Systemic Lupus Erythematosus (SLE) and Pregnancy

1. Systemic Lupus Erythematosus(SLE) and Pregnancy . Mishelle M. Hernandez, M.D.

2. Objectives • To discuss how pregnancy affects SLE in increasing lupus flare rates • To discuss the effects of SLE on maternal and fetal outcome in pregnancy • To discuss management of Lupus flare in pregnancy • To discuss ethical issues on the case

3. General Data • K. G. • 18/F • Makati City • CC: bipedal edema • DOA: 3/18/08

4. Diagnosed case of Systemic Lupus Erythematosus since Aug. 2007 1997 Revised Classification Criteria for Systemic Lupus Erythematosus [1] 1 Kliegman, Robert, M.D., et al. Nelson’s Textbook of Pediatrics. 18th ed. USA: Sanders, 2007, pp. 1015-191

5. History of Present Illness 1 yr PTA (+) alopecia, (+) malar rash 9 mo PTA (+) fever, (+) discoid rash, (+) oral ulcers (+) R eyelid swelling (+) joint pain and swelling of hands RHEUMA CLINIC A> SLE Labs: ANA (+4) homogenous 1:80 leukopenia (3,800), anemia (10), lymphopenia (ALC 0.934) BUN 2.3 mol/L (N), Crea (N), Proteinuria(++), RBC 0-1

6. History of Present Illness 2 mo PTA Pregnant discontinued Prednisone No consult done 1 wk PTA (+) persistence of cough (+) bipedal and periorbital edema 4 d PTA (+) persistence of edema (+) 2 pillow orthopnea (-) PND, palpitations, chest pain

7. History of Present Illness 2 d PTA (+) easy fatigability (+) difficulty of breathing (+) vomiting (+) epigastric pain (+) diarrhea (+) tea-colored urine (+) oliguria Rheuma clinic consult PAY

8. Review of Systems • General: (-) generalized weakness, (-) weight loss, (-) anorexia • Neurologic: (-) seizure, (-) headache, (-) change in sensorium, (-) change in behavior • HEENT: (-) eye pain, blurring of vision, (-) sore throat • Hematologic: (-)epistaxis, (-)hematemesis, (-) hematochezia, (-) hemoptysis, (-) easy bruisability, (-) increased bleeding, • Dermatologic: (-) active skin lesions

9. Past Medical History Family History Birth/Maternal History Immunization History Nutritional History No intake of other Meds except Prednisone (+) similar illness – grandmother, paternal side noncontributory Completed at Local health center Unremarkable

10. Developmental History Obstetrics/Menstrual History • At par with age • G1P0, (+) pregnancy test in February, • (+) spotting in February, (-) vaginal discharge • LMP: Dec 3, 2007, 30 days interval, 4 days duration, 3 pads/day, (+) dysmenorrhea • 2nd child from a brood of 9 • Mother is a 39 y/o,housewife. • Father is 45 y/o, nurse at PGH PICU. Personal/Social History

11. HEADSS • Home • living with parents and siblings • good relationship with them (closest to her older sister) • Education • incoming 1st year college student, taking up BS Psychology • She didn’t finished first year due to her illness • plans to finish her study and work to help her parents

12. HEADSS • Activity • hangs out with friends in the mall or in their house, go out preferably at night • love to talk about gossips • Drugs • Denies illicit drug use • occasional beverage drinker • doesn’t smoke

13. HEADSS • Sex • one relationship and sexually active, with a 15 y/o guy, who is also the father of her present pregnancy • Her boyfriend impregnated another woman prior to her • no plans of getting married now • Suicidal ideations • when scolded by parents • felt very sad when she was diagnosed with SLE

14. Physical Examination on Admission • General exam: conscious, coherent, not in cardiorespiratory distress • Vital signs: BP 140/80, PR 110, RR 24, T 38C, wt 47 kg, ht 151 cm • HEENT: slightly pale conjunctivae, anicteric sclera, (+) periorbital edema, bilateral • (-) cervical lymphadenopathy, (-) anterior neck mass, (-)neck vein engorgement, (-) tonsillopharyngeal congestion

15. Physical Examination on Admission • Chest and Lungs: Equal chest expansion, no retractions, (+) clear breath sounds, (-) crackles/wheeze • Cardiovascular: adynamicprecordium, distinct HS, tachycardic, normal regular rhythm, AB at 5th LICS MCL, (-) murmur • Abdomen: globular abdomen, (+) NABS, soft, (+) epigastric tenderness, (-) organomegaly, abdominal girth = 76 cm, fundic height = 20 cm, fetal heart tone not appreciated by stethoscope

16. Physical Examination on Admission • Internal examination: (+) vulvar edema, nulliparous vagina, corpus enlarged to AOG, cervix soft closed, (-) abnormal discharge or masses • Extremities: Pink nailbeds, FEP, (-) cyanosis, (+) bipedal edema, pitting, grade 1 • External genitalia: grossly female, SMR 4 • Skin: (-) active dermatoses • Neurologic exam: essentially normal

17. Initial Impression SLE in activity Pregnancy Uterine 17 2/7 weeks by early UTZ, NIL UTI

18. Problem List Pregnancy SLE Nephritis, Hypertension Pericarditis Anemia Pulmonary edema, noncardiogenic Pleural Effusion, B Infection

19. Pregnancy

20. Lupus Nephritis and Hypertension

21. Lupus Pericarditis

22. Anemia of Chronic Disease

23. Pulmonary Edema and Pleural Effusion

24. Infectious

25. Ward stay – 17 days • PICU stay – 10 days • Discharged – on April 15, 2008 • Home Meds • Prednisone • Aspirin • Azathioprine • Nifedipine • Methyldopa • Hydralazine • Multivitamins • Folic acid • MgSO4 • Fe

26. Whether pregnancy exacerbates lupus? • Among retrospective and prospective studies [2] • Lupus flare rates ranges from approximately 20% – 60% • Lupus that is active at the onset of pregnancy is activated further during pregnancy 2 Singh, Ajay K. Lupus nephritis and anti-phospholipid activity syndrome in pregnancy. Kidney International. Vol 58. (2000), pp 2240-2254.

