241
Journal of Neonatal-Perinatal Medicine 7 (2014) 241–246 DOI 10.3233/NPM-14814003 IOS Press
Case Report
Acute neonatal appendicitis: A diagnosis to consider in abdominal sepsis R.P. Arias-Llorentea,∗ , P. Fl´orez-D´ıeza , M. Oviedo-Guti´errezb , M. Su´arez-Rodr´ıgueza , M. Costa-Romeroa , G. Sol´ıs-S´ancheza and E. Garc´ıa-L´opeza a Service b Service
of Neonatology, AGCP, Hospital Universitario Central de Asturias, Oviedo, Spain of Pediatric Surgery, Hospital Universitario Central de Asturias, Oviedo, Spain
Received 8 January 2014 Revised 9 April 2014 Accepted 9 May 2014
Abstract. Appendicitis in the neonatal period is extremely rare. Its low incidence together with non-specific clinical symptoms often mean the diagnosis is delayed, leading to increased rates of peritonitis and mortality. We report the case of a 33-week premature infant, small for gestational age (1180 g at birth), clinically stable and receiving exclusive enteral feeding, who presented clinical manifestations of necrotizing enterocolitis at 14 days of life. Acute phase reactants were elevated and abdominal radiography showed pneumoperitoneum. Laparotomy revealed acute perforated appendicitis without intestinal involvement and purulent fluid in the peritoneum, for which appendectomy was performed. Neonatal acute appendicitis should be considered in the differential diagnosis of abdominal sepsis since early diagnosis and treatment significantly reduce associated morbidity and mortality. Keywords: Neonatal appendicitis, premature, abdominal sepsis
1. Introduction Although acute appendicitis is common in children, its incidence decreases notably in infants aged less than two years, currently constituting 2% of all cases. During the neonatal period it is extremely rare, accounting for an estimated 0.04–0.2% of childhood appendicitis [1, 2]. To explain this rarity, several factors have been proposed: the funnel-shaped appendix at birth, making it less prone to obstruction; the soft diet; the sustained recumbent position of infants, and the lower frequency of intestinal and respiratory infections in the neonatal period [3, 4]. ∗ Corresponding
author: Dr. Rosa Patricia Arias-Llorente, Service of Neonatology, Hospital Universitario Central de Asturias, Celestino Villamil s/n., Postal code: 33006 Oviedo (Asturias), Spain. Tel.: +34 686533703; E-mail: [email protected].
Its low incidence together with non-specific clinical symptoms mean the diagnosis and treatment of acute appendicitis is often delayed, resulting in a perforation rate of 75–85% [4, 5]. This usually leads to complicated peritonitis which worsens the prognosis and increases both neonatal morbidity and mortality, estimated at 28% [5]. 2. Case report The patient was a male newborn infant, the third triamniotic-trichorionic triplet, born at 33 weeks of gestation. The mother, aged 35 years, had gestational diabetes and hypertension, treated with insulin and labetalol respectively. The mother received two doses of betamethasone some days before delivery. Maternal serology was unremarkable. Prenatal ultrasound
1934-5798/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved
242
R.P. Arias-Llorente et al. / Acute neonatal appendicitis
had shown intrauterine growth restriction and vascular redistribution of the third triplet. For this reason, elective cesarean was performed at week 33, during which amniotic sac membranes were ruptured. Vaginal culture for group B streptococcus was positive. Apgar score was 9/10 and somatometry data were: weight 1180 g, length 36 cm, head circumference 27 cm, corresponding to less than 3rd percentile for gestational age. On admission to the neonatal intensive care unit, parenteral and enteral trophic nutrition was initiated. Good enteral tolerance allowed progressive increase in volume and exclusive enteral feeding was initiated at 11 days of life. Meconium was observed at 48 hours. On day 4 of admission the infant presented fever, hyporeactivity, tachycardia and pallor. Blood tests showed increased acute phase reactants (CRP: 15 mg/dl, procalcitonin: 11.5 ng/ml and interleukin 6 : 9017 pg/ml) and leukocytosis (19 800 leukocytes with 57% neutrophils and 7% bands). Otic, pharyngeal and nasal exudate cultures at birth were negative. The infant was diagnosed with nosocomial catheter-related sepsis by Enterococcus faecalis (found in peripheral blood and
