Osteoarthritis and SLE

What is osteoarthritis? (1)

Disorder of synovial joints (any joint, common in knees and hips). Damage due to repeated excessive loading/stress of joint over time/injury - triggers repair processes - leads to structural changes in joint. Wear down cartilage, bones rub (pain)

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What is osteoarthritis? (2)

Repair processes activated/compensation (may not compensate fully depending on extend of damage). Bones thicken, ligaments (compensate/contract to provide more stability. Synovial membrane, secretes more fluid to lubricate joint/swelling

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What are the typical features of OA?

Localised loss of cartilage, remodelling of adjacent bone and formation of new bone and mild synovitis

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Describe the prevalence of OA

Most common joint disease, 10% men and 18% women over 60 years of age. Most common form of arthritis

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What are the risk factors for OA?

Genetic, increased age, female, obesity, high bone density, low bone density, joint injury, exercise stress, occupation stress e.g. standing, squatting

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What is the impact of OA on patients?

Impaired quality of sleep (no mobility of leg, causes stiffness, discomfort/pain). Sleep disturbance, joint deformity/disability. Occupational impact. Anxiety/depression. Falls. Socio-economic burden. Cost of health care. Increased mortality

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Describe the diagnosis and symptoms for OA (1)

Diagnosed clinically without investigations if 45+ years, activity related joint pain and <30 mins morning related joint stiffness. On examination there may be - bone swelling/joint deformity (synovial fluid)

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Describe the diagnosis and symptoms for OA (2)

Joint warmth/tenderness (inflammatory process), joint instability/reduced motion (ligaments contracting), muscle wasting/weakness (muscle not being used as much). X-ray limited use (poor correlation to symptoms) may show joint space narrowing

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Describe the diagnosis and symptoms for OA (3)

Bone formation around joint. Symptoms differ depending on joint e.g. hand, hip, knees

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Outline the management of OA

Focus on symptoms rather than prevention. Exercise, weight loss. Pharmacological therapy. Non-pharmacological therapy - support to help with psychosocial impact. Hip/knee replacement for severe cases

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What are the pharmacological treatments (pain ladder)?

Paracetamol, NSAIDs (PO and topical). Opioids. Topical capsaicin. Corticosteroids (IV or PO - joint dependent). Hyaluronic acid (occurs naturally in joint fluid as shock absorber/lubricant - not recommended by NICE). Glucosamine (not in NICE)

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What is SLE? (1)

Chronic multi system autoimmune disease. Associated with debilitating clinical manifestations due to inflammation of multiple organ systems. Can be life threatening. Exact cause is unknown but genetic/hormonal/environmental influences have a role

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What is SLE? (2)

Pathological production of antibodies directed against self antigens. Antinuclear antibodies (ANAs) are a hallmark of disease (measurable). Abnormal activation of B/T-cell lymphocytes

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What is SLE? (3)

Natural course involves sporadic bursts of activity (disease 'flares') that cumulatively can cause irreversible damage to organs

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Why is SLE important? (1)

Mortality rates are 2-3 x that of general population (patients with SLE 5 x more likely to have cardiac arrest/higher risk of co-morbidities). Reduction in patient quality of life. Affects young women

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Why is SLE important? (2)

Pregnancy (multiple complications and increases risk of miscarriage and pre-term birth). 5 year survival 90%, 15 year survival 80% (patients on high doses of immunosuppressants/side effects/infection)

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Why is SLE important? (3)

Associated with CVD and stroke. Renal complications can lead to dialysis. Few licensed treatments

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What is the incidence and prevalence for SLE?

Occurs most commonly in women (9:1) Typically develops between 15-45 years. Prevalence/severity varies depending on ethnicity. Ethnicity (Afro-Caribbean patients at high risk of SLE)

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Describe features of SLE ACR classification (1)

SLE can be diagnosed if 4+ are present - malar rash (butterfly), discoid rash, photosensitivity, oral ulcer, arthritis, serositis (pleuritis/pericarditis), renal disorder - persistant proteinuria, neurological disorder - seizures/psychosis

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Describe features of SLE ACR classification (2)

Haematological disorders - haemolytic anaemia/leucopenia, lymphopenia, thrombosytopenia. Immunological disorders - anti-ds DNS antibody, anti-Sm antibody, anti phospholipid antibodies. Antinuclear antibody in raised titre

