1177

□ CASE REPORT □

Perforative Peritonitis caused by Appendicitisin a Patient on Peritoneal Dialysis

Masashi Mizuno 1,2, Yasuhiro Suzuki 1,2, Keisuke Nonaka 2, Yumi Sei 2, Shoichi Maruyama 2,

Seiichi Matsuo 2 and Yasuhiko Ito 1,2

Abstract

A 46-year-old man on peritoneal dialysis (PD) was hospitalized due to suspicious PD-related peritonitis.

Because the patient’s abdominal pain was unimproved by conventional antibiotics and multiple bacteria were

identified in a smear-sample of PD fluid, endogenous peritonitis was suspected. Perforated appendicitis was

finally diagnosed under exploratory laparotomy. In this patient, perforated appendicitis was difficult to diag-

nose due to the attenuated clinical symptoms and inconclusive results of abdominal computed tomography

(CT), even though the positive predictive value of CT is >95% in non-PD patients. Quickly deciding to per-

form exploratory laparotomy in patients suspected of having endogenous peritonitis is thus important, even

when the origin has not been clarified.

Key words: peritoneal dialysis, peritonitis, perforated appendicitis

(Intern Med 52: 1177-1181, 2013)(DOI: 10.2169/internalmedicine.52.9196)

Introduction

In end-stage renal disease (ESRD) patients on peritoneal

dialysis (PD), peritonitis remains an important complication

worldwide (1). In the Tokai area of Japan, we recently con-

firmed that peritonitis represents an important obstacle to

long-term PD therapy (2). The most frequent causes of peri-

tonitis are contamination during the performance of PD fluid

(PDF) exchange and PD catheter exit-site infec-

tions (1, 3, 4). On the other hand, endogenous peritonitis is

less frequent and its infectious routes vary. Gastrointestinal

perforation is one cause of endogenous peritonitis, a major

indication for emergency laparotomy and generally accom-

panied by severe abdominal symptoms, such as muscular

guarding and colicky pain. Perforations can be caused by

peptic ulcers, diverticulitis, cholecystitis, ischemic colitis,

appendicitis, malignancy, ingestion of foreign bodies, such

as fish or chicken bones, or, more rarely, bamboo sliver or

indwelling catheters (5-9). Typical findings on computed to-

mography (CT) include free air in the peritoneal cavity as

an important indicator of gastrointestinal perfora-

tion (8, 10, 11). As a tool for the diagnosis of perforated ap-

pendicitis, abdominal CT is a well-established technique for

use in patients with acute abdominal pain that generally

shows >95% sensitivity and specificity for diagnosing and

differentiating appendicitis in the early stages of dis-

ease (12, 13). We herein present the case of a PD patient

with perforated appendicitis resulting in endogenous perito-

nitis in which a final diagnosis was difficult to obtain prior

to laparotomy. In the present case, the decision to perform

exploratory laparotomy could be made quickly due to the

detection of multiple bacteria in the PD effluent.

Case Report

A 46-year-old man who had been on continuous ambula-

tory PD (CAPD) for 2.5 years due to ESRD secondary to

diabetes mellitus (DM) nephropathy experienced moderate

non-localized abdominal discomfort one afternoon. By the

late afternoon, after noticing cloudy PDF with moderate ab-

dominal pain but no nausea or vomiting, the patient came to

the emergency unit of our hospital at night and was admit-

ted with a diagnosis of peritonitis. Prior to this hospitaliza-

１Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Japan and ２Division of Nephrology, Nagoya University Gradu-

ate School of Medicine, Japan

Received for publication October 25, 2012; Accepted for publication February 1, 2013

Correspondence to Dr. Masashi Mizuno, mmizu@med.nagoya-ac.jp and masashim1jp@yahoo.co.jp

Intern Med 52: 1177-1181, 2013 DOI: 10.2169/internalmedicine.52.9196

1178

Figure　1.　Findings of abdominal computed tomography scans. a) CT performed on Day 0. b, c), d) Contrast-enhanced CT performed on Day 1 (second CT). The white arrows indicate the position of the appendix. The black arrows indicate the presence of free air in the peritoneal cavity. The white arrowheads indicate a high density area suspected to be a fecal stone. The fatty tissues around the appendix were not accompanied by high-density areas, suggesting that the inflammation might not have expanded around the appendix.

a

b

c d

tion, the patient had been on CAPD with 1.5% glucose so-

lution (Dianeal NPD4 1.5%; Baxter, Tokyo, Japan) at 2 L

three times/day and 2 L overnight. Multiple diverticula were

identified in the colon prior to the induction of PD therapy;

however, the patient had no history of diverticulitis. Like-

wise, he had no previous history of peritonitis or laparot-

omy. The patient had been diagnosed with DM (type II)

over 11 years earlier, and his hemoglobin A1c levels were

controlled to between 5.5 and 5.8%.

