID Agents Most commonly prescribed agents Many available OTC (over the counter) Provide pain relief in both OA and RA Do not prevent progression of RA ADVERSE EVENTS: – > 10 % dyspepsia – 1-10 % Gastric or small bowel bleed / ulceration Renal insufficiency – < 1% CNS confusion Hepatic / Hematologic / Rash / Respiratory – ? CARDIOVASCULAR – GREATEST CAUSE OF DEATH OF ANY MED GROUP Adapted from American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthritis Rheum. 1996; 39:723-731.  RA: Pros and Cons of Steroid Therapy Pros Cons Anti-inflammatory and Doesnot conclusively affect immunosuppressive effects disease progression RAPID ONSET so can be Tapering and discontinuation used to bridge gap between of use often unsuccessful initiation of DMARD Even low doses result in skin therapy and onset of action thinning, ecchymoses, infections and Cushingoid appearance Significant cause of steroid- induced osteopenia / increase atherosclerosis Decrease long term life expectancy  RA: Choice of cDMARD Mild Features Aggressive Features Sulfasalazine Methotrexate Avoid if Sulfa Allergy Leflunomide Hydroxychloroquine Avoid if retinal disease Azathioprine Avoid if low G6PD DMARDs: Beware the Dark Side All DMARDs have side effects HCQ can deposit in the retina after 5 years of use MTX may cause serious problems Lung Liver Bone Marrow Be on the look out for toxicity with all the DMARDs. RA: Biologic DMARDS  RA: Available Biologic Agents TNF Inhibition Infliximab Chimeric anti-TNF-α mAb Ab to TNF Etanercept TNF-receptor p75 IgG1 Soluble receptor Adalimumab IgG1 mAb (humanized) Ab to TNF Golimumab mAb Ab to TNF Certolizumab mAb attached to PEG Ab toTNF (Pegylated ) IL Inhibition Anakinra IL-1 IL-1 Receptor inhib Tocilizumab IL-6 Ab to IL-6 receptor Sarilumab IL-6 Ab to IL-6 receptor Cell Inhibitors Rituximab B-Cell Inhibitor anti-CD20 Abatacept T-Cell Inhibitor CTLA-4 Ig Oral Biologic Agents – Protein Kinase inhibitors Tofacitinib JAK Kinase inhibitor Taken Orally Baricitinib / Upadacitinib Red: IV only; Yellow: SQ only; Green: IV or SQ; White: PO  Biologic Rx: Contraindications Multiple sclerosis, optic neuritis (no TNF Rx) H/O Serious or recurrent infections History of TB or positive PPD test (untreated) – (Treat or Use t-cell therapy / Abatacept) Hepatitis B – (Avoid TNF and B-cell agents, others unclear) Congestive heart failure Lymphoma (? wait 5 years after treatment / use Rituximab) Vaccinations: No Live Virus Vaccines – (need to wait 4 weeks after live vaccination)  RA: Current Approach New Emphasis in Management Early Diagnosis (using new criteria) TREAT TO TARGET (using an objective measure of disease activity): – Early use of cDMARDs – Early use of Biologic agents – Use of multiple cDMARD regimens or combination cDMARD and Biologic agent – Appropriate use of steroids Control Co-Morbid Conditions  RA: Treat To Target Clinical Remission: – Low disease activity with no synovitis Clinical and Radiographic Remission – Low disease activity with no synovitis – No radiographic evidence of ongoing disease (US / MRI) Immunological Remission – Low disease activity with no synovitis – No radiographic evidence of ongoing disease (US / MRI) – No serologic evidence of disease presence  RA: Co-Morbid Conditions Osteoporosis – RA is an independent risk factor Cardiovascular Disease – Heart attacks – CVA Vaccinations (current recommendations) – Killed virus / recombinant vaccines: Should give Shingrix (once x 2 doses) Fluviron (yearly) Pneumovac (every 5 years x 2) Heptavac (once) TDap (every 10 years) – Try to AVOID Live Virus Vaccines: Flumist / Measles / yellow fever Aim to finish vaccination four weeks prior to Biologic treatment or