The Neurology of Immune-Mediated Disorders in Women

Abstract

Many neuroinflammatory disorders have a predilection for women; even if there is no female predominance, neuroinflammatory conditions in women pose a management challenge for several reasons. Disease activity of these conditions may change during pregnancy and commonly increases in the postpartum period. Uncontrolled disease activity may affect pregnancy outcomes. Moreover, immunomodulating agents that are used to suppress the disease activity may have a negative impact on fertility, pregnancy, and fetal outcomes, and on infants who are breastfed. Adverse effects of immunosuppressants extend beyond the reproductive issues and may include bone loss, increased risk of cancers, and infectious complications. The successful management of women with these disorders requires that not only practitioners understand and recognize the adverse effects of immunosuppressants, but also seek to prevent adverse outcomes through counseling about contraceptive choices, safety monitoring, risk surveillance, and other strategies.

Keywords

neuroinflammatory disorders - immunosuppressants - fertility - pregnancy - lactation

• References

• 1 Xanthos DN, Sandkühler J. Neurogenic neuroinflammation: inflammatory CNS reactions in response to neuronal activity. Nat Rev Neurosci 2014; 15 (01) 43-53
• 2 Beeson PB. Age and sex associations of 40 autoimmune diseases. Am J Med 1994; 96 (05) 457-462
• 3 Whitacre CC. Sex differences in autoimmune disease. Nat Immunol 2001; 2 (09) 777-780
• 4 Fish EN. The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol 2008; 8 (09) 737-744
• 5 Liang Y, Tsoi LC, Xing X. , et al. A gene network regulated by the transcription factor VGLL3 as a promoter of sex-biased autoimmune diseases. Nat Immunol 2017; 18 (02) 152-160
• 6 Bove R, McHenry A, Hellwig K. , et al. Multiple sclerosis in men: management considerations. J Neurol 2016; 263 (07) 1263-1273
• 7 Bove R, Chitnis T. The role of gender and sex hormones in determining the onset and outcome of multiple sclerosis. Mult Scler 2014; 20 (05) 520-526
• 8 Bielecki B, Mattern C, Ghoumari AM. , et al. Unexpected central role of the androgen receptor in the spontaneous regeneration of myelin. Proc Natl Acad Sci U S A 2016; 113 (51) 14829-14834
• 9 Koelman DL, Chahin S, Mar SS. , et al. Acute disseminated encephalomyelitis in 228 patients: a retrospective, multicenter US study. Neurology 2016; 86 (22) 2085-2093
• 10 Tenembaum S, Chitnis T, Ness J, Hahn JS. ; International Pediatric MS Study Group. Acute disseminated encephalomyelitis. Neurology 2007; 68 (16) (Suppl. 02) S23-S36
• 11 Granerod J, Ambrose HE, Davies NW. , et al; UK Health Protection Agency (HPA) Aetiology of Encephalitis Study Group. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 2010; 10 (12) 835-844
• 12 Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis 2012; 54 (07) 899-904
• 13 Svensson-Arvelund J, Mehta RB, Lindau R. , et al. The human fetal placenta promotes tolerance against the semiallogeneic fetus by inducing regulatory T cells and homeostatic M2 macrophages. J Immunol 2015; 194 (04) 1534-1544
• 14 Tilburgs T, Evans JH, Crespo AC, Strominger JL. The HLA-G cycle provides for both NK tolerance and immunity at the maternal-fetal interface. Proc Natl Acad Sci U S A 2015; 112 (43) 13312-13317
• 15 Fu B, Li X, Sun R. , et al. Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface. Proc Natl Acad Sci U S A 2013; 110 (03) E231-E240
• 16 Santner-Nanan B, Peek MJ, Khanam R. , et al. Systemic increase in the ratio between Foxp3+ and IL-17-producing CD4+ T cells in healthy pregnancy but not in preeclampsia. J Immunol 2009; 183 (11) 7023-7030
• 17 Arck PC, Hecher K. Fetomaternal immune cross-talk and its consequences for maternal and offspring's health. Nat Med 2013; 19 (05) 548-556
• 18 Zenclussen AC. Adaptive immune responses during pregnancy. Am J Reprod Immunol 2013; 69 (04) 291-303
• 19 Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol 2010; 63 (06) 601-610
• 20 Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. ; Pregnancy in Multiple Sclerosis Group. Rate of pregnancy-related relapse in multiple sclerosis. N Engl J Med 1998; 339 (05) 285-291
