What is a rheumatoid factor (RF)?
Rheumatoid factors are antibodies directed against the Fc region of IgG.
What percentage of patients with rheumatoid arthritis have a positive RF?
Only about 60% of patients with rheumatoid arthritis test positive for RF. The presence of a RF provides information about prognosis and disease severity, but not disease activity. Those with high titre RF are at greater risk for a severe disease course and for extra-articular manifestations.
List 4 other diseases that are associated with a positive RF.
Other conditions associated with a positive RF include:
- Sjogren’s syndrome
- mixed connective tissue disease
- systemic lupus erythematosus
- liver disease
- lung fibrosis
- older age.
Often when a patient has a positive ANA (anti-nuclear antibody) an ENA (extractable nuclear antibody) panel is also requested. Certain profiles of these antibodies are associated with particular patterns of disease.
What tests are included in an ENA panel, and with what diseases do they correspond?
The ENA panel commonly includes antibodies to Smith antigen (Sm), SS-A (Ro), SS-B (La), topoisomerase I (Scl-70), ribonuclear protein (RNP), tRNA-synthetase (Jo-1), and centromere.
Anti-Sm antibodies are very specific for SLE, but only occur in 25-30% of patients. Anti-Ro and anti-La antibodies are associated with Sjogren’s syndrome (seen in 70% and 60% of patients, respectively), SLE (30% and 15%), subacute cutaneous lupus and neonatoal lupus.
Anti-Scl-70 antibody is associated with diffuse scleroderma.
Anti-centromere antibody is associated with limited scleroderma (CREST).
Anti-RNP antibody is associated with mixed connective tissue disease.
Anti-Jo-1 antibodies are associated with dermatomyositis.
A 50 year old male presents with a 3 month history of fatigue and progressive weakness, predominantly affecting the proximal muscles of the arms and legs. There are associated myalgias and arthralgias. He has lost 8kg in the past 2 months. He is having difficulty rising from a seated position or raising his arms to wash his hair. He has noticed difficulty with swallowing, and frequently coughs when drinking liquids. Blood work demonstrates an elevated CK of 1374.
You are concerned that the patient has an inflammatory myopathy, but what other conditions should be considered in the differential of an elevated CK?
There are six general categories to consider in the differential for an elevated CK.
- Toxin or drug-induced myopathies
Some of the agents that cause this include statins, colchicine, antimalarials, AZT and alcohol.
- Neuromuscular disorders
Includes muscular dystrophies, myasthenia gravis, Eaton-Lambert and ALS.
- Metabolic and endocrine disorders
Hypothyroidism is a fairly common source of an elevated CK. Others include hyperthyroidism, acromegaly, Cushing’s disease, Addison’s disease, glycogen storage diseases, disorders of lipid metabolism, and other inherited metabolic abnormalities.
- Infectious myopathies
These can be local or generalized in association with a variety of organisms.
- Rheumatic diseases
In addition to inflammatory myopathies like polymyositis and dermatomyositis, a number of other rheumatologic conditions can include myopathy leading to CK elevations. These include lupus, mixed connective tissue disease, vasculitis and inclusion body myositis.
Muscle injury and rhabdomyolysis can occur as a result of trauma, drugs, seizures, and metabolic disorders.
On some occasions rises in CK are simply incidental. Patients of African descent often have CK values that are above the reference ranges we use. CK values rise following exercise and IM injections. Some rises in CK are idiopathic and do not lead to muscle weakness or other dysfunction.
A 62 year old man present to clinic with a two day history of a painful swollen, warm left knee. You perform a diagnostic arthrocentesis and remove 20cc of cloudy fluid. The WBC count from the aspirate is 42,000/mm3.
What 3 characteristics of the synovial fluid will help you assess whether it is inflammatory at the bedside?
Examining the clarity, colour and viscosity of the joint aspirate can give you clues regarding the degree of inflammation present in the joint.
Normal synovial fluid is clear enough that one can see the markings on the syringe through it distinctly, while inflammatory fluid may be hazy or opaque. Normal fluid is also straw-colored and viscous. This means that if a small amount of fluid is ejected from the syringe, it should form a long strand rather than falling in discrete drops. The strand that forms should be at least 10 cm in length. This is also called the “string sign.”
What is your differential diagnosis for a WBC count of 42,000/mm3?
The cell count in normal joint fluid is >200/mm3. Joint fluid is considered clearly inflammatory if the white count is over 2000/mm3. Above values of 80,000/mm3, the fluid is very suggestive of infection. However, it is important to note that infection can also be present in joints with cell counts well under 80,000/mm3, particularly in cases of partial treatment or immunosuppression.
The differential diagnosis for a WBC count of 42,000/mm3 would include infection as well as crystal arthritis, reactive arthritis or a chronic inflammatory arthritis such as psoriatic arthritis or rheumatoid arthritis.
How does allopurinol work? Name 3 indications for its use.
Allopurinol inhibits the enzyme xanthine oxidase, which is responsible for the conversion of the purine metabolites hypoxanthine and xanthine into uric acid. With the use of allopurinol, uric acid concentration falls and the concentrations of these precursors rise. This also provides a negative feedback signal that decreases purine production.
- Recurrent gouty attacks (more than 3 in the span of 1 year)
- Gouty tophi
- Renal insufficiency with hyperuricemia
Other indications include recurrent nephrolithiasis with hyperuricemia, and prophylaxis for tumour lysis syndrome.
*Note that allopurinol is generally a life-long therapy and that both its initiation and discontinuation can exacerbate gout or cause a flare. It should not be started or stopped during an acute flare of gout.