catheter tip culture, but not in cerebrospinal fluid) and treated with ampicillin and amikacin during 8 days, with good response and subsequent clinical stability. At 14 days of age, the patient presented vomiting, pallor, tachycardia, and hypoactivity. The abdomen was distended, painful and hard, but peristalsis and deposition were conserved. Given a suspected diagnosis of necrotizing enterocolitis, triple antibiotic therapy was administered with vancomycin, amikacin and clindamycin. Laboratory tests showed leukocytosis (19 300 leukocytes, 78% neutrophils), thrombocytosis (589 000 platelets per mm3 ) and elevated acute phase reactants (CRP: 20 mg/dl, procalcitonin: 1.09 ng/ml and interleukin 6 : 1045 pg/ml). Lateral decubitus abdominal radiography showed pneumoperitoneum (Fig. 1). Laparotomy revealed acute perforated appendicitis without intestinal involvement and purulent fluid in the peritoneum, and appendectomy was performed (Fig. 2). Pathological analysis of the resected specimen confirmed the diagnosis. Enteral feeding was successfully reintroduced 8 days after surgery, and intestinal transit began 2 days later. Antibiotic therapy was suspended at 12 days
Fig. 1. Radiograph showing distension of the bowel loops and signs of pneumoperitoneum.
Fig. 2. Perforated appendix at the tip.
R.P. Arias-Llorente et al. / Acute neonatal appendicitis
after surgery. This was followed by surgical wound infection with suture dehiscence and purulent exudate which proved positive for Klebsiella pneumoniae. The surgical wound infection was treated with daily topical chlorhexidine, allowing uneventful suture removal. The patient then presented nosocomial catheter-related sepsis by Staphylococcus epidermidis, successfully treated with intravenous vancomycin during 7 days. Progressive increase in the volume of enteral nutrition allowed definitive withdrawal of parenteral nutrition at 30 days of life, with good clinical evolution. Informed parental consent for publication of this case was obtained.
3. Discussion Acute appendicitis in the neonatal period is highly infrequent. During the last 20 years, fewer than 40 cases have been reported, and since 1900 there have been fewer than 200 such case reports worldwide [5, 6]. A review of the literature shows male predominance, with an estimated male to female ratio of 3 to1 [1, 5, 7], which remains unexplained to date. However, on limiting the review to cases reported in recent years, the ratio appears to be more evenly balanced (1.1 to 1) (Table 1). Within the neonatal period, there are no temporal differences. As shown in Table 1, acute appendicitis has been reported in infants from the first day of life up to 4 weeks [1–22]; there are even cases of prenatal debut [10]. Most cases are associated with prematurity or other diseases such as cystic fibrosis, Hirschsprung disease, meconium plug, inguinal or umbilical hernia, chorioamnionitis, group A streptococcal sepsis, etc. [4, 17], as shown in Table 1. The etiology of acute appendicitis in the neonatal period is thought to differ from that at other times of life [1, 16]. Taking into account the above associations, different theories have been proposed to explain the possible pathogenesis of neonatal appendicitis. Among them, three stand out [3, 17]. The first relates to immune deficiency favored by situations or conditions such as prematurity, chorioamnionitis or early sepsis, which could increase susceptibility to infectious processes. The second is based on vascular insufficiency, hypoxia or conditions producing low blood flow (perinatal asphyxia, heart disease, ECMO dependence, etc.) which could favor appendiceal perforation. The last theory posits an underlying disease (such as meconium ileus or Hirschprung disease) that
243
