Cutaneous Neonatal Lupus in Patients with Skin of Color: A Retrospective Cohort Study from a National Registry

To the Editor: Neonatal lupus (NL) is associated with the transplacental passage of maternal autoantibodies to Ro/Sjögren syndrome antigen A (SS-A), La/Sjögren syndrome antigen B (SS-B), or U1 ribonucleoprotein (U1RNP).1Neiman A.R. Lee L.A. Weston W.L. Buyon J.P. Cutaneous manifestations of neonatal lupus without heart block: characteristics of mothers and children enrolled in a national registry.J Pediatr. 2000; 137: 674-680Abstract Full Text Full Text PDF PubMed Scopus (202) Google Scholar In cutaneous neonatal lupus (cNL), erythematous annular plaques classically develop on the periorbital skin and scalp a few days after direct sun exposure, although can sometimes be present at birth.1Neiman A.R. Lee L.A. Weston W.L. Buyon J.P. Cutaneous manifestations of neonatal lupus without heart block: characteristics of mothers and children enrolled in a national registry.J Pediatr. 2000; 137: 674-680Abstract Full Text Full Text PDF PubMed Scopus (202) Google Scholar While characteristically self-limited, cNL is important to diagnose as it may signify the presence of extracutaneous NL. Diagnosing cNL is also important because its presence in one child increases the risk of cardiac NL in a subsequent child approximately 6- to 10-fold.2Izmirly P.M. Llanos C. Lee L.A. Askanase A. Kim M.Y. Buyon J.P. Cutaneous manifestations of neonatal lupus and risk of subsequent congenital heart block.Arthritis Rheum. 2010; 62: 1153-1157Crossref PubMed Scopus (93) Google Scholar This risk is especially significant in patients with skin of color (SOC), as their morbidity and mortality from cardiac NL is greater compared to White patients.3Saxena A. Izmirly P.M. Bomar R.P. et al.Factors associated with long-term cardiac dysfunction in neonatal lupus.Ann Rheum Dis. 2020; 79: 217-224Crossref PubMed Scopus (6) Google Scholar Despite the cardiac implications of cNL in patients with SOC, current data on cNL in this population are limited to case reports.4Kleitsch J. Mazori D.R. Derrick K.M. Uwakwe L.N. Glick S.A. Periorbital hypopigmentation and telangiectasias: clues to diagnosing neonatal lupus in skin of color.Pediatr Dermatol. 2021; 38: 135-136Crossref PubMed Scopus (1) Google Scholar This study sought to fill this knowledge gap. The Research Registry for Neonatal Lupus, established in 1994, was used to identify patients with cNL.5Buyon J.P. Hiebert R. Copel J. et al.Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry.J Am Coll Cardiol. 1998; 31: 1658-1666Crossref PubMed Scopus (634) Google Scholar The Research Registry for Neonatal Lupus and its informed consent are approved by the NYU Grossman School of Medicine Institutional Review Board. All mothers were required to have anti-Ro/SS-A, La/SS-B, or U1RNP antibodies. Patients were excluded if cNL age of onset was unknown. Two groups were created based on maternal race/ethnicity: SOC, defined as Asian, Hispanic, Black or multiracial, and White. Categorial and continuous variables were compared between SOC and White patients using χ2, Fisher exact, and nonparametric Kruskal-Wallis tests. Of 190 patients, 42 (22.1%) had SOC: 12 (28.6%) Asian, 15 (35.7%) Hispanic, 12 (28.6%) Black, and 3 (7.1%) multiracial (Table I). Patients with SOC were more likely to have onset of cNL at birth, compared to White patients (P < .01). Asymptomatic/undifferentiated autoimmune syndrome was the most common maternal diagnosis in both patients with SOC (54.8%) and White patients (47.3%) (P = .48). Mothers with SOC were more likely to have systemic lupus erythematosus (SLE) than White mothers (P < .01).Table ICharacteristics of patients with cutaneous neonatal lupusSkin of color (n = 42)White (n = 148)P valueMother's characteristics Age in years, median (IQR)30 (26.0-33.5)30 (28.0-33.0).26 Race/ethnicityAsian12 (28.6)0Hispanic15 (35.7)0Black12 (28.6)0Multiracial3 (7.1)0White0148 (100) Diagnosis, n (%)Asymptomatic/undifferentiated autoimmune syndrome23 (54.8)70 (47.3).48Systemic lupus erythematosus (SLE)∗Diagnosis based on 1997 American College of Rheumatology criteria, 2012 Systemic Lupus International Collaborating Clinics criteria, or 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology criteria.12 (28.6)13 (8.8)<.01Sjögren syndrome (SS)4 (9.5)36 (24.3).52SLE and SS3 (7.1)27 (18.2).10Other†Juvenile rheumatoid arthritis (n = 1), Hashimoto’s thyroiditis (n = 1).0 (0)2 (1.4)1.00 Antibody status, n (%).12Anti-Ro/SS-A positive42 (100)148 (100)Anti-La/SS-B positive30 (71.4)113 (76.4) Hydroxychloroquine use during pregnancy, n (%)1 (2.4)10 (6.8).46 Systemic steroid use during pregnancy, n (%)11 (26.2)35 (23.6).84Child's characteristics Female sex, n (%)26 (61.9)87 (58.8).86 NL manifestations, n (%)Cutaneous only25 (59.5)94 (63.5).71Cutaneous and hepatic4 (9.5)11 (7.4).75Cutaneous and hematologic0 (0)3 (2.0)1.00Cutaneous, hepatic, and hematologic3 (7.1)8 (5.4).71Cutaneous and neurologic0 (0)2 (1.4)1.00Cutaneous and cardiac10 (23.8)30 (20.3).67 Onset of cNL at birth, n (%)16 (38.1)24 (16.2)<.01 Sibling with cNL, n (%)10 (23.8)50 (33.7).26 Sibling with cardiac NL, n (%)7 (16.7)34 (23.0).52P < .05 was used as the threshold for statistical significance.Bold values are statistically significant.cNL, Cutaneous neonatal lupus; NL, neonatal lupus.∗ Diagnosis based on 1997 American College of Rheumatology criteria, 2012 Systemic Lupus International Collaborating Clinics criteria, or 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology criteria.† Juvenile rheumatoid arthritis (n = 1), Hashimoto’s thyroiditis (n = 1). Open table in a new tab P < .05 was used as the threshold for statistical significance. Bold values are statistically significant. cNL, Cutaneous neonatal lupus; NL, neonatal lupus. Our finding that patients with SOC were more likely to have cNL at birth suggests that direct sun exposure may be less of a risk factor in this population. It also suggests that there should be a higher index of suspicion for cNL in newborns with SOC and periorbital/scalp rashes, especially because cNL is often misdiagnosed as birth trauma.1Neiman A.R. Lee L.A. Weston W.L. Buyon J.P. Cutaneous manifestations of neonatal lupus without heart block: characteristics of mothers and children enrolled in a national registry.J Pediatr. 2000; 137: 674-680Abstract Full Text Full Text PDF PubMed Scopus (202) Google Scholar Additionally, we found that maternal diagnosis in both SOC and White patients was asymptomatic/undifferentiated autoimmune syndrome in approximately half of cases. This suggests that clinicians should not expect a maternal history of established autoimmune disease when evaluating patients of any skin type for the possibility of cNL. In mothers with established autoimmune disease, we found that SLE was more common in SOC, consistent with the known increased prevalence of SLE in this population. Our study’s limitations include its relatively small size, retrospective nature, and lack of data on cNL morphology or outcomes and maternal comorbidities beyond rheumatologic diagnoses. Nevertheless, our study represents the largest cohort to date of patients with SOC with cNL. Based on our findings, patients with SOC with cNL are more likely to have onset of rash at birth and a maternal history of SLE. Dr Izmirly has received consulting fees from GlaxoSmithKline and Momenta/Janssen. Dr Saxena has received consulting fees from AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb, Eli Lilly, and Kezar Life Sciences. Dr Buyon has acted as a consultant to Momenta/Janssen. Author Kleitsch, Dr Mazori, Author Masson, and Dr Glick have no conflicts of interest to declare.