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Hypereosinophilic syndrome in a trisomy 21 fetus
Hypereosinophilic syndrome in a trisomy 21 fetus Yasuki Kusanagi, MD, Hiroshi Ochi, MD, DMSc, Keiichi Matsubara, MD, DMSc, and Masaharu Ito, MD, DMSc, Background: Hypereosinophilic syndrome is characterized by peripheral blood eosinophilia and multiple organ system involvement. Only one case in a newborn has been reported. Case: Fetal sonography performed on a 33-year-old woman at 35 weeks’ gestation showed pericardial effusion and cardiomegaly. The infant was delivered by cesarean at 35 weeks’ gestation because of a worsening of the pericardial effusion. Hematologic studies revealed unexplained hypereosinophilia, and the pericardial fluid contained a large number of eosinophils. Chromosomal analysis revealed trisomy 21. The hypereosinophilia, pericardial effusion, and cardiomegaly all resolved after 8 weeks of steroid therapy. Conclusion: Hypereosinophilic syndrome caused pericardial effusion and cardiomegaly in a fetus with trisomy 21. (Obstet Gynecol 1998;92:701–2. © 1998 by The American College of Obstetricians and Gynecologists.)
Hypereosinophilic syndrome, a multisystem disease characterized by eosinophilia in the peripheral blood and the involvement of multiple organ systems, tends to occur in adults between the ages of 20 and 50.1 Only one case2 of hypereosinophilic syndrome in a newborn has been reported. We describe the echocardiographic features of this disorder in a Japanese fetus as well as the antenatal clinical findings.
Figure 1. Four-chamber view of the heart revealed pericardial effusion and cardiomegaly (cardiothoracic area ratio 40%).
immature cervix. A female infant was delivered, weighing 2478 g and with an Apgar score of 9 at 5 minutes. Physical examination of the newborn revealed hepatosplenomegaly. Neonatal echocardiography confirmed the presence of pericardial effusion and revealed a thickening of the ventricular septum and a normal cardiac anatomy. The white blood cell count at birth was 104,000/mm3, with 28% eosinophils and 27.5% blast cells. A bone marrow aspirate contained 36% mature eosinophils and 15% blast cells. Chromosomal analysis revealed 47,XX,121. Pericardiocentesis was performed in an attempt to improve the infant’s cardiac function. Approximately 14 mL of pericardial fluid containing a large number of eosinophils were removed. An intravenous infusion of prednisolone was started at a dosage of 2 mg/kg per day and was increased to 5 mg/kg on the 9th day. After 2 weeks, the treatment regimen was changed to oral administration of prednisolone, and drug therapy was stopped after 12 weeks. All hematologic measures returned to the normal range, and the pericardial effusion and cardiomegaly resolved after 8 weeks.
Case A 33-year-old Japanese woman, gravida 2, para 1, presented for prenatal care at 13 weeks’ gestation. Her previous pregnancy had been complicated by preeclampsia, and she was delivered by cesarean. We administered low-dose aspirin orally beginning at 13 weeks’ gestation to prevent preeclampsia. Routine sonographic examination of the fetus at 35 weeks’ gestation revealed a pericardial effusion. Except for cardiomegaly (cardiothoracic area ratio 40%) and a thickening of the ventricular septum (Figure 1), the fetal heart exhibited no obvious structural cardiac defects. The volume of amniotic fluid and the thickness of the placenta were within normal range. Serologic screening was negative for toxoplasmosis, rubella, and cytomegalovirus. On the 2nd day of hospitalization, the fetal pericardial effusion worsened and a cesarean was performed, in view of the
From the Department of Obstetrics and Gynecology Ehime University School of Medicine, Shigenobu, Ehime, Japan.
