COMMENTARY

When to Order Antinuclear Antibodies in Primary Care

Matthew F. Watto, MD; Paul N. Williams, MD

Disclosures

November 14, 2023

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I'm Dr Matthew Watto, here with my great friend, Dr Paul Nelson Williams. We're going to be talking about how to wisely order autoantibodies. We talked with rheumatologist Dr Matthew Carroll at one of the big national conferences this year.

Paul, I just order antinuclear antibodies (ANAs) on everybody. I like the order set that shotguns a million labs. Why isn't that the way to go?

Paul N. Williams, MD: I love the fatigue order set, as already noted, with Lyme serology and the ANA panel in there. The ANA is a bane and a blessing of rheumatology. We often order them in primary care — it's like a Hail Mary pass to see whether it will reveal something without having to have that something in mind.

The reason we do that is because it's cheap, it's easy, it's just a blood draw. Sometimes it comes back abnormal enough that you think, Alright, I found something, but it turns out that a good proportion — approximately 13% of the population — is going to have a positive ANA without actually having a rheumatologic disease.

We've talked before about what to do with an ANA of 1:40, which is positive technically, but not that positive. That number doesn't excite Dr Carroll. It's not until you get to 1:160 or 1:320 that it really becomes noteworthy and you start to pay attention to it and put it together with the clinical picture to come up with something.

Watto: The lupus guidelines from EULAR and the American College of Rheumatology list an ANA of at least 1:80 as a requirement for positivity, but that's along with other features that make you think of lupus. Have the big societies made any statements about when we should order ANA?

Williams: Excellent "leading the witness," Dr Watto. The British, American, and Canadian rheumatology societies' Choosing Wisely guidelines all recommend that you do not order an ANA level just for fatigue or malaise unless you have suspicion for lupus or connective tissue disease. Otherwise, just don't do it. That's probably wise advice because I don't know what to do with it otherwise.

Watto: On the list of nonrheumatologic conditions that can produce a positive ANA are multiple sclerosis, autoimmune hepatitis, autoimmune thyroid disease, idiopathic pulmonary hypertension, and primary biliary cirrhosis.

The way to go is to think about the illness scripts, because five conditions can result in a positive ANA: mixed connective tissue disease (a mix of other conditions), scleroderma, lupus, idiopathic inflammatory myopathy and Sjogren syndrome. Mixed connective tissue disease can overlap with features of some of those other conditions.

With scleroderma, the patient might have digital pitting, sclerodactyly (thickened skin over their fingers), Raynaud phenomenon, interstitial lung disease, or telangiectasias. We know to look for the malar rash, but patients can also have small joint arthritis, nephritis, proteinuria, or pleurisy.

Lupus is on the differential, of course. If you are thinking of lupus, then maybe getting an ANA is appropriate. We talked about some of the myopathies in a previous video — people who have muscle weakness, heliotrope rash, mechanic's hands, and dry mouth and eyes, suggesting Sjogren syndrome. Ask patients whether they've had a lot of cavities or are constantly drinking water, even at night.

Williams: Or if they are using eye drops all the time — that could be a giveaway. Patients may not even recognize their compensatory behaviors.

Watto: Exactly. So, think about rheumatologic and nonrheumatologic conditions that could cause a positive ANA, and use the illness scripts for guidance on whether the ANA is the appropriate test.

Going back to our podcast Lupus in Primary Care with Beth Jonas, MD, I remember a great pearl we learned about lupus: If the patient has oral ulcers, they might not realize it because the ulcers associated with lupus are painless compared with aphthous ulcers, which are notoriously very painful. If you suspect lupus, look at the roof of the patient's mouth for ulcers.

Williams: If the ANA comes back positive, what specific disease is causing it? Not just "something rheumy," which had my previous practice. I'm happy to be able to hone in on the diagnosis a little bit.

Watto: I don't blame people. Dr Carroll was really nice about this; he said if you get yourself into one of these quagmires, just send the patient our way. We're happy to sort it out.

The full podcast is available here.

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