• 21 Fabian M. Pregnancy in the Setting of Multiple Sclerosis. Continuum (Minneap Minn) 2016; 22 (03) 837-850
• 22 Kim W, Kim SH, Nakashima I. , et al. Influence of pregnancy on neuromyelitis optica spectrum disorder. Neurology 2012; 78 (16) 1264-1267
• 23 Fragoso YD, Adoni T, Bichuetti DB. , et al. Neuromyelitis optica and pregnancy. J Neurol 2013; 260 (10) 2614-2619
• 24 Shimizu Y, Fujihara K, Ohashi T. , et al. Pregnancy-related relapse risk factors in women with anti-AQP4 antibody positivity and neuromyelitis optica spectrum disorder. Mult Scler 2016; 22 (11) 1413-1420
• 25 Norwood F, Dhanjal M, Hill M. , et al. Myasthenia in pregnancy: best practice guidelines from a U.K. multispecialty working group. J Neurol Neurosurg Psychiatry 2014; 85 (05) 538-543
• 26 Boldingh MI, Maniaol AH, Brunborg C, Weedon-Fekjær H, Verschuuren JJ, Tallaksen CM. Increased risk for clinical onset of myasthenia gravis during the postpartum period. Neurology 2016; 87 (20) 2139-2145
• 27 Gayed M, Gordon C. Pregnancy and rheumatic diseases. Rheumatology (Oxford) 2007; 46 (11) 1634-1640
• 28 Andersen SL, Olsen J, Carlé A, Laurberg P. Hyperthyroidism incidence fluctuates widely in and around pregnancy and is at variance with some other autoimmune diseases: a Danish population-based study. J Clin Endocrinol Metab 2015; 100 (03) 1164-1171
• 29 de Man YA, Dolhain RJ, van de Geijn FE, Willemsen SP, Hazes JM. Disease activity of rheumatoid arthritis during pregnancy: results from a nationwide prospective study. Arthritis Rheum 2008; 59 (09) 1241-1248
• 30 Buchel E, Van Steenbergen W, Nevens F, Fevery J. Improvement of autoimmune hepatitis during pregnancy followed by flare-up after delivery. Am J Gastroenterol 2002; 97 (12) 3160-3165
• 31 Airas L, Saraste M, Rinta S, Elovaara I, Huang YH, Wiendl H. ; Finnish Multiple Sclerosis and Pregnancy Study Group. Immunoregulatory factors in multiple sclerosis patients during and after pregnancy: relevance of natural killer cells. Clin Exp Immunol 2008; 151 (02) 235-243
• 32 Lateef A, Petri M. Management of pregnancy in systemic lupus erythematosus. Nat Rev Rheumatol 2012; 8 (12) 710-718
• 33 Weinstein RS. Clinical practice. Glucocorticoid-induced bone disease. N Engl J Med 2011; 365 (01) 62-70
• 34 Compston J. Management of glucocorticoid-induced osteoporosis. Nat Rev Rheumatol 2010; 6 (02) 82-88
• 35 van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 2002; 13 (10) 777-787
• 36 Allen CS, Yeung JH, Vandermeer B, Homik J. Bisphosphonates for steroid-induced osteoporosis. Cochrane Database Syst Rev 2016; 10: CD001347
• 37 Overman RA, Toliver JC, Yeh JY, Gourlay ML, Deal CL. United States adults meeting 2010 American College of Rheumatology criteria for treatment and prevention of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken) 2014; 66 (11) 1644-1652
• 38 Grossman JM, Gordon R, Ranganath VK. , et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken) 2010; 62 (11) 1515-1526
• 39 Mok CC, Ho LY, Ma KM. Switching of oral bisphosphonates to denosumab in chronic glucocorticoid users: a 12-month randomized controlled trial. Bone 2015; 75: 222-228
• 40 Santana IU, Gomes AdoN, Lyrio LD, Rios Grassi MF, Santiago MB. Systemic lupus erythematosus, human papillomavirus infection, cervical pre-malignant and malignant lesions: a systematic review. Clin Rheumatol 2011; 30 (05) 665-672
• 41 Nguyen ML, Flowers L. Cervical cancer screening in immunocompromised women. Obstet Gynecol Clin North Am 2013; 40 (02) 339-357
• 42 Curtis KM, Tepper NK, Jatlaoui TC. , et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep 2016; 65 (03) 1-103
• 43 Vukusic S, Marignier R. Multiple sclerosis and pregnancy in the ‘treatment era’. Nat Rev Neurol 2015; 11 (05) 280-289
• 44 Götestam Skorpen C, Hoeltzenbein M, Tincani A. , et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016; 75 (05) 795-810
• 45 Hellwig K, Rockhoff M, Herbstritt S. , et al. Exclusive breastfeeding and the effect on postpartum multiple sclerosis relapses. JAMA Neurol 2015; 72 (10) 1132-1138
• 46 Pakpoor J, Disanto G, Lacey MV, Hellwig K, Giovannoni G, Ramagopalan SV. Breastfeeding and multiple sclerosis relapses: a meta-analysis. J Neurol 2012; 259 (10) 2246-2248