| Abstract|| |
Sickle cell hemoglobinopathy is a common genetic disorder which is prevalent in certain areas of the Kingdom of Saudi Arabia. It is characterized by repeated hemolytic and vasoocclusive crises which lead to widespread vascular occlusion and subsequent multiple organ infarctions. Affected individuals present with a wide variety of gastrointestinal disorders mimicking vasoocclusive episodes causing diagnostic confusion and delays that may catch the unwary clinician. This article briefly reviews the gastroenterological manifestations of sickle cell disease.
|How to cite this article:|
Meshikhes AWN. Gastroenterological manifestations of sickle cell disease. Saudi J Gastroenterol 1997;3:29-33
Sickle cell hemoglobinopathy is a common genetic disorder affecting many individuals in certain countries. The disease is prevalent in the eastern and south western provinces of Saudi Arabia. In the heterozygous state, i.e. sickle cell trait is due to the presence of HbS gene on one of the homologous pair of chromosome II, both adult and sickle hemoglobins (HbA and HbS) are present and the condition is usually asymptomatic except under extreme conditions of very low oxygen tension. In homozygous state, presence of the abnormal hemoglobin (HbS) renders red blood cells susceptible to sickling under reduced oxgen tension leading to sequestration and thrombosis in the arterioles with subsequent ischemic infarction which may affect any organ in the body. The frequency and severity of these sickle cell crises are determined by the level of fetal hemoglobin (HbF) which is believed to play a protective role against vasoocclusive crisis and acute chest syndrome but does not always prevent them  . The gastrointestinal tract is by no means immune from these generalised effects occurring during any crisis. These effects may present to medical and surgical gastroenterologists posing a significant medical problem and a diagnostic dilemma especially for those who are not aware of this condition. This article aims to highlight the common gastroenterological manifestations of this common genetic disorder to familiarize the unwary clinicians.
| Abdominal pain in sickle cell disease (SCD)|| |
Abdominal pain is quite common in sickle cell disease but, its exact etiology is not known. It is usually secondary to vaso-occlusion and may be a sole complaint or associated with generalized pain crisis in other parts of the body. When it is a solitary complaint, it mimics a wide range of abdominal surgical emergencies which may trap the clinician to offer surgical intervension with its attendant risks. This can be avoided by careful history, clinical examination and specific laboratory and radiological investigations. The differential diagnosis include splenic causes such as acute splenic sequestration crisis, splenic infarction and abscesses, hepatobiliary causes such as biliary colic, acute cholecystitis, hepatic crisis, hepatitis and liver abscesses ,,,, . Peptic ulcer disease and ischemic colitis need to be considered in the differential diagnosis of abdominal pain in SCD ,,, . Other possible causes include bone marrow infarction of the vertebral bodies with nerve root entrapment, enlarged mesentric and retroperitoneal lymph nodes, acute pancreatitis and other general surgical conditions common to the general population such as acute appendicitis ,,, . The diagnosis of acute splenic sequestration crisis (ASSC) is a clinical one based on sudden massive painful enlargement of the spleen with a rapid fall in hemoglobin and hematocrit due to extensive pooling of the blood in the spleen. Splenic abscess occurs secondary to infection of splenic infarcts and presents with pain in the left upper quadrant with splenic tenderness, fever and leucocytosis. The diagnosis of splenic abscess is confirmed by ultrasound or CT scan. Although the standard treatment for ASSC and splenic abscess is splenectomy, there is a recent trend to drain the latter percutaneously avoiding the high morbidity associated with surgical intervention in selected cases and to avoid splenectomy with its attendant risks such as postsplenectomy sepsis.
| The stomach and duodenum|| |
There is no conclusive evidence to suggest that the incidence of peptic ulcer in SCD is higher than that in the general population despite the depressive nature of this illness. However, dyspeptic symptoms are more common in sickle cell disease patients  .