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Describe features of SLE ACR classification (3)

SLE can affect almost any organ system. Common presenting characteristics include - rash, arthralgia, arthritis, fatigue, headache

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What are the clinical features of SLE? (1)

CNS (headache, psychosis, seizures). Eyes/mucous membranes (uveitis, mucous membrane lesions). Kidneys (haematuria, proteinuria). Blood (anaemia, thrombocytopenia). GI (nausea, vomiting, abdominal pain)

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What are the clinical features of SLE? (2)

Skin (butterfly/malar rash, photosensitivity, alopecia, Raynaud's phenomenon, urticaria). Musculoskeletal (arthritis, arthralgia, myositis). Constitutional (fatigue, fever, weight loss)

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What are the clinical features of SLE? (3)

Fatigue is a major symptom of SLE. Mainly affects eyes, heart (myocarditis), kidneys. E.g. Patient could have psychotic episode due to lupus affecting the brain

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What are the triggers of SLE? (1)

Environmental (UV light, Epstein-Bar virus). Sex hormones (90% female, male hormones or genes on X chromosome protective?). Genetic (identical twins 25% vs 2% non-identical, 8 genetic loci identified, MHC/antigen recognition, complement deficiency)

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What are the triggers of SLE? (2)

Drug induced (hydralazine - counselling points about SLE side effects, procainamide)

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Describe the defective process in apoptosis (1)

Gene susceptible, UV light damages DNA of cell, apoptosis (programmed cell death), in lupus patients – UV light induces necrosis, cell dies, DNA/histones released (self-bodies), apoptotic bodies

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Describe the defective process in apoptosis (2)

Body sees self- bodies as foreign in lupus, B-cells produce antibodies to fight apoptotic bodies. Antibody – antigen complex in blood system, where it sits (results in flare up – affects that system – presents that symptoms

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Describe the defective process in apoptosis (3)

E.g. kidney, flare up with kidney-like symptoms, heart, heart related symptoms)

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What are the current treatments for SLE?

NSAIDs, glucorticosteroids (prednisolone, methylprednisolone), antimalarials (hydroxychloroquine, mepacrine), immunosuppressants (azathioprine, MMF), cytotoxics (cyclophosphamide), DMARDs, biologics (steroids - IV for flares, oral for long term)

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What are the SLE treatment recommendations for patients without major organ manifestations (pharmacotherapy)?

Hydroxychloroquine (low dose corticosteroids, intermittent NSAIDs). Immunosuppressive agents (azathioprine, MMF, methotrexate)

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What are the SLE treatment recommendations for patients without major organ manifestations (adjunct therapy)?

Photo-protection, smoking cessation, weight control, exercise, bone protection, low oestrogen contraceptive pills, vaccination (not live)

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What are the SLE treatment recommendations for patients with major organ manifestations (neuropsychiatric)?

Immunosuppressive therapy

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What are the SLE treatment recommendations for patients with major organ manifestations (lupus nephritis)?

Induction - corticosteroids and cyclophosphamide or MMF (intensify therapy if no response after 6 months). Maintenance - azathioprine, MMF in patients who cannot tolerate azathioprine, or whose symptoms flare while on treatment

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Describe features of hydroxychloroquine (1)

Antimalarial, licensed for SLE, anti-inflammatory action (mechanism unclear). 200-400 mg PO daily (max 6.5/kg per day). Less regular blood monitoring required. Reduce dose in renal impairment. Antacids affect absorption - avoid for 4 hours

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Describe features of hydroxychloroquine (2)

Can be used in pregnancy. Side effects - alopecia, diarrhoea, vision disorders, hair colour changes (dose split to avoid S/E). Annual visual acuity checks required - retinopathy, baseline test required within 6-12 months of treatment initiation

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Describe features of hydroxychloroquine (3)

Annual screening recommended especially in those at high risk of retinal toxicity

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Describe features of azathioprine (1)

Purine analogue immunosuppressant. Used in variety of autoimmune inflammatory conditions and solid organ transplants. 50-75 mg daily initially increase - gradually maintain 100-150 mg daily. Converts 6-MP to TIMP

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Describe features of azathioprine (2)

Leading to inhibition of proliferation of B/T lymphocytes. Check TPMT status prior to initiation. Thiopurine S-methyltransferase deactivates 6-MP. Deficiency due to genetic polymorphism leads to delayed haematological toxicity (fatal)

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Describe features of azathioprine (3)

Ongoing monitoring - FBC, LFTs regularly. S/E - bone marrow depression, infection, thrombocytopenia, hepatic disorders, pancreatitis, anaemia etc.