VOL. 92, NO. 4, PART 2, OCTOBER 1998
Comment Hypereosinophilic syndrome, characterized by unexplained prolonged eosinophilia (eosinophil count exceeding 1500/mm3) that leads to end-organ involvement,1 is extremely rare in infants. A literature search by MEDLINE, using “hypereosinophilic syndrome” from 1966 to 1997, identified only two such cases,2,3 one of which had been diagnosed at birth.2 More than 75% of the patients with hypereosinophilic syndrome exhibit cardiac involvement; there is often pericardial effusion, thickening of the ventricular septum, and cardiomegaly.4 Our case exhibited echocardiographic features of this disorder in utero, which has not been described in the literature. Patients with Down syndrome are at an increased risk for transient abnormal myelopoiesis. Recently, intrauterine diagnosis of fetal hydrops in association with
0029-7844/98/$19.00 PII S0029-7844(98)00084-2
701
transient myeloproliferative disorder in Down syndrome fetuses was reported.5 Nevertheless, an association between such abnormalities and hypereosinophilic syndrome has not been established. Using blast cells from a Down syndrome patient with transient abnormal myelopoiesis, Suda et al6 demonstrated that recombinant granulocyte-macrophage colony-stimulating factor supports the differentiation of eosinophils, neutrophils, and macrophages. This in vitro finding may be applicable to the finding of eosinophilia in our patient. Down syndrome in a fetus is a relatively common cause of nonimmune hydrops. The cause of hydrops may vary from case to case, but congestive heart failure or fetal hypoxia from placental abnormalities or lymphatic obstruction commonly is implicated. Pericardial effusion in the fetus should be interpreted as a manifestation of heart failure in utero; it often increases before the appearance of hydrops.7 In our patient, eosinophilia may have caused cardiac involvement directly, or degranulation of eosinophils with deposition of the toxic eosinophil granule proteins may cause myocardial necrosis.8 Our case suggests that involvement of the fetal heart due to eosinophilic infiltration of the pericardium and myocardium may cause pericardial effusion and cardiomegaly, followed by hydrops fetalis due to heart failure.
References
2. Johansson A, Ferster A, Steppe M, Otten J. Idiopathic hypereosinophilic syndrome in a neonate. J Pediatr 1988;113:614 –5. 3. Wynn SR, Sachs MI, Keating MU, Ostrom NK, Kadota RP, O’Connel EJ, et al. Idiopathic hypereosinophilic syndrome in a 51⁄2-month-old infant. J Pediatr 1987;111:94 –7. 4. Take M, Sekiguchi M, Hiroe M, Hirosawa K, Mizoguchi H, Kijima M, et al. Clinical spectrum and endomyocardial biopsy findings in eosinophilic heart disease. Heart Vessels 1985;1 Suppl:243–9. 5. Strobelt N, Ghidini A, Locatelli A, Vergani P, Mariani S, Biondi A. Intrauterine diagnosis and management of transient myeloproliferative disorder. Am J Perinatol 1995;2:132– 4. 6. Suda J, Eguch M, Akiyama Y, Iwama Y, Furukawa T, Sato Y, et al. Differentiation of blast cells from a Down syndrome patient with transient myeloproliferative disorder. Blood 1987;69:508 –12. 7. Steinfeld L, Rappaport HL, Rossbach HC, Martines E. Diagnosis of fetal arrhythmias using echocardiographic Doppler techniques. J Am Coll Cardiol 1986;8:1425–33. 8. Tai PC, Ackerman SJ, Spry CJ, Dunnette S, Olsen EG, Gleich GJ. Deposits of eosinophil granule proteins in cardiac tissues of patients with eosinophilic endomyocardial disease. Lancet 1987;1:643–7.
Address reprint requests to:
Yasuki Kusanagi, MD Department of Obstetrics and Gynecology Ehime University School of Medicine Shigenobu Ehime, 791-02 Japan Received November 12, 1997. Received in revised form January 13, 1998. Accepted February 12, 1998.
1. Hardy WR, Anderson RE. The hypereosinophilic syndromes. Ann Intern Med 1968;68:1220 –9.
Copyright © 1998 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Postmortem DNA diagnosis of factor V Leiden in a neonate with systemic thrombosis and probable antithrombin deficiency
discovered defect, the factor V Leiden mutation, is the most frequent inherited risk factor for venous thrombosis. Case: Factor V Leiden was diagnosed postmortem in a neonate who died from complications of vena caval and aortic thrombosis. Investigation into the family history revealed that the father had a record of multiple thromboses, and blood testing demonstrated that the father had antithrombin deficiency and the mother was heterozygous for factor V Leiden. Although we were unable to demonstrate directly the presence of antithrombin deficiency in the infant, we propose that a combination of the two inherited disorders was likely the cause of fatal neonatal thrombosis. Conclusion: The present report highlights the importance of a complete prenatal genetic analysis, including factor V Leiden testing and antithrombin measurement in families with a history of thrombotic disorders. (Obstet Gynecol 1998;92:702–5. © 1998 by The American College of Obstetricians and Gynecologists.)
