rheumatoid arthritis psik

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Rheumatoid Arthritis

Hendra Wana Nur’aminDepartment of Pharmacology

Medical FacultyLambung Mangkurat University

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Skenario 1 Ny. SB seorang ibu berusia 55 tahun, dibawa ke poli

Geriatri RS dengan keluhan nyeri sendi-sendi kaki dan lutut, yang sudah dialami selama satu tahun terakhir. Tampak bengkak dan panas di sekitar sendi, terutama pada sendi-sendi kecil dan sendi kaki. Sendi terasa kaku terutama di pagi hari. Gejala ini sudah lama dirasakan oleh ibu tersebut namun sering kambuh terutama bila kondisi lingkungan yang dingin, keadaan Ny. SB sampai saat ini tidak dapat melakukan aktivitas. Hasil lab menunjukkan RA (+). Ners Zahra mencoba untuk memberikan asuhan keperawatan pada Ny. SB.

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Rheumatoid Arthritis “A chronic autoimmune disease characterized

by the inflammation of the synovial joints” Has a symmetrical bilateral effect on joints Results in joint deformity and immobilization Multiple factors increase one’s risk Progressive, systemic, inflammatory disorder Unknown etiology (multifactor?) Characterized by

Symmetric synovitis Joint erosions Multisystem extra-articular manifestations can result in severe disability

(The Arthritis Society, 2012; Gulanick & Myers, 2011; Firth, 2011)

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The Importance of Early Diagnosis RA is progressive, not benign Structural damage/disability occurs

within first 2 to 3 years of disease Slower progression of disease linked to

early treatment

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Epidemiology Incidence

1.4/10000 male, 3.6/10000 females

Prevalence 0.5-2 % male:female 1:3 Worldwide distribution

higher in native Americans absent in some parts of

Africa Onset any age but

maximum 40 - 70 years in women 60 - 70 years in men

Unclear Autoimmunity Normal

antibodies become autoantibodies and attack the tissue.

Infectious agents Genetic Factor Gender Endocrine (CRH, estrogen

synthase) Stressful events Smoking

Etiology

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Clinical features Symmetrical deforming polyarthritis

affects synovial lining of joints, bursae and tendons more then just joint disease

Presentation Variable Gradual or acute/subacute Palindromic Monoarticular Symmetrical, diffuse small joint involvement

Functional impairment: related to underlying disease activity and joint damage due to previous activity

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DiagnosisInvestigations

Haematology Hb, wcc, plts, ESR

Biochemistry LFT, CRP

Immunology RhF, ANA

Microbiology viral titres

Radiology XR, bone scan, MRI

Differential diagnosis Post viral (parvo,

rubella) Reactive arthritis SLE Polyarticular Gout Polyarticular OA

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ACR 1987 Criteria for Diagnosis Four or more of the following criteria must be

present: Morning stiffness > 1 hour Arthritis of > 3 joint areas Arthritis of hand joints (MCPs, PIPs, wrists) Symmetric swelling (arthritis) Serum rheumatoid factor Rheumatoid nodules Radiographic changes

First four criteria must be present for 6 weeks or more

2010 ACR/EULARClassification Criteria for RA

JOINT DISTRIBUTION (0-5)1 large joint 02-10 large joints 11-3 small joints (large joints not counted) 24-10 small joints (large joints not counted) 3>10 joints (at least one small joint) 5

SEROLOGY (0-3)Negative RF AND negative ACPA 0

Low positive RF OR low positive ACPA 2

High positive RF OR high positive ACPA 3

SYMPTOM DURATION (0-1)<6 weeks 0

≥6 weeks 1

ACUTE PHASE REACTANTS (0-1)Normal CRP AND normal ESR 0

Abnormal CRP OR abnormal ESR 1

≥6 = definite RA

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Rheumatoid Arthritis:Treatment Principles Confirm the diagnosis When damage begins early, start

aggressive treatment early Use the safest treatment plan that

matches the aggressiveness of the disease

Monitor treatment for adverse effects Monitor disease activity, revise Rx as

needed

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Goals of Therapy Control disease activity To relieve pain, stiffness, swelling,

fatigue To prevent joint damage/disability To improve quality of life Slow progression/rate of joint damage

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Management Education Physical therapies: Rest,

Exercise, Diet/weight control, physical/occupational therapy

Drugs analgesics NSAIDs DMARDs Immunotherapies Steroids ia, po, im, iv

Surgery

(Arthritis Foundation, 2012)

