The laboratory

		The laboratory
		The laboratory is mistaken as the most important component by many - including doctors and patients. As a rheumatologist, I often hear that "the bloods were normal, therefore it cannot be..." This is the greatest mistake, as often blood tests are negative, or even falsely positive for certain rheumatic diseases, and therefore may mislead the practitioner from making the correct diagnosis. The clinical examination remains the most important part of the assessment of rheumatic disease
		What are the most important tests ?
		1. Tests to search for the presence of inflammation
		This includes the erythrocyte sedimentation rate - ESR, the plasma viscosity and the C-Reactive protein - CRP. These are usually quite sensitive in detecting inflammation, but may occasionally be normal despite disease. They are non-specific, i.e. they do not differentiate between the many different kinds of inflammation. Once noted to be elevated for a disease process, the levels may be monitored to assess response to therapy. The ESR increases as we get older, and therefore normal ranges vary with age. The red cells in blood have a negative charge that repels them from each other. However if there is an increase in inflammatory proteins, the repellant forces are altered and the cells line up and are able to settle within a 2.5mm wide, 200mm long, column, with gravity, quicker in a specified amount of time - 1 hour by convention. A rough calculation of age divided by 2 for men and age plus 10 divided by 2 for women, approximates the upper normal ESR. The CRP is usually undetectable in normal, but assessed as abnormal if greater than 10 units. The substance is made in the liver as a response to immune chemicals produced in the inflammatory cascade. It rises rapidly as a direct measure of inflammation. I personally find it extremely useful and superior to the ESR.
		2. The full blood count
		The hemoglobin -Hb, a the measure of the amount of red blood cell concentration. Reduction of this constitutes anemia. Anemia occurs in chronic inflammation, such as rheumatoid arthritis, as a consequence of the bodies inability to utilise iron in the production of new cells. It also occurs with loss of blood, either acutely or over time. This can occur as a consequence of damage to the stomach lining by anti-inflammatory drugs. It may also occur in marrow suppression by either disease, or from the drugs used to combat disease, in particular the immune suppressing drugs. The white cell count / leukocyte count - WBC - is a measure of the bodies defensive cells against inflammation, and include the immune cells, the lymphocytes and the Neutrophils and eosinophils, which are associated also with allergy and certain parasitic infections. The WBC is elevated in inflammation, and in particular in infections, although again, is non specific. However, a differential count can be useful in splitting up the white cells into different fractions allowing better interpretation of the disease process. A low white cell count can be seen in cases of marrow suppression, as well as some rheumatic conditions where there is enlargement of the spleen, such as a condition called Felty syndrome seen in rheumatoid arthritis. The platelets are involved in clotting and may be reduced in bone marrow suppression, and spleen enlargement. Also some immune conditions may destroy the platelets, such as lupus. A low platelet count may result in bleeding. A high platelet count may be seen in inflammation, and is frequently noted in patients with active rheumatoid arthritis.
		3. Antibody tests in the rheumatic diseases
		Antinuclear antibodies are produced in some diseases and may be used to assist in diagnosis by sub-typing such antibodies and detecting their presence in an individual. The antibodies either form as a consequence of the disease or possibly cause the disease themselves. Serum from the patient is placed across a thin layer of cells either rat liver or more recently a HEp 2 cell line (a line of human epithelioma cells). Any antibodies present to the tissue, binds and can be detected by a fluorescence. A serial dilution of the fluorescent amount gives a indication of the amount of antibody present. Antinuclear factor - antinuclear antibody ANF / ANA are raised most typically in autoimmune disease They are not diagnostic, and frequently occur in low titer in normal. A titer of over 1 in 80 is usually more likely to be significant. The tests MUST be interpreted in the clinical context - i.e. constellation of symptoms and clinical and laboratory findings. Some examples: Lupus - Elevated ANA, Sm auto- antibody, double stranded anti-DNA. Drug induced lupus may be associated with anti histone antibody. Scleroderma - Elevated ANA nucleolar type in diffuse Scleroderma, anti-centromere in peripheral type, and anti SCL-70 in diffuse with lung involvement. Sjogren syndrome - Elevated ANA speckled, anti Ro and anti La antibody. Rheumatoid factor may be positive Mixed connective tissue disease - Elevated RNP ribonuclear protein, ANA speckled pattern, and may see positive rheumatoid factor. Poly / dermatomyositis - May see elevation of ANA of many subtypes, and anti Jo-1 in severe and lung and joint involvement
		4. Rheumatoid factor
		Rheumatoid factor is positive in only 85% of clinical rheumatoid arthritis patients, and diagnosis may be made in absence of the rheumatoid factor. It detects an (IgM) antibody, directed against a (the Fc) portion of human immunoglobulin, (IgG). In addition it may be seen as a false positive in a number of conditions, including other autoimmune disease, such as lupus, Sjogrens, myositis, as well as chronic inflammatory liver disease and chronic infections such as tuberculosis, syphilis and some parasite infections. Low titers may be seen with the simple ageing process in normal individuals. It has therefore got to be interpreted in the clinical context and NOT in isolation.
		5. Other useful and frequently requested blood tests
		Kidney function - the blood urea nitrogen and serum creatinine. Liver function - including, AST, ALT, GGT, Alkaline Phosphatase. - to monitor liver in drug therapy - especially methotrexate. Bone enzymes - the alkaline phosphatase - Alk-Phos, elevated in Pagets disease of bone and in destructive bone diseases, including fracture. Thyroid function tests - the TSH, T3 and T4. Thyroid under-function is a frequent cause of malaise and aching joint and muscle pain. Muscle enzymes - Creatinine phosphokinase CPK, aldolase and LDH lactate dehydrogenase, may be elevated in muscle inflammation - such as myositis. Cholesterol testing - high cholesterol may cause aching in the joints and soft tissues.

		My recommendation to do a screen on a patient presenting with pain and a suspicion for inflammatory arthritis, but little else to find, is to do the FBC, ESR, CRP and rheumatoid factor. An ANF and Anti- double stranded DNA is added if there is a suspicion for an immune disease such as lupus. Remember - blood tests can be completely normal despite disease and vice versa. They must be interpreted in the clinical context