Ans. d. Anti-CCP (Ref: Harrison 19/e p2136, 18/e p2745; CMDT 09/727)Anti-CCP antibodies are the most specific blood test for the diagnosis of rheumatoid arthritis."Anti CCP antibodies are the most specific blood test for rheumatoid arthritis (specificity ~95%)."- CMDT 09/727"Anti-cyclic citrullinated peptide (anti-CCP) antibody testing is particularly useful in the diagnosis of rheumatoid arthritis,with high specificity, presence early in the disease process, and ability to identify patients who are likely to have severe disease and irreversible damage. Anti-CCP antibodies have not been found at a significant frequency in other diseases to date, and are more specific than rheumatoid factor for detecting rheumatoid arthritis."- Oxford Journal of MedicineRheumatoid ArthritisIt is a chronic systemic inflammatory disease of unknown cause characterized by persistent involvement of synovial membrane of multiple joints and variety of systemic manifestations.More common in femalesQRA is best diagnosed by Anti-CCP antibodiesQ.Pathology:Pathology is not limited to articular cartilage alone and arthritis is typically 'erosive'QThe potential of the synovia! inflammation to cause cartilage damage and bone erosions and subsequent changes in joint integrity is the hallmark of the diseaseQ.RA is most strongly associated with the Class IIQ MHC allele HLA DR4Qand related alleles.Characteristic Features:RA most often causes symmetric arthritis with characteristic involvement of certain specific joints such as the proximal interphalangeal and metacarpophalangeal jointsQ.DIP joints are typically sparedQAxial skeleton involvement is usually limited to upper cervical spineQExtra articular manifestations are seen in up to 40% of patientsQRheumatoid nodules are seen in approximately 20% of patientsQTypically the pleural fluid contains very low levels of glucoseQRA is associated with nurmocytic normochromic anemia of chronic diseaseQAnti CCP antibodies arc the most specific blood test for RA (specificity ~95%)Felty's syndrome is seen in association with RAFelty's syndrome consists of chronic rheumatoid arthritisQ, splenomegalyQ and neutropeniaQDiagnostic criteria for Rheumatoid arthritisMorning stiffness* Stiffness in and around joints lasting 1 hour before maximal improvement.* Constitutional features indicative of the inflammatory nature of disease such as morning stiffness "support the diagnosis"Arthritis* SymmetricalQ, involving same joint areas on both sides of body simultaneously* MultipleQ: It commonly involves three or more joint areas, predominantly of the joint areas in hand (peripheral)* * Typical picture of bilateral symmetrical inflammatory polyarthritis involving small and large joints in both upper and lower extremity with sparing of axial skeleton except the cervical spineQRheumatoid nodulesQ* Demonstration of subcutaneous nodules is helpful diagnostic featureSerum Rheumatoid factorQ* An IgM antibody directed against the Fc fragment of IgG is present in sera of >75% of patientsQ.RadiographicchangesQ* Juxta articular osteoporosisQ* Joint erosion with narrowing of joint spacesQ.Rheumatoid Factor and Rheumatoid Arthritis:Rheumatoid factor in RA belongs to the igM class0 (directed against Fc fragment of IgG)QIgM Rheumatoid factor is positive in about 75-80% of patients with RAPresence of RA factor is not specific for RAQPresence of Rheumatoid factor does not establish the diagnosis of RAQRheumatoid factor is only of prognostic significance because patients with high titers tend to have more severe and progressive disease with extra-articular manifestationsQ.Causes of False Positive Rheumatoid factor* SLE (Associated with a positive Coomb's test)* Sjogren syndrome* Chronic liver disease* Sarcoidosis* Interstitial pulmonary fibrosis* Infectious mononucleosis* Hepatitis B (Associated with HbsAg)* Tuberculosis* Leprosy* Syphilis (Associated with a positive VDRL)* Subacute bacterial endocarditis* Visceral Leishmaniasis* Schistosomiasis* MalariaTreatment:DMARD's include agents that appear to have the capacity to alter the course of Rheumatoid Arthritis.Methotrexate is the DMARD of choice.DMARDs (Disease Modifying Anti-Rheumatoid Drugs)1. MethotrexateQ2. Gold compoundsQ3. D-PenicillamineQ1. Anti-malarials e.g. ChloroquinesQ2. SulfasalazineQ