6 18
Brief clinical and laboratory observations
thralgias, decreased vision from optic nerve granuloma, laryngitis with aphonia on several occasions, nodular or infiltrative parenchymal pulmonary lesions, proptosis, pseudotumor of the orbit, cutaneous nodules, and renal lesions. These patients did not appear to have any of the other vasculitic or granulomatous diseases in the differential diagnosis of Wegener granulomatosis. Although 200 cases of this disease had been reported by 1967 and several other large series have recently appeared,1. ,0 to our knowledge only seven cases of disseminated Wegener granulomatosis under the age of 16, each with a fatal outcome, have been described ~-1~ (Table I). Most of these patients had been given either symptomatic treatment or treatment with prednisone alone. Both of our patients have been treated with prednisone and cyclophosphamide. Patient 1 received 18 months of cyclophosphamide therapy. Since then she has experienced clinical improvement and maintained stable renal function. Patient 2 was treated for three months with azathioprine without apparent benefit, but had clinical improvement after cyclophosphamide was substituted. The introduction of cytotoxic therapy for this disorder has vastly improved the previous mean survival rate of five months. 2 Only three deaths have occurred among 47 patients given an adequate therapeutic trial with a variety of immunosuppressive agents, including azathioprine, chlorambucil, or cyclophosphamide.' Cyclophosphamide has been used more frequently than the other agents'. 10at a dose of 1 to 2 mg/kg by mouth or 2 to 4 mg/kg intravenously for the first week in fulminant cases. It is uncertain how long this form of therapy should be used.
Congenital complete heart block associated with hydrops fetalis Karl M. Altenburger, M.D.,* Maryann Jedziniak, M.D., William L. Roper, M.D., and Jacinto Hernandez, M.D., Denver, Colo. From The Department of Pediatrics, University of Colorado Medical Center, and The Children's Hospital. *Reprint address: Department of Pediatrics, Box C-220, University of Colorado Medical Center, Denver, CO 80262.
The Journal of Pediatrics October 1977
Most patients show evidence of remission within several weeks, but relapses are known to occur in patients apparently free of the disease for one year.' Relapses have responded to additional courses o f cyclophosphamide, with lasting improvement for as long as 689 years. We thank Scott Arnold, M.D., of Cuba City, Wis., and Jack Schroeder, M.D., of Beloit, Wis., for referral of these patients, Charles Brandenberg, M.D., for expert otolaryngologic consultation, Thomas France, M.D., for expert opthalmologic consultation, and to Ms. Joyce Bublitz for secretarial assistance. REFERENCES 1. WolffSM, Fauci AS, Horn RG, et al: Wegener's granulomatosis, Ann Intern Med 81:513, t974. 2. Walton EW: Giant-cell granuloma of the respiratory tract (Wegener's granulomatosis), Br Med J 11:265, 1958. 3. Carrington CB, and Liebow AA: Limited forms of angiitis and granulomatosis of Wegener's type, Am J Med 41:497, 1966. 4. Case records of the Mass. General Hospital, Case No. 37511, N Engl J Med 245:978, 1951. 5. Feldman F, Fink H, and Gruezo Z: Wegener's granulomatosis, Am J Dis Child 112:587, 1966. 6. Roback SA, Herdman RC, Hoyer JH, et al: Wegener's granulomatosis in a child: Observations in pathogenesis and treatment, Am J Dis Child 118:608, 1969. 7. LancosF, Erdos Z, Kadar A, et al: Wegenersche granulomatose in kindesalter, Acta Paediatr Acad Sci Hung 12:285, 1971. 8. Fahey J, Leonard E, Churg J, et al: Wegener's granulomatosis, Am J Med 17:168, 1954. 9. Isaeva LA, Fedorova AN, Lysinka GA, et al: Wegener's granulomatosis in children, Pediatriia 51:67, t972. 10. Hu C-H, O'Loughlin S, and Winkelmann RK: Cutaneous manifestations of Wegener granulomatosis, Arch Dermatol 113:175, 1977.
