Neonatal perforated appendicitis: a presentation of necrotising enterocolitis?

Abstract

In this case report, we present a late preterm growth-restricted neonate who developed signs of feeding intolerance on the second day of life, which progressed to frank peritonitis with perforation by the end of the second week of life. As necrotising enterocolitis was considered the most likely diagnosis, a glove drain was placed in the flanks. The neonate did not improve, and surgical exploration was done after medical stabilisation. On exploration, the neonate was found to have appendicular perforation and an appendicectomy was performed. During surgery, the rest of the gut was noted to be healthy. Histopathological examination of the appendix showed transmural inflammation, focal infarction and perforation. The postoperative period was uneventful, and the neonate showed rapid improvement and reached full enteral feeding in the next 5 days. Antibiotic therapy promptly resolved bacterial peritonitis, and the neonate was discharged successfully.

Background

Feed intolerance in neonates raises suspicion of underlying gut abnormality. In preterm neonates, various causes include gut dysmotility, necrotising enterocolitis, neonatal sepsis, surgical abnormalities such as intestinal atresia, malrotation, intussusception and medical diagnoses such as milk protein intolerance. Necrotising enterocolitis usually presents in the second to third week of life and has high mortality ranging from 10% to 50%.¹ We report a late preterm, growth-restricted neonate referred to a tertiary care hospital with feeding intolerance and the neonate had features of gastrointestinal tract perforation (pneumoperitoneum) at admission. Further evaluation and management uncovered an uncommon location of perforation.

Case presentation

The index neonate was born to a primigravida mother in her early 20s by vaginal delivery at an extramural centre in Western India, at a gestational age of 35 weeks 3 days and birth weight of 1555 g (<3rd centile on Fenton 2013 chart for preterm boys). Antenatally, the mother had pre-eclampsia with no severe features, oligohydramnios and poor fetal growth. There was preterm onset of labour, without rupture of membranes. The baby cried immediately after birth and was shifted to NICU for low birth weight and preterm care. This growth-restricted neonate was noticed to have feeding intolerance on day 2 in the form of abdominal distension and non-bilious vomiting. Feeding intolerance persisted and an X-ray abdomen done on day 6 of life showed dilated bowel loops (images were not available). Other investigations showed elevated C reactive protein (53 mg/L), low haemoglobin (101 g/L), normal white cell count (13.7×10⁹/L) and low platelets (9×10⁹/L). The neonate was transfused with two units of platelets and 15 mL/kg unit of packed red blood cells. Intravenous antibiotic therapy with ampicillin and amikacin was initiated on day 2, which was later changed to netilmicin and cefotaxime after 7 days. Conservative management was given, where the neonate was kept nil by mouth and intravenous fluids were continued. The neonate was referred to our hospital for further management on day 16 of life, as there was no improvement.

Investigations

The transillumination test was positive at admission to our unit (figure 1), and X-ray abdomen showed air under diaphragm (figure 2). There was haziness in bilateral lung fields. C reactive protein was elevated, anaemia and low platelet count were noted at admission. The other investigations are shown in the table. The admission blood culture has grown Candida species, while the peritoneal fluid has shown growth of Escherichia coli and Klebsiella pneumoniae. The investigations are summarised in table 1.

Figure 1.

Transillumination test. A cold light flashed through the left flank resulting in brilliant transillumination across the abdomen.

Figure 2.

Roentgenogram of chest and abdomen. Abdominal X-ray anteroposterior view showing pneumoperitoneum, air under the diaphragm (white arrows), with a feeding orogastric tube in situ.

Table 1.