• Walking• Light jogging• Water aerobics• Cycling• Yoga• Tai chi• stretching

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PharmacotherapyPharmacological treatment of RA can be divided into : Disease-modifying antirheumatic drugs (DMARDs) Anti-inflammatory agents

Glucocorticoids Non-steroidal anti-inflammatory drugs (NSAIDs,

most also act as analgesics) Analgesics

Acetaminophen Opiates Lidocaine topical

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Steroids work here

Steroids work here

NSAIDs work here

COX-1

COX-2

COX-3

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OPIOID Receptor µ: analgetic,

respiratory depression, miosis, euphoria, deacrease bowel motility µ1 : in CNS µ2 : in PNS

Receptor κ: analgetic, respiratory depression, miosis, sedative < receptor µ

Receptor δ: respiratory depression

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COX-1 membentuk prostaglandin (proses normal tubuh) proteksi mukosa lambung

COX-2 berperan dalam peradangan COX-3 varian dari COX-1, yang terdistribusi di sistem saraf

pusat.Tidak mempengaruhi lambung paracetamol

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Efek samping AINS terhadap asmaPenghambatan COX mengarahkan metabolisme asam arakidonat ke arah jalur lipoksigenase  leukotrien bronkokonstriksi

COX 2 Selektif celecoxib, rofecoxib, valdecoxib.Penghambatan secara selektif terhadap COX-2 mengkatalisis pembentukan tromboksan A2 (pembekuan darah dan bersifat vasokonstriktor  blood clots

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Non-steroidal anti-inflammatory drugs (NSAIDs)Examples General Use Side Effects Nursing

ConsiderationsAspirin, ibuprofen, naproxen, COX-2 inhibitors, propionic acid, phenylacetic acid

• anti-inflammatory:Used in the management inflammatory conditions •Antipyretic: used to control fever•Analgesic:Control mild to moderate pain

•Nausea•Vomiting•Diarrhea•Constipation•Dizziness•Drowsiness•Edema•Kidney failure•Liver failure•Prolonged bleeding•Ulcers

•Use cautiously in patients with hx of bleeding disorders•Encourage pt to avoid concurrent use of alcohol•NSAIDs may decrease response to diuretics or antihypertensive therapy

(The Arthritis Society, 2011; Day et al., 2010)

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CorticosteroidsExamples General Use Side Effects Nursing

ConsiderationsCortisone, hydrocortisone, prednisone, betamethasone, dexamethasone

• Used in the management inflammatory conditions •When NSAIDS may be contraindicated•Promptly improve symptoms of RA

•Increased appetite•Weight gain•Water/salt retention•Increased blood pressure•Thinning of skin•Depression•Mood swings•Muscle weakness•Osteoporosis•Delayed wound healing•Onset/worsening of diabetes

•Take medications as directed (adrenal suppression)•Used with caution in diabetic patients•Encourage diet high in protein, calcium, potassium and low in sodium and carbohydrates•Discuss body image•Discuss risk for infection

(The Arthritis Society, 2011; Day et al., 2010)

05/03/202325Disease-modifying anti-rheumatic drugs(DMARDS)Examples General Use Side Effects Nursing

ConsiderationsMethotrexate (the gold standard), gold salts, cyclosporine, sulfasalazine, azathioprine

•immunosuppressive activity•Reduce inflammation of rheumatoid arthritis•Slows down joint destruction•Preserves joint function

•Dizziness, drowsiness, headache•Pulmonary fibrosis•Pneumonitis•Anorexia•Nausea•Hepatotoxicity•Stomatitis•Infertility•Alopecia•Skin ulceration•Aplastic anemia•Thrombocytopenia•Leukopenia•Nephropathy•fever•photosensitivity

•May take several weeks to months before they become effective•Discuss teratogenicity, should be taken off drug several months prior to conception•Discuss body image

(The Arthritis Society, 2011; Day et al., 2010)

05/03/202326Biologic Response Modifiers (“Bioligics”)Examples General Use Side Effects Nursing

ConsiderationsEtanercept, anakinra, abatacipt, adalimumab, Infliximab (Remicade)

• Used in the management inflammatory conditions •When NSAIDS may be contraindicated•Promptly improve symptoms of RA

•Increased appetite•Weight gain•Water/salt retention•Increased blood pressure•Thinning of skin•Depression•Mood swings•Muscle weakness•Osteoporosis•Delayed wound healing•Onset/worsening of diabetes

•Take medications as directed (adrenal suppression)•Encourage diet high in protein, calcium, potassium and low in sodium and carbohydrates•Discuss body image•Discuss risk for infection

(The Arthritis Society, 2011; Day et al., 2010)

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Pain “unpleasant sensory and emotional experience.”

