Management of Autoimmune Diseases

Educational Objectives

The goals of this program are to prevent transmission of infectious diseases and improve the management of autoimmune diseases in women. After hearing and assimilating this program, the clinician will be better able to:

1. Manage a pregnancy in a patient with antiphospholipid syndrome.

2. Provide preconception counseling for a patient with an autoimmune disorder.

Summary

Overview: in patients with autoimmune conditions, concerns include miscarriage, fetal anomalies, fetal growth failure, fetal heart block, flare-ups of disease, and timing of delivery; outcomes usually favorable in patients with autoimmune disease; in Promoting Maternal-Infant Survival Everywhere study, favorable outcome seen in 81% of women; rate of fetal or neonatal death of 6% represents 10-fold risk but includes miscarriages; 9% of women delivered before 36 wk, which may not differ from outcome in general population

Antiphospholipid syndrome: antiphospholipid antibodies probably promote miscarriage by causing microclotting in placenta; venous thromboemboli (VTE) less common; 30% to 70% of untreated patients miscarry; heparin — unfractionated heparin plus aspirin superior to aspirin alone; heparin associated with loss of calcium and thrombocytopenia; speaker uses low-molecular-weight heparin; heparin does not cross placenta and may be started at time of positive pregnancy test, before pregnancy, or when fetal heartbeat detected; second and third trimester complications — include fetal growth failure and preeclampsia; treatment does not affect these complications but often continued due to possible need to prevent VTE in postpartum period (treatment in postpartum period required for patients with antiphospholipid antibodies); unexpected fetal death rare; surveillance for growth abnormalities, biophysical testing, and kick counting should identify fetuses at risk; in some studies, heparin reduced incidence of severe preeclampsia; vigilance and timely delivery reduce maternal morbidity

Fetal and neonatal effects: rashes due to acquired maternal antibodies may be observed in neonates; fetal heart block — associated with Sjögren syndrome-related antigen A (SSA) and SSB antibodies; triple therapy (including intravenous immunoglobulin and high-dose halogenated steroids) being investigated for prevention; whether antibodies actual cause of heart block debatable; SSA/Ro or SSB/La antibodies confer 2% risk for complete heart block in first child; however, risk in second child 17% to 20% if first child affected, suggesting that both antibodies and genetic predisposition required for development of complete heart block; 20% to 30% of fetuses with complete heart block die; management — most survivors require permanent pacing; rate of stillbirth high in untreated fetuses; more data needed on plasmapheresis, triple therapy, hydroxychloroquine (Plaquenil), and high-dose steroids; inability to reliably detect second-degree block in utero hampers ability to design randomized trial; steroids — PR Interval and Dexamethasone Evaluation trial unsuccessful; except in high doses, prednisone does not cross placenta; only fluorinated steroids such as betamethasone or dexamethasone cross placenta; however, in older literature, high-dose fluorinated steroids associated with impaired growth, especially of brain; maternal effects undesirable; hydroxychloroquine — in recent study of SSA antibodies, incidence of neonatal cardiac effects and fetal deaths higher in patients who stopped taking hydroxychloroquine than in patients who continued treatment

Flare-ups of disease: difficult to verify because fatigue, agitation, anemia, and elevated sedimentation rate common to pregnancy; patients should be treated based on symptoms such as severe fatigue rather than laboratory values; prednisone — used for women who develop anemia or nephrosis; anomalies of heart and lip and fetal growth restriction reported; however, drug does not cross placenta, so growth restriction in observational studies probably due to underlying diseases that prompted use of prednisone; obstetrician should monitor growth; risk-benefit ratio more important than pregnancy category of drug (eg, patients taking azathioprine may decrease their dose of prednisone); other treatments include cyclosporine, tacrolimus, tumor necrosis factor inhibitors, anakinra, and rituximab (Rituxan); physician should monitor effects of drugs; maternal flare-ups may result in renal failure or premature delivery; women who stop drugs have more flare-ups and require higher mean doses of prednisone

Fetal growth restriction: increased in women with antiphospholipid antibodies; starvation and dehydration precede asphyxiation; fetal death unlikely with careful surveillance; babies delivered before hypoxia develops have excellent outcomes, but may develop cardiac disease, obesity, and insulin resistance during lifetime

Preconception care: patients without recent flare-ups may attempt pregnancy; lupus anticoagulant, anticardiolipin antibodies, and β2-microglobulin should be checked; for patient with flare-up, objective of treatment to find combination of nonteratogenic drugs that achieve stabilization; relative contraindications to pregnancy — include severe flare-up of lupus requiring hospitalization, active nephritis, and major cardiac or pulmonary problems; pulmonary hypertension due to autoimmune disease associated with mortality rate of 50% during pregnancy and considered absolute contraindication to pregnancy; patients with chronic renal failure and creatinine level >1.5 mg/dL likely to require preterm delivery

