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Cystic fibrosis and neonatal calcified scrotal masses
Journal of Cystic Fibrosis 2 (2003) 214–216
Case report
Cystic fibrosis and neonatal calcified scrotal masses Ruth Sofermana,*, Liat Ben-Sirab, Uri Jurgensonc a
Pediatric Respiratory Clinic, Dana Children’s Hospital, 6 Weizman Street, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel b Pediatric-Roentgenology Department, Dana Children’s Hospital, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel c Pediatric Department, Dana Children’s Hospital, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Received 11 October 2002; accepted 3 July 2003
Abstract We report a case of an infant who presented with failure to thrive and in whom the identification of calcified scrotal masses led us to the diagnosis of cystic fibrosis. 䊚 2003 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. Keywords: Meconium periorchitis; Hydrocele; Neonatal hepatitis
1. Case report A 2-month-old Arab boy presented with a history of failure to thrive (FTT). He was born at 37 weeks’ gestational age, weighing 2900 g (10th percentile). The neonatal period was uneventful, and he was breast-fed. Family history disclosed that his parents were first cousins, he had one healthy sister, and there had been another sibling who died at birth at 33 weeks’ gestational age because of severe intrauterine growth retardation. Neonatal history was remarkable only for the presence of a hydrocele. Physical examination was remarkable only for low weight (3175 g, one standard deviation below the 5th percentile) and an enlarged and rigid scrotum, but with no signs of edema. Laboratory tests results were: chloride 106 mmolyl, potassium 5 mmolyl, sodium 133 mmolyl, venous blood pH 7.3, albumin 1.3 gyl, serum aspartate aminotransferase 64 mUyml, serum alanine aminotransferase 68 mUy ml, hemoglobin 9.9 gydl, and hematocrit 31%. Considering the wide range of causes of FTT, we performed a plain frontal abdomen radiograph and it *Corresponding author. Tel.: q972-3-6473411; fax: 972-36925691. E-mail address: [email protected] (R. Soferman).
revealed calcified scrotal masses (Fig. 1). This finding raised the suspicion of cystic fibrosis (CF), and the sweat test (quantitative pilocarpine iontophoresis, the Gibson and Cooke procedure) detected a chloride level of 109 mmolyl (normal-60 mmolyl). The high sweat chloride level further raised the level of suspicion of CF, and a DNA analysis for CF mutations was performed. Detection of a homozygous for the 1717–1 G™A CFTR mutation confirmed the diagnosis of CF. 2. Discussion Meconium peritonitis is a sterile chemical inflammation due to leakage of meconium from a perforated obstructed bowel in utero. The obstruction can be due to volvulus, intestinal atresia, vascular compromise of the gut, and inspissated meconium associated with CF w1,2x. Approximately 15–25% of newborns with CF have meconium ileus, a congenital obstruction of the distal ileum characterized by thick, tenacious and adherent meconium w3x. Calcified scrotal masses may occur as the end result of the passage of extraluminal meconium through the patent processus vaginalis, causing meconium periorchitis, which is a benign cause of scrotal mass in the newborn w4x. The pathological features suggestive of intrauterine periorchitis are
1569-1993/03/$30.00 䊚 2003 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. doi:10.1016/S1569-1993Ž03.00094-8
R. Soferman et al. / Journal of Cystic Fibrosis 2 (2003) 214–216
Fig. 1. Plain abdominal radiograph showing calcified scrotal masses.
granulomatous inflammation with calcifications. These calcified masses may be the initial or sole presenting clinical manifestation of prenatal meconium peritonitis w1,5x, and radiologically detectable calcifications in the abdomen or scrotum are essential diagnostic points in such instances w6x. Calcified scrotal masses can be due to other conditions such as teratomas, gonadoblastomas, Leydig cell tumors, testicular microlithiasis w7,8x, neonatal testicular torsion followed by hemorrhagic infarction and organized intrascrotal hematoma w3x. Radiological features may be diagnostic, but differential diagnosis is precluded if both scrotal and abdominal calcifications are present. In a review of 41 cases, no scrotal abnormality was identified in 10 of them at birth, the age at diagnosis ranged from the 28th week of gestation to 5 years of age, and most cases were detected by 21 months of age w1x. Most of these masses undergo spontaneous resorption of the calcifications and, therefore, the diagnosis of calcification due to intrauterine periorchitis, as is the case in CF, is helpful in avoiding unnecessary surgery w8x.
