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CONGENITAL COMPLETE HEART BLOCK IN NEONATAL LUPUS

1Alok Hemal, 2Amieleena Chabra,  3Mahesh Chand Meena

.Associate Professor1, Senior Resident,2 Postgraduate3 Departments of Pediatrics .  Post Graduate Institute of Medical Education and Research, Dr. Ram Manohar Lohia hospital, New Delhi, 110001.

 

 

 

 

Introduction

Gerbezius in 1718 was the first physician to report the slow pulse of block­­1. Morgeni in 1791 published a description of a patient with slow pulse and seizures. However it was not until 1901 that Morquio described a family in which several siblings were afflicted with a syndrome of slow pulse, syncopal attacks and sudden death in early childhood2. It is difficult to define precisely the incidence of the rare disorder in the community. In an International study3 from 44 pediatric centers in Europe, U.S.A., Canada and Mexico, a total of 599 infants and children with congenital complete heart block were evaluated. It was estimated from this study that the incidence of this disorder laid between 1:15,000 and 1:20,000 live births. It has been noted in 0.4-0.6 percent of all the children examined for possible Congenital Heart Disease in large referral Pediatric Cardiac Centers4-5.

Isolated Congenital Heart Block (CHB) in a structurally normal heart is almost invariably associated with the presence of maternal antibodies to the intracellular ribonucleoproteins Ro (SS-A) and La (SS-B) 6-7. This near universal association suggests that isolated CHB is a passively acquired autoimmune disease, in which maternal autoantibodies cross the placenta and injure the previously normal fetal heart. Other neonatal abnormalities including cutaneous manifestations, cholestasis and cytopenias are also associated with Anti Ro and La Antibodies in the maternal and fetal circulation and are now grouped under the heading Neonatal Lupus Syndrome (NLS). This term derived from the resemblance of the neonatal rash to the subacute cutaneous rash of Systemic Lupus Erythematosus (SLE) in adults – is clearly a misnomer, as the newborn does not have a systemic autoimmune disease and the mother may be completely asymptomatic. The noncardiac manifestations of NLS are generally transient, resolving at about 6 months of life coincident with the disappearance of maternal autoantibodies from the neonatal circulation. To date, however, complete (third degree) heart block is essentially irreversible. The relative rarity of autoimmune-associated CHB has posed a challenge to clinical and epidemiologic researchers8.

Case Report

A full term newborn male baby weighing 2.35 kg was admitted on second day of life with history of respiratory distress, tachypnea, feeding difficulty and groaning since birth. The child was delivered normally at a private hospital and cried immediately after birth. The patient was second in order of birth. Previous sib had Congenital Complete Heart Block and expired at 2 months of age. That child’s echocardiography had shown atrioventricular block but no structural abnormalities in the heart. There was no history of consanguinity, maternal fever, rashes, joint pain or drug intake. Mother was positive for Anti ribonucleoprotein antibody (Anti Ro +ve). Lupus Anticoagulant, Antinuclear Antibody and L.E. cells were negative. Fetal Echocardiography showed a complete heart block. The mother was not on regular follow-up in antenatal period and not receiving any treatment. On examination, the child’s general condition was unsatisfactory. The child was hypothermic, groaning and cyanosed. Cry activity and neonatal reflexes were decreased. There was marked respiratory distress; respiratory rate was 72 per minute with inter costal and sub costal recessions. Heart rate was 42 per minute and blood pressure was 60/40 mmHg. All peripheral pulses were palpable. The pupils were dilated and minimally reaction to light. There were popular rashes all over the body.

Cardiovascular system examination revealed the Apex beat on the left side in the fourth intercostal space. Heart sounds were normal and no murmur was audible all over praecordium. Liver was 3.5 cm below costal margin on the mid-clavicular line and the spleen was just palpable. Crepitations were heard bilaterally on chest examination. No other obvious congenital anomaly was found. On investigations blood sugar was 90 mg/dl, oxygen saturation 84% in room air, Hb was 13.9 gm/dl, TLC-26,900/cu mm, micro ESR – 18mm, Platelet count – 1 lack and band cells – 40% of neutrophils. Serum electrolyte, blood urea and serum calcium were within normal limits. Liver enzymes were increased (AST-418 units/1, ALT -124 units/1. Prothrombin time was prolonged. Chest X-ray showed cardiomegaly. On electrocardiogram atrial rate was 55 per minute and ventricular rate was 37 per minute. P wave marched throughout QRS complex and there was no conduction to ventricle. QRS complex deviation was 0.03 seconds. It was suggestive of complete heart block.