withhold Biologic treatment for 3 months then vaccinate and wait 4 weeks – COVID Vaccine – T cell and B cell therapies associated with poor response. Inject end of interval wait 1 week for next dose  RA: Prognosis In the past (pre-biologic era) Gold Therapy: < 5% remission Methotrexate: ~ 20 % remission Currently (Biologic Era): 60% complete remission 90% partial remission The future (Treat to target) / New agents ? Possible change in target to serologic remission Rheumatoid Arthritis: Extra Topics Extra-articular Disease Cervical Spine Disease Adult Onset Stills Disease Felty’s Syndrome Women’s Health Issues Disability RA: Extra-articular Disease Rheumatoid Nodules Ocular involvement Uveitis Rheumatoid nodules Pulmonary Disease Solitary or multiple nodules: – do not assume RA rule out CA Interstitial Lung Disease Pulmonary HTN Vasculitis Cardiac – Carditis / pericarditis Neurologic – Mononeuritis multiplex Skin – Vasculitic ulcers – Amyloidosis The Rheumatoid Neck: C1-C2 Criteria For The Diagnosis of Adult Still’s Disease All required for diagnosis: Fever > 39°C (Qoutidian: reaching normal once daily) Arthralgia or Arthritis Rheumatoid Factor < 1:80 ANA < 1:100 In addition to any two of the following: White cell count > 15,000 cells/mm3 Still’s rash Pleuritis Pericarditis Hepatomegaly or splenomegaly or generalized lymphadenopathy Adapted from Cush et al Adult Onset Still’s Disease: Rash Faint salmon-colored rash Most common on the trunk and upper extremities May also be seen on the face  Adult Onset Still’s Disease Complications Pericardial Tamponade Myocarditis Pneumonitis Intravascular coagulopathy (DIC) Increasing LFT / Hepatic Necrosis Macrophage activation syndrome (HLH) decreased plt, hgb, HSM Prognosis: Poor Prognosis: Shoulders / hips > 4 joints After 10 years 1/2 still on DMARDs 1/3 still on steroids  Adult Onset Still’s Disease LABS: Ferritin highly elevated in >70% Can be used to follow response COURSE: Monophasic: systemic features predominate < 1 year Intermittent: intermittent flares of arthritis with remissions Chronic: arthritis predominates – can be erosive  Adult Onset Still’s Disease Treatment NSAIDs: ¼ will respond High doses Beware abnormal LFTs watch closely Steroids: - For non-responders - For those with increased LFTs - For severe cases DMARDs: - Hydroxychloroquine - Increased toxicity Sulfasalazine - Methotrexate: care with LFTs Biologic Therapy: – IL-1 inhibition: Anakinra, Canakinumab – IL-6 inhibitor: has best data to date – still off label – TNF inhibitors: can work off label  Felty’s Syndrome Seropositive RA – HLA DR4 95% – More severe RA manifestations (Vasculitis, mononeuritis, Nodules, etc) Granulocytopenia Splenomegaly – most patients (90%) but not required TREATMENT: – Low Neutrophil Count: GM-CSF – RA: cDMARD / Biologics RA: Women’s Health Issues Contraception Pregnancy Lactation Menopause Women’s Health Issues: Pregnancy 80% of individuals with autoimmune disease in the US are women 50% of pregnancies are unplanned so it is important to consider a woman’s reproductive journey including the potential for pregnancy in all patients of reproductive age Its important to maintain control of disease activity and to select an agent that can be used before, during and after pregnancy. Ab transfer depends on the presence of the Fc portion and varies by trimester. No transfer the first trimester but IgG/ biologic transfer can occur as early as 13 weeks, in the 2nd trimester and peaks during the 3rd trimester.  