Crohn’s disease of the gallbladder

Abstract

Crohn’s disease (CD) is a chronic inflammatory condition, which typically involves the small and large bowel but can affect any part of the gastrointestinal tract. Common symptoms include abdominal pain, diarrhoea, fatigue, weight loss and malnutrition. Complications of CD include gallstone formation and cholecystitis. Impaired reabsorption of bile salts in the small bowel and CD-related surgeries are key factors in the development of CD-related gallstones, although other factors are also important. Direct CD-related inflammation of the gallbladder is very unusual and the typical histological features of CD are rarely encountered in cholecystectomy specimens of individuals with CD. We present a case of a man in his early 60s with CD, previous right hemicolectomy and a history of gallstones, who presented with chronic cholecystitis. Following cholecystectomy, pathological examination of the gallbladder unexpectedly demonstrated typical features of CD, including lymphoid aggregates and non-caseating mucosal granulomata.

Background

Although gallstones and gallbladder disease are commonly encountered in individuals with Crohn’s disease (CD), direct gallbladder involvement is an interesting and highly unusual pathological manifestation, which this case provides an opportunity to discuss and explore. This case demonstrates a rare manifestation of CD, its scarcity emphasised by the large number of cholecystectomies performed on this patient group—due to the increased risk of gallstone disease secondary to reduced bile salt absorption—which do not show these pathological changes on histological examination. While an uncommon occurrence, this complication of CD may be worth consideration in patients who have long-standing symptoms suggestive of chronic cholecystitis.

Case presentation

A man in his early 60s initially presented some 6 years previously with abdominal pain, symptoms of small bowel obstruction and a right-sided abdominal mass. Emergency hospital admission was required. After assessment and CT scan, right hemicolectomy and primary ileocolonic anastomosis were performed and a diagnosis of Crohn’s disease (CD) was confirmed on histological assessment of the hemicolectomy specimen. Postoperative recovery was complicated by a pulmonary embolism and intra-abdominal collection, but complete recovery was followed quickly. Diarrhoea soon re-emerged as a persistent and debilitating symptom with faecal urgency and occasional incontinence having a significant detrimental effect on his quality of life. Cholestyramine was prescribed to manage suspected bile salt malabsorption diarrhoea secondary to removal of the terminal ileum at right hemicolectomy. Azathioprine was introduced in an attempt to prevent postoperative CD recurrence, but this was quickly withdrawn due to side effects of nausea and myalgia.

A year and a half postright hemicolectomy, he was admitted with abdominal pain, acute jaundice and signs of sepsis. Magnetic resonance cholangiopancreatography (MRCP) demonstrated a shrunken, thick-walled gallbladder containing multiple stones and a dilated common bile duct (CBD) with intraductal calculi. Subsequent endoscopic retrograde cholangiopancreatography (ERCP) achieved successful clearance of calculi from the mid-CBD. A recommendation to consider cholecystectomy was made, however, a ‘wait and see’ approach was adopted reflecting a significant improvement in symptoms following ERCP and also the patient’s desire to avoid further surgical intervention.

Some 16 months later, he was admitted with a suspected flare of CD. Faecal calprotectin was elevated (512 µg/g). Recrudescent diarrhoea had become a pervasive symptom by this time. A course of corticosteroids was commenced and methotrexate was introduced as immunosuppressive therapy for CD-related intestinal inflammation. Initially, a good treatment response was achieved with a resolution of diarrhoeal symptoms sustained for several months. However, intermittent right-sided abdominal pain and nausea continued to trouble him regularly during this period. These symptoms were often postprandial. Approximately 8 months after the introduction of methotrexate, problematic diarrhoea and faecal urgency up to six times per day were developed. This was socially limiting for him and he became more or less housebound due to his symptoms.

Further outpatient evaluation was undertaken. Taking account of the pattern and timing of symptoms, clinical examination findings and review of endoscopic and radiological investigations, it was concluded that the symptoms of right-sided abdominal pain, nausea and faecal urgency were most likely due to chronic cholecystitis as opposed to active luminal CD. Plans for elective cholecystectomy were agreed and successful surgery was subsequently undertaken.

