Arthritis as a Manifestation of Systemic Disease Workup

Updated: Jan 23, 2020
  • Author: Ritu Khurana, MD; Chief Editor: Herbert S Diamond, MD  more...
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Laboratory Studies

A detailed review of the diagnostic workup of each of the illnesses discussed is beyond the scope of this article. The reader is referred to other articles in this journal that specifically deal with these diseases. See Hypothyroidism; Hyperparathyroidism; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Cushing Syndrome; Acromegaly; Hypercholesterolemia, Familial; Hemochromatosis; and Sarcoidosis

Several laboratory studies may be useful in patients presenting with arthritis. These tests include erythrocyte sedimentation rate (ESR), antinuclear antibodies (ANA), rheumatoid factor (RF), uric acid level, and an antistreptolysin O (ASO) titer. However, in patients with arthritis as a manifestation of one of the illnesses considered herein, the findings from these tests are generally negative or normal. Thus, if no rheumatic disease cause can be determined, the syndrome of arthritis as a manifestation of a systemic illness should be entertained. In patients with monoarticular arthritis, initial diagnostic considerations are gout, pseudogout, and infectious causes.

Hypothyroidism is usually readily diagnosed by measuring serum thyroid-stimulating hormone (TSH) and free thyroxine.

Hyperparathyroidism is usually suspected because of an elevated serum calcium level, but this value can be within the reference range. In most cases, simultaneous measurement of serum calcium and PTH is sufficient to obtain a diagnosis. Serum PTH must be measured by a proper assay, such as an intact molecule immunoradiometric assay. Serum calcium levels must be interpreted in light of the serum albumin level. An ionized calcium test can be useful in patients with low serum albumin or in patients with borderline-high total serum calcium.

Diabetes is diagnosed with fasting blood sugars. Cholesterol levels, hemoglobin A1c, and urine studies are important lab tests in the evaluation of diabetes.

Cushing disease diagnostic considerations include the following:

  • The screening tests are either an overnight 1-mg dexamethasone suppression test or a 24-hour urine test for cortisol. Single timed or random levels of cortisol and ACTH are not helpful.

  • Cushing disease is suggested if the serum cortisol is not below 5 mg/dL on the overnight 1-mg dexamethasone suppression test.

  • False-positive results on the overnight test and false-negative results on the urinary cortisol test may be observed. In a study from Italy, approximately 10% of patients with surgically proven Cushing syndrome had urinary cortisol values within the reference range.

Acromegaly screening tests include serum growth hormone testing or serum insulinlike growth factor–1 (IGF-1) testing, although provocative testing sometimes is required to make a definitive diagnosis.

For hyperlipidemia, total serum cholesterol without regard to eating restrictions can be used as a screening test. Fractionated cholesterol values should be measured on a specimen obtained after an overnight fast.

For hemochromatosis, serum transferrin saturation and ferriitin assays are the recommended initial screening tests; patients with transferrin saturation of 45% or higher, elevated ferritin, or both should undergo HFE genotyping; full guidelines on diagnosis have been published by the American Association for the Study of Liver Diseases [12]

No definitive laboratory test is available for sarcoidosis. Leukopenia (WBC count < 4000 cells/µL), mild eosinophilia (>5%), elevated ESR, hyperglobulinemia, an elevated level of angiotensin-converting enzyme, and mild hypercalcemia all are possible laboratory abnormalities. Synovial fluid WBC count ranges from 250-6200 cells/µL with 56-100% mononuclear cells.


Imaging Studies

Plain radiographs of the hands and feet or of the affected joints may be obtained. Findings consistent with rheumatoid arthritis, such as erosions, may eliminate the need to search for nonrheumatic illnesses.

Hypothyroidism has no characteristic radiographic features.

Hyperparathyroidism may lead to the discovery of abnormalities of osteitis fibrosa cystica that are striking, but these are rarely seen today. Other features include subperiosteal resorption in the hands, wrists, and feet and resorption in the sacroiliac joints, symphysis pubis, diskovertebral junctions, and peripheral joints. Chondrocalcinosis may also be seen.

Diabetes may lead to changes in the spine. Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by flowing ossification along the anterior aspect of the vertebral column, most prominent in the thoracic spine. Though present in only a few patients, Charcot joint is illustrated radiographically by sclerosis, osteophytosis, bony fractures, subluxation, and dislocation.

Cushing disease may present with osteopenia (or osteoporosis) as determined by bone mineral density measurement or with vertebral compression fractures.

Acromegaly has several characteristic radiographic features. These include increased thickening of the heel pad and widening of the articular space, which is best seen at the knee.

Hyperlipidemia has no characteristic radiographic features.

Hemochromatosis commonly manifests with cystic lesions on the metacarpal heads. Squared-off bone ends and hooklike osteophytes in the MCP joints, particularly in the second and third MCP joints, are characteristic findings. Chondrocalcinosis may also be visualized. Although conventional radiography is the gold standard method for the detection of structural changes in hemochromatosis, magnetic resonance imaging (MRI) has been applied in a few case series and small studies with mixed results. In a series of three patients with HH with pain and swelling of the ankles, for example, MRI identified advanced degenerative changes without notable inflammation. In another MRI study of patients with haemosiderosis (caused by regular blood transfusions due to beta-thalassemia), synovial inflammation of wrists was reported in 23% of cases. [10]  

Sarcoidosis may affect the skeleton in a focal or generalized fashion, and either osteolytic or osteosclerotic involvement may be evident (see images below). Phalangeal cysts are often considered a helpful diagnostic clue when considering sarcoidosis.

Focal osteolytic changes seen in the phalanges in Focal osteolytic changes seen in the phalanges in a patient with chronic sarcoid arthritis.

Chest radiography should be performed to rule out lung carcinomas.

Hypothyroidism, hyperparathyroidism, and hemochromatosis are associated with calcium pyrophosphate deposition (CPPD), which may be seen radiographically as chondrocalcinosis.


Histologic Findings

Sarcoidosis may have a synovial histology that is often less inflammatory in nature than rheumatoid arthritis, but, occasionally, noncaseating granulomas are observed.