RA: Women’s Health Issues SAFE – Hydroxychloroquine – Certilizumab Contraception is necessary on and after certain medicines: DMARDs – Cyclophosphamide – MTX 3-6 months after – Leflunomide 2 years after – MMF – AZA Biologic DMARDs – Anti-CD 20 – Anti-IL-6, anti- IL-1, anti-IL12/23, T cell costimulatory modulators, anti-BAFF IUD’s ? increased risk for infection BCP’s possibly improve symptoms in some  RA: Women’s Health Issues Vaccination: – Need to be up to date prior to starting a family – Live viruses vaccines need to be given before biologic agents started then wait 4-5 weeks and can start biologic Can stop biologic wait 3 months then vaccinate then wait 4- 5 weeks and restart RA: Women’s Health Issues Pregnancy Maternal issues: Favorable on Mother – 54 % improve – 46 % either remain stable or worsen, – but > 90% relapse postpartum Fetal issues: – increased risk for fetus from medicines – Outcomes related to maternal disease activity Preterm delivery Small for gestational age C-section RA: Women’s Health Issues Lactation: Some meds okay: – Hydroxychloroquine – Certilizumab Others not clear: – Biologics ? Abs with Fc portion do get into breast milk Babies with Fc receptors in GI epithelium Metabolized in GI tract? Others avoid: – MTX – Lef RA: Women’s Health Issues Menopause Increased risk of RA in post-menopausal women Coronary risk increased Coronary risk increased further in those on steroids RA is an independent risk factor for the development of Osteoporosis Disability: Was this Artist disabled ? Pierre-Auguste Renoir 1841 - 1919 Rheumatoid Arthritis 1888 - 1919 Pierre-Auguste Renoir 1841 - 1919 Rheumatoid Arthritis 1888 - 1919  Case 1 A 68 year old female patient c/o difficulty closing her fingers that has progressed over many years. Case 2 A 45 year old white female presents for evaluation of swelling in her fingers and wrists that has been present for 4 weeks.  OA / RA Cases How do we tell which patient has OA and which has RA? 1. History and Physical 2. Labs 3. X-rays 4. scans  Case 1 Hx Case 2 Hx A 68 year old female patient c/o A 45 year old white female difficulty closing her fingers that presents for evaluation of has progressed over many years. swelling in her fingers and wrists that has been present for four weeks. She denies morning stiffness or She denied any fevers or rashes. redness in the fingers but notes She also noted shoulder and knee they are knobby and was told pains as well as swelling more that she could have RA by her recently. She has stiffness in the daughter who is a nurse so she morning lasting for two hours and improving faster with a hot comes to you for your opinion. shower.  OA / RA Cases: Hx Patient 1 Patient 2 68 yo 45 yo Fingers / wrists/ Fingers shoulders/ Knees Sx with use Better with use No stiffness in am AM Stiffness  Case 1 PE Her physical exam revealed a normal general exam. Extremities with fingers showing DIP and PIP ony changes. Hips with mild decreased internal and external rotation. Knees, ankles and feet were normal. Her legs had no clubbing cyanosis or edema.  Case 2 PE Her exam revealed finger swelling as shown in the next slide bilaterally with synovitis and tenderness in the 2-4th PIP and 1,2,3rd and 5th MCP joints. Her wrists had flexion / extension of 60 degrees with mild synovitis and pain on palpation. Shoulders had slightly decreased active range of motion and passive range of motion and were tender to touch. Her knees had full range of motion but mild warmth and effusions bilaterally with tenderness to palpation. Her elbows, hips, ankles and feet were normal.  