RHEUMATOID RHEUMATOID ARTHRITISARTHRITIS

Persistent, symmetrical, deforming peripheral arthropathyPersistent, symmetrical, deforming peripheral arthropathy.. Autoimmune diseaseAutoimmune disease characterised by characterised by persistent inflammatory persistent inflammatory

synovitis.synovitis. Causative Antigen : Causative Antigen : HLA DR4HLA DR4 (Human Leukocyte Antigen DR4).(Human Leukocyte Antigen DR4).

PathophysiologyPathophysiology• Dendritic cellsDendritic cells ‘pick’ the Antigen to present it to T-lymphocytes. ‘pick’ the Antigen to present it to T-lymphocytes.• Cellular immune response….But, Cellular immune response….But, immune complexesimmune complexes are are

formed within the joint.formed within the joint.• Polymorphs Polymorphs are attracted to the synovial joints.are attracted to the synovial joints.• Phagocytosis and Phagocytosis and sustainedsustained inflammation inflammation..• Synovial hypertrophySynovial hypertrophy; ; destruction of cartilage and bonedestruction of cartilage and bone..• Persistent synovitis causes an Persistent synovitis causes an effusion of synovial fluid rich in effusion of synovial fluid rich in

protein and inflammatory cellsprotein and inflammatory cells..

Clinical ManifestationsClinical Manifestations Fatigue, malaise, stiffness, Fatigue, malaise, stiffness, diffusediffuse musculoskeletal pain. musculoskeletal pain. Joint pain, stiffness, loss of functionJoint pain, stiffness, loss of function (joints cant be fully (joints cant be fully

extended or flexed). extended or flexed). Morning stiffness of joints, which improves slightly during the Morning stiffness of joints, which improves slightly during the

day only to return slowly and worsen at night.day only to return slowly and worsen at night. Soft tissue swelling and erosions (starts in the PIP joints and Soft tissue swelling and erosions (starts in the PIP joints and

gradually spreads).gradually spreads). Ulnar deviationUlnar deviation and and volar subluxationvolar subluxation.. ‘‘Sausage-shaped’ fingersSausage-shaped’ fingers Boutonniere deformity, Swan neck deformity, Piano key Boutonniere deformity, Swan neck deformity, Piano key

fingers, Z-thumbfingers, Z-thumb.. Gradual worsening of all symptoms.Gradual worsening of all symptoms.

Complications of RA

Mayo Clinic researchers have concluded from a study (1955) that not only do people with rheumatoid arthritis have a higher risk of coronary heart disease than the general population, they have:

more silent, unrecognized heart attacks. more sudden cardiac deaths.

Interestingly, however, rheumatoid arthritis patients are much less likely to complain of chest pain.

Laboratory investigationsLaboratory investigations Rheumatoid factor +Rheumatoid factor + Elevated ESR, IgM, IgG, WBCs and platelet count.Elevated ESR, IgM, IgG, WBCs and platelet count. Hypochromic normocytic anaemia.Hypochromic normocytic anaemia. Synovial fluidSynovial fluid – yellowish, watery and turbid (due to high WBC – yellowish, watery and turbid (due to high WBC

and low glucose content).and low glucose content). X-ray of wrist, hands and feet – erosion of joint margin loss of X-ray of wrist, hands and feet – erosion of joint margin loss of

joint space due to cartilage erosion.joint space due to cartilage erosion.

Drug TherapyDrug Therapy1] 1] NSAIDsNSAIDs• Ibuprofen 1.2 – 3.2 gms in 3 – 4 doses; Ibuprofen 1.2 – 3.2 gms in 3 – 4 doses; • Piroxicam 20 mg in 1 or 2 doses; Piroxicam 20 mg in 1 or 2 doses; • Indomethacin 50 – 200 mg in 3 doses.Indomethacin 50 – 200 mg in 3 doses.

DMARDsDMARDs (Disease Modifying Anti Rheumatic Drugs) (Disease Modifying Anti Rheumatic Drugs) MethotrexateMethotrexate • Drug of choiceDrug of choice for those who don’t respond to NSAIDs. for those who don’t respond to NSAIDs.• 7.5 – 20 mg once weekly7.5 – 20 mg once weekly..• Side effects – Side effects – stomatitis, hepatitis and gastric irritationstomatitis, hepatitis and gastric irritation..

Antimalarials [Hydrochloroquine sulphate]Antimalarials [Hydrochloroquine sulphate]• 200 – 400 mg per day200 – 400 mg per day..• Low toxicity (pigmentary retinitis is rare but fatal, causing visual Low toxicity (pigmentary retinitis is rare but fatal, causing visual

loss).loss).

Gold SaltsGold Salts• For those For those who can’t tolerate methotrexatewho can’t tolerate methotrexate..• 10 mg (110 mg (1stst week) to 25 mg (2 week) to 25 mg (2ndnd week), followed by maintenance week), followed by maintenance

dose of 50 mg weekly for upto 20 weeks.dose of 50 mg weekly for upto 20 weeks.

• Side effects – dermatitis, stomatitis, proteinuria and neutropenia Side effects – dermatitis, stomatitis, proteinuria and neutropenia ((these can be controlled by corticosteroidsthese can be controlled by corticosteroids).).

Corticosteroids 10 mg per day.Corticosteroids 10 mg per day.

SulphasalazineSulphasalazine• 22ndnd line drug. line drug.• Start with 0.5 mg, increase weekly by 0.5 mg till patient feels Start with 0.5 mg, increase weekly by 0.5 mg till patient feels

better (to a maximum of 3 mg).better (to a maximum of 3 mg).• Can cause Can cause hemolysis in G6PD deficiency caseshemolysis in G6PD deficiency cases..

AzathioprineAzathioprine• Antimetabolite; for those not responding to gold or Antimetabolite; for those not responding to gold or

antimalarials.antimalarials.• Start with Start with 1 mg / kg, increased to a maximum of 3 mg1 mg / kg, increased to a maximum of 3 mg..

PenicillaminePenicillamine• For For severe RAsevere RA cases. cases.• 250 mg daily initially to a maximum of 0.75 – 1 g per day250 mg daily initially to a maximum of 0.75 – 1 g per day..• Given between meals to enhance absorption.Given between meals to enhance absorption.• Side effects – fever, rash, Side effects – fever, rash, oral ulcersoral ulcers, , aplastic anaemiaaplastic anaemia..

Minocycline 250 mg per dayMinocycline 250 mg per day for mild cases. for mild cases.

TRIPLE THERAPYTRIPLE THERAPY Methotrexate + Hydrochloroquine sulphate + SulfasalazineMethotrexate + Hydrochloroquine sulphate + Sulfasalazine

DMARDs Methotrexate (Rheumatrex, Trexall) Hydroxychloroquine (Plaquenil) Sulfasalazine (Azulfidine) Intramuscular Gold Tumor Necrosis Factor Inhibitors :• Etanercept (Enbrel), Adalimumab (Humira), Infliximab

(Remicade)

T-cell Costimulatory Blocking Agents : Abatacept (Orencia) B cell Depleting Agents : Rituximab (Rituxan) Interleukin-1 (IL-1) Receptor Antagonist Therapy : Anakinra

(Kineret)

Leflunomide (Arava)

Other Immunomodulatory and Cytotoxic agents : • Azathioprine (Imuran), Cyclophosphamide, Cyclosporine A

(Neoral, Sandimmune)

Secondary TherapySecondary Therapy Physiotherapy, Occupational therapy.Physiotherapy, Occupational therapy. Weight loss, Orthoses.Weight loss, Orthoses. Regular exercises.Regular exercises.

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