Analgetic any member of the group of drugs used to achieve analgesia — relief from pain

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DMARDs Reduce swelling & inflammation Improve pain Improve function Have been shown to reduce

radiographic progression (erosions)

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DMARDs Traditional small molecular mass drugs (synthesised chemically): Azathioprin Ciclosporin (cyclosporine A) D-penicillamine Gold salt Hydroxychloroquine Leflunomide Methotrexate (MTX) Minocycline Sulfasalazine (SSZ)

Biological agents Tumor necrosis factor

(TNFα) blockers: etanercept (Enbrel), infiximab (Remicade), adalimumab (Humira), Certolizumab pegol (Cimzia)sc (CDP-870)

Anti-B cell (CD20) antibody : rituximab (Rituxan, MabThera), Ocrelizumab

Interleukin-1 blockers : anakinra (Kineret)

Blockers of T cell activation (costimulation blockers): abatacept (Orencia)

Anti-Blys antibody: Belimumab

Anti-IL-6 receptor MAb: Tocilizumab (ActemraTM)

Protein tyrosine kinase inhibitor : Imatinib (Gleevec)

CPH82 (influences the cell cycle & cell proliferation): Reumacon

Disease-Modifying antirheumatic Drugs (DMARDs)

Drug Mechanisms Common Usual of action adverse effects Dosing regimensInjectable gold Inhibits: macorphg, Mucocutan.eruptions 50 mg/wk i.m to total Aurothioglucose angiogenesis,prot. Proteinuria dose of 1000 mg then Gold sodium kinase C Thrombocytopenia 50 mg i.m q 2-4 wk thiomalateOral gold Inhibits: macrophg, Diarrhea, Mucocutan. 3 mg p.o.b.i.d Auranofin PMN function eruptionsAntimalarials Hydroxychlorqn Inhibits: cytokine Diarrhea, mucocutan. 400 mg p.o.,q.d Chlorqn phosphat secretion,lysoso- eruptions 250 mg p.o.,q.d mal enzymes, ma crophg.functionD-Penicillamine Inhibits: helper T Mucocutan.eruptions 500-1000 mg p.o.,q.d cell function, angio Proteinuria genesis Thrombocytopenia

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Disease-Modifying antirheumatic Drugs (DMARDs)

Drug Mechanisms Common Usual of action adverse effects Dosing regimensSulfasalazine Inhibits: B cell Nausea, abd.pain, 1000 mg p.o.,b.i.d responses, angio- diarrhea, rash or t.i.d genesisMethotrexate Dihydrofolate Mucocutan.eruptions 7.5-25 mg/wk p.o. reductase inhibitor, Bone marrow (may also be admi- Antiinflammatory via Nausea, diarrhea, nistered parente- induction of adeno- Hepatic abnormalities rally SC or IM) sine release,inhibits chemotaxisLeflunomide Inhibits pyrimidine Hepatic abnorm. 20 mg/day p.o. synthesis Diarrhea,nausea (initial loading dose of 100 mg/day for 3 days

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Disease-Modifying antirheumatic Drugs (DMARDs)

Drug Mechanisms Common Usual of action adverse effects Dosing regimensAnakinra IL-1 receptor Injection site 100 mg s.c. antagonist reactions, injection daily Infections Adalimumab TNF antibody Injection site 40 mg s.c. inj. (human) reaction, q. 14 days Opportunistic infectionsInfiximab TNF antibody Infusion reactions 3 mg/kg i.v. slow (chimeric) Opportunistic infusion wk 0,2,6, infection then every 8 wk Etanercept Soluble TNF Injection site 25 mg s.c. inj. receptor reactions twice weekly or Opportunistic 50 mg/wk s.c. infections

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Disease-Modifying antirheumatic Drugs (DMARDs)

