Rheumatoid arthritis and Essential Thrombocytosis
Morning Report 8/7/2007 Jennifer O’Brien
Epidemiology
affects 0.5-1.0% of population Females > males Peak age 45-65 Smoking risk factor Genetic
RA
70% of patients with RA express HLA-DR4 twins indicate a concordance of about 15%–20%
•Osteoarthritis: wearing away of the cartilage •Rheumatoid arthritis: the synovial membrane that protects and lubricates joints becomes inflamed, causing pain and swelling. Joint erosion may follow.
Mechanism
Cytokines in the pathogenesis of rheumatoid arthritis Iain B. McInnes & Georg Schett Nature Reviews Immunology 7, 429-442 (June 2007)
Diagnosis
1987 Traditional Diagnostic Criteria of the American College of Rheumatology for the Diagnosis of RA
Morning stiffness of >1 hour most mornings Arthritis and soft-tissue swelling > 3 or 14 joints Arthritis of hand joints Symmetric arthritis Subcutaneous nodules in specific places Increased Rheumatoid factor Radiological changes suggestive of joint erosion
Note.—Criteria 1–4 must have been present for at least 6 weeks. Four or more criteria have to be met.
Joints affected
Differential Diagnosis
Sclerodema Lupus Fibromyalgia Gout Polymyalgia rheumatica Sarcoidosis Seronegative spondyloarthropathies (Psoriasis, Celiac Sprue, Reiter’s) Viral arthritis
Radiography
University of Iowa's Virtual Hospital
Tests
citrullinated peptide antibody (Anti-CCP) sensitivity: 56%, specificity 90% RF- IgM Sensitivity: 73%, specificity 82% RF IgM and anti CCP: sensitivity 48% and specificity 96% CRP and ESR elevated
Anti-cyclic
Treatment
Disease modifying antirheumatic drugs (DMARDs)
Anti-inflammatory agents and analgesics
Methotrexate Hydroxychloroqine Sulfasalazine Azithroprine Cyclosporine A D-penicillamine Gold salts Leflunomide Minocycline
Glucocorticoids NSAIDS
Treatments
Biological agents include:
tumor necrosis factor alpha (TNF-alpha) blockers –
Etanercept (Enbrel) Infliximab (Remicade) Adalimumab (Humira)
interleukin-1 blockers
Anakinra- anakinra anti-B cell (CD20) antibody Rituximab (Rituxan)
Abatacept (Orencia)
blockers of T cell activation
Thrombocytosis
Increase platelet counts can be due to a number of disease processes Essential (primary)
Essential thrombocytosis Other myeloprolifertive disorders such as CML, polycythemia vera, myelofibrosis
Reactive (secondary)
Inflammation Surgery (which leads to an inflammatory state Hyposplenism Hemorrhage/iron deficiency Bleeding and Thrombocytosis
Bleeding and thrombosis
Essential Thrombocytosis
Smear
Bone marrow biopsy
Diagnosis for ET
Consistently elecated plt count >600,000 Megakayocytic hyperplasion on bone marrow biospy Absence of Philadelphia chromsome, bcr/abl negative Absence of reactive thrombocytosis Absence of Myelodysplastic disorder Normal iron stores, ferritin, MCV
Jak-2
kinase-triggers generation of hematopoietic cells Highly specific for the diagnosis of ET Absent in reactive thrombocytosis Present in 50% of pt with ET
Tyrosine
When to treat? Risk factors
High
risk to develop complications
Age >60 A previous history of thrombosis
Risk
for Leukemic transformation
Low hgb Plts >1,000,000 Increased age
Treatment
High dose ASA contraindicated Hydroxyurea and low dose ASA
reduces risk of thrombosis Goal platelets range 100,000-400,000 Better then Anagrelide at preventing thrombosis and transformation into myelofibrosis Oral imidazoquinazoline Inhibits platelet aggregation
Anagrelide