1. Case discussion
Presenter R1 李儒

2. Basic information Name :李X芳之女 Age : 0-day Chart No : 17XXX618
Sex : female
Admission : 2016/05/30

3. Chief complaint
Bradycardia was noted at birth

4. EKG

5. Present Illness Born to a 29 year-old mother, G2P0AA1
Mother had regular prenatal care at 嘉基
Thalassemia (-), Rh(+),VDRL(-), proteinuria(-), HbsAg(-), HbeAg(-), Rubella IgG(+), HIV(-)).
Fetal bradycardia was found at 23weeks of gestation
Fetal complete AV block was diagnosed on 2016/03/14
5/30 服用SLE藥物配一口水服下(plaquenil 1#,imuran 1.5#,Gaster 1#,Dexamethasone 1#)] STAT

6. Past history Birth History: Vaccination: <24hr HBIG: yes
G2P1,CS,GA: 34+4 weeks, BBW:2158gm
APGAR score: 5->9, DOIC(-), PROM(-)
Vaccination: <24hr HBIG: yes
Maternal past History:
Systemic lupus erythematosus since 18 y/o
Right arm debridement at 22 y/o, due to Vibrio vulnificus infection

7. Maternal medical history
Systemic lupus erythematosus since 18 year-old
Plaquenil (200mg) 1# QD
Imuran 1# QD
Gaster 1# QD
Dexamethasone (0.5mg) 1# QD
Aspirin for thrombophilia and held 5 days before operation.

8. Physical examination Vital Signs：TPR：37°C/66/40 ; BP：63/48mmHg
HEENT：No cephalohematoma, no caput succedaneum
Chest：bilateral symmetric expansion, clear BS
Heart：regular heart sound, no murmur
Abdomen：soft, globular, normoactive bowel sound
Liver：1 f.b below ribs ; Spleen：impalpable
Extremities： warm, free movable
Skin：no rash, edema, petechiae or ecchymosis

9. Impression Congenital complete heart block Neonatal lupus
Congenital structural heart disease
Familial inheritance of conduction disease
Myocarditis

10. Lab data
58/26 mmHg
48/21 mmHg
48/21mmHg => 58/26mmHg

11. C/T ratio = 51％

12. Echo examination Cardiac echo Brain echo PFO、PDA 0.2cm
Periventricular echogenicity
Bilateral IVH Gr. 1

13. Lab data

14. Management Isoproterol , dobutamine
Epicardial pacemaker, permanent, rate 130min
VVIR, rate 130/min, output 3.5Volt, impedence 810 Om
non-selective β adrenoreceptor agonist  ,  stimulation of the β1-adrenoceptors

16. Final diagnosis
Congenital complete AV block, neonatal lupus related

17. Discussion
Neonatal lupus

18. Introduction Passively transferred autoimmune disease.
1 ~ 2 ％ of babies born to mothers with autoimmune disease, primarily systemic lupus erythematosus (SLE) and Sjögren's syndrome.
The most serious complication of NL is complete heart block
About 10 ％ have an associated cardiomyopathy at the initial diagnosis or develop it later.
more commonly Sjögren syndrome than SLE

19. Pathogenesis
Transplacental passage of maternal anti-Ro/SSA and/or anti-La/SSB.
In vitro studies, Ro and La antigens may be exposed on the surface of cardiac cells in the proximity of the atrioventricular node during cardiac development, thus making these antigens accessible to maternal autoantibodies.
Binding incites a local immune response, resulting in fibrosis within the conduction system.

