bs_bs_banner
NLR and C. albicans chorioamnionitis
277
Neonatal leukemoid reaction associated with Candida albicans chorioamnionitis Sota Iwatani, Masami Mizobuchi, Toshiki Sofue, Satoshi Tanaka, Hitomi Sakai, Seiji Yoshimoto and Hideto Nakao Department of Neonatology, Hyogo Prefectural Kobe Children’s Hospital Perinatal Center, Kobe, Japan Abstract
Chorioamnionitis due to Candida species is relatively rare, despite the high prevalence (20–25%) of Candida vulvovaginitis during pregnancy. We describe a case of neonatal leukemoid reaction (NLR) associated with Candida albicans chorioamnionitis. A male infant was born at 31 weeks’ gestation and weighed 1864 g. Laboratory tests at birth indicated marked leukocytosis (i.e. total leukocyte count 89.8 × 109/L including 66% polymorphonuclear leukocytes and 15% band forms). Samples of the infant’s pharyngeal mucus and tracheal aspirate were positive for Candida albicans. On further histopathology of the placenta, C. albicans mycelia had invaded the placenta, chorioamniotic membrane, and umbilical cord. Although it is not very common, C. albicans chorioamnionitis should be considered in preterm infants with NLR.
Key words Candida albicans, chorioamnionitis, genetic amniocentesis, leukemoid reaction, preterm infant.
Histological chorioamnionitis frequently develops in the preterm placentas of women who undergo preterm labor or suffer premature rupture of membranes (PROM) and is associated with positive amniotic fluid and chorioamniotic space cultures.1 The organisms involved are usually common inhabitants of the lower genital tract. Despite the high frequency of maternal vaginal candidal colonization, there are only a few reports of chorioamnionitis caused by Candida species.2 Neonatal leukemoid reactions (NLR) are relatively rare and are characterized by a white blood cell (WBC) count ≥50 × 109/L during the neonatal period.3 NLR are associated with neonatal mortality and morbidity, including sepsis, intraventricular hemorrhage, and bronchopulmonary dysplasia.4 NLR have also been reported to be associated with histological chorioamnionitis in low-birthweight infants.5 The causal factors and pathogens associated with NLR, however, have not been determined. We describe a case of NLR associated with Candida albicans chorioamnionitis.
Case report A 39-year-old, gravida 1, spontaneous abortion 1, mother was referred to the medical center at 15 weeks’ gestation due to advanced maternal age. Amniocentesis indicated that the fetus had a normal 46, XY karyotype. The pregnancy was uncomplicated. The mother had no history of Candida vaginitis; tobacco, alcohol, or intrauterine conceptive device use; human immunodeficiency virus infection; or cervical cerclage. Correspondence: Sota Iwatani, MD, Department of Neonatology, Hyogo Prefectural Kobe Children’s Hospital Perinatal Center, 1-1-1 Takakuradai-Suma, Kobe, Hyogo 654-0081, Japan. Email: iwatani [email protected] Received 30 May 2013; revised 22 October 2013; accepted 28 October 2013. doi: 10.1111/ped.12259
At 31 weeks 4 days’ gestation, the patient was admitted due to spontaneous rupture of the membranes. Her vital signs were normal, and on blood examination WBC were 11.2 × 109/L and C-reactive protein (CRP) was 0.75 mg/dL. The discharge from her uterine cervix was cultured. Magnesium sulfate tocolysis was initiated to prevent premature labor, and ampicillin therapy was given. In addition, 12 mg of betamethasone was given i.v. for 2 days to enhance fetal lung maturity. By the second day of admission, however, the tocolysis had not succeeded, and the patient’s uterine cervix discharge was found to be positive for Streptococcus agalactiae (group B Streptococcus) and C. albicans. Thus, the decision was made to deliver the baby by cesarean section at 31 weeks 6 days’ gestation. Cord blood was collected aseptically at birth, and the inflammatory cytokine levels were measured. On laboratory tests interleukin (IL)-1β was 50.0 × 109/L. NLR have been described in a number of case reports, in which they were associated with various clinical conditions including premature birth, chromosomal anomalies, exposure to antenatal corticosteroids, severe anemia, infection, or chorioamnionitis.5 Rastogi et al. suggested that hematopoietic growth factors such as granulocyte colonystimulating factor (G-CSF) and granulocyte–macrophage colony-stimulating factor (GM-CSF) play a role in leukemoid reactions in extremely low-birthweight infants.7 The present case not only involved premature labor and the use of antenatal corticosteroids but also extensive C. albicans chorioamnionitis, which might be associated with marked leukocytosis. In addition, recent studies have found that toll-like receptors (TLR), mainly TLR2 and TLR4, play a key role in the recognition of C. albicans
