Chapter 18: Lupus and Collagen Diseases

SYSTEMIC LUPUS ERYTHEMATOSUS

Introduction

Systemic lupus erythematosus (SLE) is a chronic, multiorgan, autoimmune condition characterized by intermittent periods of increased disease activity (“flares”) interspersed with periods of remission. SLE has an estimated prevalence of 20 to 150 per 100,000 individuals in the United States.^1,2,3 The incidence of SLE has nearly tripled in recent decades, most likely because of an increased diagnosis of mild cases.⁴ There are important gender differences in the burden of disease, with 88% of affected individuals being women.³ African American women are affected approximately 2.5 times more commonly than white women.¹ SLE most often presents during the reproductive years with initial symptoms that include fatigue, joint pain, fever, and rash.

The cause of SLE appears to be multifactorial, with genetic, hormonal, and environmental factors all contributing to susceptibility to the disease. High concordance for the disease (~25%) has been reported among monozygotic twins.⁵ Genome-wide association studies have identified multiple single nucleotide polymorphisms (SNPs) that appear to increase susceptibility to SLE. Those with the strongest association include deficiencies in complement components (C1q, C4A, C4B, C2) and a TREX1 gene mutation (both of which are relatively rare).⁶ More commonly identified SNPs associated with SLE include those within the major histocompatibility complex.⁶ Not surprisingly, however, such common SNPs confer only a modestly increased risk, emphasizing the complex and multifactorial nature of SLE pathogenesis. Recently, epigenetic modification (such as CpG dinucleotide methylation, histone modifications, and micro-RNAs) of SLE-predisposing genes has received attention as a potentially important mechanistic contributor to disease.^7,8

These epigenetic modifications (and the associated changes in gene expression) likely mediate some of the effects of environmental exposures on the development of SLE.⁹ Exposures identified as having an association with SLE include Epstein-Barr virus, ultraviolet light, and silica dust.⁹

As evidenced by the dramatically increased prevalence of SLE in women as compared with men, hormones appear to play an important role in the development of SLE.¹⁰ Data from the Nurses’ Health Study indicate that factors such as earlier menarche, oral contraceptives, and postmenopausal hormone replacement all increase the risk for SLE.¹¹ Because of the fact that SLE is often diagnosed during a woman’s reproductive years, clinicians will frequently be presented with the challenge of managing a pregnancy complicated by SLE.

Pregnancy can affect the management of SLE (particularly with regard to choice of medications) and SLE increases the risk of multiple adverse pregnancy outcomes, including preterm birth (PTB), preeclampsia, and intrauterine growth restriction (IUGR). Women with more severe SLE manifestations, such as those with lupus nephritis (LN), are at particularly increased risk for complications.¹² Women should be appropriately counseled (ideally preconceptionally) regarding these risks, and increased maternal and fetal surveillance is warranted to optimize outcomes.

Clinical Presentation

Although ...