could lead to cecal obstruction resulting in bacterial overgrowth proliferation and elevated intraluminal pressure in the appendix that favors perforation [6, 17]. In any case, they are conditions that per se do not lead to the development of appendicitis but combine together or with other causes, some known and others that remain to be clarified. In our case we sought to identify possible maternal factors that may have facilitated or contributed to the development of neonatal appendicitis. But the mother did not receive corticosteroid treatment for long (only two doses of betamethasone) or peripartum anbibiotic treatment despite a positive vaginal culture for GBS, since membrane rupture occurred during the cesarean section. Nor was there a history of substance abuse or complications during pregnancy, apart from gestational diabetes and hypertension. We were unable to identify any maternal condition that could plausibly predispose the infant to impaired immune status. However, prematurity of the infant, and having had a previous infection, for which he received antibiotics during 8 of his first 14 days of life, could have made our infant more susceptible to infection. In addition, our patient had intrauterine growth restriction with vascular compromise seen on prenatal Doppler ultrasound which already conditioned vascular redistribution before birth. This suggests the possibility of impaired blood flow in the peri-appendicular area which could have favored appendiceal perforation. The sum of these associations and some individual vulnerability may have contributed to the development of the disease in our newborn. The clinical presentation may be latent and initial symptoms non-specific (abdominal distension, vomiting, fever, muscular resistance, irritability etc.), as seen in other cases and our patient. This generally makes us suspect the presence of other clinical entities as the most likely diagnosis. In our case the suspected diagnosis was perforated necrotizing enterocolitis. But the differential diagnosis should also consider spontaneous intestinal perforation, Hisrchprung disease, intestinal volvulus or acute gastroenteritis [6, 14]. For all these reasons, there is often a delay in diagnosing acute appendicitis and therapeutic surgery. In past decades the diagnosis was made at autopsy in 60% of cases [5]. Today almost all cases of neonatal appendicitis are diagnosed at surgery [1–22], where perforation is found in 80–85% of cases [4, 5], as shown in Table 1. This high rate of perforation in the neonate is because the appendiceal wall is very thin and
Sex Male Female Female Male Male Male Male Female
Male Male Female Male Male Female Female Female Female
Male
Male
Female Male
Author (year)
Stifel (1998)
Swamy (1998)
Iuchtman (1999) Martins (2001)
Pressman (2001)
Beluffi (2002)
Karaman (2003)
Van Veenendaal (2004)
Nichol (2004)
Karunakara (2004)
Managoli (2004)
Karaman (2005)
Kumar (2008)
T
38
T
?
32
T
36 32 40 38 38 39 38
30
35
38 38
33 T T 28
Gestational age
26 days
23 days
5 days
13 days
15 days
14 days
28 days 22 days 18 days 4 days 11 days 11 days 23 days
18 days
6 days
6 days 4 days
1 day 3 weeks 4 weeks 7 days
Age at initial manifestations
Esophageal atresia with fistula Inguinal hernia
Respiratory distress
Prematurity, hidrops fetalis, mucormycosis cardiorespiratory failure (ECMO) None
Prematurity, chorioamnionitis Premature rupture of membranes, prematurity, hyaline membrane disease Inguinal hernia Prematurity None None None None Esophageal atresia with fistula Intestinal vascular disease
Prematurity, small placenta Hirschprung’s Cystic Fibrosis Premature rupture of membranes, prematurity Inguinal hernia Incarcerated inguinal hernia
Comorbilities
Yes
Yes
Yes
Yes
Yes
Yes
Yes Yes* Yes* Yes No No Yes
Yes
Yes
Yes No
Yes Yes Yes Yes *
Perforation
Irritability, refusal to feeds,vomiting,abdominal distention Abdominal distension, shock, edematous and tense abdominal wall Irritability, bilious vomiting, abdominal distension Irritability, abdominal mass
Vomiting, feeding refusal, abdominal distension Abdomen irritation
Abdominal distension
Intestinal obstruction manifestations Intestinal obstruction manifestations Intestinal obstruction manifestations Abdominal distension, iliac fossa mass Incarcerated inguinal hernia Incarcerated inguinal hernia, fever, vomiting Vomiting, abdominal distension
Initial clinical manifestations
Table 1 Neonatal appendicitis cases published in English in the last 20 years (1993–2013). (T): term newborn; (*):dead.
244 R.P. Arias-Llorente et al. / Acute neonatal appendicitis
? Male Male Female
Ergaz (2013) Khan (2013)
Jahangiri (2013)
Female
Saeki (2012)
Female
Malakounides (2011)
Female
T
Female Female Male
Schwartz (2011)
Kalra (2012)
T
Male
Khan (2010)
32
32 ?
