Arthritis Flashcards by Anika Gouws

What is osteoarthritis?

Slowly evolving joint disorder –> systematically benign but can cause severe disability

Women commonly experience in and joints, men in hip joints

Pain during early stage of disease –> initially upon use, dull ache improved with rest/when pressure not on joint

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What may contribute to pain during early stages of osteoarthritis development?

Osteophytes

synovitis

Bursitis

Tendonitis

Stretching of join capsule

Stretched nerve endings

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What is the pathophysiology of osteoarthritis?

Degeneration and loss of articular cartilage –> new bone form on joint surface —> body unable to properly repair —> pain and deformity

Reduced proteoglycan content in cartilage –> reduce resilience

Impaired cartilage synth due to mechanical and osmotic stress –> inc MMPs and inflammatory cytokines –> loss of collagen and aggrecan —> bone remodelling, microfractures , osteophyte development

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What are the sx and signs of osteoarthritis?

Aching pain after joint use, initially relieved by rest (pain later occurs at rest)

Joint stiffness <30 after waking –> pain w/ range of motion, may be at location other than affected joint

Physical appearance = joint enlargement/deformity, crepitus (common for knee)

Radiography = narrowing of joint space, presence of osteophytes

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What are the goals of treatment for osteoarthritis?

Reduce and control pain

Minimise disability

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What are the non-pharm tx for OA?

Rest and use assistive devices for weight bearing joints

Weight reduction

exercise

thermal therapy

joint replacement

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How can hand osteoarthritis sx be minimised?

Avoid repetitive thumb movement, prolonged grip in one position

Distribute weight of lifted objects over several joints

Use as large a grip as possible

Reduce effort needed to do tasks

Conserve energy by planning activities

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What are the topical tx for OA?

Topical NSAIDs –> directly to painful area

Capsaicin to painful area –> deplete substance P

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What analgesics are used to treat OA?

Paracetamol

Paracetamol modified release

NSAID

*Oral NSAID is more effective than paracetamol but greater chance of harm

*consider regular dosing for those with sx that persist throughout day

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List some other pharm treatments for OA

Intra-articular corticosteroids = rapid onset of action, repeated every 3 months –> allow participation in exercise

Intraarticular hyaluronan = single injection or as week for 3-5 wks, may temporarily worsen

Intraarticular joint injection of platelet rich plasma, adipocyte cell suspension and mesenchymal stem cells = not recommended, weak evidence

Duloxetine = similar efficacy as NSAIDs (may be used as adjunct)

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What CAMs can be used in the tx of OA?

Fish-oil

glucosamine

chondroitin –> evidence messy, inconclusive

Krill-oil –> no evidence

Tumeric –> inadequate evidence

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What may cause/inc risk of osteoarthritis?

Genetic predisposition = human leucocyte antigen DR4 (HLA-DR4)

Environmental factors = females at greater risk, inc risk between 25-55, risk dec after 75

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What is rheumatoid arthritis?

Autoimmune disease characterised by = persistent synovitis, systemic inflam, presence of autoantibodies

Can lead to development of bony erosions, cartilage, tendon degradation, joint deformity

40% also have inflammation at other body sites

Can cause disability and death

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What are the characteristics of articular RA?

Early morning joint stiffness >1 hr

Multiple joint involvement

Symmetrical pattern

Joint nodules

Classic signs of inflammation (heat, swelling, tenderness)

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What are the characteristics of extra-articular RA?

Constitutional = weight loss/cachexia, fever, fatigue/malaise, depression

Nodules (lung/pleura/pericardium/subcut)

Restrictive lung disease

Secondary Sjogren’s syndrome

cardiomyopathy, CAD

Vasculitis

Motor neuropathy

anaemia of chronic disease

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What joints are usually first affected in RA?

Metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of hands

Metatarsophalangeal (MTP) joints of feet and wrists

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How does RA present?

Variable clinical progression of disease
- 1/3 mild and intermittent symptoms initially, may resolve over several weeks and months, then experience sx again but worse than initial

Some have sudden sx onset followed by prolonged clinical remission

Some experience progressive uninterrupted disease and subsequent disabling joint deformities

50% will be disabled or unable to work w/in 10 yrs of prognosis

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What is the pathophysiology of RA?

Chronic inflammation –> synovial lining hyperplasia –> formation of pannus (fibro vascular build up –> highly erosive inflammatory exudate) –> attack on synovial lining and connective tissue

Inflammatory wind up (T-, B-lymphocytes, cytokines, cytotoxins) –> inc in polymorphonuclear leukocytes –> free radicals

Invasion of articular cartilage –> narrow joint spaces —> erode bone and destroy ligament and tendons –> joint deformities

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What is the prognosis of RA?

10% spontaneous remission w/in 6 months

Majority persist and progressive disease, minority have intermittent and recurrent explosive attacks

What are key indicators of poor RA prognosis?

high RF titre and/or positive anti-CCP antibody test

Sustained raised inflammatory markers (CRP or ESR)

Swelling in more than 20 joints

Impaired function early in disease

Bony erosions evidence on X-ray early in disease

smoking

What are complications of RA?

Atherosclerosis - secondary to systemic inflammation

Vasculitis

Neuropathy

depression

osteoporosis

peptic ulcers

lung disease

Atlanto-axial involvement

What are the goals of treatment of RA?