THIS REPORT describes a newborn infant with congenital complete heart block resulting in hydrops retails. CASE R E P O R T A five-hour-old white male infant was admitted to The Children's Hospital intensive care nursery because of severe hydrops and respiratory distress. He was born at 33 weeks' gestation to a healthy 31-year-old mother. At 32 weeks' gestation Abbreviation used ANA: antinuclear antibodies
I
the fetal heart rate was noted to be 40 to 60/minute. Because fetal movement' had continued unchanged, no fetal distress was presumed. One week later the mother noted decreased fetal movement. The fetal heart rate was again regular at 40 to 60 beats/minute. An ultrasound scan showed a "halo" around the fetal head, and an emergency cesarean section was performed for presumed fetal distress.
Volume 91 Number 4
A 3,340-gm infant was delivered in breech position, with Apgar scores of 3, 2, and 4 at one, five, and eight minutes, respectively. The infant was grossly hydropic. Resuscitative efforts included immediate intubation, ventilatory support, and placement of umbilical venous catheters. Initial arterial blood gases were as follows: pH 7.05, Po~ 32 mm Hg, Pco~ 64 mm Hg, and base excess -10. The infant was then given 4 mEq of sodium bicarbonate by sl0w intravenous infusion. A radiograph of the chest showed bilateral pleural effusions. Heart size could not be determined. The infant was transported to this hospital in critical condition. On admission the systolic blood pressure was 62 mm Hg, the heart rate 44 and regular, the respiratory rate 40, and the temperature 96.6~ The infant had gross edema of the head, trunk, and all extremities, with no spontaneous movement. The breath and heart sounds were barely audible due to the massive truncal edema. The abdomen was tense and distended; the liver edge was not palpable. The placenta weighed 623 gm, with an immature edematous appearance and no evidence of inflammation on histologic examination. On admission the hemoglobin was 12.9 gm/dl; hematocrit 31%; white cell count 19,400; differential-neutrophils 44%, band forms 12%, and lymphocytes 41%; platelets 35,000; and reticulocytes 4.2%. The type and Rh of the infant were 0 + and of the mother, 0 negative. Coombs tests, direct and indirect, were negative. Chemistry values on admission included a sodium concentration of 140 mEq/1, potassium 3.8 mEq/1, blood urea nitrogen 12 mg/dl, bilirubin 2.1 mg total and 0.6 mg conjugated, total protein 2.9 gm/dl, and serum glutamic oxalacetic transaminanse 23. Maternal ANA titers were 1:16 and 1:64, the latter value being weakly positive in our laboratory. Results of serum protein electrophoresis, hemoglobin electrophoresis, and immunoglobulin electrophoresis were all within normal limits. Owing to severe chest wall edema, a satisfactory electrocardiogram could not be obtained. Echocardiography showed normal intracardiac anatomy. A repeat roentgenogram examination of the chest revealed expansion of the lungs bilaterally and cardiomegaly. Because of the multiple invasive procedures, the infant was given ampicillin 150 mg/kg/day and gentamicin 7.0 mg/kg/day. Bacterial cultures of the blood, urine, and cerebrospinal fluid were negative. The infant underwent a single-volume exchange transfusion with packed red blood cells, and received two fresh plasma transfusions (10 ml/kg). Following this, a fluid regimen of 60 to 75 ml/kg/day was begun. At 18 hours of age, the infant's weight had decreased to 2,820 gm. Following the failure of an infusion of isoproterenol to alter the heart rate, a transvenous fixed-rate pacemaker was inserted at 20 hours of age, maintaining the heart rate at 100 beats/minute. Catheterization data obtained at the time of pacemaker insertion showed right-sided pressures to be equal to systemic and elevated left ventricular end-diastolic pressures. The diuresis continued over the next 24-hour period, the weight reaching 2,120 gm at 48 hours of age. The pacemaker became dislodged and ceased to trigger the heart beat on the fourth day of life, but the infant continued to improve until day seven, when the liver was palpable 4.5 em below the right costal margin and edema was noted on radiograph of the chest. No further increase in heart size was noted. The infant was treated