On admission, a physical examination revealed moderate

abdominal pain and mild tenderness unaccompanied by the

typical initial limited pain localized in the periumbilical re-

gion followed by migration of pain to the right lower quad-

rant, muscular guarding or rebound tenderness. The patient’s

body temperature was 36.8℃, his blood pressure was 105/

65 mmHg and his heart rate was 85 beats/min with a sinus

rhythm. The clinical laboratory data of the blood and serum

were as follows: peripheral white blood cell (WBC) count,

11,700 cells/mm3 (polymorphoneutrophils, 88.0%; lympho-

cytes, 8.2%); hemoglobin, 9.6 g/dL; C-reactive protein

(CRP), 1.61 mg/dL; procalcitonin, 0.4 ng/mL (normal, 0-0.5

ng/mL); amylase, 65 IU/L; albumin, 3.6 g/dL; glucose, 174

mg/dL. The WBC count was 2,110 cells/mm3 in the first

cloudy PDF, and the PDF did not smell of stool on admis-

sion. Mild swelling of the appendix with a high density sus-

pected to be a fecal stone (arrowheads; Fig. 1d) without sur-

rounding inflammation was apparent on simple abdominal

computed tomography (CT) and contrast-enhanced abdomi-

nal CT on days 0 and 1 after admission (Fig. 1), and a

small amount of free air was observed within the amount

expected due to flow into the abdominal cavity during PDF

bag changes in general PD patients. The initial CT results

were not particularly suggestive of acute perforated appendi-

citis, even to the radiologist. Although multiple diverticula

were present, no findings suggestive of diverticulitis were

seen on CT.

On admission, the patient was intraperitoneally treated

with cefazolin sodium hydrate at a dose of 1 g/day and cef-

tazidime hydrate at a dose of 1 g/day as conventional ther-

apy. However, his abdominal pain remained unimproved 12

hours after admission, and the WBC count in the PDF was

clearly increased (to 27,030/mm3; polymorphoneutrophils,

90.8%) (Fig. 2). At that time, the serum CRP and procalci-

tonin levels were increased to 7.94 mg/dL and 5.1 ng/mL,

respectively. Gram-positive cocci and Gram-negative rods

were both detected on smear samples of the PDF performed

on admission (Fig. 3). These findings suggested that the

peritonitis might represent an endogenous peritonitis, such

as gastrointestinal perforation. The intraperitoneal antibiotic

administration was therefore changed to 1.0 g/time of van-

comycin hydrochloride and 0.5 g/day of meropenem hydrate

(MEPM) and exploratory laparotomy was performed. Under

laparotomy, the appendix was found to be inflamed with a

perforation and a small amount of purulent peritoneal effu-

sion and two fecal stones in the peritoneal cavity (Fig. 4).

Finally, perforative peritonitis caused by acute appendicitis

with perforation was diagnosed. Appendectomy and perito-

neal lavage were performed intraoperatively, and indwelling

drainage tubes were inserted into the abdominal cavity for

drainage. During the operation, the PD catheter was also re-

moved, and the renal replacement therapy was changed from

PD to hemodialysis.

Later, cultures of blood obtained on admission and PDF

obtained on day 1 showed Klebsiella pneumonia, Citrobac-ter freundii, Enterococcus faecium and Fusobacterium nu-cleatum. In addition, Candida glabrata, Bacteroides thetaio-taomicron and Prevotella spp. were detected in samples ob-

tained from the purulent peritoneal effusion during surgery.

Intern Med 52: 1177-1181, 2013 DOI: 10.2169/internalmedicine.52.9196

1179

Figure　2.　Clinical course of the patient. Exploratory laparotomy was performed on Day 1 (white arrow). CAPD: continuous ambulatory peritoneal dialysis, CAZ: ceftazidime hydrate, CEZ: cefazo-lin sodium hydrate, HD: hemodialysis, MEPM: meropenem hydrate, PD WBC: white blood cells in peritoneal dialysis (PD) fluid, VCM: vancomycin hydrochloride, WBC: white blood cells, (i.p.): in-traperitoneal injection, (div.): drip infusion, TP: the serum total protein level (g/dL), Alb: the serum albumin level (g/dL)

CAPD HD

CEZ 1g/day (ip.) CAZ 1g/day (ip.)

MEPM 0.5g/day

VCM 1g (ip)

0

10,000

20,000

30,000

PD W

BC

(/m

m3 )

(ip.) (div.)

0.0

10.0

20.0

30.0

C-r

eact

ive

prot

ein

(m

g/dL

)

4,000

8,000 12,000 16,000

WB

C (/

mm

3 )

0

Laparotomy ( ) ( )

0 1 2 3 4 5 6 7 ( )

TP

(g/d

L)

Alb

(g/d

L)

( )

0 1 3 4 5 7 11 16 Day

0 10 20 30 40 50 60

0 2 4 6 8

10 12 ( ) ( )

Seru

m c

reat

inin

e le

vel (

mg/

dL)

Blo

od u

rea

nitr

ogen

leve

l (m

g/dL

)

Figure　3.　Gram-positive and Gram-negative cultures were isolated from the peritoneal dialysate fluid in the present case. Smear samples of centrifuged peritoneal fluid obtained from the patient, stained using Gram staining. Multiple bacteria were observed in the smear samples of the peritoneal dialysate fluid obtained from the patient. Black arrows, Gram-positive bacteria; white arrows, Gram-negative bacteria. Original magnification, ×1,000.

a b

These bacteria were categorized as anaerobic Gram-negative

rods. Postoperatively, the patient quickly recovered from the

peritonitis with MEPM and was discharged on day 29. The

detailed course of the patient is shown in Fig. 2.