Investigations performed on the index neonate

Day of life	Investigation	Report
16	Complete blood count C reactive protein Renal function tests Blood culture	Hb 100 g/L; platelets 47×109/L; WCC 5.7×109/L, neutrophils 74%, lymphocytes 18%, monocytes 7%, eosinophils 1%, basophils 0% 124 mg/L Urea 7.85 mmol/L; creatinine 26.52 µmol/L; sodium 138 mEq/L; potassium 4.8 mEq/L Growth of Candida species, sensitive to fluconazole, amphotericin B, flucytosine and voriconazole
18	Complete blood count C reactive protein Histopathology Peritoneum fluid culture	Hb 81 g/L; platelets 42×109/L; WCC 5.1×109/L 158 mg/L Denuded appendicular mucosa is replaced by dense necroinflammatory infiltrate composed of neutrophils, lymphocytes, plasma cells, along with lymphoid aggregates. The inflammation is extending transmurally through muscularis propria and serosa. Haemorrhage and haemosiderin laden macrophages are noted. Focal segment of wall is thinned out and infarcted. Focal site of perforation noted, filled with fibrin. Features are consistent with gangrenous appendicitis with perforation. Escherichia coli, sensitive to amikacin, imipenem and meropenem; resistant to—amoxycillin clavulanate, cefuroxime, ciprofloxacin, ofloxacin, trimethoprim/sulfamethoxazole, piperacillin-tazobactam, cefoperazone-sulbactam, gentamycin Klebsiella pneumoniae sensitive to—amikacin, trimethoprim/sulfamethoxazole; resistant to—amoxycillin clavulanate, cefuroxime, ciprofloxacin, ofloxacin, piperacillin-tazobactam, cefoperazone-sulbactam, gentamycin, cefotaxime, cefipime, imipenem, meropenem
20	Complete blood count C reactive protein Renal function tests	Hb 90 g/L; platelets 54×109/L; WCC 8×109/L 120 mg/L Urea 5.71 mmol/L; creatinine 25.64 µmol/L; sodium 130.8 mEq/L; potassium 3.7 mEq/L
25	Cerebrospinal fluid analysis Complete blood count C reactive protein	WCC 0.012 x 109/L, RCC 0.0003 x 1012/L, N 13%, L 87%, protein 42 mg/dL, glucose 22 mg/dL, culture sterile Hb 105 g/L; platelets 39×109/L; WCC 18.4×109/L 21.7 mg/L
32	Complete blood count Osteopenia workup Thyroid screen Metabolic screen Abbreviated auditory brainstem response	Hb 99 g/L; platelets 158×109/L; WCC 18.9×109/L Calcium 9 mEq/L; phosphate 4.5 mEq/L; alkaline phosphatase 347 U/L T4=145.43 nmol/L (reference interval—64.35 to 238 nmol/L); TSH=9.6 µIU/mL (reference interval—0.7 to 15.2 µIU/mL) Normal levels of 17-hydroxyprogesterone, phenylalanine, biotinidase, galactose and glucose-6-phosphate dehydrogenase Normal

Hb, haemoglobin; RCC, red cell count; T4, tetraiodothyronine; TSH, thyroid stimulating hormone; WCC, white cell count.

Differential diagnosis

In view of tense abdominal distension and positive transillumination test, a diagnosis of perforation of gastrointestinal tract was made. The same was confirmed by an abdominal X-ray. The possibility of necrotising enterocolitis (NEC) was considered most likely because of the small for gestational age status. However, other possibilities such as gastric perforation, malrotation of gut, volvulus and gut atresia could not be excluded as the age at symptom onset was as early as day 2 of life, and the gestational age at birth was about 35 weeks.

Treatment

The neonate was found to have mild respiratory distress with tachypnoea, intercostal retractions and SpO2 of 90%. Respiratory support of continuous positive airway pressure was initiated at 5 cm water, and a fraction inhaled oxygen of 21%. Intravenous piperacillin-tazobactam, gentamycin and metronidazole antibiotics were initiated, and the neonate was kept nil per oral. The paediatric surgery team was consulted, and an abdominal drain was placed. Packed red blood cells and platelet transfusions were given. On day 17, the baby’s condition deteriorated further with worsening respiratory distress requiring mechanical ventilation and a tense abdomen. Exploratory laparotomy revealed a gangrenous neonatal appendix at the base with perforation and rupture leading to peritonitis (figure 3). The rest of the bowel was normal on visualisation. An appendicectomy was done. The biopsy sent showed transmural inflammation, necrosis and perforation of the appendix (figures 4 and 5). Pus exudates sent from the peritoneum revealed the growth of E. coli and K. pneumoniae. The blood culture sent showed the growth of Candida species. Antibiotics were changed according to the sensitivity reports to meropenem, amikacin and fluconazole. Cerebrospinal fluid analysis showed no signs of meningitis. Total parenteral nutrition was initiated. On day 18 of life, signs of improvement were noted. Ventilatory parameters were gradually weaned, and the neonate was extubated to non-invasive ventilation (high flow nasal cannula) on day 19 of life and to room air on day 20. Gavage feeding was started from day 21 of life and the neonate was given full enteral feeds by day 24 of life. Direct breast feeding and spoon feeds were initiated on day 25. Antibiotics and fluconazole were stopped after 14 days. Neurosonogram, thyroid screen and hearing screen were normal.