Brief cfinical and laboratory observations
6 19
with furosemide and the pulmonary edema cleared. An electrocardiogram showed a ventricular rate of 45 and an atrial rate of 140 with a QRS duration of 0.08 second. On day 15 a reaccumulation of fluid was noted in the right chest, which again responded to furosemide therapy. The infant continued to improve and was discharged at a weight of 2,380 gm on day 28, receiving no medications. Physical examination was essentially normal except for Gradycardia. One week after discharge, mild cardiomegaly and a small right-sided pleural effusion were noted on roentgen examination. DISCUSSION H y d r o p s fetalis has b e e n frequently described with cardiac abnormalities a n d specifically with supraventricular tachyrhythmias. 1 In our p a t i e n t the k n o w n causes o f hydrops were excluded, a n d it a p p e a r s that a n o t h e r etiology should be a d d e d to those previously reported. The association o f congenital h e a r t block a n d m a t e r n a l connective tissue disease is also b e i n g recognized with increasing frequency. M c C u e a n d associates ~ recently reported a review o f 20 cases of congenital h e a r t block in which 60% o f their infants' m o t h e r s h a d e i t h e r positive A N A or r h e u m a t o i d factor titers. T h e exact relationship of congenital h e a r t block a n d hydrops fetalis is unclear. A t r i o v e n t r i c u l a r block a n d its obligatory increase in end-diastolic pressure would result in a n increase in venous pressure a n d e x u d a t i o n from the vascular space. R u d o l p h a n d H e y m a n n ' d e m o n s t r a t e d a reduction in right ventricular o u t p u t as a result o f a fall in heart rate in fetal lambs; their work would seem to indicate that the F r a n k - S t a r l i n g relationship does not play a role in the regulation o f cardiac output. K i r k p a t r i c k a n d associates 4 failed to confirm these observations, a n d the in utero effect of heart rate o n cardiac o u t p u t r e m a i n s unclear. Silber a n d D u r n i n ' speculated t h a t low cardiac o u t p u t secondary to the a r r h y t h m i a resulted in chronic tissue hypoxia a n d a b e r r a t i o n o f s e r u m osmolality, as described by Battaglia a n d associates? Postnatally, after r e m o v a l of the large v o l u m e placental circulation a n d with i m p r o v e d oxygenation, the still c o m p r o m i s e d cardiac o u t p u t could be sufficient to m a i n t a i n a d e q u a t e tissue perfusion. We thank Dr. James Strain for referring this patient to our care, Drs. Frederick C. Banaglia and Robert Wolfe for their critical comments, Dr. Richard Wesenberg for his assistance in interpreting the radiographic findings, and Dr. Robert McGrath for the echocardiographic evaluation. In addition, we thank Ms. Phyllis Hamilton for her technical assistance. REFERENCES
1. Silber DL, and Durnin RE: Intrauterine atrial tachycardia associated with massive edema in a newborn, Am J Dis Child 117:722, 1969.
620
2.
Brief clinical and laboratory observations
McCue CM, Mantakas ME, Tingelstod JB, and Ruddy S: Congenital heart block in newborns of mothers with connective tissue disease, Circulation (in press). 3. Rudolph AM, and Heymann MA: Fetal and neonatal circulation and respiration, Ann Rev Physiol 36:187, 1974. 4. Kirkpatrick SE, Pitlick PT, Naliboff J, and Friedman WF:
The Journal of Pediatrics October 1977 Frank-Starling relationship as an important determinant of fetal cardiac output, Am J Physiol 231:495, 1976. Battaglia FC, Meschia G, Hellegers A, and Barror DH: The effects of acute hypoxia on the osmotic pressure of the plasma, Q J Exp Pathol 43:197, 1958.
