Treatment Goal of treatment reduce inflammation and pain, preservation of function, prevention of deformity.

Nonpharmacological therapy Education Exercise Aerobic conditioning Strengthening Reduction of adverse mechanical factors Pacing of activities Weight reduction if obese

pharmacological therapy *simple analgesic drugs *NSAIDs *Topical creams *Opioid analgesics *Amitriptyline 'disease-modifying antirheumatic drug' ((DMARD * Corticosteroids Local injections Surgery

General Principles Undelayed use of DMARDs The major goal is full remission Remission is infrequent with a single DMARD DMARDs combinations can add benefits with little or no increase in adverse effects 4

SIMPLE ANALGESIA Paracetamol (1 g 6-8-hourly) is the oral analgesic of choice because of its efficacy, lack of contraindications or drug interactions, long-term safety, low cost and availability. Paracetamol inhibits prostaglandin synthesis centrally in the brain but has little effect on peripheral production of prostaglandins

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) These are among the top five most prescribed drugs in many countries. Oral NSAIDs are often effective for the pain and stiffness of inflammatory disease. Long-acting NSAIDs given at night are particularly helpful for marked inflammatory early morning stiffness. NSAIDs may also reduce bone pain due to secondary malignant lesions.

The major drawback of NSAIDs is gastrointestinal toxicity. Prostaglandins of the E series play a major role in gastroduodenal defence mechanisms. By depleting mucosal prostaglandin levels, aspirin and NSAIDs impair this 'cytoprotection', resulting in mucosal injury, erosions and ulceration. NSAIDs are an important aetiological factor in up to 30% of gastric ulcers.

IMPACT OF NSAID-INDUCED GASTRIC BLEEDING Endoscopic evidence of peptic ulceration is found in 20% of NSAID users even in the absence of symptoms 1% of patients with RA or OA are hospitalised each year with gastrointestinal bleeding Annual mortality in people in the US and in the UK higher than deaths from diseases such as myeloma, asthma, cervical cancer or Hodgkin lymphoma)

RISK FACTORS FOR NSAID-INDUCED ULCERS *Age > 60 years *Past history of peptic ulcer *Past history of adverse event with NSAIDs *Concomitant corticosteroid use *High-dose or multiple NSAIDs *Individual NSAID-highest with piroxicam, ketoprofen; lower with ibuprofen

PRINCIPAL INDICATIONS FOR ORAL OR PARENTERAL CORTICOSTEROID 1-For rapid, short-term (1-3 months) control of marked synovitis or systemic inflammation while awaiting efficacy from slow-acting antirheumatic agent 2-For life-threatening (e.g. vasculitis) or organ-threatening (e.g. kidney, lung, eye) inflammatory multisystem disease 3-For primary treatment of polymyalgia rheumatica 4-For control of inflammatory disease during pregnancy

LOCAL INJECTIONS Intra-articular injections Injection of a long- acting corticosteroid may be useful adjunctive therapy for short-term pain relief (OA, inflammatory arthritis) and for temporary control of synovitis of just one or a few joints. The duration of benefit varies according to joint size and the nature and severity of the arthritis, but is in the order of 2-8 weeks. Frequently repeated injections may result in joint tissue atrophy and Cushing's syndrome.

‘ Disease-modifying antirheumatic drug

Disease-modifying antirheumatic drugs Slow-acting drugs are commonly indicated for rheumatoid arthritis, seronegative spondarthritis, juvenile idiopathic arthritis and connective tissue diseases.The main indications for use are: persistent synovitis (> 6 weeks) severe extra-articular disease (e.g. vasculitis, scleritis, renal involvement) steroid-sparing effect (e.g. polymyalgia rheumatica resistant to low-dose corticosteroid) inflammatory myositis.

. Classification of DMARDs 1-Non-Immunosuppressive agents (“joint effective agents”) 2-immunosuppressive agents (“joint & systemic effective”) 3-Biological agents 16

1-Non-Immunosuppressive agents (“joint effective agents”) Sulfasalazine Hydroxychloroquine Gold salts (e.g. sodium aurothiomalate) D- penicillamine 17

2-immunosuppressive agents (“joint & systemic effective Methotrexate Azathioprine Leflunomide Ciclosporine Other cytotoxic drugs 18

. Methotrexate inhibits dihydrofolate reductase, interfering with DNA synthesis and cell division.It has high efficacy, relatively low toxicity,, among this group, most rapid onset of action (as early as 4 weeks). This drug has hematologic, pulmonary, and hepatic side effects,. Folic acid (5 mg/day) reduces the incidence of adverse effects without reducing efficacy.

Cyclophosphamide, azathioprine, and cyclosporine are immunosuppressive drugs that are effective agents in treating RA. In addition to the risk of both common and unusual infections, cyclophosphamide carries a risk of bladder and late lymphoid malignant disease; the latter risk may also be present with azathioprine.

Among the oldest of are gold salts. Given as weekly injections, gold thiomalate or thioglucose is effective in controlling disease in many patients; a few patients go into true and complete remission. However, many patients experience side effects, including bone marrow suppression, glomerulonephritis, and rash.

Biological Treatment (Anticytokines)

These drugs are more effective than standard DMARDs (with a faster onset of action, greater clinical efficacy and sustained benefit) but because of their cost many countries have set restrictive guidelines for their use. Current UK recommendations are that they should be initiated only in active RA when an adequate trial of at least two other DMARDs (including methotrexate) has failed.

3-Biological Treatment (Anticytokines) (TNF-α) and interleukin-1 (IL-1) play an important role in the pathogenesis of RA and are therefore prime therapeutic targets Infliximab anti-TNF-α monoclonal antibody which is administered by intravenous infusion every 1-2 months..

recombinant IL-1 receptor antagonist Anakinra Anakinra Competitively blocks binding of IL- 1 to its receptor Monoclonal antibody that binds CD20 antigen on B-cells surface (Rituximab) 26

Each course of rituximab consisted of two courses of either 1,000 mg or 500 mg given iv two weeks apart. Prior to each rituximab infusion, all patients received methylprednisolone 100 mg iv; most patients also received paracetamol and an antihistamine. van Vollenhoven RF, et al. EULAR 2012: Abstract THU0120 iv = intravenous; RA = rheumatoid arthritis

EXAMPLES OF COMMON USEFUL SURGICAL PROCEDURES FOR MSK DISORDERSEXAMPLES OF COMMON USEFUL SURGICAL PROCEDURES FOR MSK DISORDERS Soft tissue release decompression Carpal tunnel(Median nerve) compression Synovectomy Joint replacement arthroplasty