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Rheumatoid Testing

When a connective tissue disorder is suspected there are a number of tests you'll want to have evaluated to confirm the diagnosis, and in some cases, to monitor disease activity or even for predicting flare ups. We will talk a bit about Systemic Lupus Erythematosus, Sjogren Syndrome, Scleroderma, Dermatomyositisi or Polymyositis, and Rheumatoid Arthritis.

The hallmark of a connective tissue disorder is synovitis (hip or knee pain), which may be accompanied by other features such as the Raynaud phenomenon, serositis (tissue that protects your organs becomes inflamed), nephritis (kidney inflammation), or deceased platelet or leucocyte count. Although synovitis is common to all connective tissue disorders, there are specific features and serologic test results that characterize each one.

Systemic Lupus Erythematosus

This has already been discussed a bit in a previous post, but Lupus is the prototypic autoimmune disease characterized by production of autoantibodies resulting in end-organ inflammation. The diagnosis is made on the basis of clinical features and serologic test results. Lupus, or SLE, primarily affects women and often starts in those of childbearing age. It should be suspected in those with symptoms similar to arthritis, mucositis, and either renal, hematologic, or nervous system involvement. The hallmark of Lupus is the presence of ANA, which is found in more than 95 percent of affected individuals.

A complete metabolic panel can be ordered to evaluate renal and hepatic function, along with a complete blood count with differential to screen for lymphopenia, #thrombocytopenia, and #anemia. A urinalysis with microscopy can access for hematuria, pyuria, and proteinuria. The ANA is a predominant test, so let me dive into that a bit here before I move forward with other connective conditions. I do really like to get a few other inflammatory markers though such as an erythrocyte sedimentation rate, cRP, and homocysteine in those I suspect to have an inflammatory condition, as well as vitamin B12 and vitamin D3.

Antinuclear Antibodies

These are antibodies against a nuclear component of a cell and as mentioned, most of those who suffer with Lupus have positive ANA titers and most all of those with a negative result do not have #Lupus. The most accurate test for ANA is via indirect immunofluorescence assay using human epithelial cells, which act as a substrate for the antibody, which is 93 percent sensitive and 57 percent specific. However, this is an expensive approach to testing so many laboratories are moving away from it to a less accurate test, although sensitivity remains 81.9 percent and 79.6 percent specificity (Ali, 2018).

ANA is reported using a titer, such as 1:320. Generally, the higher the titer, the more likely the individual is to have a connective tissue disease. This ratio represents how much they had to dilute the specimen before the antibodies could not be detected, so the higher the number the more significant the concentration. Once the ANA is demonstrated itself positive, there isn't a lot of benefit to repeating it as this number can fluctuate and doesn't really reflect disease activity (Ali, 2018).

A positive ANA titer can occur in other connective tissue disorders, such a Sjogren syndrome and scleroderma so this test is helpful, but can't be used to definitively diagnose Lupus. In Lupus, the ANA will often result with a homogeneous or rim pattern. Comparatively, Sjogren syndrome will demonstrate as speckled and scleroderma in a more nucleolar pattern, although in limited scleroderma it can present more with centromere staining. Best practice is to not order antibody testing until the ANA test is positive and there is evidence of rheumatic disease (Ali, 2018).

Hashimotos can present with positive ANA, which is a false-positive. Autoimmune liver disease, viral infections such as hepatitis C and human immunodeficiency virus infections, some cancers, pulmonary fibrosis, and type one diabetes can also create false-positive ANA testing. Once positive ANA results though, anti-Smith antibodies, antiribonucleoprotein antibodies, Sjogren antibodies (anti-SS-A and anti-SS-B), anticardiolipin, and lupus anticoagulant (Ali, 2018).

The anti-double-stranded DNA antibodies are a hallmark of Lupus and can be used to monitor disease progression, particularly as it impacts the kidneys. There are those though, in which this test does not correlate with their Lupus, so again, look at presentation. Testing may be helpful early in diagnosis and then with flare-ups, because antibody levels may increase in a subset of individuals with active nephritis (Ali, 2018).

Anti-Smith antibodies have the greatest specificity for Lupus and are included in the diagnostic criteria, with high specificity but interestingly low sensitivity. A positive result is diagnostic for Lupus, but a negative result does not exclude it (Ali, 2018).

Sjogren Syndrome

Lymphocytic infiltration of exocrine glands is the prominent feature of #Sjogren syndrome, primarily the salivary and tear glands. The clinical hallmark is dryness of the mouth and eyes. Serologic testing helps diagnose this condition, primarily the ANA. Sjogren is a bit more common in those who have other connective tissue conditions as well, such as Rheumatoid arthritis. When present in those who also have Lupus, the risk of cytopenias and nephritis are also increased. Anti-SS-A does cross the placenta and can cause neonatal complications, with the risk of heart block in newborns occurring in about 2 percent of little ones (Ali, 2018).

Mixed Connective Tissue Disease

This is an overlap syndrome of Lupus, myositis, and #scleroderma. Individuals classically present with the #Raynaud phenomenon, pulmonary hypertension, arthritis, and myositis. How incredibly unfair, right? If the ANA testing is positive, follow-up testing includes antiribonucleoprotein antibodies which are also present in a number of other connective tissue diseases but it is sensitive to mixed connective tissue disease at 71 percent, and specific to upwards of 84 to 100 percent (Ali, 2018).


We've seen this on various social media outlets, even talk shows, but this is a really awful disease characterized by tightening skin, but can also include interstitial lung disease, pulmonary hypertension, and diffuse organ fibrosis. Rare condition, thankfully, but this one can often be identified by antibody testing. Of course the ANA comes first, for screening, but if that returns positive, then we move to the anticentromere and anti-Scl 70 antibodies, which are present in those with limited and diffuse scleroderma. When these antibodies are present, mortality is increased, as well as the incidence of lung disease (Ali, 2018).

Dermatomyositis & Polymyositis

The inflammatory muscle diseases, dermatomyositis and polymyositis, should be suspected in those who have muscle weakness with elevated levels of muscle enzymes such as creatine kinase, myopathic changes on electromyography, and characteristic muscle pathology. ANA is positive here about 80 percent of the time. One-third have antisynthetase syndrome, a condition that includes nonerosive arthritis, fever, the Raynaud phenomenon, interstitial lung disease, and fissures on the distal fingertips (Ali, 2018).

Rheumatoid Arthritis

This one is a small-joint arthropathy affecting the hands, fingers, wrists, and feet which is more noticeable in the morning. Autoantibody testing can be helpful in establishing the diagnosis, specifically the rheumatoid factor. Testing is typically for immunoglobulin M RF. A positive RF titer in those with joint pain increases the probability of rheumatoid arthritis. The higher the titer, the more likely erosive joint disease is occurring, even extra-articular manifestations, and ultimately, poor outcomes.

A positive RF titer does not provide a definitive diagnosis of rheumatoid arthritis as the sensitivity is only 69 percent and the sensitivity 85 percent. Other causes may be viral, endocarditis, lymphomas, or cryoglobulinemia (Ali, 2018).

Granulomatosis with Polyanglitis

This one is even more rare, characterized by necrotizing vasculitis in the small and medium blood vessels. These individuals experience recurrent sinusitis, epistaxis, airway inflammation, neuropathy, and glumerulonephritis. Biopsy is the gold standard diagnosis, an antineutrophil cytoplasmic antibody testing is helpful. This really shouldn't be ran though in those who have frequent sinusitis but lack features of systemic vasculitis (Ali, 2018).


Ali, Y. (2018). Rheumatologic tests: A primer for family physicians. American Family Physicians, 98(3), 165-170.

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