215
On interpreting this child’s lab reports, the high transaminase levels were evidence of neonatal hepatitis. There is a higher risk for hepatitis in patients with a history of meconium ileus w9x. Hepatic disorders presentation among Arab patients with CF is relatively common w10x. Hyponatremia and hypochloremia may occur as a result of excessive losses in sweat often seen in CF. Hypoalbuminemia at diagnosis of CF in infancy is common, and appears to reflect the severity of illness, but its capability to predict the subsequent course of the disease is controversial w11x. Diagnostic testing for CF should be of high priority in a child with evidence of meconium periorchitis such as calcified scrotal masses. In our patient, the high level of chloride sweat strengthened the suspicion of this diagnosis, which was finally confirmed by the DNA analysis. Approximately 4 days had passed from the child’s presentation until we received the positive result of the sweat test. The genotype–phenotype relationship caused by the splice mutation, 1717–1 G™A, is a severe form of the disease w12x. Meconium ileus may be an early indication of a more severe phenotype w13x, and a positive association was found between delta F508 and G542X and meconium ileus w14x. The presence of meconium ileus was associated with a poor nutritional status and a lower survival rate compared to the general CF population w15x, although an earlier diagnosis does provide some benefits by enabling earlier implementation of treatment w16x. Studies of sibling pairs with CF and identical CFTR genotypes have indicated the presence of modifier genes for meconium ileus on chromosome 19 w17x. The modifier genes could explain other aspects of the CF phenotype w18x, but a discussion of their effects is beyond the scope of this case report. Acknowledgments We thank Esther Eshkol for editorial assistance. References w1x Varkonyi I, Fliegel C, Rosslein R, Jenny P, Ohnacker H. Meconium periorchitis: case report and literature review. Eur J Pediatr Surg 2000;10:404 –7. w2x Park RW, Grand RJ. Gastrointestinal manifestations of cystic fibrosis: a review. Gastroenterology 1981;81:1143 –61. w3x Boccon-Gibod L, Roucayrol AM. Meconium periorchitis. Pediatr Pathol 1992;12:851 –6. w4x Brown-Harrison MC, Harrison AM, Reid BS, Cartwright PC. Meconium periorchitis—a cause of scrotal mass in the newborn. Clin Pediatr 2000;39:179 –82. w5x Kenney PJ, Spirt BA, Ellis DA, Patil U. Scrotal masses caused by peritonitis: prenatal sonographic diagnosis. Radiology 1985;154:362. w6x Salman AB, Karaoglanoglu N, Suma S. Abdominal, scrotal, and thoracic calcifications owing to healed meconium peritonitis. J Pediatr Surg 1999;34:1415 –6. w7x Dehner LP, Scott D, Stocker JT. Meconium periorchitis. Pediatr Pathol 1992;12:851 –6.
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w8x Garat JM, Algaba F, Gomez L. Meconium vaginalitis. Brit J Urol 1991;68:430 –1. w9x Colombo C, Battezzati PM, Crosignani A, Morabito A, Costantini D, Padoan R, et al. Liver disease in cystic fibrosis: a prospective study on incidence, risk factors, and outcome. Hepatology 2002;36:1374 –82. w10x Nazer H, Rahheeni Z. Cystic fibrosis and the liver—a Saudi experience. Ann Trop Pediatr 1994;14:189 –94. w11x Reisman J, Petrou C, Corey M, Stringer D, Durie P, Levison H. Hypoalbuminemia at initial examination in patients with cystic fibrosis. J Pediatr 1989;115:755 –8. w12x Schloesser M, Arleth S, Lenz U, Bertele RM, Reiss J. A cystic fibrosis patient with non-sense mutation G542X and the splice site mutation 1717-1. J Med Genet 1991;28:878 –80. w13x Evans AKC, Fitzgerald DA, McKay KO. The impact of meconium ileus on the clinical course of children with cystic fibrosis. Eur Respir J 2001;18:784 –9.
w14x Feingold J, Guilloud-Bataille M. Genetic comparisons of patients with cystic fibrosis with or without meconium ileus. Clinical centers of French CF registry. Ann Genet 1999;42:147 –50. w15x Oleveira MC, Reis FJ, Monteiro AP, Penna FJ. Effect of meconium ileus on the clinical prognosis of patients with cystic fibrosis. Braz J Med Biol Res 2002;35:31 –8. w16x Siret D, Bretaudeau G, Branger B, et al. Comparing the clinical evolution of cystic fibrosis screened neonatally to that of cystic fibrosis diagnosed from clinical symptoms: a 10-year retrospective study in a French region (Brittany). Pediatr Pulmonol 2003;35:342 –9. w17x Zielenski J, Corey M, Rozmahel R, et al. Detection of a cystic fibrosis modifier locus for meconium ileus on human chromosome 19q13. Nat Genet 1999;22:128 –9. w18x Acton JD, Wilmott RW. Phenotype of CF and the effect of possible modifier genes. Pediatr Respir Rev 2001;2:332 –9.