Maximise long term QoL

Control sx, normalise physical function

enable social and work participation

prevent joint damage

minimise cardiovascular complications

What is disease remission in the context of RA?

symptomatic relied, normalisation of inflammatory markers

absence of joint swelling

achieved in 40% of cases with aggressive DMARDs

How can NSAIDs be used to treat RA?

Used on prn basis, dont alter disease progression but good sx relief

May be used intermittently with methotrexate

Superior to opioids for pain

How can NSAIDs be used safely in RA?

Lowest dose compatible w/ sx relief reduce dose and cease if possible, when good DMARD response achieved use gastro-protection esp >65yrs, past hx of peptic ulcers

What are some important points when using corticosteroids in RA?

Rapidly improve patient functional status, using lowest dose possible for shortest possible time

What monitoring should be done for corticosteroid use in RA?

HTN Weight gain diabetes infections (chicken pox/shingles) osteoporosis

Why are DMARDs effective in treating RA?

Slow: - joint destruction - synovitis and soft tissue destruction - ulnar deviation and sublaxation - pain and disability - secondary consequences (e.g. CV complications) *Don't have any analgesic or rapid anti-inflammatory properties

What are some characteristics of csDMARDs? (name some drugs too)

conventional synthetic = very old drugs made by chemists that have general immunosuppressant properties Azathioprine cyclophosphamide hydroxychloroquine cyclosporin leflunomide methotrexate mycophenolate sulfasalazine

What are some characteristics of bDMARDs? (name some drugs too)

Biological DMARDs = more targeted therapies working via biological mechanism all end in either -mab or -cept

What are some characteristics of tsDMARDs? (name some drugs too)

Targeted synthetic DMARDs = made by a chemist in a lab but targeted therapy apremilast, tofacitinib

How/when is methotrexate used in RA?

1st line in almost all patients, highly effective both as monotherapy and combination maximal efficacy attained after 4-6 months Under dosing is common = optimal dose --> 25-30mg/wk w/ folate or less in case of dose limiting effect for at least 8 wks C/I in hepatic or renal disease

How does the dosing frequency of methotrexate change when given w/ other csDMARDS?

Given weekly rather than daily, serious tox can occur if take more frequently Calcium folinate/folic acid dec risk of ADRs (GI, liver transaminits, mouth ulcers) - should not be given on same day as weekly methotrexate dose

How does csDMARD therapy change if methotrexate use is C/I?

Sulfasalazine (20mg/day) or leflunomide (3-4g/day) considered initially Antimalarials (hydroxychloroquine and chloroquine) = can be considered as monotherapy or part of combination therapy in px with low disease activity

When would bDMARDs be used in RA treatment?

Stepping up from MTX monotherapy to bDMARDs (more effective than csDMARD combination)

What bDMARDs target T cells and B-cells?

T cells = abatacept, belimumab B-cells = rituximab

What role do tsDMARDs play in RA treatment?

Apremilast - phosphodiesterase-4 = reduce production of pro-inflam cytokines (TNF-alpha, IL-17/-23), inc anti-inflam cytokines (IL-10) - associated with development of depression Tofacitinib - Janus Kinases (JAK 1, 2, 3) = reduce activation of T lymphocytes and release pro-inflam cytokines, suppress immune response - C/I w/ other cytokine modulators or potent immunosuppressants

When/how should glucocorticoids be used in RA treatment?

Low-dose = should be considered as part of initial treatment plan in combination w/ 1 or more csDMARDS --> 6 months Used for flareups during tx - I.D. comorbid conditions that may be exacerbated by tx glucocorticoid monotherapy is not recommended, except in exceptional cases in which all DMARDs are C/I

What does the early treatment of RA consist of?

DMARD-naive patients w/ early symptomatic RA = DMARD monotherapy - methotrexate preferred Moderate or high disease activity despite DMARD therapy (w/ or w/out glucocorticoids) = combination therapy (w/ or w/out methotrexate) -- DMARDs or TNFi or non-TNF biologic Moderate or high disease activity (despite tx) --> add low dose glucocorticoids

What is the early treatment of an RA flare?

Add short term glucocorticoids = <3 months at lowest dose for shortest possible duration

How are patients treated when they're in RA remission or have low disease activity?

Low disease activity, no remission = Continue DMARD, TNFi, non-TNF biologic or tofacitinib rather than discontinuing In remission = DO NOT discontinue tx - Taper DMARD, TNFi, non-TNF biologic or tofacitinib

What RA drugs should be avoided in those w/ CHF?

Avoid TNFi

What is the RA tx for someone w/ Hep B and Hep C?

Hep B - If on antivirals = tx as normal - Chronic untreated Hep B --> antiviral tx before immuno suppression Hep C - If on antivirals tx as normal - if not on/not req antiviral --> use DMARD rather than TNFi

What is the RA tx for someone w/ Serious infection (latent TB)?

Combination DMARD therapy OR abatacept AVOID TNFi

What is the RA tx for someone w/ malignancies?

Current or previous skin cancer = use DMARDs Lymphoproliferative disorder = rituximab and avoid TNFi Previous solid organ cancer = tx as normal

Why are TNFi avoided in the tx of patients w/ some cancers or infections?

IL and TNF-alpha are involved in pathogenesis of RA However, they are important immune defences against tumours and infections

What are some important points about vaccine use in RA?

Live vaccines = not be given for those on immunomodulatory drugs, give 4 wks before starting tx - except varicella and zoster vaccines for those w/ low level immunosuppression Inactivated vaccines = 2wks before immunosuppression (larger or repeated doses may be req Live attenuated virus vaccines = NOT to be given to patients on biologics