36
30
42 40 40
T
36
Male
Jancelewicz (2008)
Gestational age
Sex
Author (year)
20 days
30 days 11 days
2 days
13 days
5 days
4 weeks
9 days 13 days 15 days
23 days
9 days
Age at initial manifestations
Prematury, placental abruption
Inguinal hernia None
Prematurity, chorioamnionitis None
None
None
None None None
Fallot’s tetralogy, esophageal atresia None
Comorbilities
Table 1 (Continued)
Yes
Yes Yes*
Yes
Yes
Yes
No
No* Yes* Yes
Yes
Yes
Perforation
Vomiting, shock, obstruction Fever, abdominal distension Fever, diarrhea, tense, painful abdomen Vomiting, fever, abdominal distension Bilious vomiting, abdominal distension Abdominal distention, small aspirates prior to feeds Ill looking patient, abdominal distension Edematous, tense scrotum Abdominal distension, reluctance to feeds Irritability, abdominal distention
Feeding refusal, vomiting, abdominal distension, fever, tachycardia
Fever, abdominal distension
Initial clinical manifestations R.P. Arias-Llorente et al. / Acute neonatal appendicitis 245
246
R.P. Arias-Llorente et al. / Acute neonatal appendicitis
has poor blood flow, the omentum is underdeveloped and the abdominal cavity is relatively small, which allows for faster contamination of the peritoneum [1]. This means it is often associated with peritonitis, thus increasing the severity of the picture. Attributable mortality was 78% for the years 1901 to 1975, but declined significantly to 28% in the period 1985 to 2000 [5], and is currently estimated as 18.2% according to a review of published cases, shown in Table 1. Our patient survived despite the intraoperative diagnosis, the perforated appendix and complicated peritonitis, but associated morbidity was considerable. In conclusion, acute appendicitis must be considered in the differential diagnosis of abdominal sepsis, especially when the infant has any predisposing factor or pathology. If this entity is taken into account, we may avoid diagnostic delay before surgery, and if this is performed early, the frequency of perforations should decrease, and associated morbidity and mortality may continue to decline.
[6] [7]
[8]
[9] [10]
[11] [12]
[13]
[14]
[15]
Financial disclosure statement Authors declare no conflict of interest. References [1]
[2]
[3]
[4]
[5]
Stiefel D, Stallmach T, Sacher P. Acute appendicitis in neonates: Complication or morbus sui generis? Pediatr Surg Int 1998;14:122-3. Martins JL, Peterlini FL, Martins ECS. Neonatal acute appendicitis: A strangulated appendix in an incarcerated inguinal hernia. Pediatr Surg Int 2011;17:644-5. Van Veenendal M, Pl¨otz FB, Nikkels PGJ, Bax NMA. Further evidence for an ischemic origin of perforation of the appendix in the neonatal period. J Pediatr Surg 2004;39:e11-2. Schwartz KL, Gilad E, Sigalet D, Yu W, Wong AL. Neonatal acute appendicitis: A proposed algorithm for timely diagnosis. J Pediatr Surg 2011;46:2060-4. Karaman A, Cavus¸o˘glu YH, Karaman I, Cakmak O. Seven cases of neonatal appendicitis with a review of the English
[16]
[17] [18]
[19] [20]
[21] [22]
language literature of the last century. Pediatr Surg Int 2003;19:707-9. Khan RA, Menon P, Rao K. Beware of neonatal appendicitis. J Indian Assoc Pediatr Surg 2010;15:67-9. Saeki I, Yamanouchi T, Tanaka S, Kawanami T, Mori R, Zaizen Y. Neonatal appendicitis mimicking intestinal duplication: A case report. J Med Case Rep 2012;6:286. Swamy M, Pejaver RK, Babu A, Maiya PP, Rizwani A. Appendicular perforation in necrotising enterocolitis. Indian Pediatr 1998;35:59-61. Iuchtman M, Kirshon M, Feldman M. Neonatal pyoscrotum and perforated appendicitis. J Perinatol 1999;19:536-7 Pressman A, Kawar B, Abend M, Steiner Z, Mogilner G. Acute perforated neonatal appendicitis associated with chorioamnionitis. Eur J Pediatr Surg 2001;11:204-6. Beluffi G, Alberici E. Acute appendicitis in a premature baby. Eur Radiol 2002;12:S152-4. Nichol PF, Corliss RF, Rajpal S, Helin M, Lund