Practical Serology Pearls for Dermatologists
At the 2026 Masterclasses in Dermatology Annual Meeting, Joseph F. Merola, MD, MMSc, FAAD, FACR, delivered a practical, evidence-based roadmap for navigating autoimmune serologies in dermatology. His goal was not to order more labs, but to order smarter ones.
Dr Merola opened by emphasizing that antinuclear antibody (ANA) interpretation is “all about clinical context.” ANA positivity varies dramatically depending on serum dilution and age. At a 1:40 dilution, more than 30% of healthy individuals may test positive, whereas 1:160 likely offers the optimal balance of sensitivity and specificity in most laboratories.
For patients with cutaneous lupus erythematosus (CLE), initial evaluation should include complete blood cell count (for cytopenias), creatinine, liver function tests, urinalysis (for nephritis screening), and ANA by indirect immunofluorescence on HEp-2 cells—the American College of Rheumatology-recommended gold standard. Second-line testing may include dsDNA, SSA/SSB, RNP, Smith antibodies, complement levels (C3/C4), and antiphospholipid antibodies depending on clinical suspicion.
Importantly, a positive ANA does not need to be repeated routinely. Complement levels and dsDNA may track with disease activity, and urinalysis abnormalities should prompt quantification with a spot urine protein-to-creatinine ratio.
Dr Merola also addressed the concept of “ANA-negative lupus,” noting that it is rare but may occur in patients with SSA/Ro antibodies. When suspicion is high, particularly in subacute CLE, photosensitivity, Sjögren syndrome, or pregnancy, separate Ro/SSA testing by enzyme-linked immunosorbent assay should be considered.
He reviewed the updated American College of Rheumatology and European Alliance of Associations for Rheumatology classification criteria for systemic lupus erythematosus (SLE), which require ANA ≥1:80 as an entry criterion plus ≥10 additional points from weighted clinical and immunologic domains.
Advanced testing, including complement-bound assays (such as erythrocyte-bound C4d and B-cell-bound C4d), may help in diagnostic uncertainty. In 1 cohort, 65% of AVISE-positive patients without prior SLE developed SLE vs 10.3% of non-positive patients (P < .0001). Dr Merola clarified that AVISE adds value in borderline ANA with evolving CLE, but not in clear systemic lupus or pure cutaneous disease.
Antiphospholipid antibody panels should include lupus anticoagulant, anticardiolipin (IgG/IgM), and anti–β2-glycoprotein-1 (IgG/IgM); “not beta2-microglobulin.”
Hydroxychloroquine blood level monitoring also plays a role in adherence and toxicity risk. Levels <100 ng/mL are highly suggestive of nonadherence, whereas ~300–700 ng/mL represents the therapeutic range.
Dr Merola closed with a reminder that drug-induced lupus is drug-specific in both clinical and laboratory profiles. For dermatologists managing connective tissue disease, thoughtful serologic testing—guided by phenotype, not reflex panels—remains essential to delivering precise, person-centered care.
For more meeting coverage, visit the Masterclasses in Dermatology newsroom.
Reference
Merola J. Serologies and autoimmune testing for the dermatologist. Presented at: Masterclasses in Dermatology; February 19–22, 2026; Sarasota, FL.
