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Rheumatoid arthritis (ref. Hari. 18th ed., pg-2738)

RA is a chronic autoimmune multisystem disease having inflammatory arthritis and systemic manifestation.


Pathogenesis –

  1. Women (30 to 50 years) are more commonly affected
  2. HLA-DR 4 Q is a risk factor for RA.
  3. Initial site of disease is synovial membrane

Initiation phase – It is due to non – specific inflammation


Amplification phase – Due to T cell activation


Chronic inflammatory phase – Due to cytokines IL – 1, TNF- alpha (AIPG 2009) and IL – 6


Diagnostic criteria (Ref. Hari. 18th ed., Pg 2089)– Four of seven criteria are requiredQ

  1. Morning stiffness – lasting 1 hour before maximal improvement
  2. Arthritis of 3 or more joint areas – 14 possible joint areas are right or left PIP MCP, wrist, elbow, knee, ankle and MTP joints
  3. Arthritis of hand joints.
  4. Symmetrical arthritis.
  5. Rheumatoid nodules.Q
  6. Positive Serum rheumatoid factorQ
  7. Radiographic changes – including erosions or unequivocal bong decalcification localized in or most marked adjacent to the involved joint.

Note: There is change in diagnostic criteria of RA in 18th Edition of Harrison



Classification Criteria for Rheumatoid Arthritis





Joint involvement

1 large joint (shoulder, elbow, hip, knee, ankle)



2–10 large joints



1–3 small joints (MCP, PIP, Thumb IP, MTP, wrists)



4–10 small joints



>10 joints (at least 1 small joint)



Negative RF and negative ACPA



Low-positive RF or low-positive anti-CCP



antibodies (3 times ULN)



High-positive RF or high-positive anti-CCP



antibodies (>3 times ULN)


Acute-phase reactants

Normal CRP and normal ESR



Abnormal CRP or abnormal ESR


Duration of symptoms

<6 weeks



≥ 6 weeks



Note: application of the newly revised criteria yields a score of 0-10, with a score of ≥ 6 fulfilling the requirements for definite RA. (Ref. Hari. 18th ed., page 2745)



  1. These criteria are aimed at classification of newly presenting patients who have at least 1 joint with definite clinical synovitis that is not better explained by another disease.
  2. Application of the newly revised criteria yields a score of 0–10, with a score of ≥ 6 fulfilling the requirements for definite RA.

Important Points: DIP involvement occurs in OA & Psoriasis

In RA, Articular manifestations (Erosive arthritis) –

  1. Pain aggravated by movement is the most common manifestation
    1. Joint swelling, tenderness and limitation of motion
    2. The DIP joints rarely involved. Q
    3. Baker’s cyst – caused by extension of inflamed synovium into the popliteal space.
    4. Axial involvement is limited to atlantoaxial joint Q (cervical spine)
    5. Characteristic deformities of hand include –
  2. Z deformity – Radial deviation of wrist with ulnar deviation of the digits, Ulnar deviation of fingers is Pathognomic (AIIMS May 2007)
  3. Swan – neck deformity – Extension contracture of PIP joints with compensatory flexion of DIP joints
  4. Boutonniere deformity – flexion of PIP joints with extension of DIP joints.
  5. Eversion at hindfoot (subtalar joint), plantar subluxation of metatarsal heads, widening of forefoot, hallux valgus, and lateral deviation and dorsal subluxation of toes; hammer toe.
  6. Wind - sweep deformities of toes i.e. valgus deformities of toes in one foot and varus in other, (as wind sweeps all the structure in one direction).
  7. A hammer toe (LQ 2012) or contracted toe is a deformity of the proximal interphalangeal joint of the second, third, or fourth toe causing it to be permanently bent, resembling a hammer. Mallet toe is a similar condition affecting the distal interphalangeal joint.
  8. Claw toe is another similar condition, with dorsiflexion of the proximal phalanx on the lesser metatarsophalangeal joint, combined with flexion of both the proximal and distal interphalangeal joints. Claw toe can affect the second, third, fourth, or fifth toes.

Radial deviation of wrist & ulnar deviation of finger is the most pathognomic feature. (AIIMS May 07)

Extra Edge of RA: Back ache is not a symptom.

Extra articular manifestations –

  1. Rheumatoid nodules – occur in 20 – 30% cases.
  2. Rheumatoid vasculitis – Vasculitis can cause polyneuropathy, mononeuritis multiplex, digital gangrene, myocardial infarction.
  3. Pleuropulmonary manifestations –
    It include – Pleuritis, pleural effusion (More common on left side, low pleural fluid sugar), interstitial fibrosis, pleuropulmonary nodules, pneumonitis and arteritis.
    Caplan’s syndrome – Pneumoconiosis + RA + lung nodules.
    Pericarditis – Usually asymptomatic. Chronic constrictive pericarditis may also occur.

