eMedicine Specialties > Rheumatology > Miscellaneous Inflammatory Arthritis

Arthritis as a Manifestation of Systemic Disease: Differential Diagnoses & Workup

Author: R Hal Scofield, MD, Professor, Department of Medicine, Section of Endocrinology, University of Oklahoma Health Sciences Center; Associate Member, Arthritis and Immunology Program, Oklahoma Medical Research Foundation
Coauthor(s): Linda A Zacharias, MD, Fellow, Department of Medicine, Section of Rheumatology, Oklahoma University Health Sciences Center
Contributor Information and Disclosures

Updated: Aug 29, 2006

Differential Diagnoses

[Reactive Arthritis and Reiter Syndrome]
Fibromyalgia
Acromegaly
Hemochromatosis
Amyloidosis, Immunoglobulin-Related
Hyperparathyroidism
Calcium Pyrophosphate Deposition Disease
Hypothyroidism
Cushing Syndrome
Osteoarthritis
Diabetes Mellitus, Type 1
Rheumatoid Arthritis
Diabetes Mellitus, Type 2
Sarcoidosis
Enteropathic Arthropathies
Systemic Lupus Erythematosus

Workup

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, gout, pseudogout, and infectious causes should be considered first.
  • Hypothyroidism is usually readily diagnosed by measuring serum thyroid-stimulating hormone (TSH) and free thyroxine.
  • Hyperparathyroidism
    • This disorder is usually suspected based on 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
    • 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 IGF-1 testing, although provocative testing sometimes is required to make a definitive diagnosis.
  • 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.
  • Hemochromatosis
    • Measuring serum iron, total iron-binding capacity, ferritin, and percent of iron saturation are considered the best screening tests (see Schmitt, 2005, for a systematic review).
  • 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. No definitive laboratory test is available for sarcoidosis.
    • 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. 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.
  • Sarcoidosis may affect the skeleton in a focal or generalized fashion, and either osteolytic or osteosclerotic involvement may be evident (see Images 2-3). Phalangeal cysts are often considered a helpful diagnostic clue when considering sarcoidosis.
  • Hypothyroidism, hyperparathyroidism, and hemochromatosis are associated with 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.

More on Arthritis as a Manifestation of Systemic Disease

Overview: Arthritis as a Manifestation of Systemic Disease
Differential Diagnoses & Workup: Arthritis as a Manifestation of Systemic Disease
Treatment & Medication: Arthritis as a Manifestation of Systemic Disease
Follow-up: Arthritis as a Manifestation of Systemic Disease
Multimedia: Arthritis as a Manifestation of Systemic Disease
References
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References

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Further Reading

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Keywords

arthralgia, joint disease, joint pain, joint ache, musculoskeletal manifestations, acute monoarthritis, pseudogout, chronic polyarthritis, polyarticular arthritis, acute sarcoid arthritis, hypothyroidism, hyperparathyroidism, Cushing disease, acromegaly, hypercholesterolemia, hyperlipidemia, hemochromatosis, sarcoidosis, calcium pyrophosphate deposition disease, CPPD, carpal tunnel syndrome, tendon xanthomas, Lofgren syndrome, diabetes mellitus, type 1 diabetes, type 2 diabetes, Dupuytren contracture, Dupuytren's, flexor tenosynovitis, adhesive capsulitis, Charcot joint

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Contributor Information and Disclosures

Author

R Hal Scofield, MD, Professor, Department of Medicine, Section of Endocrinology, University of Oklahoma Health Sciences Center; Associate Member, Arthritis and Immunology Program, Oklahoma Medical Research Foundation
R Hal Scofield, MD is a member of the following medical societies: American Association of Immunologists, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American College of Rheumatology, American Diabetes Association, American Federation for Medical Research, Endocrine Society, and Oklahoma State Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Linda A Zacharias, MD, Fellow, Department of Medicine, Section of Rheumatology, Oklahoma University Health Sciences Center
Linda A Zacharias, MD is a member of the following medical societies: American College of Physicians and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Kristine M Lohr, MD, MS, Program Director, Professor, Department of Internal Medicine, Division of Rheumatology and Women's Health, University of Kentucky School of Medicine
Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians, American College of Rheumatology, and American Medical Women's Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Lawrence H Brent, MD, Associate Professor of Medicine, Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center
Lawrence H Brent, MD is a member of the following medical societies: American Association of Immunologists, American College of Physicians, and American College of Rheumatology
Disclosure: Genentech Honoraria Speaking and teaching; Genentch Honoraria Consulting; Genentech Grant/research funds Other; Abbott Immunology Honoraria Speaking and teaching; Amgen Honoraria Speaking and teaching; Wyeth Honoraria Speaking and teaching

CME Editor

Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Arthur Weinstein, MD, Professor of Medicine, Georgetown University Medical Center; Associate Chairman, Department of Medicine, Director, Section of Rheumatology, Washington Hospital Center
Disclosure: Nothing to disclose.

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