RxCircle

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

§ 2^nd 3^rd 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]

§ 2^nd 3^rd 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]

§ 2^nd 3^rd 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