Secondary Sclerosing Cholangitis After Emphysematous Cholecystitis

ABSTRACT

A 64-year-old woman was diagnosed with emphysematous cholecystitis. An open cholecystectomy was performed immediately. After the cholecystectomy, jaundice and multiple bile duct strictures that were not present preoperatively appeared. The patient was diagnosed with sclerosing cholangitis secondary to emphysematous cholecystitis. Endoscopic biliary stenting and endoscopic biliary balloon dilatation were performed. However, jaundice did not improve. She developed candidemia 75 days after cholecystectomy. The patient died of multiple organ failures 92 days after cholecystectomy. Although rare, secondary sclerosing cholangitis occurred after emphysematous cholecystitis, and endoscopic treatment was ineffective in this case.

INTRODUCTION

Sclerosing cholangitis is a cholestatic disease of the biliary system characterized by patchy inflammation, fibrosis, and stricture. Primary sclerosing cholangitis, which is idiopathic, is the most common form of sclerosing cholangitis. Sclerosing cholangitis caused by other diseases is called secondary sclerosing cholangitis. Various diseases have been reported to cause secondary sclerosing cholangitis, and cholecystitis is one of them.¹ Cholecystitis is common in clinical practice; however, it rarely causes secondary sclerosing cholangitis. Here, we present a rare case of secondary sclerosing cholangitis after emphysematous cholecystitis. The patient underwent multiple endoscopic procedures including stent placement and bile duct balloon dilatation; however, these procedures were ineffective.

CASE REPORT

A 64-year-old woman was referred to a hospital with a sudden onset of fever and abdominal pain. She had been taking 5 mg of prednisolone and 1 mg of tacrolimus for rheumatoid arthritis, but had no other underlying diseases or medical history. Computed tomography (CT) revealed wall thickening and swelling of the gallbladder, gas in the gallbladder, ascites, and gas in the portal vein (Figure 1). No strictures or dilatations of the bile duct were observed. She was diagnosed with emphysematous cholecystitis, and open cholecystectomy was performed immediately. After the cholecystectomy, jaundice and multiple bile duct strictures that were not present preoperatively appeared. There were no pathologically malignant findings in the resected gallbladder. Jaundice did not improve, and endoscopic retrograde cholangiopancreatography (ERCP) was performed; however, no evidence of bile duct injury or choledocholithiasis was found. Although the patient had no choledocholithiasis, a biliary stent was placed owing to the possibility of cholestasis because of sludge. Contrast-enhanced CT and magnetic resonance cholangiopancreatography revealed multiple bile duct strictures and dilation of the peripheral bile ducts that were not observed preoperatively (Figure 2). On day 42 after cholecystectomy, the patient was transferred to our hospital.

Figure 1.

Computed tomography scan showing wall thickening and swelling of the gallbladder, gas in the gallbladder (arrow), ascites, and gas in the portal vein (arrowhead). No bile duct strictures or dilatations were observed.

Figure 2.

(A) Contrast-enhanced computed tomography and (B) magnetic resonance cholangiopancreatography revealed multiple intrahepatic bile duct strictures and dilation of the peripheral bile ducts, which were not observed before surgery.