Baby’s blood group was A+ve and mother’s O+ve. TORCh and VDRL of both mother and baby were negative. Antiribonucleoprotein (Anti Ro) of mother was positive. 2D-Echocardiography revealed Complete Heart Block, Atrial rate was 55 per minute and ventricular rate was 35 per minute. The child was diagnosed as a case of Congenital Complete Heart Block with septicemia. The child was transferred to intensive care unit. The baby was kept nil orally and managed with oxygen inhalation, intravenous fluid, antibiotics and warmer care. Injection Atropine in a dosage of 0.03 mg/dose subcutaneously was given, whenever required. Inspite of all resuscitative measure, the child expired within few hours of admission.

Discussion

The classic description of neonatal lupus is one of a fetus or newborn discovered to have a slow heart rate due to CHB in the absence of causative structural abnormalities, for which laboratory investigation revealed Antibodies to Ro and /or La in the maternal serum. Although the mother may have SLE, Sjogren’s Syndrome (SS) or an undifferentiated autoimmune syndrome, many mothers are entirely asymptomatic. Our child had Heart Rate of 42 per minute, 2-D Echo had shown Atrioventricular Block without any structural abnormalities in the heart. Anti ribonucleoprotein of mother was positive, although mother was asymptomatic.

 

The mechanism of damage and causative pathways in neonatal lupus congenital heart block are not completely understood. Presumable the fetus develops normally until maternal IgG antibodies against the intracellular ribonuclear proteins Ro and La are actively transported across the placenta beginning at 12 weeks of gestation9. The antibodies are thought to bind to cells of the fetal conduction system, producing an early inflammatory cascade, later scarring and fibrosis10-11. The mechanism of late cardiomyopathy is unclear since maternal antibodies are often absent.

Many cases are discovered in utero most commonly between 18 and 24 weeks of gestation. The degree of heart block includes all levels from first degree discovered only incidentally on electrocardiogram (i.e. after birth), though third degree complete heart block with ventricular rates below 50 beats per minutes. Mortality (including feta demise) is 20; the highest mortality occurs in prematurely delivered newborns in the first few month of life8. Current practice suggests that virtually all patients with complete heart block will have a pacemaker at some point in their lives8. Unfortunately, conduction system disease alone in not the whole story in NLS. There is a disturbingly high incidence of late cardiomyopathy leading to low output congestive heart failure, death or transplant, even after successful pacemaker implantation for the associated heart block8,12. Other organ systems maybe involved in the newborn, in the presence or absence of CHB. The characteristic NLS rash involves the scalp and face, particularly the periorbital region and is photosensitive. Occasionally newborns of mother with Anti Ro/ La antibodies may present with various cytopenias6, 12,13 and/or liver enzyme abnormalities14,15. The incidence of neonatal lupus in an offspring of a mother with Anti Ro antibodies is estimated at 1-5%7, 16,17. When an Anti Ro positive mother has previously given birth to a child with NLS, the risk of CHB in a subsequent pregnancy rises to approximately 18%12,18.

Our child had completed Atrioventricular Block. Previous sib also had complete Atrioventricular Block and expired at 2 month of age. This child had cutaneous rashes and liver enzymes were raised.

The identification of fetal bradycardia by either auscultation or routine obstetric ultrasound should prompt two immediate responses. The first is to obtain a 2- dimensional and M-mode fetal echocardiographic and Doppler ultrasound to document whether there is an Atrial arrhythmia or AV block and to what degree. The second response is to evaluate the mother’s serum for the presence of Anti Ro with or without Anti La antibodies. The ELISA is the most common and probably the most sensitive method for detection of these antibodies.

In our child 2-D fetal echocardiography suggested complete heart block. Unfortunately, mother was not on regular follow-up and had not received any medication.

Because CHB is most often identified between 18 and 24 weeks of gestation, intrauterine therapy ought to be possible. The clinical approach includes obstetric and rheumatologic management of both the fetus identified with CHB and the fetus with a normal heart rate but at high risk of developing CHB. In either situation the critical decision is whether or not any treatment is necessary. Guidelines are not well established and are based empirically on anecdotal evidence. Several intrauterine therapeutic regimens have been tried, including dexamethasone19, 20 which is not metabolized by the placenta and is available to the fetus in an active form and plasmaphoresis21. Recently in the United States a multicenter prospective trial has been initiated to evaluate the efficacy of 4 mg/day of dexamethasone (taken orally by the mother) in the treatment of newly identified first, second or third degree block.