a
b
c
d
e
f
Fig. 1 Histological staining of the (a,d) placenta, (b,e) chorioamniotic membrane, and (c,f) umbilical cord using periodic acid–Schiff stain (a–c, low magnification; d–f, high magnification). Candida albicans mycelia had invaded the fetal surface of the placenta, chorioamniotic membrane, and umbilical cord. © 2014 The Authors Pediatrics International © 2014 Japan Pediatric Society
bs_bs_banner
NLR and C. albicans chorioamnionitis and the activation of the host immune response,8 which might lead to increased levels of G-CSF or GM-CSF and leukemoid reactions. In the present case, although we assessed the cord blood level of inflammatory cytokines, including IL-1β, IL-8, and TNF-α, in order to evaluate whether a fetal inflammatory response had occurred, those of G-CSF and GM-CSF were not assessed. The cord blood levels of G-CSF and/or GM-CSF might be useful for clarifying the mechanisms responsible for NLR associated with chorioamnionitis. Preterm infants suffering from systemic Candida infections are at great risk of serious morbidity and even death. Prophylactic systemic antifungal therapy has been reported to prevent death and morbidity in very low-birthweight infants.9 In the present case, antifungal agents were not used for the following reasons: (i) prophylactic systemic antifungal therapy is not indicated for infants with birthweight >1500 g; (ii) the infant’s blood cultures were negative; and (iii) the infant had no symptoms of infection. Fortunately, the infant had a good clinical course without antifungal therapy, and his leukemoid reaction was resolved within 4 weeks of birth. These findings indicated that he had not contracted congenital candidiasis, despite the presence of extensive chorioamnionitis due to C. albicans. He was diagnosed with fetal inflammatory response syndrome (FIRS), however, based on elevated IL-6 (>11 pg/mL) and the presence of funisitis.10 Therefore, we speculate that FIRS associated with C. albicans chorioamnionitis might have caused the NLR that developed in the present case. The lack of skin lesions and pneumonia,6 which are common symptoms of congenital candidiasis, also support this explanation. In conclusion, we report a case of NLR associated with C. albicans chorioamnionitis. NLR might be a characteristic manifestation of C. albicans chorioamnionitis.
279
Acknowledgments We thank Dr Makiko Yoshida of the Department of Pathology, Hyogo Prefectural Kobe Children’s Hospital, for her invaluable assistance. The authors have no conflicts of interest to declare.
References 1 Romero R, Salafia CM, Athanassiadis AP et al. The relationship between acute inflammatory lesions of the preterm placenta and amniotic fluid microbiology. Am. J. Obstet. Gynecol. 1992; 166: 1382–8. 2 Rode ME, Morgan MA, Ruchelli E, Forouzan I. Candida chorioamnionitis after serial therapeutic amniocentesis: A possible association. J. Perinatol. 2000; 20: 335–7. 3 Hsiao R, Omar SA. Outcome of extremely low birth weight infants with leukemoid reaction. Pediatrics 2005; 116: e43–51. 4 Duran R, Ozbek UV, Ciftdemir NA, Acunas¸ B, Süt N. The relationship between leukemoid reaction and perinatal morbidity, mortality, and chorioamnionitis in low birth weight infants. Int. J. Infect. Dis. 2010; 14: e998–1001. 5 Zanardo V, Vedovato S, Trevisanuto DD et al. Histological chorioamnionitis and neonatal leukemoid reaction in low-birthweight infants. Hum. Pathol. 2006; 37: 87–91. 6 Aldana-Valenzuela C, Morales-Marquec M, Castellanos-Martinez J, Deanda-Gomez M. Congenital candidiasis: A rare and unpredictable disease. J. Perinatol. 2005; 25: 680–82. 7 Rastogi S, Rastogi D, Sundaram R, Kulpa J, Parekh AK. Leukomoid reaction in extremely low-birth-weight infants. Am. J. Perinatol. 1999; 16: 93–7. 8 Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM. Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J. Exp. Med. 2003; 197: 1107–17. 9 Manzoni P, Stolfi I, Pugni L et al. A multicenter, randomized trial of prophylactic fluconazole in preterm neonates. N. Engl. J. Med. 2007; 356: 2483–95. 10 Gotsch F, Romero R, Kusanovic JP et al. The fetal inflammatory response syndrome. Clin. Obstet. Gynecol. 2007; 50: 652–83.