Discussion

In the present case, peritonitis resulted from acute perfo-

rative appendicitis. On admission, the patient did not display

any severe abdominal symptoms, such as nausea, vomiting,

local abdominal pain, tenderness or rebound tenderness. Al-

though CT was performed repeatedly before making the de-

cision to perform emergency surgery, perforation of the ap-

pendix was not apparent. The patient’s initial symptoms and

radiological findings were most likely masked by the fre-

quent PDF changes, which attenuated the symptoms. The

decision to perform emergency laparotomy was made and

laparotomy was performed within 24 hours because the pa-

tient’s clinical symptoms remained unimproved and multiple

bacteria were detected on smear samples of the PDF. How-

ever, the diagnosis of perforation of the appendix could not

be made without performing laparotomy.

Intern Med 52: 1177-1181, 2013 DOI: 10.2169/internalmedicine.52.9196

1180

Figure　4.　Visualization of the perforated appendix with focal inflammation and fecal stones in the abdominal cavity during laparotomy. The white arrows indicate perforation of the appendix under the operation field (a) and the resected appendix obtained via appendectomy (b). Fecal stones were found in the abdominal cavity intraoperatively (c). The scales are placed in the right bottom corners in (b) and (c).

1cm

a

b

c 1cm

Acute appendicitis in non-ESRD patients is usually ac-

companied by characteristic features, such as nausea, local-

ization of severe abdominal pain from the periumbilical to

the right lower quadrant area and iliac fossa, rebound ten-

derness and muscle rigid guarding, in terms of clinical

symptoms and the results of physical examinations, and per-

foration occurs in <15% of total appendicitis cases (14). In

contrast, because gastrointestinal perforation is often difficult

to diagnose before laparotomy and is delayed in ESRD pa-

tients on PD (11), the prognosis can be poor (10). The main

reasons for diagnostic problems in PD patients are that clini-

cal symptoms are attenuated because frequent PD bag ex-

changes provide peritoneal lavage and drainage and empiric

antibiotics are administered intra-abdominally in patients

with PD-related peritonitis (10, 11, 15). When multiple bac-

teria and/or anaerobic bacteria are identified as the causative

microorganisms of peritonitis in PD patients, complicated

types of peritonitis, such as diverticulitis and gastrointestinal

perforation, are suspected (16). However, it is difficult to

make a final diagnosis of perforated peritonitis without per-

forming exploratory laparotomy. Some reports have de-

scribed delays in the diagnosis of �10 days and operative

mortality rates of 16-50% in PD patients (10, 15, 17). Car-

meci et al. reported a mortality rate for perforated appendi-

citis of -33% (10). On the other hand, the mortality rate for

perforated peritonitis is only -4% in non-PD patients, and

the risk of an extended duration before laparotomy is rela-

tively lower (18). However, even in non-PD patients, the

mortality rates are reportedly increased with durations of >

32 hours before laparotomy (19). The interval required to

reach a diagnosis is very important. Eliminating the perfora-

tion as soon as possible is thus imperative when gastrointes-

tinal perforation is suspected in PD patients. In the present

case, another obstacle to identifying endogenous peritonitis

was the presence of multiple diverticula. Although diverticu-

litis is one cause of endogenous peritonitis, a report by the

European Renal Best Practice Advisory Board suggested

that only the appearance of a diverticulum is not a contrain-

dication (20), and our previous report showed that the pres-

ence of a diverticulum without any prior history of diver-

ticulitis is not a risk factor for endogenous peritonitis (21).

In this case, only the use of laparotomy made it possible to

achieve a final diagnosis of perforated appendicitis.

In the present case, even if appendicitis had extended into

the perforation, the definitive diagnosis still would have

been difficult to obtain without laparotomy. In PD patients,

gastrointestinal perforation leading to endogenous peritonitis

can represent a severe, emergency complication. Gastrointes-

tinal perforation should thus be kept in mind as a differen-

tial diagnosis in PD patients presenting with peritonitis, es-

pecially when multiple enteric bacteria and/or anaerobic bac-

teria are identified, even if findings of CT, symptoms and

physical examinations are not sufficient to identify gastroin-

testinal perforation. For these reasons, obtaining bacterial

cultures and smear samples of the PDF is very important to

achieve a diagnosis and determine the need for surgery.

With endogenous peritonitis in PD patients, making a quick

diagnosis is essential in order to prevent life-threatening

complications, and immediately administering appropriate

therapeutic approaches, including exploratory laparotomy, is

essential in order to optimize the prognosis of PD patients if

gastrointestinal perforation is suspected, even when the ori-

gin has yet to be confirmed.

The authors state that they have no Conflict of Interest (COI).

Intern Med 52: 1177-1181, 2013 DOI: 10.2169/internalmedicine.52.9196

1181

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