 

References

 

1.     Major RH. Disease of the circulatory system. In. Classical Description of Disease. Oxford, Blackwell Scientific Publications.1948; 326-329.

2.     Morquio, Maladie S. Infantile et familiable Characterises Pardes modification Permanantes dupouls de attaques Syncapales et epileptiformes et al. Morte subite. Arch Med Eng. 1901;4: 467-69.

3.     Michaelson M, Engle MA. Congenital complete Heart Block: An International study of the naturalhistory. Cardiovasc Clin 1972; 4:85 -7.

4.     Keith JD, Row RD, Vlad P. Heart Disease in infancy and childhood. 3rd ed. Mac Millan; New York 1978; 290-94.

5.     Karpawich PP, Gillette PC, Garson A Jr, Hesslein PS, Porter C, Mc Namara DG. Congenital Complete Atrioventricular Block: Clinical and electro physiologic predictors of need for pacemake insertion. Am J Cardiol 1981; 48: 1098.

6.     Buyon JP. Neonatal Lupus Syndrome. In Lahita R, ed. Systemic Lupus Erythematosus, 3rd edn. New York; Academic Press; 1998:337-359.

7.     Lee LA. Neonatal lupus erythematosus. J Invest Derm 1993; 100:95-135.

8.     Buyan JP, Hiebert R, and Copel J et al. Autoimmune associated congenital heart block: Motality, morbidity and recurrence rates obtained from a national neonatal lupus registry. J Am Coll Cardiol 1998; 31: 1658-1666.

9.     Wells M, Fox H. immunology and the immunopathology of the maternofetal interface. In Coulam CB, Faulk WP, Me Intyre JA (eds.) Immunological obstetrics, New York, WW Norton & Co. 1992; 166-176.

10.  Scott JS, Maddison PJ, Taylor PV, Esscher E, Scott O, Skinner RP. Connective tissue Disease, Antibodies to ribonucleoprotein and congenital heart block. New Eng1 J Med 1983; 309: 209-212.

11.  Clancy R, As Kanase AD, Chiopelas E, Azar N, Miranda ME, Buyan JP. Pivotal role of human fetal cardiac fibroblasts in the pathogenesis of autoantibody-associated congenital heart block. Arthritis Rheum 2001; 44(Suppl):S160.

12.  Moak JP, Barrons KS, Hougen TJ et al. Congenital heart block: development of late onset cardiomyopathy, a previously underappreciated Sequela. J Am Coll Cardio.2001; 37:238-42.

13.  Watson R, Kang JE, May M, Hudak M, Kickler T, Provost TT. Thrombocytopenia in the neonatal lupus syndrome. Arch Dermato 1988; 124: 560-63.

14.  Laxer RM, Roberts EA, Gross KR, Britton JR, Cutz E, Dimmick J, Petty RE, Silverman ED. Liver disease in neonatal lupus erythematosus. J Pediatr 1990; 116: 238-42.

15.  Lee LA, Soko1 RJ, Buyon JP. Hepatobiliary disease in neonatal lupus: Prevalence and clinical characteristics in cases enrolled in a national registry. Pediatrics 2002; 109: E11.

16.  Ramsey-Goldmann R, Hom D, Deng JS et al. Anti SS-A Antibodies and fetal outcome in maternal systemic lupus erythematosus. Arthritis Rheum 1986; 29: 1269-73.

17.  Brucato A, Frassi M, Franceschini P, Cimaz R, Faden D, Pisoni MP et al. Risk of Congenital Complete Heart Block in newborns of mothers with Anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis : a prospective study of 100 women. Arthritis Rheum 2001; 44: 1832-38.

18.  Julkunen H, Eronen M. The rate of recurrence of isolated congenital heart block: A population-based study. Arthritis Rheum 2001; 44:487-88.

19.  Rosenthal D, Druzin M, Chin C, Dubrin A. A new therapeutic approach to the fetus with Congenital Complete Hear Block: Preemptive, targeted therapy with Dexamethasone. Obstet Gynecol 1998; 92: 689-91.

20.  Saleeb S, Copel J, Friedman D, Buyon JP. Comparison of treatment with fluorinated glucocorticoids to the natural history of autoantibody-associated congenital heart block: Retrospective review of the Research Registry for neonatal lupus. Arthritis Rheum 1999; 42: 2335-45.

21.  Buyon JP, Swersky Sh, Fox HE, Bierman FZ, Winchester RJ. Intrauterine therapy for presumptive fetal myocarditis with acquired heart block due to systemic lupus erythemtosus. Experience in a mother with a predominance of SS-B(La) antibodies. Arthritis Rheum