Perforation of enteric duplication during chemotherapy for osteosarcoma Tatsuya Morishima,1 Itaru Kato,1 Katsutsugu Umeda,1 Hidefumi Hiramatsu,1 Shinya Okamoto,5 Akihiro Furuta,2 Takeharu Nakamata,3 Souichi Adachi,4 Toshio Heike1 and Ken-ichiro Watanabe1 Departments of 1Pediatrics, 2Diagnostic Imaging and Nuclear Medicine, 3Orthopaedic Surgery and 4Human Health Sciences, Graduate School of Medicine, Kyoto University, and 5Department of Pediatric Surgery, Kyoto University Hospital, Kyoto, Japan Abstract
A 9-year-old boy undergoing chemotherapy for conventional osteosarcoma complained of severe abdominal pain associated with rebound tenderness and muscular defense. Abdominal computed tomography indicated intraperitoneal free air. On surgical investigation, a diverticulum-like lesion, perforated at the base, was found on the sidewall of the ileum. The anatomic location of the lesion was indicative of enteric duplication. Although the frequency of complications is very rare, perforations of the digestive tract should be considered in patients suffering severe abdominal pain while receiving chemotherapy.
Key words chemotherapy, enteric duplication, gastrointestinal disturbance, osteosarcoma, perforation. Correspondence: Itaru Kato, MD PhD, Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Email: [email protected] Received 30 April 2013; revised 18 July 2013; accepted 28 October 2013. doi: 10.1111/ped.12251
© 2014 The Authors Pediatrics International © 2014 Japan Pediatric Society
NLR and C. albicans chorioamnionitis
277
Neonatal leukemoid reaction associated with Candida albicans chorioamnionitis Sota Iwatani, Masami Mizobuchi, Toshiki Sofue, Satoshi Tanaka, Hitomi Sakai, Seiji Yoshimoto and Hideto Nakao Department of Neonatology, Hyogo Prefectural Kobe Children’s Hospital Perinatal Center, Kobe, Japan Abstract
Chorioamnionitis due to Candida species is relatively rare, despite the high prevalence (20–25%) of Candida vulvovaginitis during pregnancy. We describe a case of neonatal leukemoid reaction (NLR) associated with Candida albicans chorioamnionitis. A male infant was born at 31 weeks’ gestation and weighed 1864 g. Laboratory tests at birth indicated marked leukocytosis (i.e. total leukocyte count 89.8 × 109/L including 66% polymorphonuclear leukocytes and 15% band forms). Samples of the infant’s pharyngeal mucus and tracheal aspirate were positive for Candida albicans. On further histopathology of the placenta, C. albicans mycelia had invaded the placenta, chorioamniotic membrane, and umbilical cord. Although it is not very common, C. albicans chorioamnionitis should be considered in preterm infants with NLR.
Key words Candida albicans, chorioamnionitis, genetic amniocentesis, leukemoid reaction, preterm infant.
Histological chorioamnionitis frequently develops in the preterm placentas of women who undergo preterm labor or suffer premature rupture of membranes (PROM) and is associated with positive amniotic fluid and chorioamniotic space cultures.1 The organisms involved are usually common inhabitants of the lower genital tract. Despite the high frequency of maternal vaginal candidal colonization, there are only a few reports of chorioamnionitis caused by Candida species.2 Neonatal leukemoid reactions (NLR) are relatively rare and are characterized by a white blood cell (WBC) count ≥50 × 109/L during the neonatal period.3 NLR are associated with neonatal mortality and morbidity, including sepsis, intraventricular hemorrhage, and bronchopulmonary dysplasia.4 NLR have also been reported to be associated with histological chorioamnionitis in low-birthweight infants.5 The causal factors and pathogens associated with NLR, however, have not been determined. We describe a case of NLR associated with Candida albicans chorioamnionitis.