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Describe features of azathioprine (4)

Need enzyme TIMP to be on this drug (if low TIMP – use low dose). No TIMP – cannot be treated with azathioprine (toxicity). BNF monitoring instructions

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Describe features of mycophenolate (1)

Licensed for prevention of solid organ transplant rejection. Prevents proliferation of B/T lymphocytes by inhibiting purine synthesis. CI in pregnancy/breastfeeding. 1-2 g daily in divided doses. S/E - alopecia, bone marrow disorders, dyslipidaemia

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Describe features of mycophenolate (2)

Infection, renal impairment etc. Monitor - baseline (FBC, RF, LFTs, ESR, CRP, chest x-ray, HIV, hepatitis). Ongoing FBC weekly - 2 weekly - monthly. Not started in women of child bearing potential

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Describe features of IV cyclophosphamide (1)

Pulse 500 mg IV every 2 weeks for 6 doses. Inhibitor effect on T/B cells. Pre-treatment screening. Pre-treatment counselling. Teratogenic. Male infertility (sperm storage). Neutropenia/thrombocytopenia, bladder toxicity-MESNA prophylaxis (reduce SE)

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Describe features of IV cyclophosphamide (2)

Antiemetic required - domperidone or ondasetron. Administered by specialised nurses only. Pregnancy - negative test prior to each tx course and avoid pregnancy for 6 months after

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Describe features of IV cyclophosphamide (3)

Treatment with 6 month gap, check renal/liver function, counsel patient for side effects relating to reproductive system e.g. males – reduce sperm count. Need to check blood within 48 hours before administering dose

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Describe features of IV cyclophosphamide (4)

Not given when patient has an infection/cold (due to being an immunosuppressant). Cyclophosamide – method of clearing can lead to bleeding and cystitis. Only administered by specialised, screened by specialised pharmacist

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Describe features of belimumab (1)

B-lymphocyte stimulator (BLyS) inhibitor. BLyS is elevated in patients with SLE and correlates with disease activity/flares. Stimulates B cells to produce autoantibodies

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Describe features of belimumab (2)

10 mg/kg IV infusion days 0, 14, 28 then 4 weekly. First licensed biologic in SLE. Very expensive, NICE approved June 2016. Recommended as add on treatment when standard treatment for active autoantibody-positive SLE

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Describe features of belimumab (3)

(if all the recommendations highlighted by NICE apply). Biologic used in lupus, expensive, monthly infusions, only IV

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Describe features of rituximab (1)

Can induced substantial long lasting remission in SLE. Used when patients failing or intolerant of or CI in oral immunosuppressants e.g. azathioprine, hydroxychloroquine, MMF, methotrexate, and IV cyclophosphamide

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Describe features of rituximab (2)

May only need to give 1-2 infusions to induce long lasting remission. NHS England fund if certain criteria is met. Doses 2-3 times a year, not always first line – expensive

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Describe features of immunoglobulin-intravenous gammaglobulin (IVIG)

May be of benefit in severe disease. Limited efficacy but last option in some cases. Individually funded based on patient circumstances but difficult to obtain. IVIG – used depending on location of lupus flares

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Outline the treatment pyramid of disease activity for SLE

NSAIDs, analgesics, topical corticosteroids - hydroxychloroquine, azathioprine, methotrexate, mycophenolate mofetil, corticosteroids - rituximab, cyclophosphamide - belimumab IVIG

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What are the roles of a pharmacist in SLE? (1)

Drug expenditure, formulary applications, individual funding requests, unlicensed/off-label use, education/training/clinical guidelines, patient information, medicines information to prescribers, patient adherence, risk factor advice

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What are the roles of a pharmacist in SLE? (2)

Nurses – check blood tests over long period. Organ damage detected – e.g. lupus affecting kidneys only. Link between secondary conditions/co-morbidities

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Osteoarthritis and SLE

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