Antinuclear Antibodies

Antinuclear antibodies (ANAs) are autoantibodies against parts of the cell's nucleus. Combined with clinical features, ANA testing can help diagnose certain collagen vascular

Table 1S-7 Causes of Elevated Amylase and Lipase Levels

Amylase

Lipase

Pancreatic Diseases

Acute pancreatitis Chronic pancreatitis Pancreatic pseudocyst Pancreatic cancer Pancreatic trauma

Acute pancreatitis Chronic pancreatitis

Nonpancreatic Diseases

Salivary gland disorders

Intestinal perforation, ischemia, or obstruction

Diabetic ketoacidosis

Perforated peptic ulcer

Ruptured ectopic pregnancy

Renal failure

Macroamylasemia

Pregnancy

Acute cholecystitis Intestinal infarction Perforated peptic ulcer Renal failure

disorders (Table 15-8). The likelihood that an ANA test will help with diagnosis depends on the pretest probability of disease. ANA tests are reported as negative (no staining) or positive at the highest cutoff of dilution of the serum that shows immunofluorescent nuclear staining. If positive, the description of the pattern is noted. When the ANA test is positive, testing for specific nuclear antigens should be guided by the clinical findings.

Although the ANA is 95% sensitive for systemic lupus erythematosus (SLE), it is not specific and is seen in other diseases. Higher titers are more specific for SLE but may be seen in the other autoimmune diseases. About 20% of normal people have an ANA titer of 1:40 or higher, and 5% have a titer of 1:160 or higher. Less than 5% of patients with definite SLE have a negative ANA titer. Because of the high prevalence of positive ANAs in normal people, physicians need to reserve the diagnosis of SLE for patients who have clinical findings compatible with SLE. ANA titers correlate poorly with relapses, remission, and severity of disease and are not helpful in monitoring the course or response to therapy. ANA testing should be ordered when a connective tissue disease is considered, but it is not generally helpful in the evaluation of nonspecific complaints, such as fatigue or back pain (Solomon et al., 2002).

For patients with a positive ANA titer, further testing for specific nuclear antibodies can be obtained, guided by the pattern of ANA staining and the clinical findings. The interpretation of testing for specific nuclear antigens can also be difficult; most of the "specific" antigens are not 100% specific for a particular disease and need to be interpreted in the clinical context. The anti-DNA test is highly specific for SLE, with about 95% specificity but only 50% to 60% sensitivity, and it can be used as a confirmatory test in patients with a positive ANA. Similarly, the anti-Sm (Smith) test is also highly specific for SLE, but with 30% sensitivity. Anti-SSA/Ro and anti-SSS/La are often used to diagnose Sjogren's syndrome but can also be found in SLE. Anti Scl-70 is found in scleroderma but is not a requirement for diagnosis.

Table 15-8 Conditions Associated with Positive Antinuclear Antibody (ANA) Test

ANA very useful for diagnosis

Systemic lupus erythematosus Systemic sclerosis

ANA somewhat useful for diagnosis

Sjögren's syndrome

Polymyositis-dermatomyositis

ANA very useful for monitoring or prognosis

Drug-associated lupus Mixed connective tissue disease Autoimmune hepatitis

ANA not useful or has no proven value for diagnosis, monitoring, or prognosis

Rheumatoid arthritis

Multiple sclerosis

Thyroid disease

Infectious diseases

Idiopathic thrombocytopenia purpura Fibromyalgia

From Solomon DH, Kavanaugh AJ, Schur PH, et al. Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing. Arthritis Rheum 2002;47:434-444.

Osteoarthritis

Osteoarthritis

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