Case report A 39-year-old, gravida 1, spontaneous abortion 1, mother was referred to the medical center at 15 weeks’ gestation due to advanced maternal age. Amniocentesis indicated that the fetus had a normal 46, XY karyotype. The pregnancy was uncomplicated. The mother had no history of Candida vaginitis; tobacco, alcohol, or intrauterine conceptive device use; human immunodeficiency virus infection; or cervical cerclage. Correspondence: Sota Iwatani, MD, Department of Neonatology, Hyogo Prefectural Kobe Children’s Hospital Perinatal Center, 1-1-1 Takakuradai-Suma, Kobe, Hyogo 654-0081, Japan. Email: iwatani [email protected] Received 30 May 2013; revised 22 October 2013; accepted 28 October 2013. doi: 10.1111/ped.12259
At 31 weeks 4 days’ gestation, the patient was admitted due to spontaneous rupture of the membranes. Her vital signs were normal, and on blood examination WBC were 11.2 × 109/L and C-reactive protein (CRP) was 0.75 mg/dL. The discharge from her uterine cervix was cultured. Magnesium sulfate tocolysis was initiated to prevent premature labor, and ampicillin therapy was given. In addition, 12 mg of betamethasone was given i.v. for 2 days to enhance fetal lung maturity. By the second day of admission, however, the tocolysis had not succeeded, and the patient’s uterine cervix discharge was found to be positive for Streptococcus agalactiae (group B Streptococcus) and C. albicans. Thus, the decision was made to deliver the baby by cesarean section at 31 weeks 6 days’ gestation. Cord blood was collected aseptically at birth, and the inflammatory cytokine levels were measured. On laboratory tests interleukin (IL)-1β was 50.0 × 109/L. NLR have been described in a number of case reports, in which they were associated with various clinical conditions including premature birth, chromosomal anomalies, exposure to antenatal corticosteroids, severe anemia, infection, or chorioamnionitis.5 Rastogi et al. suggested that hematopoietic growth factors such as granulocyte colonystimulating factor (G-CSF) and granulocyte–macrophage colony-stimulating factor (GM-CSF) play a role in leukemoid reactions in extremely low-birthweight infants.7 The present case not only involved premature labor and the use of antenatal corticosteroids but also extensive C. albicans chorioamnionitis, which might be associated with marked leukocytosis. In addition, recent studies have found that toll-like receptors (TLR), mainly TLR2 and TLR4, play a key role in the recognition of C. albicans
a
b
c
d
e
f
Fig. 1 Histological staining of the (a,d) placenta, (b,e) chorioamniotic membrane, and (c,f) umbilical cord using periodic acid–Schiff stain (a–c, low magnification; d–f, high magnification). Candida albicans mycelia had invaded the fetal surface of the placenta, chorioamniotic membrane, and umbilical cord. © 2014 The Authors Pediatrics International © 2014 Japan Pediatric Society
bs_bs_banner
NLR and C. albicans chorioamnionitis and the activation of the host immune response,8 which might lead to increased levels of G-CSF or GM-CSF and leukemoid reactions. In the present case, although we assessed the cord blood level of inflammatory cytokines, including IL-1β, IL-8, and TNF-α, in order to evaluate whether a fetal inflammatory response had occurred, those of G-CSF and GM-CSF were not assessed. The cord blood levels of G-CSF and/or GM-CSF might be useful for clarifying the mechanisms responsible for NLR associated with chorioamnionitis. Preterm infants suffering from systemic Candida infections are at great risk of serious morbidity and even death. Prophylactic systemic antifungal therapy has been reported to prevent death and morbidity in very low-birthweight infants.9 In the present case, antifungal agents were not used for the following reasons: (i) prophylactic systemic antifungal therapy is not indicated for infants with birthweight >1500 g; (ii) the infant’s blood cultures were negative; and (iii) the infant had no symptoms of infection. Fortunately, the infant had a good clinical course without antifungal therapy, and his leukemoid reaction was resolved within 4 weeks of birth. These findings indicated that he had not contracted congenital candidiasis, despite the presence of extensive chorioamnionitis due to C. albicans. He was diagnosed with fetal inflammatory response syndrome (FIRS), however, based on elevated IL-6 (>11 pg/mL) and the presence of funisitis.10 Therefore, we speculate that FIRS associated with C. albicans chorioamnionitis might have caused the NLR that developed in the present case. The lack of skin lesions and pneumonia,6 which are common symptoms of congenital candidiasis, also support this explanation. In conclusion, we report a case of NLR associated with C. albicans chorioamnionitis. NLR might be a characteristic manifestation of C. albicans chorioamnionitis.