Differential diagnosis of multiple pulmonary nodules

  1. Caplan's syndrome
  2. Wegener's granulomatosis
  3. Silicosis

Recent Advances – (Ref. Hari. 18th ed., page 2742)

  1. Mitral regurgitation is the most common valvular abnormality in RA
  2. CVS is the most common cause of death in RA followed by infection.
  1. Neurological symptoms –
    1. Peripheral neuropathy – due to vasculitis.
    2. Cord compression – due to atlanto axial subluxation
    3. Nerve entrapment – due to proliferative, synovitis (Carpal tunnel syndrome due to median nerve compression, tarsaltunnel syndrome due to Posterior tibial nerve compression).
  2. Eye –
    1. Episcleritis
    2. Scleritis
    3. Conjunctivitis
    4. Scleromalacia (Rupture of the Globe) can occurs
      (Important Points: Uveitis is not a feature)
  3. Felty’s syndrome = RA + splenomegaly + neutropenia
Extra Edge: Cause of leukopenia in RA is (Ref. Hari. 18th ed., Page 2740)
  1. Drug induce – most common
  2. Felty’s syndrome
  3. T-LGL
  1. Skin: vasculitis, in some cases skin may be involved extensively causing skin necrosis. This is known as malignant rheumatoid arthritis.
  2. Sjögren syndrome. RA is the most common cause of secondary Sjögren syndrome.
  3. Blood: There is anemia of chronic disease. Anaemia in RA is normocytic normo chromic
  4. Fever.

Important Points: Renal involvement as such is not an important feature of RA.


It may be involved by drug therapy (Gold & penicillamine) or amyloidosis.


Complications of RA

  1. Amyloidosis: It can present as nephrotic syndrome.
  2. Septic arthritis (Usually by staph aureus)

Laboratory findings


RA factor (IgM) is positive in 75% patients of RA though it is found in 5% of healthy persons.


Other conditions in which RA factor is positive are – (AIPG 2009)


Rheumatoid factor: (It is of diagnostic & prognostic significance but it is not a test for screening)

  1. It is an autoantibody It is an antibody against the Fc portion of IgG. (LQ)
  2. RF and IgG join to form immune complexes which contribute to the disease process.
  3. It can play a role in both diagnosis and disease prognosis. (LQ)
  4. It is part of the usual disease criteria of rheumatoid arthritis.
  5. Patients on treatment, a decline in the level of rheumatoid factor is associated with reduced clinical disease activity. (LQ 2012)

Other conditions where RA factor may be positive:

  1. 5% of the normal population,
  2. SLE,
  3. Sjogren’s syndrome,
  4. Interstitial pulmonary fibrosis,
  5. Hepatitis B,
  6. Leprosy,
  7. Bacterial endocarditis,
  8. After vaccination/transfusion in normal individuals,
  9. Chronic liver disease,
  10. Sarcoidosis,
  11. Infectious mononucleosis,
  12. Tuberculosis,
  13. Syphilis,
  14. Visceral leishmaniasis,
  15. Malaria
Extra Edge:

1RA factor is a diagnostic criteria and also a prognostic criteria but it is not used as a screening criteria.
2. RA factor is positive in hepatitis B (HBsAg) syphilis (VDRL), SLE (Positive Coombs’ test)


Anti CCP antibody are seen.

  1. Anemia – Normocytic normochromic anemia and is due to ineffective erythropoiesis
  2. ESR – It is increased in all patients with active RA.
  3. C – reactive protein and ceruloplasmin are increased
  4. Synovial fluid analysis –
    1. Turbid
    2. Decreased viscosity Q,
    3. Increase protein content
    4. Decrease glucose concentration
    5. WBC count is 5000 – 50000 per ml

Recent Advances: As per new criteria of diagnosis RA, anti CCP has been included as one of the criteria for diagnosing RA) (H-18th Pg- 2745)




Stages of X-ray progression in Rheumatoid Arthritis

  1. Periarticular osteoporosis
  2. Loss of articular cartilage (‘joint space’)
  3. Erosions
  4. Subluxation and ankylosis

Important Points: Juxta articular osteopenia occur within weeks of onset.

Marker of active disease

  1. Anaemia of chronic disease
  2. ESR
  3. CRP
  4. Platelet count
  5. Synovial fluid viscosity

Important Points: (Ref. Hari. 18th ed., Pg- 2746)

  1. The WBC count is usually normal, but a mild leukocytosis may be present.
  2. Leukopenia may also exist without the full-blown picture of Felty's syndrome.
  3. Eosinophilia, when present, usually reflects severe systemic disease.