Figure 3.

Intraoperative findings. Intraoperative image showing a gangrenous appendix (black arrow).

Figure 4.

Gross microscopy of the histopathological specimen. (1) Appendicular lumen, (2) perforation, (3) submucosa, (4) follicles, (5) mucosa.

Figure 5.

Magnified view of the appendix. H&E staining of appendix showing inflammatory infiltrate in the appendix.

Outcome and follow-up

The baby was discharged home on day 34 of life with adequate growth and feeding. Human milk fortification of expressed breast milk was advised. The discharge weight was 1815 g. The neonate was seen 11 days after discharge. The neonate was doing well, and was on exclusive breastfeeding, with a weight of 2145 g, and a good weight gain of 33 g/day.

Discussion

The neonatal perforated appendix (NPA) is a rare occurrence, with very few cases reported in the literature.² The appendix is less prone to obstruction in the neonate due to the soft diet, recumbent position and infrequent infections causing lymphadenopathy of the gut.³ Moreover, the clinical features are non-specific (abdominal distension, vomiting, lethargy, etc). Various localising signs such as lump, tenderness and erythema in the right upper quadrant of the abdomen are uncommonly seen.² Because of the lower incidence, non-specific clinical manifestations and infrequent localising signs, the diagnosis is rarely made preoperatively.

Various causes of NPA include inguinal hernia, Hirschsprung’s disease, cardiorespiratory failure and prematurity.^{2 4} Necrotising enterocolitis of the appendix is uncommon. More and more reports suggest that some cases of NPA could be a localised NEC. In a review of 95 published cases of NPA, about 10 cases were attributed to necrotising enterocolitis.⁴ Most of these cases occurred in preterm neonates (n=8/10, 80%), with abdominal distension being the universal presentation. Nine of these 10 neonates required surgical intervention in the second week of life, and a preoperative diagnosis localising the pathology to the appendix was rarely made. The findings are similar in our index case, where the presence of significant risk factors for early necrotising enterocolitis (prematurity and small for gestational age status), onset of symptoms in the first week, subacute progression, presence of thrombocytopaenia and hyponatraemia, presence of significant amount of gas in peritoneal cavity and the absence of underlying appendicular lumen obstruction probably favour necrotising enterocolitis as the aetiology. It is also well known that histopathological findings are overlapping in necrotising enterocolitis and other ischaemic bowel conditions.⁵

The outcomes of necrotising enterocolitis of appendix may be better than a non-specific necrotising enterocolitis of the intestines. We reviewed four recently published cases of neonatal appendicular perforation attributable to NEC.^6–9 In all these cases, the small and large intestines were healthy. The recovery in the postoperative period was mentioned to be uneventful, like our index case.

Patient’s perspective.

My child was admitted to NICU with complaints of abdominal distension in critical condition. I was received by the NICU team who acted quickly to find the cause of abdominal distension. The surgical team was informed and advised of the need for immediate surgical intervention. Postsurgery, the entire team of NICU from the doctors to the nurses, took very good care of my baby. I was informed about the condition of my baby on a day-to-day basis. I want to express my gratitude to the NICU team who treated my child for this ailment and will always be grateful for that. The narrative was written by the baby’s father and was translated from the Kannada language to English by the authors.

Learning points.

• Necrotising enterocolitis in a predisposed neonate can involve the appendix and result in neonatal perforated appendicitis.

• Although difficult to diagnose preoperatively, we should look for localising signs in the right iliac fossa, both clinically and radiologically, as they can enable an early diagnosis.

• Timely diagnosis and surgery can result in good outcomes, as the functional part of the gut (small and large intestines) may be healthy in these neonates.

Ethics statements

Patient consent for publication

Consent obtained from parent(s)/guardian(s).