Investigations

Cross-sectional imaging from the time of initial presentation with CD to the time of cholecystectomy illustrates the pathophysiological evolution of gallbladder disease. Review of imaging from the initial CT scan of the abdomen and pelvis prior to right hemicolectomy showed no changes to the gallbladder (figure 1). At first follow-up CT scan 2 months after surgery, the gallbladder was once again noted to have a normal appearance (figure 2). Another scan performed 7 months postoperatively demonstrated new thickening of the gallbladder wall, pericholecystic fluid and surrounding fat stranding (figures 3 and 4). No gallstones were identified. Although suggestive of cholecystitis, the radiological findings were not felt to be clinically relevant at that stage. MRCP performed 19 months postsurgery in the context of pain, jaundice and sepsis and showed the gallbladder to be contracted around several gallstones (figures 5 and 6). A calculus measuring approximately 8 mm was reported in the mid-CBD, causing an upper CBD dilatation of 11 mm in diameter. Images from the ERCP used to relieve the obstruction demonstrate the offending calculus (figure 7). This series of scans highlights the fact that gallbladder disease can develop in a short period in the setting of ileocaecal CD and/or right hemicolectomy.

Figure 1.

Oblique coronal multiplanar reconstruction of thin slice (2 mm). CT scan with intravenous iodinated contrast. Normal appearances of the gallbladder (red arrow). A, anterior; I, inferior; S, superior.

Figure 2.

(A–C) CT abdomen and pelvis with intravenous and oral iodinated contrast postright hemicolectomy. Again, normal appearances of gallbladder are seen (red arrows). Sagittal (A), axial (B) and coronal (C) views are shown.

Figure 3.

Sagittal reconstruction of intravenous contrast-enhanced CT of abdomen and pelvis. The gallbladder (red arrow) is thickened with marked inflammatory change in the adjacent fat (short white arrows). P, posterior; S, superior.

Figure 4.

Axial reconstruction of intravenous contrast-enhanced CT showing cholecystitis. Note the pericholecystic fluid (white arrows) in keeping with inflammation. A, anterior; L, left; R, right.

Figure 5.

Axial T2 MRI sequence of the upper abdomen. The gallbladder (red arrow) contains multiple low signal filling defects in keeping with gallstones. A, anterior; L, left.

Figure 6.

Coronal thin slice T2 cholangiogram sequences from magnetic resonance cholangiopancreatography show a low signal filling defect in the proximal common bile duct consistent with choledocholithiasis. L, left; R, right; S, superior.

Figure 7.

Spot radiograph from endoscopic retrograde cholangiopancreatography shows the endoscope in position (thick white arrow). The common bile duct (CBD) has been cannulated (thin white arrow) with balloon occlusion cholangiography. The proximal CBD stone is shown (red arrow).

Treatment

Open subtotal cholecystectomy was performed 5.5 years after initial diagnosis of CD. No gross evidence of active CD was observed during the procedure, but the gallbladder was shrunken and densely adherent to the liver with the cystic duct pulling the CBD towards the gallbladder. The duodenum was mobilised off the gallbladder and the gallbladder fossa was dissected using diathermy. The gallbladder was opened, the gallstones were removed and subsequent excision of the fundus and body of the gallbladder were undertaken.

Outcome and follow-up

Pathological examination of the subtotal cholecystectomy specimen found both neural and muscular hypertrophy of the gallbladder wall (figure 8). Pyloric gland metaplasia could be seen throughout the mucosa with numerous lymphoid aggregates extending transmurally (figure 9). Extensive subserosal fibrosis was noted as well as numerous well-formed non-caseating granulomata within the lamina propria without evidence of adjacent active inflammation (figure 10). While some of these features can be seen in long-standing gallstone disease, given the exuberant nature of these findings and the clinical context of known CD, the overall picture was considered confirmatory of direct CD involvement of the gallbladder on a background of established cholelithiasis.

Figure 8.

Cross-section of gallbladder wall demonstrating prominent neuromuscular hypertrophy (blue arrow) and chronic inflammatory infiltrate situated in the subserosa (red arrow) (H&E, 2×).

Figure 9.

