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Rheumatoid Arthritis

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Definition

Immune-complex disease that manifests as a chronic polyarticular arthritis.

Clinical Features

Immune-complex disease
Manifests as chronic polyarticular arthritis
Usually women during second and third decades of life1
Joints involved:
- nearly always:
  - feet
  - hands
- frequently:
  - elbows
  - knees
  - wrists
  - ankles
  - hips
  - spine
  - temporomandibular articulations
Osteoporosis:
- occurs early
- may result in spontaneous fractures of long bones, particularly:
  - femoral neck
  - pelvis2
Two most common extra-articular manifestations:3,4
- rheumatoid nodules:
  - also in:
    - synovial membrane 5
  - not specific
May be polyneuritis
Amyloidosis:
- significant complication:
- most common disorder associated with amyloid deposition in US

Pathogenesis

Lysosomes and interleukins mediate inflammatory reaction6–8
Basic fibroblastic growth factor may play role in synovial hyperplasia and joint destruction 9
Granulation tissue of subchondral area and pannus within joint attack cartilage10
Etiology unknown:
- viral participation long suspected11
HLA linkage and autoantibody production in most patients support autoimmune element12

Gross Pathology

Prominent pannus:
- forms over articular cartilage (Fig. 1
  Fig. 1: Advanced rheumatoid arthritis involving femur. There is prominent proliferation of synovium and almost complete destruction of overlying articular cartilage.
  )
- cartilage and bone formation within
May be fibrous ankylosis and bony ankylosis
Increased articular pressure may lead to:
- bursting of joint capsule and acute joint rupture13
- bone cysts (rheumatoid geodes)14
- herniation of capsule into soft tissues15
Bone cysts:
- radiographically similar to those of degenerative joint disease
- contain granulation tissue (instead of fluid or myxoid material in degenerative joint disease)

Histopathology

Earliest morphologic changes in synovial membrane:
- hyperemia (first change)
- proliferation of synovial lining cells
- infiltration by plasma cells and lymphocytes16 (Fig. 2
  Fig. 2: Synovial hyperplasia and heavy lymphoplasmacytic infiltrate in rheumatoid arthritis.
  )
- often:
  - lymphoid follicles17
  - fibrin deposits close to synovial lining or within stroma
- small synovial blood vessels lined by plump endothelial cells
In second phase granulation tissue grows into subchondral bone marrow
Rheumatoid nodules:
- necrotic center:
  - impregnated with fibrin
  - surrounded by predominantly histiocytic inflammatory reaction often arranged in palisading fashion (Fig. 3
    Fig. 3: Rheumatoid nodule with early cystic change of the ‘necrobiotic’ center. Note the peripheral palisading of histiocytes.
    )
- Nonnecrotizing arteritis in 10% of cases18
- Necrotizing arteritis also described19,20

Two Additional Nonspecific Microscopic Features

Synovial giant cells:
- no correlation with serologic titer 21,22
- also seen in tuberculosis, traumatic arthritis, and villonodular synovitis 22
Bone and cartilage fragments within actual synovial membrane:23
- tend to occur in advanced disease
- appear to arise as result of erosive destructive process of articular surface
- can be distinguished by their position and clear demarcation from metaplastic cartilage and bone that sometimes arises from synovial cells
- also seen in synovial membranes of:
  - osteoarthritis
  - osteochondritis dissecans
  - chondromalacia patellae
  - particularly neuropathic joints23,24

Diagnosis

Microscopic changes correlate:
- not too closely with clinical findings 25

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Rheumatoid Arthritis

Rheumatoid nodules:
- morphologically indistinguishable nodules occur in:
  - rheumatic fever
  - systemic lupus erythematosus
  - children in absence of apparent disease:26,27
    - rheumatoid factor may develop years later 28
also need to be distinguished from suture granulomas from previous surgical procedures29

References

1 Sokoloff L. Pathology of rheumatoid arthritis and allied disorders. McCarty DJ editors. Arthritis and applied conditions. ed. 9. Philadelphia: Lea & Febiger; 1979.

2 Taylor RT, Huskisson EC, Whitehouse GH, Hart FD. Spontaneous fractures of pelvis in rheumatoid arthritis. Br Med J. 1971;4:663–664.

3 Hart FD. Rheumatoid arthritis. Extra-articular manifestations. Br Med J. 1969;3:131–136.

4 Hart FD. Rheumatoid arthritis. Extra-articular manifestations. Part II. Br Med J. 1970;2:747–752.

5 Roberts WC, Kehol JA, Carpenter DF, Golden A. Cardiac valvular lesions in rheumatoid arthritis. Arch Intern Med. 1968;122:141–146.