DP. Perforation of the appendix from intestinal mucormycosis in a neonate. J Pediatr Surg 2004;-39:1133-5. Karunakara BP, Ananda Babu MN, Maiya PP, Rijwani A; Sunil I. Appendicitis with perforation in a neonate. Indian J Pediatr 2004;71:355-6. Managoli S, Chaturvedi P, Vilhekar KY, Gupta D, Ghosh S. Perforated acute appendicitis in a term neonate. Indian J Pediatr 2004;71:357-8. Karaman A, C¸avus¸o˘glu YH, Erdo˘gan D, Karaman I, C¸akmak O. Appendiceal mass in a neonate after surgery for esophageal atresia and tracheoesophageal fistula: Report of a case. Surg Today 2005;35:80-1. Kumar R, Mahajan JK, Rao KLN. Perforated appendix in hernia sac mimicking torsion of undescended testis in a neonate. J Pediatr Surg 2008;43:e9-10. Jancelewicz T, Kim G, Miniati D. Neonatal appendicitis: A new look at an old zebra. J Pediatr Surg 2008;43:e1-5. Malakounides G, John M, Rex D, Mulhall J, Nandi B, Mukhtar Z. Laparoscopic surgery for acute neonatal appendicitis. Pediatr Surg Int 2011;27:1245-48. Kalra VK, Natarajan G, Poulik J, Arora P, Gayer C, Altaany D et al. Pediatr Surg Int 2012;28:439-41. Ergaz Z, Simanovsky N, Vromen A, Meir K, Bar-Oz B. Amyand’s hernia with perforated appendicitis in a premature infant. Eur J Pediatr 2014;174:541-3. Khan Y, Zia K, Saddal NS. Perforated neonatal appendicitis with pneumoperitoneum. APSP J Case Rep 2013;4:21. Jahangiri M, Hosseinpour M, Jazayeri H, Mohammadzadeh M, Motaharizad D, Mirzadeh AS. Perforated acute appendicitis in a preterm neonate. Iran Red Crescent Med J 2013;15:497-9.
Journal of Neonatal-Perinatal Medicine 7 (2014) 241–246 DOI 10.3233/NPM-14814003 IOS Press
Case Report
Acute neonatal appendicitis: A diagnosis to consider in abdominal sepsis R.P. Arias-Llorentea,∗ , P. Fl´orez-D´ıeza , M. Oviedo-Guti´errezb , M. Su´arez-Rodr´ıgueza , M. Costa-Romeroa , G. Sol´ıs-S´ancheza and E. Garc´ıa-L´opeza a Service b Service
of Neonatology, AGCP, Hospital Universitario Central de Asturias, Oviedo, Spain of Pediatric Surgery, Hospital Universitario Central de Asturias, Oviedo, Spain
Received 8 January 2014 Revised 9 April 2014 Accepted 9 May 2014
Abstract. Appendicitis in the neonatal period is extremely rare. Its low incidence together with non-specific clinical symptoms often mean the diagnosis is delayed, leading to increased rates of peritonitis and mortality. We report the case of a 33-week premature infant, small for gestational age (1180 g at birth), clinically stable and receiving exclusive enteral feeding, who presented clinical manifestations of necrotizing enterocolitis at 14 days of life. Acute phase reactants were elevated and abdominal radiography showed pneumoperitoneum. Laparotomy revealed acute perforated appendicitis without intestinal involvement and purulent fluid in the peritoneum, for which appendectomy was performed. Neonatal acute appendicitis should be considered in the differential diagnosis of abdominal sepsis since early diagnosis and treatment significantly reduce associated morbidity and mortality. Keywords: Neonatal appendicitis, premature, abdominal sepsis
1. Introduction Although acute appendicitis is common in children, its incidence decreases notably in infants aged less than two years, currently constituting 2% of all cases. During the neonatal period it is extremely rare, accounting for an estimated 0.04–0.2% of childhood appendicitis [1, 2]. To explain this rarity, several factors have been proposed: the funnel-shaped appendix at birth, making it less prone to obstruction; the soft diet; the sustained recumbent position of infants, and the lower frequency of intestinal and respiratory infections in the neonatal period [3, 4]. ∗ Corresponding
author: Dr. Rosa Patricia Arias-Llorente, Service of Neonatology, Hospital Universitario Central de Asturias, Celestino Villamil s/n., Postal code: 33006 Oviedo (Asturias), Spain. Tel.: +34 686533703; E-mail: [email protected].
