Perforated Appendicitis After Intravenous Immunoglobulin Therapy

CASE REPORT
Perforated Appendicitis After Intravenous Immunoglobulin
Therapy in a Term Neonate with Haemolytic Jaundice
Basak Yildiz Atikan1, Ozge Altun Koroglu2, Mehmet Yalaz2, Orkan Ergun3, Zafer Dokumcu3,
Basak Doganavsargil4, Mete Akisu2 and Nilgun Kultursay2
ABSTRACT
Neonatal appendicitis is a rare clinical condition that may cause high morbidity and mortality if diagnosis is delayed. There
is usually an underlying disease; it can also be a localized form of necrotizing enterocolitis. Here, we present a term
neonate who was treated with intravenous immunoglobulin because of severe isoimmune hemolytic jaundice. The patient
developed abdominal symptoms within 10 hours of therapy, was diagnosed with acute perforated appendicitis and
completely recovered after surgery.
Key Words: Newborn. Appendicitis. Necrotizing enterocolitis. Intravenous immunoglobulin. Hemolytic jaundice.
INTRODUCTION
Appendicitis is known as inflammation in the appendix of
cecum which can be seen frequently in the childhood
and very rarely in the neonatal period. Neonatal
appendicitis can be associated with inguinal or umbilical
hernia, Hirschsprung's disease, meconium plug, cystic
fibrosis, group B Streptococcal septicemia and chorioamnionitis. There are reported cases with isolated
appendicitis or as a component of Necrotizing
Enterocolitis (NEC).1
Although there are NEC cases in newborns with
hemolytic jaundice who had received Intravenous
Immunoglobulin (IVIg) treatment, to the authors'
knowledge this is the first report of neonatal appendicitis
in a jaundiced infant with a history of IVIg treatment.
Since appendicitis has a higher rate of morbidity and
mortality with unspecific clinical presentation in this age
group, the potential of severe hemolysis and/or IVIg
treatment deserves attention of clinicians as risk factors
for this rare disease that needs prompt diagnosis and
intervention for favorable outcomes.
CASE REPORT
A term neonate at the 98th hour of life was admitted to
the neonatal intensive care unit with jaundice. She was
1
2
3
4
Department of Pediatrics, Ege University, Faculty of Medicine,
Izmir, Turkey.
Department of Pediatrics, Division of Neonatology, Ege
University, Faculty of Medicine, Izmir, Turkey.
Department of Pediatric Surgery, Ege University, Faculty of
Medicine, Izmir, Turkey.
Department of Pathology, Ege University, Faculty of Medicine,
Izmir, Turkey.
Correspondence: Dr. Basak Yildiz Atikan, Department of
Pediatrics, Ege University, Faculty of Medicine,
35100-Bornova, Izmir, Turkey.
E-mail: [email protected]
Received: February 10, 2014; Accepted: August 16, 2014.
296
born after an uneventful pregnancy to a 29 years old
mother via elective caesarean section with a birth weight
of 2500 g. The mother whose blood group was ARh (-)
had received Anti-D globulin after her first delivery, but
not after her second pregnancy that ended with abortus.
Laboratory tests of the infant revealed unconjugated
hyperbilirubinemia (19 mg/dl), high lactate dehydrogenase
level and mild anemia (hematocrit = 34%). There were
signs of hemolysis in the blood smear. The infant had a
blood group of ARh (+) and direct Coombs test was
strongly positive. There were no other pathological signs
or symptoms in her physical examination and laboratory
tests. Intensive phototherapy was started according
to the clinical practice guidelines of AAP for the
management of hyperbilirubinemia in newborns.2 Intravenous Immunoglobulin (IVIg) therapy was given in a
dose of 1 g/kg over 6 hours due to rapidly increasing
bilirubin levels despite 6 hours of intensive phototherapy.
Total bilirubin level decreased to 15.3 mg/dl at the 8th
hour of IVIg treatment.
The patient developed abdominal distention, bilious
retention and bloody stools 10 hours after IVIg therapy
was completed. Repeated
blood count and biochemical tests revealed
thrombocytopenia
(89000/mm3), leukopenia
(3500/mm3) and elevated
C-reactive protein (3.3
mg/dl, N < 0.8 mg/dl) with
no other abnormality. Ddimer level was also
normal. Abdominal X-ray
showed intestinal dilatation
and pediatric surgery was
consulted for possible NEC
and peritonitis (Figure 1).