Drugs used:-



  1. To control the symptoms and signs of local inflammatory process.
  2. These drugs have minimal effect on the progression of the disease.
  3. Usually Acetaminophen is not used in the treatment of RA because it does not have anti-inflammatory property.
  4. But if a patient of RA also has associated hemophilia then Acetaminophen is the analgesic of choice.

Disease modifying antirheumatic drugs -

  1. These drugs alter the course of RA.
  2. These drugs have minimal effect on the inflammation, So are not useful as analgesics.
  3. These drugs should be used early in the course of the disease as they slow the progression of disease.

Disease modifying antirheumatic drugs:

  1. Methotrexate,
  2. D- penicillamine,
  3. Sulfasalazine
  4. Gold
  5. Hydroxychloroquine.

The most commonly used DMARD is Methotrexate.

Side effects:


Penicillamine / Gold = Nephrotic syndrome, pancytopenia


(OH) chloroquine = Retinopathy


Methotrexate = Liver dysfunction


Sulphasalazine = Skin rash

  1. Glucocorticoid therapy
    Indications of Glucocorticoid therapy
    1. Pleural effusion
    2. Pericarditis
    3. Eye involvement.
    4. Mononeuritis multiplex (AIPG 97)

Recent Advances:

  1. Biologicals (Ref. Hari. 18th ed., page 2749)
    1. Anti TNF alpha drugs are:
      1. Infliximab
      2. Golimumab
      3. Adalimumab
      4. Certolizumab
      5. Etanercept

Side effects - (Ref. Hari. 18th ed., Pg- 2777) (AIIMS Nov 2009)

  1. Serious infections, including disseminated tuberculosis;
  2. pancytopenia;
  3. demyelinating disorders;
  4. exacerbation of congestive heart failure;
  5. systemic lupus erythematosus–
  6. hypersensitivity
  7. severe liver disease.

No increased incidence of malignancy has been observed in patients treated for over 5 years.

  1. IL-1 Receptor antagonist = ANAKINRA Q (It is a new drug)
  2. Rituximab (anti CD20 antibody) (AIIMS May 2008)
    1. It is a monoclonal antibody.
    2. It works by attaching to (B cells) and killing them.
    3. It is an anti-CD20 antibody.
  3. That also has clinical activity CLL, NHL (relapsed or refractory low-grade or follicular B cell non-Hodgkin's lyphoma.) and Ca colon.
  4. Abatacept: It is a fusion protein. (it is a new drug).
  1. Gene therapy - Genes which intercept the pathway of inflammatory cascade reaction are used.
  2. Surgery - Synovectomy, tenosynovectomy, arthroplasty and total joint replacements.
  3. Immunosuppressive therapy - The immunosuppressive drugs used are –
    1. Azathioprine,
    2. Leflunomide (It is a new drug),
    3. Cyclosporine
    4. Cyclophosphamide.

Extra Eddge: (Ref. Hari. 18th ed., Pg-2749)

  1. Tocilizumab
  2. Adalimumab
  3. Golimumab
  4. Etanercept

Anti-TNF agents should be avoided in patients with active infection or a history of hypersensitivity to these agents.

A major concern is the increased risk for infection, especially opportunistic fungal infection and reactivation of latent tuberculosis.

Tocilizumab is a humanized monoclonal antibody directed against the membrane and soluble forms of the IL-6 receptor. IL-6 is a proinflammatory cytokine implicated in the pathogenesis of RA, with detrimental effects on both joint inflammation and damage.


Important Points: - Recent Advances:

  1. Trastuzumab
    A humanized monoclonal anti-HER-2/neu antibody.
    It is a monoclonal antibody that acts as an antagonist of the HER2/neu receptor tyrosine kinase is effective in therapy of human breast cancers associated with overexpression of this growth factor receptor.
  2. Ibritumomab tiuxetan
    A anti-CD20 murine monoclonal antibody labeled with either Yttrium-90 or Indium-111.
    Approved for use in patients with relapsed or refractory low-grade, follicular, or B cell non-Hodgkin's lymphoma (NHL), including patients with rituximab-refractory follicular NHL.

Recent Advances


New Drugs

  1. Etodolac: is a chiral NSAID, for the treatment of rheumatoid arthritis.
  2. Licofelone: Dual inhibitors that block both cyclooxygenase (COX) and lipoxygenase (LOX) metabolic pathways of arachidonic acid. It has analgesic, anti-inflammatory, and antiasthmatic effects at doses that cause no GI side effects.
  3. Flupirtine:
    It is a selective neuronal potassium channel opener that also has NMDA receptor antagonist properties. Flupirtine is a non-opioid, non-NSAID, non-steroidal, analgesic
    All these are new drug not give in Harrison’s 18th Edition also.
  4. Tramadol a centrally acting analgesic inhibits serotonin reuptake and inhibits norepinephrine reuptake, enhancing inhibitory effects on pain transmission in the spinal cord.

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