Management of pregnancy: first trimester — place patient on anticoagulant therapy if antiphospholipid antibody present; second trimester — perform anatomic ultrasonography at ≈19 wk; third trimester — monitor growth; other interventions — obtain and monitor serial laboratory values; no dietary or physical activity restrictions required; delivery — if fetus still growing, do not deliver before 39 wk; patients should begin unfractionated heparin before onset of labor to allow administration of epidural analgesia; patients who received steroids during pregnancy require stress doses during labor and for 16 hr postpartum

Readings

Suggested Reading

Assaad U et al: Pneumonia immunization in older adults: review of vaccine effectiveness and strategies. Clin Interv Aging 2012;7:453-61; Carvalheiras G et al: Fetal outcome in autoimmune diseases. Autoimmun Rev 2012 May;11(6-7):A520-30; Clowse ME: Managing contraception and pregnancy in the rheumatologic diseases. Best Pract Res Clin Rheumatol 2010 Jun;24(3):373-85; Gleicher N and Elkayam U: Preventing congenital neonatal heart block in offspring of mothers with anti-SSA/Ro and SSB/La antibodies: a review of published literature and registered clinical trials. Autoimmun Rev 2013 Sep;12(11):1039-45; Izmirly PM et al: Evaluation of the risk of anti-SSA/Ro-SSB/La antibody-associated cardiac manifestations of neonatal lupus in fetuses of mothers with systemic lupus erythematosus exposed to hydroxychloroquine. Ann Rheum Dis 2010 Oct;69(10):1827-30; Joura EA et al: A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med 2015 Feb 19;372(8):711-23; Kuleva M et al: Clinical course and outcome of antenatally detected atrioventricular block: experience of a single tertiary centre and review of the literature. Prenat Diagn 2014 Dec 8. [Epub ahead of print]; Langan SM et al: Herpes zoster vaccine effectiveness against incident herpes zoster and post-herpetic neuralgia in an older US population: a cohort study. PLoS Med 2013;10(4):e1001420; Llanos C et al: Recurrence rates of cardiac manifestations associated with neonatal lupus and maternal/fetal risk factors. Arthritis Rheum 2009 Oct;60(10):3091-7; Mangen MJ et al: Rationale and design of the costs, health status and outcomes in community-acquired pneumonia (CHO-CAP) study in elderly persons hospitalized with CAP. BMC Infect Dis 2013 Dec 19;13:597; Martínez-Sánchez N et al: The effect of a triple therapy on maternal anti-Ro/SS-A levels associated to fetal cardiac manifestations. Autoimmun Rev 2015 Jan 17 [Epub ahead of print]; Munoz FM et al: Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap) immunization during pregnancy in mothers and infants: a randomized clinical trial. JAMA 2014 May 7;311(17):1760-9; Ruffatti A et al: A combination therapy protocol of plasmapheresis, intravenous immunoglobulins and betamethasone to treat anti-Ro/La-related congenital atrioventricular block. A case series and review of the literature. Autoimmun Rev 2013 May;12(7):768-73; Tsang P et al: Immunogenicity and safety of Fluzone(®) intradermal and high-dose influenza vaccines in older adults ≥65 years of age: a randomized, controlled, phase II trial. Vaccine 2014 May 1;32(21):2507-17; Vesikari T et al: Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine(4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomised trials. Lancet 2013 Mar 9;381(9869):825-35. Erratum in: Lancet 2013 Mar 9;381(9869):804; Ward JI et al: Bordetella pertussis infections in vaccinated and unvaccinated adolescents and adults, as assessed in a national prospective randomized Acellular Pertussis Vaccine Trial (APERT). Clin Infect Dis 2006 Jul 15;43(2):151-7; Ward JI et al: Efficacy of an acellular pertussis vaccine among adolescents and adults. N Engl J Med 2005 Oct 13;353(15):1555-63.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Moore was recorded at Pregnancy and Lactation in Women with Autoimmune Diseases: Sharing Knowledge Across Disciplines, held February 6-7, 2015, in San Diego, CA, and sponsored by the University of California, San Diego, School of Medicine in collaboration with MotherToBaby. For information about upcoming CME activities sponsored by the University of California, San Diego, School of Medicine, visit cme.ucsd.edu. The Audio Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

OB620802

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.