Persistent Facial Redness in a Patient Treated for Rosacea

Editor's Note: In this new On the Case series, we ask a dermatologist to share how they would treat the presented case.

A 29-year-old woman with a 9-year history of rosacea and acne was referred to dermatology. Three months prior, the patient reported to the office with papules and pustules coalescing in an irregular plaque on the right cheek and diffuse background erythema with superficial telangiectasias of the central face (Figure 1). She was prescribed azithromycin 250 mg daily for 1 week then twice weekly and metronidazole gel 0.75% to the face nightly. The patient reported that she was trying to get pregnant and was told to stop oral antibiotics if she became pregnant. 

At 3 months’ follow up, the papules and pustules on the right cheek had resolved, but there was persistent redness in the plaque and a more diffuse erythema that had not improved (Figure 2). The patient reported regular use of azithromycin and topical metronidazole; however, she was now pregnant. An antinuclear antibody (ANA) test with HEp-2 substrate was positive at 1:160 with a dense, fine speckled pattern. The patient was scheduled for patch testing to evaluate for underlying components of contact dermatitis. 

 

At Wake Forest University School of Medicine in Winston-Salem, NC, Victoria E. McGuirt is a clinical research fellow in the department of dermatology and Dr Feldman is a professor of dermatology, pathology, social sciences and health policy, and molecular medicine and translational science and currently leads the Center for Dermatology Research. He is also the chief medical editor of The Dermatologist.
 

On the Case

John Robert Edminister, MD | Atrium Health Wake Forest Baptist Dermatology, Winston-Salem, NC 

In this case of an erythematous facial rash in a young pregnant woman with ANA positivity, there are a few “can’t miss” diagnoses and concerns that must be addressed: lupus, the presence of antiphospholipid antibodies, and the presence of Ro/La antibodies. The first and foremost concern is whether the patient may have acute cutaneous lupus erythematosus, which is invariably associated with systemic lupus erythematosus (SLE). 

The most striking feature of this case is the ANA indirect immunofluorescence (IIF) pattern reported by the laboratory—the nuclear, dense, fine speckled pattern, which is designated AC-2 by the International Consensus on Antinuclear Antibody Patterns. The reporting of this IIF pattern should give the clinician immediate pause because the monospecific presence of this pattern’s associated antibody (DFS70) is an extremely strong negative predictor of autoimmune connective tissue disease (AICTD) when all other specific ANAs are found to be negative (dsDNA, Smith, RNP, Ro, La).¹ For this reason, I would defer biopsy on this patient until further serologic workup is complete, knowing that false positives can occur in facial biopsies and with acute sunburn itself being known to cause vacuolar interface changes. 

After ensuring that typical ANAs are negative (dsDNA, Smith, RNP, Ro, La), I would test for the monospecific presence of DFS70 antibodies. If positive, I would reassure the patient that her laboratory findings strongly argue against a diagnosis of lupus, dermatomyositis, or any other systemic autoimmune rheumatic disease. Furthermore, this pregnant patient could be provided assurance that a study demonstrated no association with anti-DFS70 antibody positivity and adverse pregnancy outcomes, such as thrombosis or recurrent pregnancy loss.²

To be completely sure, I would assess for SLE using other elements of the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology classification criteria for SLE.³ I would check for the presence of hematologic abnormalities, such as cytopenias and hemolysis; hypocomplementemia; proteinuria; and antiphospholipid antibodies. A negative workup would provide reassurance that she has been safely placed in the category of “healthy” individuals with ANA positivity. Of note, our workup argues against SLE and provides insightful knowledge into 2 other disease processes that could harm the patient and her developing infant: the presence of Ro/La antibodies, which are correlated with intrauterine heart block, regardless of the presence of AICTD, and the presence of antiphospholipid antibodies, which also confers gestational morbidity with or without an associated AICTD. 

With the above workup complete, I would begin to address the patient’s facial concerns with a working diagnosis of erythematotelangiectatic rosacea. I would recommend she defer treatments until after pregnancy, at which time she could consider a trial of topical vasoconstrictors, with caution for rebound erythema, or procedural therapies such as laser and intense pulsed light.

Reference
1. Infantino M, Pregnolato F, Bentow C, et al. Only monospecific anti-DFS70 antibodies aid in the exclusion of antinuclear antibody associated rheumatic diseases: an Italian experience. Clin Chem Lab Med. 2019;57(11):1764-1769. doi:10.1515/cclm-2019-0454

2. Bizzaro N, Pesce G, Trevisan MT, et al. Anti-DFS70 antibodies detected by specific methods in patients with thrombosis or recurrent pregnancy loss: no evidence of an association. Sci Rep. 2020;10(1):7748. doi:10.1038/s41598-020-64550-y

3. Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019;71(9):1400-1412. doi:10.1002/art.40930