Acute cholecystitis is one of the most commonly diagnosed diseases; more than 90% of cases arise after bile stasis due to gallstones in the gallbladder. The most common bacterial agents known to cause acute cholecystitis are Escherichia coli (E. coli), Klebsiella pneumoniae, Enterobacter spp., Citrobacter spp., Pseudomonas spp., Salmonella typhi, Salmonella paratyphi, Streptococcus spp., Enterococcus faecalis, Clostridium spp., Bacteroides spp., Proteus spp. Although uncommon, E. coli producing multiple-resistant extended spectrum betalactamase, methicillin-resistant Staphylococcus aureus, and Acinetobacter baumannii are found in hospital-acquired cholecystitis. Among viruses, hepatitis A virus, hepatitis B virus, Epstein-Barr virus, and cytomegalovirus, and among parasites, Ascaris lumbricoides, Fasciola hepatica, Clonorchis sinensis, Opisthorchis spp. are the microorganisms reported to cause cholecystitis.[1-4]
Brucellosis, also known as Malta fever or Mediterranean fever, is a zoonotic infectious disease that can cause significant economic losses and serious health problems in developing countries. Unpasteurized milk and dairy products are the primary sources of infection in humans, but direct contact with infected animals is also possible. It is considered endemic in the Mediterranean basin, the Arabian peninsula, the Indian subcontinent, and parts of Mexico, Central, and South America. The disease's incidence ranges from 0.01 to >200 per 100,000 people, especially in endemic areas. Türkiye is one of the endemic areas for this disease, with an estimated incidence of 23/100,000 people. Brucella subtypes include Brucella abortus, Brucella melitensis, Brucella suis, and Brucella canis. Brucella melitensis is the most frequent in our country. Due to its many systemic symptoms, brucellosis is included in the differential diagnosis of many diseases. The most common involvement in brucellosis is osteoarticular involvement.[5,6] Brucella spp, however, can settle in various organs and cause atypical clinical manifestations due to their potential to cause bacteremia. Cholecystitis is one of these rare involvements.[5,7,8] In this study, we aimed to evaluate gallbladder involvement, an atypical involvement of brucellosis that is endemic in our country, in the light of the literature.
BRUCELLA-INDUCED CHOLECYSTITIS
General information
According to research, about 30% of patients with brucellosis experience gastrointestinal symptoms. The most prevalent gastrointestinal complication is reactive hepatitis with or without granulomas. Less common complications include appendicitis, peritonitis, intra-abdominal abscesses, colitis, ileitis, and pancreatitis. Acute cholecystitis as a brucellosis complication is relatively uncommon. Brucella species typically induce bacteremia and systemic infection. They can enter the gallbladder or liver via the blood or lymphatic system. There is insufficient data on the chronic carriage of these bacteria in the gallbladder, however, the microorganism can remain latent in the body for many years before causing symptoms.[5-7]
Diagnosis
Physical examination is crucial in the diagnosis of Brucella-induced cholecystitis. Undulant fever may be observed in situations of fever. There may be a fever one week and fever-free the next. In conditions of cholecystitis, Murphy's sign may be positive on abdominal examination.[8]
If there is bone marrow involvement in laboratory tests, leukopenia, thrombocytopenia, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and C-reactive protein levels may increase.[5-7]
Imaging techniques include abdominal ultrasonography, whole-abdomen imaging, and magnetic resonance cholangiography. Gallbladder inflammation and wall thickness may occur in the absence of surrounding fluid or distension.[8]
There are two approaches for diagnosing brucellosis: direct diagnosis and indirect diagnosis. Isolation of the causative agent from blood culture, bone marrow, tissues, or other body fluids allows for direct diagnosis. In 15-70% of cases, blood culture positivity is identified. Culture positivity is most commonly detected on days 7-21. This period can be completed in three days using automated culture systems. The causative agent cannot be identified in indirect diagnosis, and antibodies against the causative agent are examined. Serologic tests are more routinely employed in diagnosis since cultures give late results and the probability of growth in culture is low. The Rose Bengal test is a slide agglutination test that employs the Brucella abortus 99-S strain. The test is very sensitive (>99%), has low specificity, and has a high negative predictive value. The Wright test is a tube agglutination test. It is the most often utilized diagnostic test. In active infection, the titer is usually 1/160 or higher. In endemic locations, treatment might begin in the presence of 1/80 and symptoms.[7-12]
Granulomas may be found during a liver biopsy as part of the diagnostic.[6,7] In one case reported in the literature, Brucella-induced cholecystitis was diagnosed in a patient who had no growth in blood culture due to Brucella melitensis growth in gallbladder culture after postoperative cholecystectomy.[9]
Treatment
Antibiotics that can affect the intracellular acidic environment and macrophages are employed in treatment. Due to the high relapse rates associated with monotherapies, combination treatments should be considered. Traditionally, medications such as trimethoprim/ sulfamethoxazole, gentamicin, rifampicin, doxycycline, ciprofloxacin, and streptomycin have been used. The most common treatment regimens are doxycycline (six weeks) and streptomycin (two or three weeks) or doxycycline (six weeks) and rifampicin (six weeks). It is thought that the combination of doxycycline and streptomycin is more effective than the combination of doxycycline and rifampicin. Fluoroquinolones can also be used with doxycycline or rifampicin. The combination of doxycycline and streptomycin is commonly used in the presence of bone infections due to brucellosis and in cases of drug toxicity or relapse.[5,10]
In Brucella-induced cholecystitis, surgical treatment is unnecessary unless there is perforation of the gallbladder. In a case report, even in the presence of gallbladder empyema, medical treatment without cholecystectomy was reported to be successful.[8] Yet, even if a cholecystectomy is performed, it has been reported that Brucella-induced cholecystitis cannot be treated without medical treatment.[11]
REVIEW OF THE LITERATURE
Following the publication of the first case of Brucella-induced cholecystitis in 1934, similar cases were reported in the literature.[4] Morris et al.[13] published the first case in the PubMed database in 1979. While there was an increase in case reports worldwide between 1999 and 2010, the most current case was reported in 2019 by Speiser et al.[14]
Since 2000, the majority of the 14 cases (78.5%) reached were male. Most of the patients (72%) were over the age of 45. The youngest case was a Mexican-born child living in the United States. According to reports, the majority of cases responded to medical treatment, 21.5% were diagnosed postoperatively, and the vast majority (88%) were detected in endemic countries.[5-14] Table 1 shows cases reported in the literature since 2000.
In conclusion, acute cholecystitis caused by Brucella does not require surgical treatment. This may lead to reduced invasive interventions, lower mortality and morbidity, and, indirectly, lower healthcare costs. Brucellosis should be considered in the differential diagnosis of cholecystitis, especially in endemic regions such as our country.