Brief clinical and laboratory observations
thralgias, decreased vision from optic nerve granuloma, laryngitis with aphonia on several occasions, nodular or infiltrative parenchymal pulmonary lesions, proptosis, pseudotumor of the orbit, cutaneous nodules, and renal lesions. These patients did not appear to have any of the other vasculitic or granulomatous diseases in the differential diagnosis of Wegener granulomatosis. Although 200 cases of this disease had been reported by 1967 and several other large series have recently appeared,1. ,0 to our knowledge only seven cases of disseminated Wegener granulomatosis under the age of 16, each with a fatal outcome, have been described ~-1~ (Table I). Most of these patients had been given either symptomatic treatment or treatment with prednisone alone. Both of our patients have been treated with prednisone and cyclophosphamide. Patient 1 received 18 months of cyclophosphamide therapy. Since then she has experienced clinical improvement and maintained stable renal function. Patient 2 was treated for three months with azathioprine without apparent benefit, but had clinical improvement after cyclophosphamide was substituted. The introduction of cytotoxic therapy for this disorder has vastly improved the previous mean survival rate of five months. 2 Only three deaths have occurred among 47 patients given an adequate therapeutic trial with a variety of immunosuppressive agents, including azathioprine, chlorambucil, or cyclophosphamide.' Cyclophosphamide has been used more frequently than the other agents'. 10at a dose of 1 to 2 mg/kg by mouth or 2 to 4 mg/kg intravenously for the first week in fulminant cases. It is uncertain how long this form of therapy should be used.
Congenital complete heart block associated with hydrops fetalis Karl M. Altenburger, M.D.,* Maryann Jedziniak, M.D., William L. Roper, M.D., and Jacinto Hernandez, M.D., Denver, Colo. From The Department of Pediatrics, University of Colorado Medical Center, and The Children's Hospital. *Reprint address: Department of Pediatrics, Box C-220, University of Colorado Medical Center, Denver, CO 80262.
The Journal of Pediatrics October 1977
Most patients show evidence of remission within several weeks, but relapses are known to occur in patients apparently free of the disease for one year.' Relapses have responded to additional courses o f cyclophosphamide, with lasting improvement for as long as 689 years. We thank Scott Arnold, M.D., of Cuba City, Wis., and Jack Schroeder, M.D., of Beloit, Wis., for referral of these patients, Charles Brandenberg, M.D., for expert otolaryngologic consultation, Thomas France, M.D., for expert opthalmologic consultation, and to Ms. Joyce Bublitz for secretarial assistance. REFERENCES 1. WolffSM, Fauci AS, Horn RG, et al: Wegener's granulomatosis, Ann Intern Med 81:513, t974. 2. Walton EW: Giant-cell granuloma of the respiratory tract (Wegener's granulomatosis), Br Med J 11:265, 1958. 3. Carrington CB, and Liebow AA: Limited forms of angiitis and granulomatosis of Wegener's type, Am J Med 41:497, 1966. 4. Case records of the Mass. General Hospital, Case No. 37511, N Engl J Med 245:978, 1951. 5. Feldman F, Fink H, and Gruezo Z: Wegener's granulomatosis, Am J Dis Child 112:587, 1966. 6. Roback SA, Herdman RC, Hoyer JH, et al: Wegener's granulomatosis in a child: Observations in pathogenesis and treatment, Am J Dis Child 118:608, 1969. 7. LancosF, Erdos Z, Kadar A, et al: Wegenersche granulomatose in kindesalter, Acta Paediatr Acad Sci Hung 12:285, 1971. 8. Fahey J, Leonard E, Churg J, et al: Wegener's granulomatosis, Am J Med 17:168, 1954. 9. Isaeva LA, Fedorova AN, Lysinka GA, et al: Wegener's granulomatosis in children, Pediatriia 51:67, t972. 10. Hu C-H, O'Loughlin S, and Winkelmann RK: Cutaneous manifestations of Wegener granulomatosis, Arch Dermatol 113:175, 1977.