OA / RA Cases: PE Patient 1 Patient 2 Finger swelling (Boney) Finger swelling (Boggy) DIP and PIP MCP and Wrists No redness or warmth Red / Warm No other swollen joints Other joints: Shoulders / Knees  Cases LABS What labs are needed to tell which of these is OA or RA? a. ANA and RF b. ESR and C-RP c. RF and ACA d. All of the above e. None of the above Which labs do you want to check to determine how to treat these patients ? a. CBC b. Chemistries c. LFT d. U/A e. All of the above  Putting It All Together MONOARTHRITIS ACUTE Trauma ? Yes – X Ray No - ?inflammation Inflammation ? YES – Aspirate No - TP’s ? CHRONIC Inflammation ? Yes – Aspirate / Bx No - TP’s ? POLYARTHRITIS Synovitis? No TP? Bursitis /Tendonitis CASE 1 STS: Hard /bony Firm /nodular YES ACUTE Asymm DGI, Staph, Lyme, Early SpdA /CTD Symm Viral, SBE, ARF, GC, CTD CHRONIC Asymm SpdA, Cryst, CTD, Atyp RA CASE 2 Symm CTD (see labs)  Case 1 Irrelevant of labs, which of the following treatments should be avoided in the first patient but started as soon as possible in the second patient? a. NSAIDs b. Acetaminophen c. Tramadol d. DMARD therapy e. Steroid injections  Case 2 45 year old white female swelling in her fingers and wrists stiffness in the morning for two hours for 4 weeks Synovitis on exam – multiple joints Her joint count is: 18 Swollen 20 Tender Site Hands Wrists Elbows Shoulders Knees Totals Swollen 14 2 0 0 2 18 Tender 14 2 0 2 2 20  Case 2 Her labs revealed: Her Serologies reveal: CBC: WBC= 6.2 Hgb = 10.5 ESR = 95 (nl < 20) Plt = 185 K C-RP = 15 (nl < 1) MCV = 90 RDW = 12 RF = 28 (nl < 14) SMA7: Cr = 1.0 ACPA = > 250 LFT: nl ANA = negative TFT: nl X-rays of her hands and wrists are normal. DOES she have RA based on the: 1987 Criteria ? 2010 Criteria ?  Case 2 1987 Criteria: Criteria she has: Criteria she does not have: hand and wrist involvement X-ray changes Symmetric pattern Rheumatoid Nodules >3 joints Am Stiffness RF * SYMPTOMS MUST BE PRESENT FOR 6 WEEKS TO COUNT 2010 Criteria DOMAIN POINTS Joint Involvement 5 Serology 3 Acute Phase Reactants 1 Duration (>6 weeks) 0 Total 9  2010 ACR Criteria for RA: 1) have at least 1 joint with definite clinical synovitis (swelling) 2) with the synovitis not better explained by another disease (fulfill criteria if score of A-D is ≥ 6/10) A Joint Involvement Score 1 large joint 0 2 – 10 large joints 1 1 – 3 small joints (with or without large joint) 2 4 – 10 small joints (with or without large joint) 3 > 10 joints (at least 1 small joint) 5 B Serology (at least 1 test result is needed for classification) Negative RF and negative ACPA 0 Low-positive RF or low-positive ACPA 2 High-positive RF or high-positive ACPA 3 C Acute-phase reactants (at least 1 test result is needed) Normal CRP and normal ESR 0 Abnormal CRP or abnormal ESR 1 D Duration of symptoms < 6 weeks 0 > 6 weeks 1 What if the ANA was Positive? Does she have RA? Does she have SLE?  Interpretation of a Positive ANA Actual Ratio RA:SLE = 40:1 80%RF 95% ANA 20% ANA 30%RF Patients with SLE Patients with RA  Evaluation of the patient with Symmetric Polyarthritis > 6 weeks Rheumatoid Factor + - ANA ANA + - + - RA, SLE or Strong evidence SLE or other Strong evidence against SLE against SLE other CVD CVD Seroneg RA, Possible RA or other Spondylo- Check other immune stimulatory RA unlikely arthropathy or other Autoantibody disease immune complex studies Check other disease (SBE, Cryo) Autoantibody studies Osteoarthritis Rheumatoid Arthritis A degenerative disease An inflammatory disease involving primarily of unknown etiology. cartilage. The most common form There is an increased of arthritis. mortality associated with this disease. Treatment is aimed at Treatment is aimed at pain control and controlling disease activity improvement / hopefully slowing the joint preservation of function. damage, alleviating pain and maintaining function. Surgery is reserved for those with severe disease symptoms unresponsive to medical therapy.