| Abstract|| |
Brucellosis is hyperendemic in the Kingdom of Saudi Arabia (KSA) with more than 8,000 cases reported each year to the public health authorities. The disease can affect almost any organ system in the body including the gastrointestinal system. In some instances, gastrointestinal manifestations may be the only presenting features of the disease. These range from milder complaints like diarrhea, vomiting to more serious complications like involvement of the liver, the spleen and the gallbladder to rarely lifethreatening complications like colitis, pancreatitis, peritonitis and intestinal obstruction. Recognition of this type of presentation of brucellosis is important because early diagnosis and treatment usually result in complete recovery without complications
Keywords: Brucellosis, gastrointestinal manifestations
|How to cite this article:|
Aziz S, Al-Anazi AR, Al-Aska AI. A review of gastrointestinal manifestations of Brucellosis. Saudi J Gastroenterol 2005;11:20-7
Brucellosis More Details is a true zoonotic disease caused by either one of the 4 types of Brucella More Details namely B. abortus, B. melitensis, B. suis and B. canis. Early recognition of the disease and institution of appropriate treatment results in good recovery without complications in the majority of cases , . Brucellosis is hyperendemic in KSA as shown by several studies over the past 15 years ,,,,,,,,,,,,,,, and there are more than 8000 cases reported each year to the public health authorities , . In 1998, brucellosis ranked as number one reportable communicable disease (22.5%) in KSA National Guard communities ,,) The infection has been reported all over the kingdom, but with much higher incidence in Al-Jouf, Asir, Qasim, Al-Kharj, Al-Hafouf and Al-Hassa areas ,,,, . Gastrointestinal manifestations are diverse and maybe the only features of the disease. These range from relatively milder complaints like anorexia, vomiting, diarrhea, constipation to more serious complications like mesenteric lymphadenitis. Liver or spleen involvement (in the form of hepatitis or ,'granuloma formation and/or abscess formation in any of the two organs) and cholecystitis to rarely life-threatening complications like colitis, pancreatitis, peritonitis and intestinal obstruction.
| Pathophysiological aspects|| |
Brucellosis has a worldwide distribution. Human infection occurs mainly by ingestion of raw milk or milk products and contact with animals  . The organism can gain entry through abraded skin, mucous membranes and conjunctiva  . Entry of the organism through any of these surfaces invites phagocytic neutrophil cells to the site of entry and the organism is phagocytosed by neutrophils and tissue macrophages. They carry the ingested organism to the regional lymph nodes. If the organism escapes host defense mechanisms in the regional lymph node, spread to the circulation occurs resulting in bacteremia. These free organisms in circulation are phagocytosed by the neutrophils and localization occurs primarily to the liver, spleen and bone marrow with formation of granulomas  . The basic pathophysiological mechanisms are illustrated in [Figure - 1]. Complications of brucellosis like endocarditis, osteomyelitis, neurobrucellosis are rare if appropriate antimicrobial therapy is started during the first few weeks of the illness  . Gastrointestinal manifestations of brucellosis are summarized in the table.
| Hepatomegaly|| |
This is the most common clinical finding in the gastrointestinal tract in patients with brucellosis. It is quite understandable by the fact that the liver being the largest organ of reticuloendothelial system in the body, is actively engaged in phagocytosis of any circulating microorganisms. The incidence is reported from 32-63.3%. ,,
The incidence of clinical and biochemical involvement of liver in brucellosis is far less common than indicated by studies of liver biopsies, which according to some studies is 100%  . Patients with hepatic involvement may have right upper quadrant pain along with other systemic features of the disease. Mild jaundice may appear however, deep jaundice is uncommon. Patients with long-standing brucella hepatitis may develop discharging sinus at the right upper quadrant of the abdomen and brucella or anisms can be isolated from the discharge  . Liver function tests (LFTs) are commonly normal even when liver biopsy shows evidence of hepatitis. The most frequent abnormalities in LFTs are raised transaminases and alkaline phosphatase, which are nonspecific.