20. Pathogenesis Associated with maternal anti-Ro and anti-La antibodies.
Anti-ribonucleoprotein (anti-RNP) have also been reported.
The pathogenesis of disease probably involves more than simple transplacental passage of antibodies since the disease is rare

21. Clinical manifestations
Rash
Heart
Hepatic：Asymptomatic elevated liver function tests, Mild hepatosplenomegaly, Cholestasis, Hepatitis
Hematologic：Anemia, Neutropenia, Thrombocytopenia, Aplastic anemia
Neurologic：Hydrocephalus, Macrocephaly

22. Rash
Annular or macular rash typically affecting the face (especially the periorbital area), trunk, and scalp.
May not develop until after exposure to ultraviolet (UV) light.
Self limiting
Almost always resolves by six to eight months of age
macular rash is a skin rash that appears as small, flat red spots.
half-life of immunoglobulin G (IgG) antibodies is approximately 21 to 25 days

23. Heart block Irreversible
NL is responsible for ％ of all cases of congenital complete heart block diagnosed in utero or in the neonatal period.
Much less common cause of heart block presenting after the neonatal period (5 ％ ).
Second-degree block in utero and first- or second-degree heart block in infants at birth can progress to complete heart block.
3 - 4 % in fetuses with conduction abnormalities exposed to maternal anti-Ro/SSA antibodies.

24. Other cardiac abnormalities
Structural heart disease has been reported occasionally.
Ventricular septal defect
Persistent patent ductus arteriosus
Patent foramen ovale
Ostium secundum type atrial septal defects
Cardiomyopathy
Endocardial fibroelastosis

25. Diagnosis No specific diagnostic criteria
A fetus or newborn of a mother with anti-Ro/SSA and/or anti-La/SSB, or possibly anti-ribonucleoprotein (RNP), antibodies develops heart block and/or the typical rash or hepatic or hematologic manifestations in the absence of another explanation.

26. Prenatal screening For mother with Lupus Sjögren syndrome
An undifferentiated autoimmune disease
Neonatal lupus in a previous pregnancy

27. Monitoring for heart block
Weekly-pulsed Doppler fetal echocardiography from the 18th ~ 26th week of pregnancy
Every other week during 27th ~ 32th weeks
Most vulnerable period for the fetus：18th ~ 24th weeks gestation
New onset of heart block is less likely during 26th ~ 30th week, and it rarely develops after 30 weeks of pregnancy
Normal sinus rhythm can progress to complete block in seven days during this high-risk period.

28. Postnatal diagnosis
Any neonate with heart block-absent causal structural abnormalities
Infants up to eight months of age with
Annular or polycyclic rash
+/- Any degree of heart block

29. Treatment - prenatal Third-degree block Second-degree heart block
Not advised
Require cardiac pacing
Second-degree heart block
Fluorinated glucocorticoids, such as dexamethasone (4 mg per day) and betamethasone (3 mg per day) as soon after detection as is feasible
First-degree block
Conntroversial
Treatment of third-degree block without any signs of myocarditis with glucocorticoids is generally not advised. Most of these patients will require cardiac pacing.
Treatment of first-degree block is perhaps the most controversial.

30. Treatment - preemptive
Hydroxychloroquine
May decrease the overall risk of cardiac-NL
400 mg orally once a day
Pregnant women with anti-Ro/SSA antibodies who have previously given birth to a child with cardiac-NL
Between 6 and 10 weeks gestation in women
Not recommend
Glucocorticoids
IVIG
IVIG 400 mg/kg given every three weeks from weeks 12 to 24
40 exposed and 217 unexposed to hydroxychloroquine) were identified. Cardiac-NL developed in 3 of 40 (7.5 percent) of exposed fetuses and 46 of 217 (21.2 percent) of unexposed fetuses

31. Prognosis Early outcome Long-term
Little risk of later cardiac involvement in patients without evidence of heart block or with noncardiac manifestations of NL
Gestational age <20 weeks, ventricular rate ≤50 bpm, fetal hydrops, and impaired LV function at diagnosis
10-fold increase before birth
6-fold increase in the neonatal period
Long-term
Increased risk of developing an rheumatic and/or autoimmune disease (12 percent)

32. Reference
Nelson Pedia 19th
Uptodate – neonatal lupus

33. Thanks for your attention!!