Its low incidence together with non-specific clinical symptoms mean the diagnosis and treatment of acute appendicitis is often delayed, resulting in a perforation rate of 75–85% [4, 5]. This usually leads to complicated peritonitis which worsens the prognosis and increases both neonatal morbidity and mortality, estimated at 28% [5]. 2. Case report The patient was a male newborn infant, the third triamniotic-trichorionic triplet, born at 33 weeks of gestation. The mother, aged 35 years, had gestational diabetes and hypertension, treated with insulin and labetalol respectively. The mother received two doses of betamethasone some days before delivery. Maternal serology was unremarkable. Prenatal ultrasound
1934-5798/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved
242
R.P. Arias-Llorente et al. / Acute neonatal appendicitis
had shown intrauterine growth restriction and vascular redistribution of the third triplet. For this reason, elective cesarean was performed at week 33, during which amniotic sac membranes were ruptured. Vaginal culture for group B streptococcus was positive. Apgar score was 9/10 and somatometry data were: weight 1180 g, length 36 cm, head circumference 27 cm, corresponding to less than 3rd percentile for gestational age. On admission to the neonatal intensive care unit, parenteral and enteral trophic nutrition was initiated. Good enteral tolerance allowed progressive increase in volume and exclusive enteral feeding was initiated at 11 days of life. Meconium was observed at 48 hours. On day 4 of admission the infant presented fever, hyporeactivity, tachycardia and pallor. Blood tests showed increased acute phase reactants (CRP: 15 mg/dl, procalcitonin: 11.5 ng/ml and interleukin 6 : 9017 pg/ml) and leukocytosis (19 800 leukocytes with 57% neutrophils and 7% bands). Otic, pharyngeal and nasal exudate cultures at birth were negative. The infant was diagnosed with nosocomial catheter-related sepsis by Enterococcus faecalis (found in peripheral blood and
catheter tip culture, but not in cerebrospinal fluid) and treated with ampicillin and amikacin during 8 days, with good response and subsequent clinical stability. At 14 days of age, the patient presented vomiting, pallor, tachycardia, and hypoactivity. The abdomen was distended, painful and hard, but peristalsis and deposition were conserved. Given a suspected diagnosis of necrotizing enterocolitis, triple antibiotic therapy was administered with vancomycin, amikacin and clindamycin. Laboratory tests showed leukocytosis (19 300 leukocytes, 78% neutrophils), thrombocytosis (589 000 platelets per mm3 ) and elevated acute phase reactants (CRP: 20 mg/dl, procalcitonin: 1.09 ng/ml and interleukin 6 : 1045 pg/ml). Lateral decubitus abdominal radiography showed pneumoperitoneum (Fig. 1). Laparotomy revealed acute perforated appendicitis without intestinal involvement and purulent fluid in the peritoneum, and appendectomy was performed (Fig. 2). Pathological analysis of the resected specimen confirmed the diagnosis. Enteral feeding was successfully reintroduced 8 days after surgery, and intestinal transit began 2 days later. Antibiotic therapy was suspended at 12 days
Fig. 1. Radiograph showing distension of the bowel loops and signs of pneumoperitoneum.
Fig. 2. Perforated appendix at the tip.
R.P. Arias-Llorente et al. / Acute neonatal appendicitis
after surgery. This was followed by surgical wound infection with suture dehiscence and purulent exudate which proved positive for Klebsiella pneumoniae. The surgical wound infection was treated with daily topical chlorhexidine, allowing uneventful suture removal. The patient then presented nosocomial catheter-related sepsis by Staphylococcus epidermidis, successfully treated with intravenous vancomycin during 7 days. Progressive increase in the volume of enteral nutrition allowed definitive withdrawal of parenteral nutrition at 30 days of life, with good clinical evolution. Informed parental consent for publication of this case was obtained.