The total serum bilirubin may be only slightly elevated. Serum albumin may be low in cases where liver is severely affected by the disease but is usually normal. Brucella organisms can be isolated from liver tissue by culture. Patients with longstanding brucella hepatitis may develop any of the following forms of liver involvement:
- Non-specific hepatitis  , with mononuclear cell infiltrate.
- Granulomatous hepatitis ,, the granulomas are typically non-caseating, but caseating granulomas may form, particularly in infection with Brucella suis. The granulomatous response is seen more commonly in patients with predominant monocytic cell response, however, with intense inflammation, central caseation may occur in some patients.
- Liver abscess  , may form especially in patients infected with Brucella suis. This type of response is seen more commonly inpatients with predominant neutrophil cell response
- Cirrhosis  , is a rare sequelae of brucella hepatitis. The hi stopatho logical findings may show any of the four patterns of liver involvement as mentioned above. Plain radiograph of the abdomen may show calcified nodules in the liver and these are usually associated with suppuration, abscess and sinus formation  . Treatment of brucella hepatitis is the same as brucellosis. However, large liver bscesses may need drainage 
| Splenomegaly|| |
Splenic enlargement in brucellosis has been reported in 29-56.6% of the cases ,,
The spleen may enlarge as a part of the reticuloendothelial system reaction to infection. Also there may be formation of granulomas and single or multiple abscesses in the spleen , Spontaneous rupture of spleen has been reported in one patient  . Calcific lesions within the spleen can also occur, which appear characteristically as "Bull's-eye" calcification on radiography  . According to case reports of splenic abscess and rupture, patients were managed conservatively with good response ,
| Anorexia|| |
This is a common complaint of patients with brucellosis and has been reported in 22-45% of the patients , . The underlying pathophysiology of this complaint is not known. However, it can be due to the effect of inflammatory cytokines like INF gamma and TNF-α upon the appetite centre (ventromedial nucleus of hypothalamus). Weight loss in patients with brucellosis may be due to a combination of decreased appetite and increased energy demand due to ongoing inflammatory responses within the body.
| Vomiting|| |
This is a nonspecific complaint seen in many diseases. In brucellosis, it has been reported in 7-18% of the cases , . Exact cause is not known, however, it can be due to a direct effect of the organism upon stomach causing gastritis or due to central effect of cytokines like INF-gamma and TNF-α.
| Abdominal pain and tenderness|| |
Abdominal pain has been reported in 917% and abdominal tenderness in 15% of the patients with brucellosis ,,,,,,, . Possible underlying causes of these complaints include mesenteric lymphadenitis ,. Peyer's patches lymphadenitis or ulceration  , liver involvement in the form of hepatitis or abscess formation, splenic abscess, colitis, cholecystitis, pancreatitis, etc. In fact, patients with mesenteric lymphadenitis can present with acute abdomen.
According to one of the case reports, a young patient underwent laparotomy for suspected appendicitis when he presented with abdominal pain, fever, vomiting and right iliac fossa tenderness. The appendix was found to be normal, but many enlarged mesenteric lymph nodes were identified, which histologically showed reactive lymphadenitis. Patient's blood culture grew Brucella melitensis and he continued to spike high grade fever post appendectomy, but he recovered completely with anti-brucella treatment.  Patients with Peyer's patches ulcerations may have abdominal pain and tenderness like typhoid fever and with severe ulceration may have bleeding per rectum as well.
| Constipation|| |
This is seen in 2-12% of the patients with brucellosis  . Alteration in eating habits and physical activity due to the disease and profuse sweating may be responsible for this complaint.
| Diarrhoea|| |
This is reported in 3-6% of the patients with brucellosis. , The exact underlying cause is not known. However, it may be due to intestinal mucosal ulceration like Peyer's patches ulceration as in typhoid fever or colitis. Also, gastroenteritis can be caused by other microorganisms present in contaminated raw milk such as E. coli, Salmonella More Details, Shigella, etc.