Richard S. Newman, MD, Gerald S. Spear, MD, and Nancy Kirschbaum, PhD Background: Spontaneous neonatal thrombosis due to heritable gene defects has been reported in the past. A recently
From the Department of Pathology, University of California Irvine Medical Center, Orange, California; and the Hemostasis Reference Laboratory, Blood Center of Southeastern Wisconsin, Milwaukee, Wisconsin.
702 0029-7844/98/$19.00 PII S0029-7844(98)00065-9
The factor V Leiden mutation, a guanine nucleotide–to– adenine nucleotide transition at position 1691 of the
Obstetrics & Gynecology
Hypereosinophilic syndrome, a multisystem disease characterized by eosinophilia in the peripheral blood and the involvement of multiple organ systems, tends to occur in adults between the ages of 20 and 50.1 Only one case2 of hypereosinophilic syndrome in a newborn has been reported. We describe the echocardiographic features of this disorder in a Japanese fetus as well as the antenatal clinical findings.
Figure 1. Four-chamber view of the heart revealed pericardial effusion and cardiomegaly (cardiothoracic area ratio 40%).
immature cervix. A female infant was delivered, weighing 2478 g and with an Apgar score of 9 at 5 minutes. Physical examination of the newborn revealed hepatosplenomegaly. Neonatal echocardiography confirmed the presence of pericardial effusion and revealed a thickening of the ventricular septum and a normal cardiac anatomy. The white blood cell count at birth was 104,000/mm3, with 28% eosinophils and 27.5% blast cells. A bone marrow aspirate contained 36% mature eosinophils and 15% blast cells. Chromosomal analysis revealed 47,XX,121. Pericardiocentesis was performed in an attempt to improve the infant’s cardiac function. Approximately 14 mL of pericardial fluid containing a large number of eosinophils were removed. An intravenous infusion of prednisolone was started at a dosage of 2 mg/kg per day and was increased to 5 mg/kg on the 9th day. After 2 weeks, the treatment regimen was changed to oral administration of prednisolone, and drug therapy was stopped after 12 weeks. All hematologic measures returned to the normal range, and the pericardial effusion and cardiomegaly resolved after 8 weeks.
Case A 33-year-old Japanese woman, gravida 2, para 1, presented for prenatal care at 13 weeks’ gestation. Her previous pregnancy had been complicated by preeclampsia, and she was delivered by cesarean. We administered low-dose aspirin orally beginning at 13 weeks’ gestation to prevent preeclampsia. Routine sonographic examination of the fetus at 35 weeks’ gestation revealed a pericardial effusion. Except for cardiomegaly (cardiothoracic area ratio 40%) and a thickening of the ventricular septum (Figure 1), the fetal heart exhibited no obvious structural cardiac defects. The volume of amniotic fluid and the thickness of the placenta were within normal range. Serologic screening was negative for toxoplasmosis, rubella, and cytomegalovirus. On the 2nd day of hospitalization, the fetal pericardial effusion worsened and a cesarean was performed, in view of the
From the Department of Obstetrics and Gynecology Ehime University School of Medicine, Shigenobu, Ehime, Japan.
VOL. 92, NO. 4, PART 2, OCTOBER 1998
Comment Hypereosinophilic syndrome, characterized by unexplained prolonged eosinophilia (eosinophil count exceeding 1500/mm3) that leads to end-organ involvement,1 is extremely rare in infants. A literature search by MEDLINE, using “hypereosinophilic syndrome” from 1966 to 1997, identified only two such cases,2,3 one of which had been diagnosed at birth.2 More than 75% of the patients with hypereosinophilic syndrome exhibit cardiac involvement; there is often pericardial effusion, thickening of the ventricular septum, and cardiomegaly.4 Our case exhibited echocardiographic features of this disorder in utero, which has not been described in the literature. Patients with Down syndrome are at an increased risk for transient abnormal myelopoiesis. Recently, intrauterine diagnosis of fetal hydrops in association with
0029-7844/98/$19.00 PII S0029-7844(98)00084-2
701
transient myeloproliferative disorder in Down syndrome fetuses was reported.5 Nevertheless, an association between such abnormalities and hypereosinophilic syndrome has not been established. Using blast cells from a Down syndrome patient with transient abnormal myelopoiesis, Suda et al6 demonstrated that recombinant granulocyte-macrophage colony-stimulating factor supports the differentiation of eosinophils, neutrophils, and macrophages. This in vitro finding may be applicable to the finding of eosinophilia in our patient. Down syndrome in a fetus is a relatively common cause of nonimmune hydrops. The cause of hydrops may vary from case to case, but congestive heart failure or fetal hypoxia from placental abnormalities or lymphatic obstruction commonly is implicated. Pericardial effusion in the fetus should be interpreted as a manifestation of heart failure in utero; it often increases before the appearance of hydrops.7 In our patient, eosinophilia may have caused cardiac involvement directly, or degranulation of eosinophils with deposition of the toxic eosinophil granule proteins may cause myocardial necrosis.8 Our case suggests that involvement of the fetal heart due to eosinophilic infiltration of the pericardium and myocardium may cause pericardial effusion and cardiomegaly, followed by hydrops fetalis due to heart failure.