Figure 1: Abdominal X-ray: dilated
intestinal loops.
She was put on antibiotics
Journal of the College of Physicians and Surgeons Pakistan 2015, Vol. 25 (4): 296-298
Perforated appendicitis after use of intravenous immunoglobulin
for sepsis as soon as blood and urine cultures were
obtained. Yellow-green colored and cloudy peritoneal
lavage fluid had a bilirubin of 640 mg/dl (180 mg/dl
conjugated), lactate dehydrogenase 1760 U/L, amylase
and lipase levels below < 3 U/L. Upon these finding, the
patient was operated with the suspicion of bowel
perforation. A localized perforation in the appendix of
cecum was observed during laparotomy. Other parts of
intestines were found healthy.
Histopathological examination showed inflammation and
tissue damage in appendix (Figure 2). The patient was
completely recovered and was discharged within 4 days
after surgery. Differential diagnostic tests to exclude
other causes of neonatal appendicitis; such as sepsis,
urinary tract infection, congenital cytomegalovirus
infection, cystic fibrosis and Hirschsprung’s disease
were all negative.
Figure 2: Histopathological examination of the appendix.
A:Low power view of appendix. A totally necrotic gangrenous mucosa with a
few residual glands and prominent flegmonous inflammation throughout the
wall. (Haematoxylin-eosin, x40)
B: Close up view of mucosa. Polymorphonuclear leucocyte-rich inflammation
and residual lymphoid aggregates. (Haematoxylin-eosin, x100)
C: Ganglion cells (arrows). (Haematoxylin-eosin, x200)
D: Subserosal congested vessels with small fibrin clots in some of them
(arrow). (Haematoxylin-eosin, x200).
DISCUSSION
Acute appendicitis is an uncommon entity in infants. It is
difficult to diagnose, gets easily perforated, and is
associated with high morbidity and mortality due to lack
of specific clinical signs and symptoms in infancy. A
treatment delay less than 48 hours is associated with a
35% incidence of perforation and is greater than 98%
after 48 hours in early childhood. Therefore, the
incidence of perforated appendicitis is high and ranges
from 36.5% to 94% in infancy.3 Although diagnosed in
the first day of admission; the patient also had
perforation but recovered shortly after surgery. The thin
and inelastic appendiceal wall with its meager blood
supply and large amount of lymphoid tissue; small
undeveloped omentum and relatively long mesenteries
of the hollow viscera are defined as possible causes of
high perforation rates in small infants. The relatively
small size of the peritoneal cavity allows a more rapid
spread of contamination in this population. There is
usually an underlying risk factor such as disseminated
NEC, Hirschsprung's disease, cystic fibrosis, inguinal or
umbilical hernia, meconium plug or infections like CMV
enterocolitis or group-B Streptococcal sepsis.4,5 Clinical
signs and symptoms include irritability, respiratory
distress indicating peritoneal inflammation, abdominal
distention, vomiting, and inflammation on abdominal
wall. Abdominal X-ray may show abnormal gas pattern,
free peritoneal fluid and air, thickening on abdominal
wall, right scoliosis and obliteration of psoas margin.6,7
In this case, there were no known risk factors or
underlying diseases. However, the presence of NEC
cases reported after IVIg administration, had brought a
possible effect of IVIg for the development of
appendicitis to mind. Time range after administration of
IVIg seems to be similar to cases reported in literature
and it is usually between 2-96 hours.8,9 It is known that
IVIg therapy reduces the need for exchange transfusion
in severe isoimmune hemolytic jaundice. However,
important adverse reactions of this treatment are also
well described. Hyperviscosity of the IVIg solutions may
increase the risk for intestinal thrombosis. Since IVIg is
generally administered during the first day of life, its
prothrombotic effect may also increase the physiologic
hypercoagulability of the fetus and newborn after birth.10
The estimated mortality of neonatal appendicitis has
remained about 20 - 25% over the past 30 years. It is
important to exclude acute appendicitis in newborns with
abdominal distention, even if there is another underlying
disease. Clinicians should also be aware that IVIg
treatment and/or severe hemolysis may increase the risk
of compromised intestinal circulation possibly by
causing hyperviscosity.
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Basak Yildiz Atikan, Ozge Altun Koroglu, Mehmet Yalaz, Orkan Ergun, Zafer Dokumcu, Basak Doganavsargil, Mete Akisu and Nilgun Kultursay
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