HIS26: Rheumatoid Arthritis Describe the manifestations and consequences of rheumatoid arthritis.

RA symmetrically forming pain and swelling in small joints of hands and feet RA can also effect other body organs: kidneys, eye, lungs, vasculitis (feet) RA decreases lifespan by 7-10 years caused by MI/stroke caused by uncontrolled inflammation. Gout is urate crystal deposition progressively resulting in hyperuricaemia, acute gouty arthritis, chronic tophaceous gout NSAIDS, steroids, Xanthine Oxidase inhibitors Allopurinol

Symptomatic Treatments:
NSAIDs help with function but does not change progression of disease Low dose prednisone (may substitute NSAID) Intra-articular/parenteral steroids For flares of symptoms

Outline use of DMARDs in management of RA.

Disease Modifying Anti-Rheumatic Drugs (Methotrexate) Controls current inflammatory features Effectively reduces joint damage/deformity, radiographic progression, and long term disability

Methotrexate is the first choice drug and works by competitively inhibiting the enzyme
dihydrofolate reductase (DHFR). DHFR is responsible for reducing FH2 to FH4 Decreases amount of intracellular FH4 available and affects metabolic pathways which are FH4-dependant (including purine and pyrimidine pathways) 50% Protein bound, partially metabolized in liver, removed active renal tubular circ. Side Effects: Hepatotoxicity, pulmonary damage, GI problems (nausea, stomach upset, loose stools), stomatitis, soreness of mouth, infection, alopecia. Only given once a week, avoid pregnancy and alcohol

**Dose reduction required if renal or hepatic impairment present, folic acid supplement as well

Sulfasalazine: anti-inflammatory (salicylic acid) and antibiotic (sulfapyridine)

Reduced by a bacterial enzyme (azoreductase) to sulfapyridine and 5-ASA in bowel Active moiety is sulfapyridine, not 5-aminosalicyclic acid (opposite for other diseases) Side Effects: Skin reactions, hepatitis, pneumonitis, agranulocytosis, aplastic anaemia o Males Oligospermia and infertility

Hydroxychloroquine anti malarial medication found treatable for inflammatory arthritis.

Interferes with cells ability to degrade and process proteins Side Effects: Rash, nausea, diarrhea, OCULAR RETINOPATHY, depigmentation, myopathy

Discuss the use of biologic therapies in RA.

Specifically designed to treat inflammatory types of arthritis such as rheumatoid/psoriatic Function to inhibit cytokines such as TNF (neutralize the cytokines, block the receptor or activate the anti-inflammatory pathway) such as Infliximab Some TNF is required to produce an inflammation response, when all TNF is inhibited, it makes the patient more susceptible to infection such as tuberculosis. Anti CD20 Rituximab binds to CD20 beneficial in RA treatment.