Case report
Cystic fibrosis and neonatal calcified scrotal masses Ruth Sofermana,*, Liat Ben-Sirab, Uri Jurgensonc a
Pediatric Respiratory Clinic, Dana Children’s Hospital, 6 Weizman Street, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel b Pediatric-Roentgenology Department, Dana Children’s Hospital, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel c Pediatric Department, Dana Children’s Hospital, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Received 11 October 2002; accepted 3 July 2003
Abstract We report a case of an infant who presented with failure to thrive and in whom the identification of calcified scrotal masses led us to the diagnosis of cystic fibrosis. 䊚 2003 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. Keywords: Meconium periorchitis; Hydrocele; Neonatal hepatitis
1. Case report A 2-month-old Arab boy presented with a history of failure to thrive (FTT). He was born at 37 weeks’ gestational age, weighing 2900 g (10th percentile). The neonatal period was uneventful, and he was breast-fed. Family history disclosed that his parents were first cousins, he had one healthy sister, and there had been another sibling who died at birth at 33 weeks’ gestational age because of severe intrauterine growth retardation. Neonatal history was remarkable only for the presence of a hydrocele. Physical examination was remarkable only for low weight (3175 g, one standard deviation below the 5th percentile) and an enlarged and rigid scrotum, but with no signs of edema. Laboratory tests results were: chloride 106 mmolyl, potassium 5 mmolyl, sodium 133 mmolyl, venous blood pH 7.3, albumin 1.3 gyl, serum aspartate aminotransferase 64 mUyml, serum alanine aminotransferase 68 mUy ml, hemoglobin 9.9 gydl, and hematocrit 31%. Considering the wide range of causes of FTT, we performed a plain frontal abdomen radiograph and it *Corresponding author. Tel.: q972-3-6473411; fax: 972-36925691. E-mail address: [email protected] (R. Soferman).
revealed calcified scrotal masses (Fig. 1). This finding raised the suspicion of cystic fibrosis (CF), and the sweat test (quantitative pilocarpine iontophoresis, the Gibson and Cooke procedure) detected a chloride level of 109 mmolyl (normal-60 mmolyl). The high sweat chloride level further raised the level of suspicion of CF, and a DNA analysis for CF mutations was performed. Detection of a homozygous for the 1717–1 G™A CFTR mutation confirmed the diagnosis of CF. 2. Discussion Meconium peritonitis is a sterile chemical inflammation due to leakage of meconium from a perforated obstructed bowel in utero. The obstruction can be due to volvulus, intestinal atresia, vascular compromise of the gut, and inspissated meconium associated with CF w1,2x. Approximately 15–25% of newborns with CF have meconium ileus, a congenital obstruction of the distal ileum characterized by thick, tenacious and adherent meconium w3x. Calcified scrotal masses may occur as the end result of the passage of extraluminal meconium through the patent processus vaginalis, causing meconium periorchitis, which is a benign cause of scrotal mass in the newborn w4x. The pathological features suggestive of intrauterine periorchitis are
1569-1993/03/$30.00 䊚 2003 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. doi:10.1016/S1569-1993Ž03.00094-8
R. Soferman et al. / Journal of Cystic Fibrosis 2 (2003) 214–216
Fig. 1. Plain abdominal radiograph showing calcified scrotal masses.
granulomatous inflammation with calcifications. These calcified masses may be the initial or sole presenting clinical manifestation of prenatal meconium peritonitis w1,5x, and radiologically detectable calcifications in the abdomen or scrotum are essential diagnostic points in such instances w6x. Calcified scrotal masses can be due to other conditions such as teratomas, gonadoblastomas, Leydig cell tumors, testicular microlithiasis w7,8x, neonatal testicular torsion followed by hemorrhagic infarction and organized intrascrotal hematoma w3x. Radiological features may be diagnostic, but differential diagnosis is precluded if both scrotal and abdominal calcifications are present. In a review of 41 cases, no scrotal abnormality was identified in 10 of them at birth, the age at diagnosis ranged from the 28th week of gestation to 5 years of age, and most cases were detected by 21 months of age w1x. Most of these masses undergo spontaneous resorption of the calcifications and, therefore, the diagnosis of calcification due to intrauterine periorchitis, as is the case in CF, is helpful in avoiding unnecessary surgery w8x.