| Colitis|| |
This is rare but serious complication of brucellosis. There are only few reported cases of this complication ,, Patient may present with fever, acute abdominal pain and bleeding per rectum. On colonoscopic examination, the mucosa may appear red, friable with multiple pseudo-polyps 
Histological examination may show acute and chronic inflammatory cell infiltrate in the mucosa with mucosal effacement and goblet cell depletion. The lamina propria may show extensive infiltration with lymphocytes and plasma cells with many macrophages and some neutrophils  . One of the case reports suggested diverticulitis as the cause of acute abdominal pain in a patient rowing brucella melitensis from the blood  . However, the finding was not substantiated by colonoscopy or other tests.
| Pancreatitis|| |
This is another rare complication of brucellosis. Patients may present with fever, vomiting, abdominal pain and constipation  . Brucella melitensis is usually the causative organism , . According to case reports antibrucella treatment resulted in good recovery without complications , .One of the case report recorded impairment of glucose metabolism during the course of illness possibly due to pancreatic involvement 
| Cholecystitis|| |
Again, this is a rare complication of brucellosis and there are eight reported cases in literature. Six of the patients were males. In six out of eight patients, Brucella melitensis was the causative organism and in one patient Brucella suis was the cause of infection. In the remaining one patient, diagnosis was made with positive brucella serology and history of contact with sheep and goat. Four of these patients grew brucella from bile cultures and six patients grew brucella from blood cultures. All the patients underwent cholecystectomy and received antibrucella chemotherapy later on and recovered without any complications. Histological examination of the gall bladder showed changes of acute cholecystitis, in five patients, mixed with chronic cholecystitic changes in one of those patients. Two patients showed changes of chronic cholecystitis with granuloma formation in one patient and abscess formation in gallbladder wall in the other patient. One patient showed changes of subacute cholecystitis. In five out of eight patients, gallstones were also present. Brucella species may reach the gall bladder either by lymphatic spread from the intestine or via the blood as part of a brucella bacteraemia. It is suggested that a chronic latent infection in the gallbladder may lead to the formation of gallstones  .
| Peritonitis, ascites and intestinal obstruction|| |
This is a very rare complication of brucellosis with few case reports in English literature ,,,,,,,, According to one of the case reports, intestinal obstruction was caused by band adhesions obstructing the small gut which needed surgical intervention  . In all the reported cases where cultures from peritoneal fluid or blood were positive, they grew Brucella melitensis. The majority of the patients (53.84%) with this complication had underlying liver cirrhosis. Two patients had brucella hepatitis, one patient had congestive heart failure (CHF) and congestive hepatopathy with ascites and one patient was on chronic ambulatory peritoneal dialysis. Two patients were having ventriculoperitoneal shunts and they had simultaneous involvement of the CNS and peritoneum. Brucella melitensis grew from the peritoneal fluid in 61.5% of the patients, and from blood in 46.15%. However, in 30.76% of the cases there was no growth from these sites and the diagnosis was based on positive brucella serology in titres from 1:640 to 1:1280 and good response to antibrucella treatment with disappearance of ascites ,
| Bloody diarrhea|| |
Bleeding per rectum is rare in brucellosis. It can be due to colitis, Peyer's patches ulceration or coagulopathies associated with brucellosis.
| Tonsillitis and sore throat|| |
Tonsillitis and sore throat are also well recognized features of brucellosis and Brucella abortus s been grown from the tissue cultures of surgically removed human tonsils
In Conclusion, the gastrointestinal manifestations of brucellosis are usually mild in the form of hepatosplenomegaly, anorexia and vomiting. More serious manifestations like colitis, pancreatitis, and cholecystitis are rare. However, it is important for the clinicians to be aware of these complications particularly in areas where Brucellosis is endemic, because early recognition and treatment results in complete recovery.
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Department of Medicine, King Khalid University Hospital, P 0 Box 7809, Riyadh 11472
Source of Support: None, Conflict of Interest: None
[Figure - 1]
[Table - 1]