Hydroxychloroquine may protect against cutaneous neonatal lupus
In utero exposure to hydroxychloroquine (HCQ) appears to reduce the risk of developing cutaneous neonatal lupus (cNL) erythematosus, as shown in a multicentre case-control study. Moreover, there is a trend toward delayed rash onset in HCQ-exposed infants with cNL.
These findings may have important clinical relevance as preventing cNL can reduce the occurrence of permanent scarring, such as telangiectasia, epidermal atrophy and cutaneous pigmentation changes, according to the authors.
The study included 122 cNL patients and 434 controls born to women with systemic autoimmune rheumatic diseases (SARDs). Significantly more infants in the control group were exposed to HCQ (34 percent vs 16 percent) or nonfluorinated steroids (44 percent vs 25 percent; p<0.01) in utero.
In multivariate generalized estimating equations (GEE) models, cNL was associated with a lower likelihood of in utero exposure to HCQ (odds ratio [OR], 0.4; 95 percent CI, 0.2–0.7; p<0.01), suggesting that HCQ might protect against cNL. [Ann Rheum Dis 2018;doi:10.1136/annrheumdis-2018-213718]
Factors associated with increased cNL risk included female sex (OR, 1.7; 1.1–2.6; p=0.02) and exposure to maternal anti-La antibody (OR, 2.7; 1.7–4.3; p<0.01).
“Exposure to HCQ remained significantly associated with a reduced cNL risk in the analyses limited to mothers with systemic lupus erythematosus (SLE) and those who developed rash ≤1 month,” the authors said.
Finally, in a secondary analysis including 262 infants with cNL irrespective of maternal diagnosis, HCQ-exposed infants were older at cNL onset compared with nonexposed infants (6.0 vs 4.4 weeks), although the difference was not statistically significant (p=0.21).
The findings regarding HCQ's effect on timing of cNL, despite being inconclusive, are valuable as the survival curves showed a delayed onset of rashes during the first 6 weeks of life in infants exposed to HCQ in utero, the authors pointed out.
A drug frequently used in women with SARDs, HCQ exerts a protective effect through inhibition of toll-like receptor activation and signalling. The drug has been shown to effectively treat subacute cutaneous lupus, which closely resembles cNL. [Arch Dermatol 2012;148:479-484]
“Our study is the first to address the effect of HCQ exposure on cNL. Cutaneous involvement in NL may result in unnecessary medical consultations, investigations and treatments and lead to permanent scarring,” the authors said. “Using an inexpensive and safe medication to prevent cNL and therefore minimize these issues is definitely appealing.”
“All analyses performed suggest that prenatal exposure to HCQ may have an impact on the development of cNL and support the need for further studies addressing the underlying pathophysiology of cNL and potential preventive use of maternal HCQ for cNL,” they added.
The authors acknowledged several limitations to the study. First, medication adherence in mothers was not measured specifically during pregnancy but was determined only during routine prenatal rheumatology follow-up. Second, confounding by indication could have occurred as women with SLE are more likely to be prescribed HCQ than women with other SARDs.