Cross-section of gallbladder wall demonstrating prominent neuromuscular hypertrophy (blue arrows—neural hypertrophy). There is widespread pyloric gland hyperplasia and a well-formed granuloma (green arrow) (H&E, 4×).

Figure 10.

Gallbladder mucosa with granulomata (green arrows) (H&E, 10×).

At surgical clinic, a few weeks postcholecystectomy, the patient was suffering from left upper quadrant pain and mild tenderness that was just adjacent to his midline scar. However, there had been a resolution of right upper quadrant pain and nausea. He reported no recent alteration in his bowel habit, his weight was stable and there was no blood or mucus in his stool. He continued to improve and 2 months later, all abdominal pain had completely subsided.

At his most recent gastroenterology clinic appointment, he reported ‘losing confidence’ in his methotrexate therapy and had stopped taking it 4 weeks prior to his appointment. His faecal calprotectin value at this time was 742 µg/g stool. From a symptom perspective, he continued to report faecal urgency and occasional faecal incontinence, which were having a negative impact on his quality of life and were causing significant anxiety and a fear of leaving his house.

It was suspected that active luminal CD was responsible for both the symptoms and raised faecal calprotectin. Repeat CT enterography was undertaken showing a 30 cm segment of small bowel with contiguous diffuse mural thickening and mucosal hyperaemia involving the neoterminal ileum (figures 11 and 12). A recommendation was made to commence anti-TNFα treatment.

Figure 11.

Coronal CT of abdomen and pelvis shows mild thickening of the neo-terminal ileum (red arrow) and engorgement of the vasa recta (white arrow) consistent with active inflammation. L, left; S, superior.

Figure 12.

Axial CT shows a cross-section of a thickened loop of distal ileum (red arrow). A, anterior; L, left.

Discussion

As a significant proportion of patients with CD develop cholecystitis secondary to dysfunctional bile acid metabolism, cholecystectomy specimens in this patient group are in abundance.¹ If direct inflammatory involvement of the gallbladder by CD was a common occurrence, then this would be reported in the literature as such. However, a literature search using MEDLINE and Web of Science only retrieved seven such cases in the English literature.^2–8 An additional case was reported in French literature, however, the present authors could not assess this.⁹

In one of the reports, the gallbladder was in fact the only site of CD inflammation, with no evidence of inflammatory bowel disease (IBD) throughout the gastrointestinal tract.³ Unlike the other cases reported, gross changes were seen in this specimen, including the characteristic ‘cobblestoning’. In another case report, a gallbladder carcinoma was found on a background of histological features in keeping with CD.⁵ As inflammation is a known risk factor for developing cancer, it is a possibility that the presence of CD inflammation within the gallbladder may have played a role in this malignancy’s pathogenesis.

One study looked at the differences in cholecystectomy specimen histology from patients with no history of IBD against patients with diagnosed ulcerative colitis (UC) or CD.¹⁰ The authors found that granulomas within cholecystectomy specimens were exceedingly rare and were not seen significantly more in patients with CD relative to UC or matched patients with non-IBD.¹⁰ It may be that the low threshold to performing cholecystectomy in patients with CD does not allow enough time for the gallbladder to be involved by the condition. This may explain why our patient, in whom cholecystectomy was delayed 6 years, has been found to have this rare manifestation.

It is not known whether conventional treatments for CD such as immunomodulators (eg, azathioprine) or biologics (eg, infliximab) exert any influence over inflammatory activity of CD within the GB. There are no radiological or clinical signs that predict the presence of granulomatous inflammation of the GB and this, coupled with the rarity of the condition, mean that the clinical significance of this disease manifestation remains unclear. In patients with CD with GB disease who are not fit enough for cholecystectomy, the potential for malignant change may be a cause for concern.

Learning points.

• Individuals with Crohn’s disease (CD) are at increased risk of gallbladder disease.

• Gallbladder and biliary pathology should be considered in individuals with CD and unexplained abdominal symptoms.

• Direct inflammatory involvement of the gallbladder is a rare but intriguing complication of CD.

• The significance of this rare manifestation of CD is unknown due to the limited cases in the literature, however, a change in current management is unlikely to be required.

• This rare consequence of CD may be associated with cholecystitis and gallbladder malignancy.

Ethics statements

Patient consent for publication

Obtained.