Rheumatology Advance Access originally published online on July 25, 2008
Rheumatology 2008 47(9):1438-1439; doi:10.1093/rheumatology/ken290
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Comment on: Intravenous immunoglobulin therapy in pregnant patients affected with systemic lupus erythematosus and recurrent spontaneous abortion
1Department of Rheumatology, Gaziantep University School of Medicine, Gaziantep, Turkey
Correspondence to: H. Buyukhatipoglu, Hatipoglu Ins., Kalyon is merkezi No:17-18 Sehitkamil/Gaziantep, Turkey. E-mail: buyukhatipoglu{at}gmail.com
SIR, As rheumatologists practicing in a developing country where the birth rate is relatively high, pregnancy with SLE constitutes a major problem for us. We have encountered a growing number of pregnancies in women with SLE, and many of these pregnancies have been associated with a variety of complications, including recurrent spontaneous abortions (RSAs), premature delivery, renal complications, hypertension, pre-eclampsia and premature membrane rupture. Some of these complications seem to be due to the SLE itself; but other complications have been ascribed to the drugs used to treat the SLE during pregnancy. Nonetheless, rheumatologists have limited therapeutic options. Only a small proportion of drugs can be said to be safe in pregnancy. Most of the medications used in SLE either are not safe or have not yet been proven safe during pregnancy. Therefore, the results from this study by Perricone et al [1] are critical, providing important evidence on the use of Intravenous immunoglobulins (IVIGs), even though the study involved only a small number of subjects.
However, we have several concerns. First, we know that RSAs and pregnancy complications are more common in patients with the combination of aPL syndrome and SLE than among those with SLE alone [2]. Several studies have showed that the use of IVIGs in aPL and aPL + SLE patients does not produce any significant benefit [3, 4]. Second, the results from the largest meta-analysis regarding this issue demonstrated that, in patients with otherwise-unproven RSA, immunotherapy (including IVIG) fails to significantly enhance the percentage of live births [5]. Even though the studies addressing this issue were insufficient to be considered conclusive, from the results of the current study and the previous ones, it is reasonably clear that IVIG improves outcomes mostly in patients with SLE alone, and not in those with both SLE and aPL. This suggests that different mechanisms might play a role in RSAs in patients with SLE alone. Interpreting the results of these studies, IVIG probably provides improvement by decreasing the activity of SLE via yet unclear mechanisms. In other words, IVIGs also may act via non-immunological mechanisms. In addition, the lack of any benefit of IVIGs in SLE + aPL patients may be based mostly in the condition's pathophysiology; that is, the cause of fetal losses in SLE + aPL patients primarily is due to arteriovenous thromboses, attributable to the aPL, rather than as a result of any SLE-related autoimmunity. In conclusion, we feel that IVIG may exert its beneficial effects in patients with SLE + RSA by means of several mechanisms that include reducing the disease activity of lupus, anti-DNA antibodies and complement levels, all of which are related to fetal losses in pregnancy [6]. Certainly, larger studies may provide new insights and new therapeutic options in this very unclear area.
Disclosure statement: The authors have declared no conflicts of interest.
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- Perricone R, De Carolis C, Kröegler B, et al. Intravenous immunoglobulin therapy in pregnant patients affected with systemic lupus erythematosus and recurrent spontaneous abortion. Rheumatology (2008) 47:646–51.
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- Triolo G, Ferrante A, Ciccia F, et al. Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospolipid antibodies. Arthritis Rheum (2003) 48:728–31.[CrossRef][Web of Science][Medline]
- Spinnato JA, Clark AL, Pierangeli SS, Harris EN. Intravenous immunoglobulin therapy for the antiphospolipid syndrome in pregnancy. Am J Obstet Gynecol (1995) 172:690–4.[CrossRef][Web of Science][Medline]
- Porter TF, LaCoursiere Y, Scott JR. Cochrane Database. Syst Rev (2006) CD000112.
- Clowse ME, Magder LS, Witter F, Petri M. Early risk factors for pregnancy loss in lupus. Obstet Gynecol (2006) 107:293–9.[Web of Science][Medline]
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