When transferred to our hospital, her temperature, blood pressure, pulse, respiratory rate, and O₂ saturation were recorded as 36.7°C, 128/68 mmHg, 80/min, 17/min, and 98% on room air, respectively. Her level of consciousness was E3V5M6 on the Glasgow Coma Scale. Her abdomen was flat, soft, and not tender. In addition, she suffered from severe anorexia, and a central venous catheter was inserted from the right internal jugular vein. Her blood tests revealed severe jaundice with a serum total bilirubin level of 21.2 mg/dL (Table 1). She was given 5 mg of prednisolone and 1 mg of tacrolimus both at her previous hospital and after being transferred to our hospital. The patient was diagnosed with sclerosing cholangitis secondary to emphysematous cholecystitis. Jaundice associated with secondary sclerosing cholangitis did not improve spontaneously; therefore, we decided to perform endoscopic biliary drainage was performed. On day 43 after cholecystectomy, ERCP was performed, and 2 plastic stents of 7 Fr were placed in the right intrahepatic bile duct (Figure 3). During ERCP, a brush scraping of the bile duct stricture was performed, but there was no pathological malignancy. At the time of ERCP, the guidewire could not be inserted in the left intrahepatic bile duct. For biliary drainage of the left intrahepatic bile duct, endoscopic ultrasound–guided hepaticogastrostomy (EUS-HGS) was performed 46 days after cholecystectomy, and a plastic stent of 7 Fr was placed in the B2 of the left intrahepatic bile duct (Figure 4). On day 52 after cholecystectomy, the serum total bilirubin level improved to 17.2 mg/dL. However, the improvement in jaundice was insufficient. We decided to perform balloon dilatation of as many bile ducts as possible. On day 64 after cholecystectomy, dilatation of the right intrahepatic bile duct and B2 was performed using 4- and 6-mm dilatation balloon catheters. After biliary dilatation, a new hepaticogastrostomy stent of B2 was placed. However, there was little improvement in jaundice. CT revealed an improvement in the dilation of the right intrahepatic bile duct. However, because the dilatation of the left intrahepatic bile duct persisted, we decided to perform a drainage of B3 (Figure 5). On day 71 after cholecystectomy, EUS-HGS was performed again, and a plastic stent of 7 Fr was placed into B3 (Figure 6). A fever developed after the second EUS-HGS, and the antibiotic drugs, cefepime and metronidazole, were administered. Despite these endoscopic procedures, the jaundice hardly improved. On day 73 after cholecystectomy, it was discovered that she had candidemia because of a Candida albicans infection. Jaundice did not improve, multiple organ failures occurred because of candidemia, and the patient died 92 days after the cholecystectomy. The underlying cause of candidemia is believed to be a Candida albicans invasion through the central venous catheter, which was further exacerbated by a weak immune system compromised by long-term jaundice and anorexia.

Table 1.

Blood test data at the time of transfer to our hospital

WBC	12,700/μL	TP	5.7 g/dL	ALP	1,323 IU/L
RBC	385×104/μL	Alb	1.7 g/dL	LDH	384 IU/L
Hb	11.7 g/dL	BUN	16 mg/dL	T-Bil	21.2 mg/dL
Hct	35.5%	Cre	0.77 mg/dL	D-Bil	15.4 mg/dL
MCV	92.2 fL	Na	134 mEq/L	Amy	58 mg/dL
MCH	30.4 pg	K	3.7 mEq/L	CRP	2.99 mg/dL
MCHC	33.0 g/dL	AST	218 IU/L	CEA	2.2 ng/mL
Plt	17.7×104/μL	ALT	199 IU/L	CA19-9	1,056 IU/mL
		γ-GTP	717 IU/L	IgG4	70.8 mg/dL

Alb, albumin; ALP, alkaline phosphatase; ALT, alanine aminotransferase; Amy, amylase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CA19-9, carbohydrate antigen 19-9; CEA, carcinoembryonic antigen; Cre, creatinine; CRP, C-reactive protein; D-Bil, direct bilirubin; Hb, hemoglobin; Hct, hematocrit; IgG4, immunoglobulin G subclass 4; K, potassium; LDH, lactate dehydrogenase; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; Na, sodium; Plt, platelet; RBC, red blood cell; T-Bil, total bilirubin; TP, total protein; WBC, white blood cell; γ-GTP, γ-glutamyl transpeptidase.

Figure 3.

On the 43rd day after cholecystectomy, endoscopic retrograde cholangiopancreatography was performed. (A) There were multiple strictures in the intrahepatic bile ducts. (B) Two plastic stents of 7 Fr were placed in the right intrahepatic bile duct.

Figure 4.

Endoscopic ultrasound–guided hepaticogastrostomy was performed 46 days after cholecystectomy, and a plastic stent of 7 Fr was placed in the B2 of the left intrahepatic bile duct.

Figure 5.