27. Table 1. Distribution of SLE flares occurring during pregnancy a [3] 3 Cortez-Hernandez, J., et al. Clinical Predictors of Fetal and Maternal Outcome in Systemic Lupus Erythematosus, a Prospective Study. Rheumatology. 2002; 41: 643-50.

28. How to treat SLE flare during pregnancy? • Prednisone (1-2 mg/kg/day) – drug of choice for most SLE manifestation • Methylprednisone pulse 1g/day fowllowed by oral Prednisone at 0.5-1.0 mg/kg/day – severe systemic disease • Azathioprine (2 mg/kg/day) – for initial mild flare • Stress doses of Hydrocortisone – for emergency surgery, cesarean section, prolonged labor and delivery 5 Obstetric Emergencies: Management of Lupus Flare. www.obgmanagement.com. May 2006.

29. 6 Mackillop, Lucy H., et al. Pregnancy plus Systemic Lupus Erythematosus. BMJ.2007; 335: 93336.

30. Table 2. Evidence for adverse effects of immunosuppressant used in pregnancy and breastfeeding[6] 6 Mackillop, Lucy H., et al. Pregnancy plus Systemic Lupus Erythematosus. BMJ.2007; 335: 93336.

31. Refractory cases • Rule: To treat the lupus flare before irreparable maternal harm occurs • Use of other new line immunosuppressive drugs • Benefits must be outweighed by potential risks • No conclusive data suggest pregnancy termination will ameliorate lupus flare. 5 Obstetric Emergencies: Management of Lupus Flare. www.obgmanagement.com. May 2006.

32. Management Preconception Visit • counseled on appropriate timing of planned pregnancy • remission of at least 6 months and preferably more than 12 months and minimal or no need of immunosuppressives • Risks to patient and fetus are discussed in detail • The following baseline investigations are obtained at the start • CBC • Urea, creatinine, electrolytes • Liver function tests • ANA, anti dsDNA, aPL, anti-Ro/anti-La Mackillop, Lucy H., et al. Pregnancy plus Systemic Lupus Erythematosus. BMJ.2007; 335: 93336.

33. Management after conception • follow-up frequency is dependent on disease activity • hydroxychloroquine is given to prevent flares • Low dose aspirin is administered to prevent preeclampsia • If APLS positive or history of thrombosis or fetal loss, treatment with heparin or LMWH and low dose aspirin Mackillop, Lucy H., et al. Pregnancy plus Systemic Lupus Erythematosus. BMJ.2007; 335: 93336.

34. Management after conception • fetus is regularly monitored by obstetrician using Doppler UTZ • 20 weeks, a detailed morphology scan is done • Regular growth scans at 28, 32 and 36 weeks is done • If with anti-Ro and anti-La, fetal heart pulsed Doppler echocardiography at 18 weeks and 3rd trimester • Delivery method and timing depends on obstetric indications Mackillop, Lucy H., et al. Pregnancy plus Systemic Lupus Erythematosus. BMJ.2007; 335: 93336.

35. Management after conception • Nutrition management • Megavitamin therapy • adequate dietary intake • Breastfeeding is contraindicated when taking the following drugs: mycophenolate, cyclophosphamide, methotrexate and leflunomide • Breastfeeding is appropriate if the maternal dose of prednisone is <30 mg/d, to take her medications just after breast-feeding Ferris, Ann M., et al. Nutritional consequences of chronic maternal conditions during pregnancy and lactation: lupus and diabetes. American Journal of Clinical Nutrition. 1994; 59 (suppl): 465S-73S.

36. How SLE affects pregnancy? • Spontaneous abortion • Preeclampsia • IUGR • Fetal death rate • Preterm delivery • Thromboembolism • Lupus nephritis • Renal failure • Antiphospholipid syndrome • Active disease at conception • First presentation of SLE at pregnancy 7 Molad, Yair. Sytemic Lupus in Pregnancy. Current Opinion in Obstetrics and Gynecology.2006; 18: 613-617.

37. Table 4. Fetal Outcome [8] 8 Valdez, Corazon, et al. Systemic Lupus Erythematosus in Pregnancy: a 23-year review. Acta Medica Philippina

38. Updates on the Patient • On regular follow up to Rheuma, Renal, Perinatology • Maintained on Prednisone, Azathioprine, Aspirin, megavitamin • Controlled hypertension • Normal fetus on serial scans • EDC: Aug. 26, 2008the • Awaiting APAS • Father is alienating the patient.

39. Conclusion • Whether pregnancy does exacerbate SLE is a controversial issue. • Women with SLE can have successful pregnancies. • In the care of lupus pregnant patient, the most diffiucult dilemma is saving both the mother and the unborn child.