Management of Rheumatoid Arthritis Raad Makadsi

NICE guidelines on the management of Rheumatoid Arthritis Feb 2009 Key priorities for implementation Referral for specialist treatment

Investigations Rheumatoid factor Anti-cyclic citrullinated peptide (CCP) antibodies if: they are negative for rheumatoid factor, and X-ray the hands and feet Once the diagnosis is made there is a need to inform decision-making about starting combination therapy

Communication and education Explain the risks and benefits of Treatment Offer verbal and written information Education Offer the opportunity to take part in existing educational activities, including self-management programmes

The multidisciplinary team Specialist nurse - who is responsible for coordinating the care Physiotherapy Occupational therapy Psychological interventions (for example, relaxation, stress management and cognitive coping skills ] ) Podiatrist (Functional insoles and therapeutic footwear)

DMARDs Offer a combination of DMARDs Ideally within 3 months Corticosteroids oral, intramuscular or intra- articular

DMARDs When sustained and satisfactory levels of disease control have been achieved, cautiously try to reduce drug doses If combination DMARD therapy is not appropriate, start DMARD mono-therapy Patients in whom disease-modifying or biological drug doses are being decreased or stopped, arrangements should be in place for prompt review

Glucocorticoids Short-term - recent-onset or established disease to rapidly decrease inflammation Long - term - In established RA continue glucocorticoids when: - the long-term complications of glucocorticoid therapy have been fully discussed - all other treatment options (including biological drugs) have been offered

Biological drugs Offer anti-TNF if patient failed two DMARDs including Methotrexate Do not offer the combination of tumour necrosis factor-α (TNF-α) inhibitor therapy and anakinra for RA

Symptom control Paracetamol, codeine or compound analgesics) Oral NSAIDs/COX-2 inhibitors should be used at the lowest effective dose for the shortest possible period of time If RA patient needs to take low-dose aspirin consider other analgesics before substituting or adding an NSAID or COX-2 inhibitor (with a PPI)

Monitoring rheumatoid arthritis Measure CRP and DAS28 regularly In early active RA, measure CRP and DAS28 monthly until treatment has controlled the disease to a level previously agreed with the person with RA

Monitoring rheumatoid arthritis In satisfactorily controlled established RA Offer patients review appointments at a frequency and location suitable to their needs Make sure they: - have access to additional visits for disease flares - know when and how to get rapid access to specialist care - Have an on going drug monitoring

RA annual review Assess disease activity and damage Functional ability (HAQ) Comorbidities, such as hypertension, IHD, osteoporosis and depression Look for complications, such as vasculitis and cervical spine, lung or eyes involvement

RA annual review Organise appropriate cross referral within the multidisciplinary team Need for referral for surgery The effect the disease is having on a person's life

Vit D role Calcium homeostasis Bone metabolism Regulates many other cellular functions including immunmodulations

SOURCES Sunlight and ultraviolet light - photoisomerize provitamin D to vitamin D3 (cholecalciferol) in the skin Diet fortified milk, fatty fish, cod-liver oil, and, to a lesser extent, eggs

ABSORPTION AND METABOLISM Dietary vitamin D micelles, -absorbed by enterocytes, -packaged into chylomicrons. Chylomicrons - liver - Vit D hydroxylation to form 25-hydroxyvitamin D (25OHD) Kidney- hydroxylation to 1,25- dihydroxyvitamin D (1,25OHD) 1,25OHD active form of vitamin D

ABSORPTION AND METABOLISM More than 25 metabolites identified, each with different biologic activities The synthesis of vitamin D is closely coupled to calcium homeostasis, and is modulated by parathyroid hormone, serum calcium, and phosphorus levels

DEFICIENCY AND RESISTANCE caused by one of four mechanisms : Inadequate dietary vitamin D, fat malabsorptive disorders, and/or lack of photoisomerization Impaired hydroxylation by the liver to produce 25-hydroxyvitamin D Impaired hydroxylation by the kidneys to produce 1,25-dihydroxyvitamin D End organ insensitivity to vitamin D metabolites (hereditary vitamin D resistant rickets)

In early stage Vitamin D deficiency, hypophosphatemia is more marked than hypocalcemia Persistent deficiency, hypocalcemia occurs and causes secondary hyperparathyroidism, This leads to phosphaturia, demineralization of bones More prolonged, lead to osteomalacia in adults and rickets in children. Glucocorticoids inhibit intestinal vitamin D- dependent calcium absorption and therefore can cause osteomalacia Vitamin D stores decline with age, especially in the winter Vit D and calcium supplementation can reduce the risk of falls and fractures in the elderly

The Recommended Dietary Allowance for vitamin D is 600 International Units for adults Age 70 years and for children 1 to 18 years of age For adults 71 years and older, 800 units (20 micrograms) daily is recommended

Excessive doses of vit D in adults can result in intoxication Symptoms of acute intoxication are due to hypercalcemia and include confusion, polyuria, polydipsia, anorexia, vomiting, and muscle weakness Long-term intoxication can cause bone demineralization and pain. In children, the hypercalcemia can cause brain injury

CLINICAL MANIFESTATIONS Osteomalacia may be asymptomatic and present radiologically as osteopenia. Diffuse bone pain polyarthralgias, muscle weakness, and difficulty walking - Waddling gate Fracture Muscle spasms, cramps

Investigations Alkaline phosphatase elevated Serum calcium and phosphorus reduced 25-hydroxyvitamin D (calcidiol) <15 ng/mL PTH elevated

Radiographic findings Changes in vertebral bodies — softening leads to a concavity of the vertebral bodies called codfish vertebrae. The vertebral disks appear large and biconvex. There may be spinal compression fractures, but these are more common in osteoporosis. Looser zones — Looser pseudofractures, Stress fractures

Vitamin D3 (cholecalciferol) is available in 400, 800, 1000, 2000, 5000, 10,000, and 50,000 unit capsules Vitamin D3 (cholecalciferol) IM injection can be extremely painful Vitamin D2 (ergocalciferol) is available for oral use in 400 and 50,000 unit capsules Vitamin D2 (ergocalciferol) A previously available IM preparation is now difficult to obtain