279
Acknowledgments We thank Dr Makiko Yoshida of the Department of Pathology, Hyogo Prefectural Kobe Children’s Hospital, for her invaluable assistance. The authors have no conflicts of interest to declare.
References 1 Romero R, Salafia CM, Athanassiadis AP et al. The relationship between acute inflammatory lesions of the preterm placenta and amniotic fluid microbiology. Am. J. Obstet. Gynecol. 1992; 166: 1382–8. 2 Rode ME, Morgan MA, Ruchelli E, Forouzan I. Candida chorioamnionitis after serial therapeutic amniocentesis: A possible association. J. Perinatol. 2000; 20: 335–7. 3 Hsiao R, Omar SA. Outcome of extremely low birth weight infants with leukemoid reaction. Pediatrics 2005; 116: e43–51. 4 Duran R, Ozbek UV, Ciftdemir NA, Acunas¸ B, Süt N. The relationship between leukemoid reaction and perinatal morbidity, mortality, and chorioamnionitis in low birth weight infants. Int. J. Infect. Dis. 2010; 14: e998–1001. 5 Zanardo V, Vedovato S, Trevisanuto DD et al. Histological chorioamnionitis and neonatal leukemoid reaction in low-birthweight infants. Hum. Pathol. 2006; 37: 87–91. 6 Aldana-Valenzuela C, Morales-Marquec M, Castellanos-Martinez J, Deanda-Gomez M. Congenital candidiasis: A rare and unpredictable disease. J. Perinatol. 2005; 25: 680–82. 7 Rastogi S, Rastogi D, Sundaram R, Kulpa J, Parekh AK. Leukomoid reaction in extremely low-birth-weight infants. Am. J. Perinatol. 1999; 16: 93–7. 8 Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM. Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J. Exp. Med. 2003; 197: 1107–17. 9 Manzoni P, Stolfi I, Pugni L et al. A multicenter, randomized trial of prophylactic fluconazole in preterm neonates. N. Engl. J. Med. 2007; 356: 2483–95. 10 Gotsch F, Romero R, Kusanovic JP et al. The fetal inflammatory response syndrome. Clin. Obstet. Gynecol. 2007; 50: 652–83.
Perforation of enteric duplication during chemotherapy for osteosarcoma Tatsuya Morishima,1 Itaru Kato,1 Katsutsugu Umeda,1 Hidefumi Hiramatsu,1 Shinya Okamoto,5 Akihiro Furuta,2 Takeharu Nakamata,3 Souichi Adachi,4 Toshio Heike1 and Ken-ichiro Watanabe1 Departments of 1Pediatrics, 2Diagnostic Imaging and Nuclear Medicine, 3Orthopaedic Surgery and 4Human Health Sciences, Graduate School of Medicine, Kyoto University, and 5Department of Pediatric Surgery, Kyoto University Hospital, Kyoto, Japan Abstract
A 9-year-old boy undergoing chemotherapy for conventional osteosarcoma complained of severe abdominal pain associated with rebound tenderness and muscular defense. Abdominal computed tomography indicated intraperitoneal free air. On surgical investigation, a diverticulum-like lesion, perforated at the base, was found on the sidewall of the ileum. The anatomic location of the lesion was indicative of enteric duplication. Although the frequency of complications is very rare, perforations of the digestive tract should be considered in patients suffering severe abdominal pain while receiving chemotherapy.
Key words chemotherapy, enteric duplication, gastrointestinal disturbance, osteosarcoma, perforation. Correspondence: Itaru Kato, MD PhD, Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Email: [email protected] Received 30 April 2013; revised 18 July 2013; accepted 28 October 2013. doi: 10.1111/ped.12251
© 2014 The Authors Pediatrics International © 2014 Japan Pediatric Society
