Autoimmune Serologies in Dermatology
Clinical Summary
Cutaneous/Systemic Lupus: Autoimmune Serologies—Pitfalls, Interpretation, and Referral
-
ANA interpretation pitfalls: Negative ANA → very unlikely SLE; low-titer positives (e.g., 1:40 in ~30% healthy individuals) require clinical context. High titers increase specificity; isolated positive ANA with normal labs in asymptomatic patients may warrant reassurance/monitoring, not overdiagnosis.
-
Testing strategy & monitoring: Avoid broad panels; use targeted labs. dsDNA and complement levels track disease activity; urinalysis screens for nephritis. Do not repeat ANA titers for monitoring.
-
Clinical context & referral: Base testing on pretest probability (history, ROS, exam). Dermatologists manage cutaneous lupus and screening; co-manage with rheumatology when systemic features or end-organ involvement are present.
Reviewed by Riya Gandhi, MA, Associate Editor of Immunology Group
Dr Joseph Merola breaks down how dermatologists can accurately interpret autoimmune serologies, with a focus on ANA testing, clinical context, and avoiding unnecessary labs. Learn which tests matter for screening versus monitoring in lupus, how to apply pre-test probability in practice, and when collaboration with rheumatology is essential for optimal patient care.
Transcript
Hi, I'm Dr Joseph Merola. I'm a dermatologist and rheumatologist and professor and chair of dermatology at UT Southwestern Medical Center in Dallas, Texas, where I'm also in the Department of Rheumatology and the Public Health School.
What are the most common pitfalls dermatologists encounter when ordering or interpreting autoimmune serologies?
Dr Merola: So we had a really nice session looking at interpretation of autoimmune serologies, what to order, how to monitor disease, and a little bit pearls and pitfalls. I'd say to begin with that one dreaded stop for the dermatologist is the ANA for many reasons. And we help to unpack a little bit that it's an important screening test. In fact, one take home pearl is a patient who has a negative ANA is very unlikely to have systemic lupus. And I think that's important both to reassure patients, reassure us, and to help us triage where we're headed with a given patient maybe who has skin lupus, for example. So we talked about that scenario.
We also unpacked a little bit that the ANA is all about clinical context. So first of all, the serum dilution is key as we know up to 30% of individuals who are otherwise healthy in a randomly selected group would have a positive ANA at one to 40, for example. Whereas as we go up in those dilution titers, it becomes more and more specific. We also covered a little bit about clinical context again, that the ANA is only as good as what we're seeing in the patient clinically, as well as the serologies that help support and other tests that help support it. So for example, a positive ANA with an otherwise negative serology panel, extractable nuclear antigen panel, normal blood counts, et cetera, et cetera. And a patient that feels well is something perhaps to be monitored or just to reassure around. Whereas again, we contextualize that lab test around a patient who has systemic features of disease or perhaps some other lab testing that would suggest active disease.
We then went on to talk about which labs are important for initial screening versus which we monitor over time. And just to remind you that we don't need to order a huge panel, an expensive panel every time a patient comes back with lupus, but instead there are some targeted labs that we look at for lupus monitoring over time. Just to mention a few double-stranded DNA and complements, we know to track with disease activity over time, those are useful over time. A urinalysis is a very cost effective screening test for nephritis and simple tests like that really go a long way. We don't have to repeat, and it's not valuable to repeat ANA titers over time, for example, or a lot of other lab testing.
And lastly, we covered a little bit, some newer opportunities, complement split products, and some newer testing that may help us to offer better prognostic information to our patients and help drive screening and monitoring in a more personalized manner for our patients with cutaneous and systemic lupus.
How can clinicians better incorporate pre-test probability and clinical context to avoid overtesting or misinterpretation?
Dr Merola: So when we think about how best to utilize many of the tests and serologic tests in our armamentarium, it's really important to think about pretest probability. Is the patient in front of us? I'm sorry to say the art of medicine is not yet gone because we really have to talk to our patients. We have to get a basic history. We have to get a review of systems because the tests are only as good as their clinical context. That's especially true with, for example, antinuclear antibody testing. As we covered in our serology section, many of the antibodies that we will talk about similarly may be present once in disease, but in terms of disease activity, don't track with disease activity. And so it's all about asking the patient questions, do they have active arthritis? What's their level of fatigue? Do they have, et cetera, et cetera, et cetera.
And so I think it's incredibly important for us to understand which serologies to test in which scenario, which track with disease activity, which don't. And then again, back to the art of medicine, history and review of systems and physical exam are not dead, which is good news, I think, for those of us who enjoy clinical care. And it helps us really contextualize these other data points that we're getting from lab testing.
When should dermatologists manage serologic findings independently, and when is collaboration with rheumatology essential?
Dr Merola: So one question that comes up not infrequently is when do I have to collaborate with the rheumatologist around, in particular, my skin lupus patient? And we've published a nice algorithm to this end that really, if we have a patient who has skin lupus, some portion of those patients ... So first of all, everyone should be screened. We should be asking everyone about their medical history, making sure that we've done a reasonable review of systems to make sure that we're not missing other manifestations of disease. For those patients who feel otherwise well, there's some basic serologic testing that would be ideal as part of that screening process. And thereafter, we have the question of when to co-manage. And for patients who have in particular chronic cutaneous lupus, discoid variant, for example, that may be limited to an area, feel otherwise well, have even potentially negative serologies, those are our patients.
I mean, those are patients that don't necessarily even need a rheumatologist and really live with us in dermatology. For those who have some systemic features, even some positive lab testing, but no real end-organ disease, no systemically active disease, I think it's up to the dermatologist to be at their comfort level to say, "I'm managing their skin. I'm going to continue to screen them. And if I need help, I will call my friendly local rheumatologist and co-manage others who would like to co-manage at that point." That's very reasonable, but we still have to own treatment of the skin and the screening and monitoring. And then I would say once patients have full-blown systemic lupus, especially with an end organ manifestation, those are the patients we can agree safely need to be co-managed with a specialist, with a rheumatologist and/or someone who specializes in that end organ, for example, a nephrologist in the case of lupus, nephritis, but we're not off the hook as dermatologists and we really, particularly as we have a pipeline of drugs coming to this disease state, we have to be the ones that are diagnosing and confirming diagnosis of skin lupus. We have to be the one counseling our patients about what that means for going on potentially to systemic disease. We should be doing some basic screening and monitoring and then deciding at what point we want to co-manage.