Drug Mechanisms Common Usual of action adverse effects Dosing regimensCyclosporine Inhibits: synthesis Hypertension 2.5-4 mg/kg p.o. of IL-2 & other T Renal insuff. q.d. cell cytokines HirsutismAzathioprine Inhibits DNA Bone marrow 1-2 mg/kg p.o,q.d synthesis supprression Mycophenolate Inhibits lymphocyte GI, leukopenia 1.0-1.5 g p.o,b.i.dMofetil proliferation nausea,hepatic abnormalities Cyclophos- Crosslinks DNA Nausea, emesis 1-2 mg/kg p.o,q.dphamide & inhibits cellular Bone marrow proliferation suppression Ovarian failure Hemorrhagic cystitis risk of cancer

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Disease-Modifying antirheumatic Drugs (DMARDs)

Drug Mechanisms Common Usual of action adverse effects Dosing regimensMinocycline Inhibits biosyn- Diarrhea,nausea 100 mg p.o, b.i.d thesis & activity Photosensitivity of MMPsRituximab Anti-CD20 mono- Hypotension 1 g IV q.14 days clonal antibody Hypertension (chimeric) RA exacerb.

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Methotrexate (MTX) Dihydrofolate reductase inhibitor ↓ thymidine & purine nucleotide

synthesis “Gold standard” for DMARD therapy 7.5 – 30 mg weekly Absorption variable Elimination mainly renal

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MTX adverse effects Hepatotoxicity Bone marrow suppression Dyspepsia, oral ulcers Pneumonitis Teratogenicity Folic acid reduces GI & BM effects Monitoring

FBC, ALT, Creatinine

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Pathogenesis of RA

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Tumour Necrosis Factor (TNF) TNF is a potent inflammatory cytokine,

produced mainly by macrophages and monocytes. Major contributor to the inflammatory and destructive changes that occur in RA.

Blockade of TNF results in a reduction in a number of other pro-inflammatory cytokines (IL-1, IL-6, & IL-8)

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TNF-α Inhibitor Drugs Certolizumab pegol Infliximab (Remicade ®) Adalimumab Golimumab Etanercept

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Adverse Effects of TNF-α Inhibitors Injection site reactions Increased risk of bacterial, viral, and/or

fungal infections Bone marrow suppression Generation of antibodies to drugs,

resulting in reduced efficacy over time Drug-induced lupus-like syndromes Emergence of lymphoma and skin cancers

over long-term use

Combination therapy is well tolerated and associated with no significant increase in the rate of adverse events compared with monotherapy.

Methotrexate-sulfasalazine, Methotrexate-chloroquine, Methotrexate-ciclosporin, Methotrexate-leflunomide, Methotrexate-intramuscular-gold Methotrexate-doxycycline are effective combination regimens.

Nat Clin Pract Rheumatol. 2007; 3(8):450-458.05/03/2023 44

Triple DMARD therapy is better than various DMARD monotherapy and dual therapy regimens. Methotrexate and hydroxychloroquine may have synergistic anti-inflammatory properties. Clinical trial evidence to support the use of other methotrexate and sulfasalazine combinations is often weak or lacking.

Nat Clin Pract Rheumatol. 2007; 3(8):450-458.05/03/2023 45

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STEM CELL THERAPY Hematopoietic stem cells may be beneficial as a

treatment for rheumatoid arthritisBingham SJ, Moore JJ. Stem cell transplantation for autoimmune disorders. Rheumatoid arthritis. Best Pract Res Clin Haematol 2004; 17(2): 263-76.

Hematopoietic stem cell transplantation is being investigated as a treatment for patients with severe refractory rheumatoid arthritis that is unresponsive to conventional therapies. The stem cells are well tolerated in patients with rheumatoid arthritis. The authors review the research and suggest future protocols for treatments.

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Prognosis Life expectancy reduced by

7 years in men 3 years in women

Severe morbidity sudden onset do better than gradual early knee involvement bad Bad RA has a worse prognosis than IHD

or Hodgkins

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Risk Factors for Increased Morbidity and Mortality in RA Social factors

Low socioeconomic status Lack of formal education Psychosocial stress Low HAQ scores

Physical factors Extra-articular manifestations Elevated CRP and ESR High titers of RF Erosions on x-ray Duration of disease

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Rheumatoid Arthritis: Treatment Plan Summary A variety of treatment options are

available Treatment plan should match

The current disease activity The documented and anticipated pace of

joint destruction Consider a rheumatology consult to help

design a treatment plan

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Contact: hendranuramin@gmail.com