Effect of in utero hydroxychloroquine exposure on the development of cutaneous neonatal lupus erythematosus

Abstract

Objective: Cutaneous neonatal lupus (cNL) occurs in possibly 5%-16% of anti-Ro±anti-La antibody-exposed infants. Data suggest in utero exposure to hydroxychloroquine (HCQ) may prevent cardiac NL. The aim was to assess whether in utero exposure to HCQ decreases the risk of cNL and/or delays onset.

Methods: A multicentre case-control study was performed with 122 cNL cases and 434 controls born to women with a rheumatological disease who had documentation of maternal anti-Ro±anti-La antibodies at pregnancy and confirmation of medication use and the child's outcome. A secondary analysis was performed on 262 cNL cases, irrespective of maternal diagnosis, to determine if HCQ delayed time to cNL onset.

Results: Twenty (16%) cNL cases were exposed to HCQ compared with 146 (34%) controls (OR 0.4 (95% CI 0.2 to 0.6); p<0.01). Exposure to HCQ was associated with a reduced risk of cNL; exposure to anti-La antibody and female gender were associated with an increased risk of cNL. Exposure to HCQ remained significantly associated with a reduced cNL risk in the analyses limited to mothers with systemic lupus erythematosus and those who developed rash ≤1 month. When analysing all 262 cNL cases, HCQ-exposed infants were older (6.0 (95% CI 5.7 to 6.3) weeks) at cNL onset versus HCQ-non-exposed infants (4.4 (95% CI 3.9 to 5.0) weeks), but the difference was not statistically significant (p=0.21).

Conclusion: Exposure to HCQ was associated with a reduced risk of cNL. Among cNL cases, those exposed to HCQ tend to have later onset of rash. Both findings suggest a protective effect of HCQ on cNL.

Keywords: Sjøgren's syndrome; systemic lupus erythematosus; treatment.

Figure 1. Diagram of included and excluded patients

A total of 737 infants were screened. Forty-one infants were excluded for missing key variables. A total of 696 infants were eligible: 262 cNL cases and 434 controls. Among the 262 cNL cases, 122 were born to women with a SARD diagnosed before pregnancy and were therefore included into the primary analysis, with 434 controls. The first subgroup analysis included only infants born to women with SLE (cNL cases=85; controls=300). The second subgroup analysis was restricted to cNL cases with onset of rash in the first 4 weeks after birth (cNL cases=48; controls=434). The secondary analysis included 262 cNL cases, regardless of maternal diagnosis: 122 infants born to women with a SARD diagnosed before pregnancy, 10 infants born to women with a SARD diagnosed during pregnancy, 6 infants born to women with autoimmune diseases other than SARD and 124 infants born to women who were asymptomatic or had an undifferentiated autoimmune syndrome (UAS).

Figure 2. Kaplan-Meier analysis of time of onset of cNL in HCQ exposed vs. non-exposed infants

Kaplan-Meier analysis of the 262 cNL infants for time to onset of cutaneous involvement in HCQ exposed (represented by the green line) vs. HCQ non-exposed (represented by the blue line) infants. Although HCQ exposed infants were older (6.0 [95%CI 5.7-6.3] weeks) at cNL onset than HCQ non-exposed infants (4.4 [95%CI 3.9-5.0] weeks), the difference was not statistically significant (p=0.21).