Upper gastrointestinal endoscopy was abnormal in 20 out of 51 patients with upper abdominal symptoms (14 with duodenal ulcer; 4 with gastric ulcer and 2 with gastritis)  . The etiology of these ulcers is associated with the reduced mucosal resistance as a result of repeated ischemic infarction during sickle cell crisis  . Healing of such ulcers is usually impaired due to vascular impairment and the rate of complications such as stenosis, hemorrhage and perforation is high , . Rao et al reported a fatal case of bleeding duodenal ulcer in a 14-year-old SCD patient; the first case of duodenal ulcer encountered by the author in over 600 cases  . The diagnosis was confirmed by endoscopy which was repeated eight weeks after intensive medical therapy  . Ulcer healing may be promoted by monthly packed red cell transfusions over six months. Surgical option should be offered early for poorly healing ulcers.
| The intestine|| |
Ischemic colitis occurs in very young sicklers due to massive intravascular sickling  . Exact pathology is not known, but cytokines such as interleukin and tumor necrosis factor may play an important role. Kimmelstiel has suggested that the pre-shock state occurring during sickle crisis cause mesenteric vascular thrombosis with subsequent vascular necrosis  . However, presence of extensive collaterals in the colon renders this complication rare. The diagnosis should be considered in any SCD patient presenting with severe abdominal pain, rectal bleeding and signs of localized peritonism. Presence of leucocytosis, fever and persistent abdominal pain indicates bending bowel infarction, and signs of peritonitis mean perforation necessitating exploratory laparotomy  . In the early stages the diagnosis can be suspected if thumbprinting is present on abdominal radiograph or barium enema , . The treatment is by nasogastric suction, broad spectrum antibiotics and hemodynamic support including exchange blood transfusion  . Repeated clinical examination is essential, but exploratory laparotomy should be undertaken without delay in presence of high fever, leucocytosis and signs of peritonism or peritonitis.
| Hepatobiliary system|| |
Sickle cell disease patients are at an increased risk of hepatic necrosis, cholelithiasis, choledocholithiasis and acute hepatic failure.
| The liver in SCD:|| |
Liver biopsy in SCD shows sinusoidal dilatation, Kupffer cell hyperplasia and erythrophagocytosis . These findings were confirmed in an autopsy series which reviewed 70 patients with hemoglobin SS and SC disease and showed 34% of patients to have focal necrosis, 20% with portal fibrosis and 16% with micronodular cirrhosis  . Abnormal liver function tests are present in many patients with SCD, but the hepatic origin is doubtful. Hemolysis and liver disease contribute to the elevation of direct and indirect bilirubin. Although serum alkaline phosphatase is elevated in adults and rises further with crises, this rise may originate from the bone rather than the liver  . Prothrombin time is prolonged in more than 21% of patients. The abnormalities in liver function tests tend to be more severe in vasoocclusive episodes.
A variety of causes such as obstruction of sinusoids by sickle cells with subsequent hepatic infarction during vasoocclusive episodes, cholelithiasis and cardiac failure may contribute to hepatocellular damage in SCD, but by far the most common causes are those related to repeated blood transfusion such as hemosiderosis and viral hepatitis C and B (HCV and HBV) which lead to chronic liver disease  . Grmer et al reviewed the liver biopsies of nine patients referred for elevated aminotransferases and alkaline phosphatase and found hemosiderosis in all patients, cirrhosis in two and chronic hepatitis in two  . All liver biopsies showed erythrophagocytosis, sinusoidal dilatation an kupffer cell hyperplasia. Although these histological findings were also seen in 90% of autopsied cases, the prevalence of chronic liver disease appears to be low , . An association between focal nodular hyperplasia (FNH) and SCD has been questioned  . This may be explained by repeated blockage of small vessels by sickle cells and sequestration with subsequent ischemic infarction and necrosis and this act as a stimulant to development of FNH but this needs to be substantiated  .
| Hepatic crisis|| |
Diggs estimated hepatic crisis to affect 10% of patients with SCD admitted to hospital  . This was confirmed by another study of 378 admissions over 10-year period  . It may be difficult to distiguish this from viral hepatitis but transaminases are unlikely to be higher than 1000 in the former and fall more gradually in the latter. Liver biopsy reveals sickle cell changes only.