THIS REPORT describes a newborn infant with congenital complete heart block resulting in hydrops retails. CASE R E P O R T A five-hour-old white male infant was admitted to The Children's Hospital intensive care nursery because of severe hydrops and respiratory distress. He was born at 33 weeks' gestation to a healthy 31-year-old mother. At 32 weeks' gestation Abbreviation used ANA: antinuclear antibodies
I
the fetal heart rate was noted to be 40 to 60/minute. Because fetal movement' had continued unchanged, no fetal distress was presumed. One week later the mother noted decreased fetal movement. The fetal heart rate was again regular at 40 to 60 beats/minute. An ultrasound scan showed a "halo" around the fetal head, and an emergency cesarean section was performed for presumed fetal distress.
Volume 91 Number 4
A 3,340-gm infant was delivered in breech position, with Apgar scores of 3, 2, and 4 at one, five, and eight minutes, respectively. The infant was grossly hydropic. Resuscitative efforts included immediate intubation, ventilatory support, and placement of umbilical venous catheters. Initial arterial blood gases were as follows: pH 7.05, Po~ 32 mm Hg, Pco~ 64 mm Hg, and base excess -10. The infant was then given 4 mEq of sodium bicarbonate by sl0w intravenous infusion. A radiograph of the chest showed bilateral pleural effusions. Heart size could not be determined. The infant was transported to this hospital in critical condition. On admission the systolic blood pressure was 62 mm Hg, the heart rate 44 and regular, the respiratory rate 40, and the temperature 96.6~ The infant had gross edema of the head, trunk, and all extremities, with no spontaneous movement. The breath and heart sounds were barely audible due to the massive truncal edema. The abdomen was tense and distended; the liver edge was not palpable. The placenta weighed 623 gm, with an immature edematous appearance and no evidence of inflammation on histologic examination. On admission the hemoglobin was 12.9 gm/dl; hematocrit 31%; white cell count 19,400; differential-neutrophils 44%, band forms 12%, and lymphocytes 41%; platelets 35,000; and reticulocytes 4.2%. The type and Rh of the infant were 0 + and of the mother, 0 negative. Coombs tests, direct and indirect, were negative. Chemistry values on admission included a sodium concentration of 140 mEq/1, potassium 3.8 mEq/1, blood urea nitrogen 12 mg/dl, bilirubin 2.1 mg total and 0.6 mg conjugated, total protein 2.9 gm/dl, and serum glutamic oxalacetic transaminanse 23. Maternal ANA titers were 1:16 and 1:64, the latter value being weakly positive in our laboratory. Results of serum protein electrophoresis, hemoglobin electrophoresis, and immunoglobulin electrophoresis were all within normal limits. Owing to severe chest wall edema, a satisfactory electrocardiogram could not be obtained. Echocardiography showed normal intracardiac anatomy. A repeat roentgenogram examination of the chest revealed expansion of the lungs bilaterally and cardiomegaly. Because of the multiple invasive procedures, the infant was given ampicillin 150 mg/kg/day and gentamicin 7.0 mg/kg/day. Bacterial cultures of the blood, urine, and cerebrospinal fluid were negative. The infant underwent a single-volume exchange transfusion with packed red blood cells, and received two fresh plasma transfusions (10 ml/kg). Following this, a fluid regimen of 60 to 75 ml/kg/day was begun. At 18 hours of age, the infant's weight had decreased to 2,820 gm. Following the failure of an infusion of isoproterenol to alter the heart rate, a transvenous fixed-rate pacemaker was inserted at 20 hours of age, maintaining the heart rate at 100 beats/minute. Catheterization data obtained at the time of pacemaker insertion showed right-sided pressures to be equal to systemic and elevated left ventricular end-diastolic pressures. The diuresis continued over the next 24-hour period, the weight reaching 2,120 gm at 48 hours of age. The pacemaker became dislodged and ceased to trigger the heart beat on the fourth day of life, but the infant continued to improve until day seven, when the liver was palpable 4.5 em below the right costal margin and edema was noted on radiograph of the chest. No further increase in heart size was noted. The infant was treated
