Rheumatoid Arthritis

Epidemiology and Etiology:

o Etiology unknown

§ Autoimmune likely (unknown autoantigen)

· CD4+ T cells role

· B cells role

· TNF and IL-1 important roles

§ Genetically susceptible individuals

· Well-defined familial predisposition

· Most loci have not been identified

· Class II HLA locus is one known

o F:M = 2-3:1

o 40-70y most common

§ Any age possible

Common sites:

o Joints

§ MCP

§ PIP

§ MTP

§ IP

§ Wrists

§ Ankles

§ Elbows

§ Knees

o Skin (Rheumatoid nodules in 25%)

§ Regions subjected to pressure

· Ulnar aspect of forearm

· Elbows

· Occiput

· lumbosacral

o Blood vessels

§ Aorta

§ Medium to small arteries similar to PAN

· Kidneys not involved (unlike PAN)

o Heart

o Lungs

o Muscles

o spleen

Gross features:

o symmetric typically

o joints:

§ initial:

· edematous, thickened synovium

· hyperplastic synovium with delicate and bulbous fronds

o rheumatoid nodule (skin, others):

§ firm

§ round to oval

§ subcutaneous in skin

o splenomegaly (Felty syndrome, with neutropenia)

o

Histologic features:

o joints:

§ joint destruction is main attribute

§ hypertrophy and hyperplasia of the synovium (papillary / polypoid)

§ infiltration of synovial stroma by dense perivascular inflammatory cells with lymphoid follicles

· B cells and CD4+ cells, plasma cells, and macrophages

§ Increased vascularity

§ Superficial hemosiderin deposits

§ Acute fibrinous surface exudate maybe

· Organizing fibrin aggregates covering portions of the synovium and floating in the joint space (rice bodies)

· Neutrophils in the synovial fluid and along the synovial surface

o Usually not deep in the stroma

§ Bone and cartilage fragments in the synovium maybe

§ Osteoclastic activity in underlying bone

§ Pannus formation

· Synovium and stroma with inflammatory cells, granulation tissue, and fibroblasts which grows over the articular cartilage and destroys it

· Bridges the apposing bones over time (fibrous ankylosis)

· Eventually ossifies (bony ankylosis)

§ Inflammation of the tendons, ligaments frequently

§ Inflammation of adjacent skeletal muscle occasionally

§ Synovial giant cells maybe

o Skin (rheumatoid nodules):

§ Subcutaneous

§ Central zone of fibrinoid necrosis

§ Prominent rim of epithelioid histiocytes (pallisading)

§ Numerous lymphocytes and plasma cells

o Vasculitis

o Lungs (pleuropulmonary)

§ Fibrosis

§ serositis

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

·

Other features:

o Rheumatoid nodules are firm, non-tender

o Bakers cysts may arise secondarily

o Rheumatoid factor

§ IgM antibody reactive to Fc portions of patients own IgG

§ Not sensitive or specific

o Most have progressive disease for life

o Vasculitis may be life threatening

o Histologic DDx:

§ SLE

§ Psoriasis

§ Other arthritides

References:

· Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004.

· Washington Manual of Surgical Pathology, 2^nd ed (2012)