3. Discussion Acute appendicitis in the neonatal period is highly infrequent. During the last 20 years, fewer than 40 cases have been reported, and since 1900 there have been fewer than 200 such case reports worldwide [5, 6]. A review of the literature shows male predominance, with an estimated male to female ratio of 3 to1 [1, 5, 7], which remains unexplained to date. However, on limiting the review to cases reported in recent years, the ratio appears to be more evenly balanced (1.1 to 1) (Table 1). Within the neonatal period, there are no temporal differences. As shown in Table 1, acute appendicitis has been reported in infants from the first day of life up to 4 weeks [1–22]; there are even cases of prenatal debut [10]. Most cases are associated with prematurity or other diseases such as cystic fibrosis, Hirschsprung disease, meconium plug, inguinal or umbilical hernia, chorioamnionitis, group A streptococcal sepsis, etc. [4, 17], as shown in Table 1. The etiology of acute appendicitis in the neonatal period is thought to differ from that at other times of life [1, 16]. Taking into account the above associations, different theories have been proposed to explain the possible pathogenesis of neonatal appendicitis. Among them, three stand out [3, 17]. The first relates to immune deficiency favored by situations or conditions such as prematurity, chorioamnionitis or early sepsis, which could increase susceptibility to infectious processes. The second is based on vascular insufficiency, hypoxia or conditions producing low blood flow (perinatal asphyxia, heart disease, ECMO dependence, etc.) which could favor appendiceal perforation. The last theory posits an underlying disease (such as meconium ileus or Hirschprung disease) that
243
could lead to cecal obstruction resulting in bacterial overgrowth proliferation and elevated intraluminal pressure in the appendix that favors perforation [6, 17]. In any case, they are conditions that per se do not lead to the development of appendicitis but combine together or with other causes, some known and others that remain to be clarified. In our case we sought to identify possible maternal factors that may have facilitated or contributed to the development of neonatal appendicitis. But the mother did not receive corticosteroid treatment for long (only two doses of betamethasone) or peripartum anbibiotic treatment despite a positive vaginal culture for GBS, since membrane rupture occurred during the cesarean section. Nor was there a history of substance abuse or complications during pregnancy, apart from gestational diabetes and hypertension. We were unable to identify any maternal condition that could plausibly predispose the infant to impaired immune status. However, prematurity of the infant, and having had a previous infection, for which he received antibiotics during 8 of his first 14 days of life, could have made our infant more susceptible to infection. In addition, our patient had intrauterine growth restriction with vascular compromise seen on prenatal Doppler ultrasound which already conditioned vascular redistribution before birth. This suggests the possibility of impaired blood flow in the peri-appendicular area which could have favored appendiceal perforation. The sum of these associations and some individual vulnerability may have contributed to the development of the disease in our newborn. The clinical presentation may be latent and initial symptoms non-specific (abdominal distension, vomiting, fever, muscular resistance, irritability etc.), as seen in other cases and our patient. This generally makes us suspect the presence of other clinical entities as the most likely diagnosis. In our case the suspected diagnosis was perforated necrotizing enterocolitis. But the differential diagnosis should also consider spontaneous intestinal perforation, Hisrchprung disease, intestinal volvulus or acute gastroenteritis [6, 14]. For all these reasons, there is often a delay in diagnosing acute appendicitis and therapeutic surgery. In past decades the diagnosis was made at autopsy in 60% of cases [5]. Today almost all cases of neonatal appendicitis are diagnosed at surgery [1–22], where perforation is found in 80–85% of cases [4, 5], as shown in Table 1. This high rate of perforation in the neonate is because the appendiceal wall is very thin and
Sex Male Female Female Male Male Male Male Female
Male Male Female Male Male Female Female Female Female
Male
Male
Female Male
Author (year)
Stifel (1998)
Swamy (1998)
Iuchtman (1999) Martins (2001)
Pressman (2001)
Beluffi (2002)
Karaman (2003)
Van Veenendaal (2004)
Nichol (2004)
Karunakara (2004)
Managoli (2004)
Karaman (2005)
Kumar (2008)
T
38
T
?