6 Baumann H, Kushner I. Production of interleukin-6 by synovial fibroblasts in rheumatoid arthritis. Am J Pathology. 1998;152:641–644.

7 Harris ED. Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med. 1990;322:1277–1289.

8 Zvaifer NJ. Rheumatoid arthritis. The multiple pathways to chronic synovitis (editorial). Lab Invest. 1995;73:307–310.

9 Qu Z, Huang X-N, Almadi P, Andresevic J, Planck SR, Hart CE, et al. Expression of basic fibroblast growth factor in synovial tissue from patients with rheumatoid arthritis and degenerative joint disease. Lab Invest. 1995;73:339–346.

10 Cooper NS. Pathology of rheumatoid arthritis. Med Clin North Am. 1968;52:607–621.

11 Ziegler B, Gay RE, Huang GQ, Fassbender HG, Gay S. Immunohistochemical localization of HTLV-I p19- and p24-related antigens in synovial joints of patients with rheumatoid arthritis. Am J Pathol. 1989;135:1–5.

12 Winchester R. The molecular basis of susceptibility to rheumatoid arthritis. Adv Immunol. 1994;56:389–466.

13 Dixon AStJ, Grant C. Acute synovial rupture in rheumatoid arthritis. Clinical and experimental observations. Lancet. 1964;1:742–745.

14 Palmer DG. Synovial cysts in rheumatoid disease. Ann Intern Med. 1969;70:61–68.

15 Jayson MI, Dixon AS, Kates A, Pinder I, Coomes EN. Popliteal and calf cysts in rheumatoid arthritis. Treatment by anterior synovectomy. Ann Rheum Dis. 1972;31:9–15.

16 Koizumi F, Matsuno H, Wakaki K, Ishii Y, Kurashige Y, Nasamura H. Synovitis in rheumatoid arthritis: scoring of characteristic histopathological features. Pathol Int. 1999;49:298–304.

17 Imai Y, Sato T, Yamakava M, Kasajima T, Suda A, Watanabe Y. A morphological and immunohistochemical study of lymphoid germinal centers in synovial and lymph node tissues from rheumatoid arthritis patients with special reference to complement components and their receptors. Acta Pathol Jpn. 1989;39:127–134.

18 Sokoloff L, Wilen SL, Bunim JJ. Arthritis of striated muscle in rheumatoid arthritis. Am J Pathol. 1951;27:157–173.

19 Mongan ES, Cass FM, Jacox RF, Vaughan JH. A study of the relation of seronegative and seropositive rheumatoid arthritis to each other and to necrotizing vasculitis. Am J Med. 1969;47:23–25.

20 Schmid FR, Cooper NS, Ziff M, McEwen C. Arteritis in rheumatoid arthritis. Am J Med. 1961;30:56–83.

21 Grimley PM, Sokoloff L. Synovial giant cells in rheumatoid arthritis. Am J Pathol. 1966;49:931–954.

22 Bhan AK, Roy S. Synovial giant cells in rheumatoid arthritis and other joint diseases. Ann Rheum Dis. 1971;30:294–298.

23 Muirden KD. Giant cells, cartilage and bone fragments within rheumatoid synovial membrane. Clinicopathological correlations. Aust Ann Med. 1970;2:105–110.

24 Horwitz T. Bone and cartilage debris in the synovial membrane. Its significance in the early diagnosis of neuro-arthropathy. J Bone Joint Surg (Am). 1948;30:579–588.

25 Matsuno H, Yodoh K, Nakazawa F, Koizumi F. Relationship between histological findings and clinical findings in rheumatoid arthritis. Pathol Int. 2002;52:527–533.

26 Beatty EC. Rheumatic-like nodules occurring in nonrheumatic children. Arch Pathol. 1959;68:154–159.

27 Hahn BH, Yardley JH, Stevens MB. “Rheumatoid” nodules in systemic lupus erythematosus. Ann Intern Med. 1970;72:49–58.

28 Berardinelli JL, Hyman CJ, Campbell EE, Fireman P. Presence of rheumatoid factor in ten children with isolated rheumatoid-like nodules. J Pediatr. 1972;81:751–757.

29 Marcus VA, Roy I, Sullivan JD, Sutton JR. Necrobiotic palisading suture granulomas involving bone and joint: report of two cases. Am J Surg Pathol. 1997;21:563–565.

Last updated: 6 Mar 2006