Brief cfinical and laboratory observations
6 19
with furosemide and the pulmonary edema cleared. An electrocardiogram showed a ventricular rate of 45 and an atrial rate of 140 with a QRS duration of 0.08 second. On day 15 a reaccumulation of fluid was noted in the right chest, which again responded to furosemide therapy. The infant continued to improve and was discharged at a weight of 2,380 gm on day 28, receiving no medications. Physical examination was essentially normal except for Gradycardia. One week after discharge, mild cardiomegaly and a small right-sided pleural effusion were noted on roentgen examination. DISCUSSION H y d r o p s fetalis has b e e n frequently described with cardiac abnormalities a n d specifically with supraventricular tachyrhythmias. 1 In our p a t i e n t the k n o w n causes o f hydrops were excluded, a n d it a p p e a r s that a n o t h e r etiology should be a d d e d to those previously reported. The association o f congenital h e a r t block a n d m a t e r n a l connective tissue disease is also b e i n g recognized with increasing frequency. M c C u e a n d associates ~ recently reported a review o f 20 cases of congenital h e a r t block in which 60% o f their infants' m o t h e r s h a d e i t h e r positive A N A or r h e u m a t o i d factor titers. T h e exact relationship of congenital h e a r t block a n d hydrops fetalis is unclear. A t r i o v e n t r i c u l a r block a n d its obligatory increase in end-diastolic pressure would result in a n increase in venous pressure a n d e x u d a t i o n from the vascular space. R u d o l p h a n d H e y m a n n ' d e m o n s t r a t e d a reduction in right ventricular o u t p u t as a result o f a fall in heart rate in fetal lambs; their work would seem to indicate that the F r a n k - S t a r l i n g relationship does not play a role in the regulation o f cardiac output. K i r k p a t r i c k a n d associates 4 failed to confirm these observations, a n d the in utero effect of heart rate o n cardiac o u t p u t r e m a i n s unclear. Silber a n d D u r n i n ' speculated t h a t low cardiac o u t p u t secondary to the a r r h y t h m i a resulted in chronic tissue hypoxia a n d a b e r r a t i o n o f s e r u m osmolality, as described by Battaglia a n d associates? Postnatally, after r e m o v a l of the large v o l u m e placental circulation a n d with i m p r o v e d oxygenation, the still c o m p r o m i s e d cardiac o u t p u t could be sufficient to m a i n t a i n a d e q u a t e tissue perfusion. We thank Dr. James Strain for referring this patient to our care, Drs. Frederick C. Banaglia and Robert Wolfe for their critical comments, Dr. Richard Wesenberg for his assistance in interpreting the radiographic findings, and Dr. Robert McGrath for the echocardiographic evaluation. In addition, we thank Ms. Phyllis Hamilton for her technical assistance. REFERENCES
1. Silber DL, and Durnin RE: Intrauterine atrial tachycardia associated with massive edema in a newborn, Am J Dis Child 117:722, 1969.
620
2.
Brief clinical and laboratory observations
McCue CM, Mantakas ME, Tingelstod JB, and Ruddy S: Congenital heart block in newborns of mothers with connective tissue disease, Circulation (in press). 3. Rudolph AM, and Heymann MA: Fetal and neonatal circulation and respiration, Ann Rev Physiol 36:187, 1974. 4. Kirkpatrick SE, Pitlick PT, Naliboff J, and Friedman WF:
The Journal of Pediatrics October 1977 Frank-Starling relationship as an important determinant of fetal cardiac output, Am J Physiol 231:495, 1976. Battaglia FC, Meschia G, Hellegers A, and Barror DH: The effects of acute hypoxia on the osmotic pressure of the plasma, Q J Exp Pathol 43:197, 1958.