On the 64th day after cholecystectomy. (A) Dilatation of the right intrahepatic bile duct and B2 was performed using 4- and 6-mm dilatation balloon catheters. (B) After biliary dilatation, a new hepaticogastrostomy stent of B2 was placed. (C) Computed tomography scan revealed an improvement in the dilation of the right intrahepatic bile duct. However, the dilatation of the left intrahepatic bile duct remained (arrows).

Figure 6.

On the 71st day after cholecystectomy, endoscopic ultrasound–guided hepaticogastrostomy was performed again, and a plastic stent of 7 Fr was placed into B3.

DISCUSSION

Various diseases have been reported to cause secondary sclerosing cholangitis, including autoimmune pancreatitis, eosinophilic cholangitis, gallstones, surgical trauma, abdominal injury, portal biliopathy, hepatic inflammatory pseudotumor, mast cell cholangiopathy, acquired immunodeficiency syndrome cholangiopathy, recurrent pyogenic cholangitis, or ischemic cholangitis.^2–5 Cholecystitis is commonly encountered; however, leading secondary sclerosing cholangitis is rare. In our case, the oral administration of prednisolone and tacrolimus for rheumatoid arthritis, which suppressed immunity and increased the degree of infection, may be involved with leading secondary sclerosing cholangitis after emphysematous cholecystitis. Prednisolone is an immunosuppressive agent and is believed to have anti-inflammatory properties. However, its efficacy against primary sclerosing cholangitis has not yet been demonstrated. On the other hand, there is a report that the use of tacrolimus improved serum alkaline phosphatase in patients with primary sclerosing cholangitis. However, it is not widely used and is reportedly poorly tolerated because of drug-related adverse events.⁶

Appropriate therapy may improve secondary sclerosing cholangitis caused by immunoglobulin G subclass 4, acquired immunodeficiency syndrome cholangiopathy, recurrent pyogenic cholangitis, and gallstones.¹ Therefore, the causes of secondary sclerosing cholangitis should be considered in all patients. However, some cases do not improve with therapy for sclerosing cholangitis, and in some other cases, therapy for the cause is impossible. Liver transplantation should be considered for patients with advanced sclerosing cholangitis. Endoscopic treatment is widely performed for primary sclerosing cholangitis. Endoscopic therapy includes balloon dilatation and stent placement through ERCP.⁷ The indications for liver transplantation in primary sclerosing cholangitis are similar to those for other liver diseases, with the majority listed and transplanted with a qualifying model for end-stage liver disease score in patients with cirrhosis.⁸ Regarding the prognosis, a study that retrospectively reviewed the data of patients diagnosed with secondary sclerosing cholangitis showed that they had poorer outcomes than matched primary sclerosing cholangitis controls and also reported that 9 of 31 patients with secondary sclerosing cholangitis ultimately required liver transplantation, and 4 patients died.⁵ In our patient, severe jaundice developed rapidly, and endoscopic treatment was ineffective. After several endoscopic treatments, candidemia and multiple organ failure developed. Liver transplantation was not possible, and the patient died. Endoscopic treatment was not effective because bile duct strictures occurred in many places and bile flow could not be sufficiently improved. Notably, some cases of secondary sclerosing cholangitis do not respond to endoscopic treatment, including the present case.

In conclusion, we present a case of secondary sclerosing cholangitis after emphysematous cholecystitis. The patient suddenly developed severe jaundice, and several endoscopic procedures including bile duct dilation and stent placement were performed. However, these treatments were ineffective. Secondary sclerosing cholangitis because of cholecystitis is very rare but should be noted after treatment for cholecystitis.

DISCLOSURES

Author contributions: K. Takahashi wrote the manuscript and is the article guarantor. H. Ohyama, Y. Takiguchi, Y. Sekine, S. Toyama, N. Yamada, C. Sugihara, M. Kan, M. Ouchi, H. Nagashima, Y. Iino, Y. Kusakabe, K. Okitsu, I. Ohno, and N. Kato edited the manuscript and revised it for intellectual content. All authors approved the final version of the manuscript.

Acknowledgments: The authors express their gratitude to all the staff involved in the treatment of our patient at Chiba University Hospital. The authors thank Editage for the English language review.

Financial disclosure: None to report.

Informed consent was obtained for this case report.