Rheumatology Advance Access originally published online on June 30, 2007
Rheumatology 2007 46(9):1506; doi:10.1093/rheumatology/kem170
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Maternal exposure to leflunomide associated with blindness and cerebral palsy
Department of Rheumatology, Stoke Mandeville Hospital, Aylesbury, Buckinghamshire and 1Department of Rheumatology, Royal Berkshire and Battle Hospitals NHS Trust, Reading, Berkshire, UK
Correspondence to: Dr C. Neville, Department of Rheumatology, Stoke Mandeville Hospital, Mandeville Road, Aylesbury, Buckinghamshire, HP21 8AL, UK. E-mail: cai_neville{at}yahoo.co.uk
SIR, We report the case of a 43-year-old woman with sero-positive nodular erosive rheumatoid arthritis who became pregnant whilst taking leflunomide. The drug was only stopped after 16 weeks of gestation.
Leflunomide has been reported to cause teratogenic effects in animals. Fetal death, anopthalmia, micropthalmia and hydrocephalus have occurred following exposure. Its active metabolite can be detected 2 years after discontinuation of the drug making pregnancy following exposure risky. Few human births have occurred following exposure to this drug. A recent review concluded that its use during pregnancy in humans had not caused any known fetal abnormalities or deaths [1]. De Santis et al. [2] reported two healthy births with maternal exposure and one healthy birth following paternal exposure. No patients had taken leflunomide while pregnant.
Our patient had very active disease, since diagnosis in 1993, which had been difficult to control. She was intermittently compliant with blood tests and clinic visits because of a fear of hospitals. Sulphasalazine was ineffective and methotrexate was discontinued after a chest infection. The patient refused to retry the drug. Azathioprine caused diarrhoea so she was maintained for 4 years on prednisolone alone. Her disease was poorly controlled until leflunomide was started in March 2001. Before starting the drug, the patient was counselled specifically about the risks of pregnancy and the need for adequate contraception. Written advice was also given to the patient who was literate. Within 6 months her disease came under control on leflunomide and her disease went into remission.
She became pregnant after failing to use contraception; her last menstrual period was in December 2001. At this stage, she had been taking leflunomide for at least 8 months at a dose of 20 mg daily. The patient was seen urgently by an obstetrician at 21 weeks of gestation, she refused amniocentesis and termination. Fetal well being scan on that day appeared normal. Leflunomide was discontinued and cholestyramine was given. An apparently healthy male was born 9 weeks prematurely, but was subsequently found to be blind in the right eye, and to have cerebral palsy with left sided spasticity.
The patient had three previous pregnancies. Her first baby died within 24 h of birth in 1982 with a congenital heart defect. She subsequently had a healthy daughter in 1988 and a son born in 1991, who has recently been diagnosed with autism.
We report the first documented congenital malformation following maternal exposure to leflunomide during the first trimester of pregnancy. The case was reported to the National Teratology Information Service. Patients on leflunomide and other teratogenic drugs should use contraception and be frequently reminded during clinic visits of the dangers of pregnancy and the potential for teratogenicity of DMARDS.
The authors have declared no conflicts of interest.
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- Temprano KK, Bandlamudi R, Moore TL. Antirheumatic drugs in pregnancy and lactation. Semin Arthritis Rheum (2005) 35:112–21.[CrossRef][Web of Science][Medline]
- De Santis M, Straface G, Cavaliere A, Carducci B, Caruso A. Paternal and maternal exposure to leflunomide: pregnancy and neonatal outcome. Ann Rheum Dis (2005) 64:1096–7.
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