| Acute hepatic failure|| |
There have been few reported cases of this very severe complication of sickle cell disease , . Patients presented with abdominal pain, severe jaundice and tender hepatomegaly. Prothrombin time is very prolonged and liver biopsy shows features typical of sickle cell disease with or without centrilobular necrosis ,, . Yohannan et al reported two children with hepatitis A virus infection presented with fulminant hepatic failure; one of them died and the other made full recovery  . The treatment consists of intravenous dextrose, oral neomycin, lactulose, vitamin K and packed cell transfusion. Although patients may develop progressive coma and death, reversible intrahepatic cholestasis and full recovery after exchange transfusion has been reported ,, .
| Cholelithiasis|| |
Patients with SCD are at an increased risk of developing pigmented gallstones. This risk increases with age. It is estimated that 80% of patients will have radiologically detected gallstones by the age of 40 years  . The features of hepatic crisis may be indistinguishable from that of acute cholecystitis e.g. right upper quadrant pain, jaundice, leucocytosis and raised transaminases  . This may create diagnostic confusion which can be avoided by cholecystectomy. However, surgery in SCD has a potentially high morbidity rate, especially if preoperative hemoglobin S is greater than 45%. The introduction of minimally invasive techniques is believed to be safer in SCD and associated with minimal morbidity and mortality , . Its impact on management of SCD patients with symptomatic gallstones is apparent to a degree that some hematologists are screening their young SCD patients for gallstones and referring them much earlier for laparoscopic cholecystectomy  . Certain precautions to guard against vasoocclusive crises have to be undertaken. This entails adequate hydration, oxygenation, prophylaxis against sepsis and measures to avoid hypothermia. Furthermore, preoperative simple or exchange blood transfusion to reduce HbS to less than 45%, a level at which sickling crisis are less likely is helpful  . In our early experience with LC in SCD patients, none of our 30 patients needed exchange transfusion and simple transfusion with packed red blood cells to raise Hb to at least 10% was sufficient and safe  . A single mortality in our series has prompted us to change our preoperative transfusion policy. All patients with high HbS are now given preoperative exchange transfusion to reduce HbS to less than 45% and thereby reducing the risk of vasoocclusive crisis  .
The role of laparoscopic cholecystectomy for asymptomatic gallstones is controversial. Although, the natural history of asymptomatic stones suggests no future problems in the majority of patients, the author as well as others advocate laparoscopic cholecystectomy in young SCD patients with asymptomatic gallstones to avoid future complications and diagnostic confusion , .
| Choledocholithiasis|| |
Choledocholithiasis is a major complication of gallstones presenting as obstructive jaundice or acute biliary pancreatitis. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) should be performed selectively in any patient with dilated common bile duct on ultrasonography (>7 cm) or acute biliary pancreatitis before laparoscopic cholecystectomy is performed. The author advocates routine endoscopic papillotomy in any patient with SCD undergoing ERCP prior to laparoscopic cholecystectomy even in the absence of common bile duct stones.
| Conclusion|| |
The medical and surgical gastroenterologist may be faced with sickle cell patients presenting with symptoms and signs of various gastroenterological and hepatobiliary conditions which may mimic abdominal sickle cell crises. Careful history and clinical examination augmented by specific laboratory and radiological tests are essential to avoid unnecessary and often life-threatening surgical exploration. If surgery is warranted, precautions to guard against vasoocclusive events such as adequate hydration, oxygenation and exchange transfusion together with prophylactic measures against sepsis, deep venous thrombosis and hypothermia are adhered to, to ensure safe surgical intervention with minimal morbidity and mortality. Close collaboration between medical and surgical staff is of paramount importance.
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Abdul-Wahed Nasir Meshikhes
Consultant Surgeon, Damman Central Hospital, P.O. Box 18418, Qatif 31911