32
T
36 32 40 38 38 39 38
30
35
38 38
33 T T 28
Gestational age
26 days
23 days
5 days
13 days
15 days
14 days
28 days 22 days 18 days 4 days 11 days 11 days 23 days
18 days
6 days
6 days 4 days
1 day 3 weeks 4 weeks 7 days
Age at initial manifestations
Esophageal atresia with fistula Inguinal hernia
Respiratory distress
Prematurity, hidrops fetalis, mucormycosis cardiorespiratory failure (ECMO) None
Prematurity, chorioamnionitis Premature rupture of membranes, prematurity, hyaline membrane disease Inguinal hernia Prematurity None None None None Esophageal atresia with fistula Intestinal vascular disease
Prematurity, small placenta Hirschprung’s Cystic Fibrosis Premature rupture of membranes, prematurity Inguinal hernia Incarcerated inguinal hernia
Comorbilities
Yes
Yes
Yes
Yes
Yes
Yes
Yes Yes* Yes* Yes No No Yes
Yes
Yes
Yes No
Yes Yes Yes Yes *
Perforation
Irritability, refusal to feeds,vomiting,abdominal distention Abdominal distension, shock, edematous and tense abdominal wall Irritability, bilious vomiting, abdominal distension Irritability, abdominal mass
Vomiting, feeding refusal, abdominal distension Abdomen irritation
Abdominal distension
Intestinal obstruction manifestations Intestinal obstruction manifestations Intestinal obstruction manifestations Abdominal distension, iliac fossa mass Incarcerated inguinal hernia Incarcerated inguinal hernia, fever, vomiting Vomiting, abdominal distension
Initial clinical manifestations
Table 1 Neonatal appendicitis cases published in English in the last 20 years (1993–2013). (T): term newborn; (*):dead.
244 R.P. Arias-Llorente et al. / Acute neonatal appendicitis
? Male Male Female
Ergaz (2013) Khan (2013)
Jahangiri (2013)
Female
Saeki (2012)
Female
Malakounides (2011)
Female
T
Female Female Male
Schwartz (2011)
Kalra (2012)
T
Male
Khan (2010)
32
32 ?
36
30
42 40 40
T
36
Male
Jancelewicz (2008)
Gestational age
Sex
Author (year)
20 days
30 days 11 days
2 days
13 days
5 days
4 weeks
9 days 13 days 15 days
23 days
9 days
Age at initial manifestations
Prematury, placental abruption
Inguinal hernia None
Prematurity, chorioamnionitis None
None
None
None None None
Fallot’s tetralogy, esophageal atresia None
Comorbilities
Table 1 (Continued)
Yes
Yes Yes*
Yes
Yes
Yes
No
No* Yes* Yes
Yes
Yes
Perforation
Vomiting, shock, obstruction Fever, abdominal distension Fever, diarrhea, tense, painful abdomen Vomiting, fever, abdominal distension Bilious vomiting, abdominal distension Abdominal distention, small aspirates prior to feeds Ill looking patient, abdominal distension Edematous, tense scrotum Abdominal distension, reluctance to feeds Irritability, abdominal distention
Feeding refusal, vomiting, abdominal distension, fever, tachycardia
Fever, abdominal distension
Initial clinical manifestations R.P. Arias-Llorente et al. / Acute neonatal appendicitis 245
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R.P. Arias-Llorente et al. / Acute neonatal appendicitis
has poor blood flow, the omentum is underdeveloped and the abdominal cavity is relatively small, which allows for faster contamination of the peritoneum [1]. This means it is often associated with peritonitis, thus increasing the severity of the picture. Attributable mortality was 78% for the years 1901 to 1975, but declined significantly to 28% in the period 1985 to 2000 [5], and is currently estimated as 18.2% according to a review of published cases, shown in Table 1. Our patient survived despite the intraoperative diagnosis, the perforated appendix and complicated peritonitis, but associated morbidity was considerable. In conclusion, acute appendicitis must be considered in the differential diagnosis of abdominal sepsis, especially when the infant has any predisposing factor or pathology. If this entity is taken into account, we may avoid diagnostic delay before surgery, and if this is performed early, the frequency of perforations should decrease, and associated morbidity and mortality may continue to decline.
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Financial disclosure statement Authors declare no conflict of interest. References [1]
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