RHEUMATOID ARTHRITIS (RA)

Introduction RA is a chronic, systemic inflammatory disorder of unknown etiology characterized by the manner in which it involved joints. Progressive joint destruction and deformity leads to variable degrees of incapacitation. F:M=2-3: years old

Etiology Genetic factors HLA-DR4 Infection

Etiology Rheumatoid factors (RF) are antibodies with specificity for antigenic determinates on the Fc portion of human or animal IgG. Currently, the most popular notion that RF arise as antibodies to “altered”autologous IgG.

Ab Ab HLA pathogen

Pathology Synovitis edema, cell proliferation Rheumatoid pannus, a vascular granulation tissue composed of proliferation fibroblasts, numerous small blood vessels, and various numbers of inflammatory cells. Vasculitis a widespread necrotizing arteritis of small and medium sized arteries

Pathology Rheumatoid nodules Characteristic histologic changes in nodules showing granulomatous foci with central zones of cell necrosis, surrounded by a palisade of proliferated mononuclear and peripheral fibrosis and chronic inflammatory cell infitration.

Clinical features The onset of RA is frequently heralded by prodromal symptoms such as fatigue, anorexia, weight loss, weakness and generalized aching and stiffness. *Joint disease * Extraarticular manifestations

Clinical features Joint disease The small joints of the hands, the wrists, knees, and feet are most commonly involved. It usually is bilateral, symmetrical, and polyarticular.

Clinical features Joint disease * Morning stiffness * Swelling * Typical hand deformities * Limited joint motion

Clinical features Extraarticular manifestations * Rheumatoid nodules * Vasculitis * Pleuropulmonary manifestations * Cardiac manifestations * Neuropathy * Sjogren’s syndrome *Sicca features: Xerostomia & Xerophthalmia

Xerostomia (Dry Mouth) Xerophthalmia (Dry Eyes)

Rheumatoid Vasculitis RA Deformities

Laboratory Tests for RA

Laboratory findings Anemia of moderate degree ESR  a useful parameter for assessing response to therapy C-reactive protein  RF (usually IgM) CIC , complements  ANA Anti-CCP (cyclic citrullinated peptide)

Rheumatoid Factor  Antibodies to Fc portion of IgG  75-80% of Patients have during course of disease  Useful for prognosis

Rheumatoid Factor IgG Molecule Fc Portion Antigen Binding Groove Autoantibodies (IgM) directed against the Fc Fragment of IgG An Antibody to an Antibody Their Role in RA is not understood

Rheumatoid Factor RFs are human auto-Abs that react with the Fc portion of normal polyclonal IgG. Most routine clinical assays for RF detect only IgM RFs, although RFs can be any class of immunoglobulin Named thus because their first description was in patients with rheumatoid arthritis

Rheumatoid Factor RF test is approximately 65%-75% sensitive for the diagnosis The presence of RF, even in high titers or large amounts, is not specific for RA

Condition Assoc. With(+) Tests for RF Rheumatologic Diseases Rheumatoid arthritis (~70%) Sjögren’s syndrome (~90%) Lupus (~20%) Cryoglobulinemia syndrome (90%) Lung Diseases Interstitial fibrosis Silicosis Infections Hepatitis C virus Acute viral infections Endocarditis Tuberculosis Miscellaneous Sarcoidosis Malignancies Aging

Laboratory findings Synovial fluid Radiology Bony decalcification localized to or most marked adjacent to the involved joints and not just degenerative changes Rheumatoid nodules