215
On interpreting this child’s lab reports, the high transaminase levels were evidence of neonatal hepatitis. There is a higher risk for hepatitis in patients with a history of meconium ileus w9x. Hepatic disorders presentation among Arab patients with CF is relatively common w10x. Hyponatremia and hypochloremia may occur as a result of excessive losses in sweat often seen in CF. Hypoalbuminemia at diagnosis of CF in infancy is common, and appears to reflect the severity of illness, but its capability to predict the subsequent course of the disease is controversial w11x. Diagnostic testing for CF should be of high priority in a child with evidence of meconium periorchitis such as calcified scrotal masses. In our patient, the high level of chloride sweat strengthened the suspicion of this diagnosis, which was finally confirmed by the DNA analysis. Approximately 4 days had passed from the child’s presentation until we received the positive result of the sweat test. The genotype–phenotype relationship caused by the splice mutation, 1717–1 G™A, is a severe form of the disease w12x. Meconium ileus may be an early indication of a more severe phenotype w13x, and a positive association was found between delta F508 and G542X and meconium ileus w14x. The presence of meconium ileus was associated with a poor nutritional status and a lower survival rate compared to the general CF population w15x, although an earlier diagnosis does provide some benefits by enabling earlier implementation of treatment w16x. Studies of sibling pairs with CF and identical CFTR genotypes have indicated the presence of modifier genes for meconium ileus on chromosome 19 w17x. The modifier genes could explain other aspects of the CF phenotype w18x, but a discussion of their effects is beyond the scope of this case report. Acknowledgments We thank Esther Eshkol for editorial assistance. References w1x Varkonyi I, Fliegel C, Rosslein R, Jenny P, Ohnacker H. Meconium periorchitis: case report and literature review. Eur J Pediatr Surg 2000;10:404 –7. w2x Park RW, Grand RJ. Gastrointestinal manifestations of cystic fibrosis: a review. Gastroenterology 1981;81:1143 –61. w3x Boccon-Gibod L, Roucayrol AM. Meconium periorchitis. Pediatr Pathol 1992;12:851 –6. w4x Brown-Harrison MC, Harrison AM, Reid BS, Cartwright PC. Meconium periorchitis—a cause of scrotal mass in the newborn. Clin Pediatr 2000;39:179 –82. w5x Kenney PJ, Spirt BA, Ellis DA, Patil U. Scrotal masses caused by peritonitis: prenatal sonographic diagnosis. Radiology 1985;154:362. w6x Salman AB, Karaoglanoglu N, Suma S. Abdominal, scrotal, and thoracic calcifications owing to healed meconium peritonitis. J Pediatr Surg 1999;34:1415 –6. w7x Dehner LP, Scott D, Stocker JT. Meconium periorchitis. Pediatr Pathol 1992;12:851 –6.
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R. Soferman et al. / Journal of Cystic Fibrosis 2 (2003) 214–216
w8x Garat JM, Algaba F, Gomez L. Meconium vaginalitis. Brit J Urol 1991;68:430 –1. w9x Colombo C, Battezzati PM, Crosignani A, Morabito A, Costantini D, Padoan R, et al. Liver disease in cystic fibrosis: a prospective study on incidence, risk factors, and outcome. Hepatology 2002;36:1374 –82. w10x Nazer H, Rahheeni Z. Cystic fibrosis and the liver—a Saudi experience. Ann Trop Pediatr 1994;14:189 –94. w11x Reisman J, Petrou C, Corey M, Stringer D, Durie P, Levison H. Hypoalbuminemia at initial examination in patients with cystic fibrosis. J Pediatr 1989;115:755 –8. w12x Schloesser M, Arleth S, Lenz U, Bertele RM, Reiss J. A cystic fibrosis patient with non-sense mutation G542X and the splice site mutation 1717-1. J Med Genet 1991;28:878 –80. w13x Evans AKC, Fitzgerald DA, McKay KO. The impact of meconium ileus on the clinical course of children with cystic fibrosis. Eur Respir J 2001;18:784 –9.
w14x Feingold J, Guilloud-Bataille M. Genetic comparisons of patients with cystic fibrosis with or without meconium ileus. Clinical centers of French CF registry. Ann Genet 1999;42:147 –50. w15x Oleveira MC, Reis FJ, Monteiro AP, Penna FJ. Effect of meconium ileus on the clinical prognosis of patients with cystic fibrosis. Braz J Med Biol Res 2002;35:31 –8. w16x Siret D, Bretaudeau G, Branger B, et al. Comparing the clinical evolution of cystic fibrosis screened neonatally to that of cystic fibrosis diagnosed from clinical symptoms: a 10-year retrospective study in a French region (Brittany). Pediatr Pulmonol 2003;35:342 –9. w17x Zielenski J, Corey M, Rozmahel R, et al. Detection of a cystic fibrosis modifier locus for meconium ileus on human chromosome 19q13. Nat Genet 1999;22:128 –9. w18x Acton JD, Wilmott RW. Phenotype of CF and the effect of possible modifier genes. Pediatr Respir Rev 2001;2:332 –9.