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Rheumatoid Arthritis
Epidemiology
- Genetic predisposure is unknown
- Environmental factors may be necessary for expression of the disease
- MHC (major histocompatibility complex) located on T lymphocyte plays a major role. These molecules can be characterized using human lymphocyte antigen (HLA) typing.
- Majority patients have HLA-DR4, HLA-DR1 or both
Clinical Presentation
- Usually over several weeks to a month
- Fatigue, weakness, low-grade fever, loss of appetite, and joint pain.
- Stiffness and muscle aches (myalgias), Joint swelling (synovitis)
- American Rheumatism Association Criteria for Classification of Rheumatoid Arthritis
o Morning Stiffness
o Arthritis of three or more joint areas simultaneously
o Arthritis of hand joints
o Symmetric arthritis
o Rheumatoid Nodules
o Serum Rheumatoid Factor
o Radiographic changes
Treatment
- Non-pharmacological therapy
o Rest, weight loss, surgery, assistive dives, physical therapy, occupational therapy
Pharmacological therapy
- NSAIDS
o Only in patient with mild disease
o No more than 3 month unless patients demonstrate a satisfactory response.
- DMARDs
o Methotrexate [Rheumatrex Dose Pack]
§ Best one because less toxicity or stronger efficacy
§ Toxicity
· Gastrointestinal, hematologic, pulmonary, and hepatic
§ Side Effect
· Nausea, vomiting 10%
· Thrombocytopenia 3%
· Pulmonary fibrosis, pneumonitis rare
§ Other
· It is a folic acid antagonist, it induce folic acid deficiency.
· Supplementation with folic acid has been shown to alleviate some adverse effect.
o Gold
§ When refractory to Methotrexate
§ Oral (auranofin) or IM (aurothioglucose, gold sodium thiomalate)
§ Side effect
· Metallic taste, skin rah, stomatitis, proteinuria hemathrombocytopenia, nausea, vomiting, , diarrhea,
· Gold salt: nitritoid reaction-flushing, palpitations, hypotension, tachycardia, HA, or blurred vision
o Hydroxychloroquine [plaquenil]
§ When refractory to Methotrexate
§ Delay reaction of 6 weeks. But 6 month delay result of therapeutic failure
§ Major advantage of this is lack of myelosuppressive, hepatic and renal toxicities.
§ Side Effect
· Nausea, vomiting, diarrhea, ocular toxicity, benign corneal deposits, blurred vision, scotomas, night blindness, rash, alopecia, skin pigmentation increase, headache, vertigo, insomnia.
o Sulfasalazine
§ 2nd 3rd choice
§ a prodrug, cleaved by bacteria in the colon into sulfapyridine and 5-aminosalicylic acid (5-ASA)
§ Working in 1-2 month
§ Side Effect
§ Nausea, vomiting, diarrhea, anorexia, rash, urticaria, leukopenia, alopecia, stomatitis, elevated hepatic enzymes, turn yellow urine.
§ Drug Interaction
· Absorption decreased when antibiotics are used destroy the colonic bacteria
· Binds iron supplements, lead to decreased absorption of the drug potentate warfarin effect by displacing it from protein binding site
o Penicillamine [cuprimine]
§ 2nd 3rd choice
§ working in 3-4 weeks. But 12 week month delay result in therapeutic failure
§ Side Effect
· Bone-narrow suppression
o Stop until suppression reversed.
· GI intolerance, oncogenic potential, stomatitis, infections, drug fever, and hepatoxicity.
§ Drug interaction
· When use with allopurinol, dose of azathioprine should be decrease to 30% of regular dose
o Azathioprine [Imuran]
§ 2nd 3rd choice
§ metal chelating agent. Shouldn’t take with antacids, iron because absorption.
§ Working in 1-3 month
§ Side effect
· Pruritic, erythematosus skin rash, metallic taste
· Hypogeuisia may last 2-3 month
· Rash or metallic taste after 6 month of therapy
o Drug to be decreased or withheld
· Stomatitis, nausea, vomiting, anorexia, dyspepsia, glomerular nephritis, proteinuria, hematuria,
· Auto immune - polymyositis, thematosus, pemphigus
o Discontinue the drug
Corticosteroids
- In controlling symptoms before the onset of action of DMARDs
- In acute flares
- Low dose when DMARDs do not provide adequate disease control.
- Ways of using
o Bridging
§ Low dose therapy or high dose to control flares of RA
o Control pain and synovitis when using DMARDs
§ Alternative dose is ineffective
- Side effect
o HPA suppression, cushing’s syndrome, osteoporosis, myopathy, glaucoma, cataract, gastritis, hypertension, hirsutism, electrolyte imbalance, glucose intolerance, skin atrophy, increased susceptibility to infection.
- Long term therapy should give patient calcium and vitamin D to minimize bone loss
Leflunomide [Arava]
- Inhibit pyrimidine synthesis
- Loading dose of 100mg for 3 days, then 20 mg daily.
- Working in 1 month
- Reduce the progression of erosion in disease
- Side effect
o Liver function abnormalities
§ ALT monitoring
o Teratogenic
§ Avoid pregnancy
o Cholestyramine is recommended to help clear the drug from plasma more rapidly
§ Shouldn’t conceive until drug’s metabolite drop less then 0.02 ug/ml.
Etanercept
- Human tumor necrosis factor TNF p75 fusion protein
- Preventing binding to inflammatory cell surface receptor
- Reduce disease activity
- Subcutaneous injection
o 25mg twice weekly
- Contraindication
o Life threatening infection, high risk for sepsis
§ Discontinue drug
Complication
- Vasculitis
- Ocular
- Cardiac
- Pulmonary complication
