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Effect of in utero hydroxychloroquine exposure on the development of cutaneous neonatal lupus erythematosus
  1. Julie Barsalou1,
  2. Nathalie Costedoat-Chalumeau2,
  3. Adey Berhanu3,
  4. Cesar Fors-Nieves4,
  5. Ummara Shah5,
  6. Patrick Brown6,
  7. Carl A Laskin7,
  8. Nathalie Morel2,
  9. Kateri Levesque2,
  10. Jill P Buyon4,
  11. Earl D Silverman1,
  12. Peter M Izmirly4
  1. 1 Division of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada
  2. 2 Department of Internal Medicine, Cochin Hospital, Centre de Référence Maladies Auto-Immunes et Systémiques Rares, AP-HP, Université Paris Descartes-Sorbonne Paris Cité, Paris, France
  3. 3 Arthritis & Rheumatism Associates, PS Wheaton, Maryland, USA
  4. 4 Division of Rheumatology, New York University School of Medicine, New York City, New York, USA
  5. 5 Division of Allergy, Immunology and Rheumatology, University of Rochester, School of Medicine and Dentistry, Rochester, USA
  6. 6 Department of Statistical Science, University of Toronto, Centre for Global Health Research, St Michael's Hospital, Toronto, Ontario, Canada
  7. 7 Department of Medicine, Obstetrics and Gynaecology, University of Toronto, TRIO Fertility, Toronto, Ontario, Canada
  1. Correspondence to Dr Julie Barsalou, Division of Rheumatology and Immunology, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada; juliebarsalou{at}


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.

  • systemic lupus erythematosus
  • Sjøgren's syndrome
  • treatment

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  • Handling editor Josef S Smolen

  • Contributors Study conception and design: JB, NC-C, JPB, EDS, PMI. Acquisition of data: JB, NC-C, AB, CF-N, US, CAL, NM, KL, JPB, EDS, PMI. Analysis and interpretation of data: JB, NC-C, PB, JPB, EDS, PMI. All authors were involved in drafting the article and/or revising it critically for important intellectual content, and all authors approved the final version. JB and PMI had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding Funding for RRNL was provided by National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS) contract N01-AR-4-2220-11-0-1 and grant 5R37AR042455, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) grants R01HD079951-01A1 and R03 HD069986, and a Lupus Foundation of America LFA Lifeline Program grant to JPB.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval The study was approved by the Hospital for Sick Children Ethics Boards (REB1000037488), RRNL IRB (protocol no. 7820), French RNL IRB Pitié-Salpetrière.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement There are no unpublished data provided in the manuscript.