References
2. Johansson A, Ferster A, Steppe M, Otten J. Idiopathic hypereosinophilic syndrome in a neonate. J Pediatr 1988;113:614 –5. 3. Wynn SR, Sachs MI, Keating MU, Ostrom NK, Kadota RP, O’Connel EJ, et al. Idiopathic hypereosinophilic syndrome in a 51⁄2-month-old infant. J Pediatr 1987;111:94 –7. 4. Take M, Sekiguchi M, Hiroe M, Hirosawa K, Mizoguchi H, Kijima M, et al. Clinical spectrum and endomyocardial biopsy findings in eosinophilic heart disease. Heart Vessels 1985;1 Suppl:243–9. 5. Strobelt N, Ghidini A, Locatelli A, Vergani P, Mariani S, Biondi A. Intrauterine diagnosis and management of transient myeloproliferative disorder. Am J Perinatol 1995;2:132– 4. 6. Suda J, Eguch M, Akiyama Y, Iwama Y, Furukawa T, Sato Y, et al. Differentiation of blast cells from a Down syndrome patient with transient myeloproliferative disorder. Blood 1987;69:508 –12. 7. Steinfeld L, Rappaport HL, Rossbach HC, Martines E. Diagnosis of fetal arrhythmias using echocardiographic Doppler techniques. J Am Coll Cardiol 1986;8:1425–33. 8. Tai PC, Ackerman SJ, Spry CJ, Dunnette S, Olsen EG, Gleich GJ. Deposits of eosinophil granule proteins in cardiac tissues of patients with eosinophilic endomyocardial disease. Lancet 1987;1:643–7.
Address reprint requests to:
Yasuki Kusanagi, MD Department of Obstetrics and Gynecology Ehime University School of Medicine Shigenobu Ehime, 791-02 Japan Received November 12, 1997. Received in revised form January 13, 1998. Accepted February 12, 1998.
1. Hardy WR, Anderson RE. The hypereosinophilic syndromes. Ann Intern Med 1968;68:1220 –9.
Copyright © 1998 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Postmortem DNA diagnosis of factor V Leiden in a neonate with systemic thrombosis and probable antithrombin deficiency
discovered defect, the factor V Leiden mutation, is the most frequent inherited risk factor for venous thrombosis. Case: Factor V Leiden was diagnosed postmortem in a neonate who died from complications of vena caval and aortic thrombosis. Investigation into the family history revealed that the father had a record of multiple thromboses, and blood testing demonstrated that the father had antithrombin deficiency and the mother was heterozygous for factor V Leiden. Although we were unable to demonstrate directly the presence of antithrombin deficiency in the infant, we propose that a combination of the two inherited disorders was likely the cause of fatal neonatal thrombosis. Conclusion: The present report highlights the importance of a complete prenatal genetic analysis, including factor V Leiden testing and antithrombin measurement in families with a history of thrombotic disorders. (Obstet Gynecol 1998;92:702–5. © 1998 by The American College of Obstetricians and Gynecologists.)
Richard S. Newman, MD, Gerald S. Spear, MD, and Nancy Kirschbaum, PhD Background: Spontaneous neonatal thrombosis due to heritable gene defects has been reported in the past. A recently
From the Department of Pathology, University of California Irvine Medical Center, Orange, California; and the Hemostasis Reference Laboratory, Blood Center of Southeastern Wisconsin, Milwaukee, Wisconsin.
702 0029-7844/98/$19.00 PII S0029-7844(98)00065-9
The factor V Leiden mutation, a guanine nucleotide–to– adenine nucleotide transition at position 1691 of the
Obstetrics & Gynecology