Symptomatic patients with chronic cholecystitis usually present with dull right upper abdominal pain that radiates around the waist to the mid back or right scapular tip. The pain may be exacerbated by fatty food intake but the classical post-prandial pain of acute cholecystitis is less common. Nausea and occasional vomiting also accompany complaints of increased bloating and flatulence. Often the symptoms occur in the evening or at night. Symptoms are usually present over weeks to months as opposed to the abrupt, severe presentation of acute cholecystitis. There might be a gradual worsening of symptoms or an increase in the frequency of episodes. Fever and tachycardia are rare. Elderly patients with cholecystitis may present with vague symptoms and they are at risk of progression to complicated disease. Hence a high index of clinical suspicion is required in the diagnosis of this condition. 

Laboratory testing is not specific or sensitive in making a diagnosis of chronic cholecystitis. Leukocytosis and abnormal liver function tests may not be present in these patients, unlike the acute disease. However basic laboratory testing in the form of a metabolic panel, liver functions, and complete blood count should be performed. Cardiac testing including EKG and troponins should be considered in the appropriate clinical setting.

The diagnostic investigation of choice when chronic cholecystitis is suspected clinically is a right upper quadrant ultrasound. This non-invasive study that is readily available in most facilities can accurately evaluate the gallbladder for a thickened wall or inflammation. It also aids in the evaluation of gallstones or sludge. Computerized tomography (CT) with intravenous contrast usually reveals cholelithiasis, increased attenuation of bile, and gallbladder wall thickening. The gallbladder itself may appear distended or contracted, however, pericholecystic inflammation and fluid collection are usually absent.[6] A distended gallbladder and increased enhancement of adjacent hepatic tissue go more in favor of acute cholecystitis, whereas hyperenhancement of the gallbladder wall is more commonly seen in the chronic disease.[7] Given the overlapping findings between acute and chronic cholecystitis, sometimes ultrasound and CT may be adequate to come to a final diagnosis. A magnetic resonance imaging (MRI) study is a useful alternative in patients who are unable to undergo a CT scan due to radiation concerns or renal injury.[8] The diagnostic test of choice to confirm chronic cholecystitis is the hepatobiliary scintigraphy or a HIDA scan with cholecystokinin(CCK). The most common scintigraphic findings are delayed gallbladder visualization (between 1-4 hours) and delayed increased biliary to bowel transit time.[9] The tracer is injected intravascularly and gets concentrated in the gallbladder. CCK is then administered and the percentage of gallbladder emptying (ejection fraction - EF) is calculated. An EF below 35% at the 15-minute cutoff is considered a dyskinetic gallbladder and is suggestive of chronic cholecystitis.  

The preferred treatment for chronic cholecystitis is elective laparoscopic cholecystectomy. It has a low morbidity rate and can be performed as an outpatient surgery. An open cholecystectomy is also an option however requires hospital admission and longer recovery time. This surgery is indicated in patients who are not laparoscopic candidates such as those with extensive prior surgeries and adhesions. Endoscopic retrograde cholangiopancreatography (ERCP) is usually done when choledocholithiasis is a concern. These patients usually undergo ERCP prior to elective surgery. 

Patients who are not surgical candidates or who prefer not to undergo surgery can be closely observed and managed conservatively. A low-fat diet can help reduce the frequency of symptoms. In patients with symptomatic cholelithiasis, the use of ursodeoxycholic acid (UDCA or ursodiol) has been shown to decrease rates of biliary colic and acute cholecystitis.[10] However, the literature on its role in chronic cholecystitis is limited. The management of asymptomatic patients with incidentally detected chronic cholecystitis depends on patient characteristics. Asymptomatic patients with no radiological or clinical concerns of malignancy can also be closely monitored with follow-up imaging. 

There are other common medical conditions that can mimic the presentation of chronic cholecystitis. A thorough analysis of the clinical presentation often can guide appropriate workup. Common clinical features of these disorders are as follows:

• Acute cholecystitis: A continuous, severe pain in the right side of the abdomen lasting for hours associated with fever, nausea, and vomiting in an ill-looking patient is suggestive of acute cholecystitis[11].
• Gall bladder cancer: Chronic abdominal symptoms associated with weight loss or other constitutional symptoms should raise suspicion of this. Imaging and histology are helpful in making a definitive diagnosis.
• Peptic ulcer disease: The presence of epigastric abdominal pain and early satiety should alert the possibility of peptic ulcer disease. Alarm symptoms include weight loss, anemia, melena or dysphagia[12].
• GERD: Burning sensation in the epigastrium or retrosternal region that may be associated with regurgitation of food material.
• Gastric cancer: the presence of alarm symptoms of peptic ulcer disease, persistent vomiting, evidence of malignancy or other risk factors should alert to the possibility of this[13].
• Myocardial infarction: In cases of the inferior wall or right ventricular ischemia, the presenting symptoms may be epigastric pain with nausea and vomiting. Other cardiac symptoms like dizziness or SOB or risk factors for coronary ischemia should prompt a workup for the same[14].
• Mesenteric ischemia: the acute variant presents with severe acute abdominal pain and the chronic variant typically with post-prandial pain. Old age, risk factors for atherosclerosis, blood in stools, and weight loss are concerning features of this condition[15].
• Mesenteric vasculitis: presence of ongoing abdominal symptoms unexplained by regular workup and the presence of other features consistent with systemic vasculitis could be related to this relatively underrecognized but dangerous condition[16].

The majority of uncomplicated cases of cholecystitis have an excellent outcome. In many cases, supportive treatments can help with symptoms. Most cases are treated with elective cholecystectomy to prevent future complications. While surgery is safe, bile duct injuries can happen and need to be monitored in the post-operative period.

The proliferation of bacteria in the gallbladder can lead to acute cholecystitis or pus collections. In some cases, the gallstone may erode into the duodenum and impact in the terminal ileum, presenting as gallstone ileus. Rarely the patient may develop emphysematous cholecystitis due to the presence of gas-forming organisms like clostridia, E.coli, and klebsiella. This presentation is most common in diabetics and carries a high mortality rate. The relationship between chronic cholecystitis and gall bladder cancer is controversial. Though chronic inflammation has been shown to be associated with increased risk of cancer[17], the data on this is limited. Xanthogranulomatous cholecystitis is a variant of chronic cholecystitis in which continued inflammation leads to extensive thickening and fibrosis extending locally beyond the gall bladder wall. In this severe variant, the occurrence of complications like abscesses and fistulas are more common. It is considered a pre-malignant condition. Porcelain gallbladder tends to be asymptomatic in most cases. The association with malignancy is again controversial but the consensus is that it carries a slightly increased risk of cancer.[18]

The diagnosis is usually made at the level of primary care or in the inpatient setting. A gastroenterology consult is mandated when gallstone obstruction of the biliary system is suspected. Otherwise, most patients are referred to general surgery for consideration of elective cholecystectomy. 

The diagnosis and management of cholecystitis is a multi-disciplinary team approach. A high index of suspicion is vital in the diagnosis. Referral to the surgical team followed by decision making on the need for laparoscopic surgery are the next steps. Good surgical care with good postoperative follow up is also essential. Counseling for food habits with nutritionist support and lifestyle changes are crucial in patients being treated conservatively.