Guide to Laboratory Testing in Patients With Suspected Rheumatic Disease

Differentiating rheumatic disorders can be difficult. This guide will assist PCPs in selecting which tests to order and why.

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A simple paradigm can be useful during the initial evaluation of any patient with a suspected rheumatic disease. Is the patient presenting with joint swelling, or rather only with joint pain? In other words, is the problem more likely arthritis vs an arthralgia (Figure 1)?1

In general, primary care providers (PCPs) should be prepared to recognize possible rheumatic diseases and to provide a rapid referral to a rheumatologist. Importantly, the earlier therapy is initiated, the better the long-term outcome for the patient. Therefore, a timely diagnosis is central to optimal management.2 This article will review which diagnostic laboratory tests should or should not be ordered when making a diagnosis of rheumatic disorders.

A guide to the proper tests when diagnosing rheumatic diseases.

Basic Principles

The differential diagnosis of rheumatic disease may seem complex at first but can be subdivided into 3 discernible categories: inflammatory arthritis, non-inflammatory arthritis, and non-articular pain. If the swelling is associated with inflammation, inflammatory arthritis should be suspected. When there is no evidence of joint inflammation, non-inflammatory arthritis is much more likely (Figure 1).

The most common types of inflammatory arthritis affecting 1 to 2 joints include crystal-induce—either gout or pseudogout and joint infection. These are definitively diagnosed by a synovial fluid analysis. The most common inflammatory arthritis affecting multiple joints is rheumatoid arthritis (RA).3 However, there are many other forms of inflammatory polyarthritis, such as psoriatic arthritis and arthritis associated with inflammatory bowel disease, making the differential diagnosis more difficult. Most cases of non-inflammatory arthritis, whether monoarticular or polyarticular, are related to osteoarthritis (OA).

In contrast, arthralgias (non-articular pain) may be regional or generalized, but there is no obvious joint or soft-tissue inflammation. Examples of focal arthralgias include many types of tendonitis, bursitis, and muscle strain. Fibromyalgia is the most common widespread soft-tissue pain.

When to Order Lab Tests

Joint Swelling

Any time that joint swelling is found, especially if it is of recent origin, the affected joint should be aspirated. The PCP (if qualified) can perform the joint aspiration in the office. Identifying monosodium urate or calcium pyrophosphate (CPPD) crystals in the synovial fluid provides a definitive diagnosis of gout or pseudogout. Seeing bacteria on gram-stain smear or by culture is the only way to be certain of the diagnosis of bacterial arthritis.

In other joint effusions, a synovial fluid analysis will not provide an exact diagnosis but can give important clues as to the etiology of the joint swelling. Based primarily on the number of cells in the aspirate sample, joint effusions are classified as non-inflammatory, inflammatory, or highly inflammatory (purulent) (Table 1). For example, non-inflammatory joint effusions are relatively acellular, usually containing less than 1,000 cells/mm3, whereas inflammatory effusions, such as seen in RA or psoriatic arthritis, usually contain 5,000 to 20,000 cells/mm3. Septic arthritis should always be suspected if the synovial fluid cell count is greater than 50,000 cells/mm3 and mainly polymorphonuclear leukocytes (polys), although sometimes non-septic, inflammatory arthritis or crystal-induced effusions may be in that range. Bloody joint effusions are primarily related to joint trauma or bleeding disorders.

Blood testing

The only appropriate rheumatology “screening” laboratory tests are the acute phase reactants, either the erythrocyte sedimentation rate (ESR) or the C-reactive protein (CRP). These tests are almost always elevated in any inflammatory rheumatic disease. Therefore, they provide clues as to whether the patient has an inflammatory or non-inflammatory rheumatic condition. They also are helpful in tracking treatment efficacy in inflammatory diseases, such as polymyalgia rheumatica (PMR) or RA. Furthermore, these tests are simple and inexpensive. However, they are not specific and are most helpful when a patient has no physical findings suggestive of systemic inflammation, as illustrated in the following case studies.

Case Study 1

A 64-year-old man presented to the office feeling “very stiff and achy” for the past 2 weeks. He had a low-grade fever on 2 readings at home and has lost 5 pounds due to a lack of appetite over in last few weeks. He noted being especially stiff in the morning and feeling exhausted.

The patient’s physical examination was quite unremarkable: both strength testing and joint exam were normal. He was afebrile at the time of this visit.

What laboratory testing and treatment would be appropriate?

In this case, the patient presented with a characteristic history of PMR. I would recommend an initial ESR and a CRP blood test. A highly elevated ESR or CRP would help to confirm the clinical suspicion of PMR. It is possible that this patient may also be anemic and have thrombocytosis. A modest anemia and thrombocytosis would also be indicative of an inflammatory disease.

Treatment with low doses of prednisone should rapidly improve the patient’s symptoms and, within a few weeks, the ESR/CRP would be expected to return to normal.

Case Study 2

A 45-year-old female patient was referred, by her dermatologist, to be evaluated for hair loss and fatigue. She had no history of rash, joint swelling, or significant systemic symptoms.

Prior testing included a positive antinuclear antibody (ANA). She stated that she had been losing clumps of hair for 10 months. She also complained of being “tired and run-down” and often felt achy.

Her physical examination, including scalp and skin, was unremarkable, as was the joint examination.

Last updated on: September 27, 2017

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