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Dubin-Johnson Syndrome

Dubin-Johnson syndrome (DJS) is a rare type of hereditary hyperbilirubinemia with a relatively benign course.


Presentation

Obtaining a full history is usually the first port of call regarding clinical evaluation for individuals with Dubin-Johnson syndrome or other suspected causes of conjugated hyperbilirubinemia [7].

Wild mushrooms, environmental chemicals (e.g solvents) and drugs (potential toxins) have to be excluded carefully. Failing to appropriately diagnose toxic hepatitis often leads to hepatic failure and death.

It is equally important to elicit some of the possible risk factors for viral hepatitis. Some of these possible risk factors are: Exposure to an infected individual, multiple sexual partners, intravenous drug use and transfusion [8].

Intravenous Drugs
  • Some of these possible risk factors are: Exposure to an infected individual, multiple sexual partners, intravenous drug use and transfusion. Presence of abdominal pain or fever suggests gallstone disease.[symptoma.com]
Pleural Effusion
  • Autopsy revealed a black liver, atrophy of fat tissue on the mesentery, and pneumonia with bilateral pleural effusion.[ncbi.nlm.nih.gov]
Jaundice
  • Possible Complications Complications are unusual, but may include the following: Reduced liver function Severe jaundice When to Contact a Medical Professional Call your health care provider if any of the following occurs: Jaundice is severe Jaundice gets[web.archive.org]
  • Dubin-Johnson syndrome is a condition characterized by jaundice, which is a yellowing of the skin and whites of the eyes. In most affected people jaundice appears during adolescence or early adulthood.[ghr.nlm.nih.gov]
  • Liver biopsy and histochemical stain may be helpful to identify the reason of jaundice and avoid misdiagnosis or an indefinite diagnosis.[ncbi.nlm.nih.gov]
  • Biphasic pattern of jaundice attack was observed in one patient who was followed for 20 y, with jaundice subsiding before 1 y of age and recurring at adolescence.[ncbi.nlm.nih.gov]
  • There was a history of jaundice since infancy.[ncbi.nlm.nih.gov]
Hepatomegaly
  • It is characterized by mild recurrent jaundice with hepatomegaly. Pathophysiology This is a rare genetic autosomal recessive disorder.[labpedia.net]
  • Affected infants typically also have enlarged livers (hepatomegaly) and a severely reduced ability to produce and release a digestive fluid called bile (cholestasis).[ghr.nlm.nih.gov]
  • If there is tricuspid insufficiency with hepatomegaly or severe right heart failure hepatic congestion may be present. Sepsis, hepatitis ischemia and opportunistic infections should be considered for patients with severe intercurrent illnesses.[symptoma.com]
  • Main findings of the disease are hepatomegaly associated with abdominal pain and jaundice.[accessanesthesiology.mhmedical.com]
Stroke
  • The patient was followed for one yr, and the results were satisfactory for an increase in oral intake and protein uptake, no recurrence of metabolic stroke and there was a gradual catch-up with regard to physical development despite having a persistently[ncbi.nlm.nih.gov]
Hyperactivity
  • Hyperactive pericentral Kupffer cells which are involved in the response to pigmentary material originating from disintegrated hepatocytes may play an essential role in the development of DJS.[ncbi.nlm.nih.gov]

Workup

Accurate laboratory testing for DJS and other cases of conjugated hyperbilirubinemia is dependent on the physical examination findings and clinical history of the patient [9]. However, all patients of this condition should be tested for:

  • Alpha-1 antitrypsin fractionation and other relevant studies if considering hereditary liver diseases.
  • Copper studies if Wilson disease is suspected.
  • Iron and genetic studies if hemochromatosis is suspected.
  • Antinuclear antibodies (ANAs), smooth-muscle antibodies, and other types of serologic studies if autoimmune hepatitis is suspected.
  • Antimitochondrial antibody if primary biliary cirrhosis is suspected.
  • Alkaline phosphatase (ALP): If an obstruction is suspected or if it is elevated, it is important to obtain images of the bile ducts.
  • Blood alcohol or acetaminophen levels. This often proves useful later on.
  • Fractionated bilirubin.
  • Serologic screen for hepatitis. This should include hepatitis C virus (HCV) antibody and hepatitis B surface antigen (HBsAg) or antihepatitis B core antibody (anti-HBcAb).
  • Serum aminotransferases (aspartate aminotransferase [AST], alanine aminotransferase [ALT]).
  • Complete blood cell (CBC) count to confirm hemolysis when present.
Acanthocytes
  • Peripheral blood smears revealed numerous acanthocytes. Despite the administration of antibiotics and nutritional support, the patient died.[ncbi.nlm.nih.gov]
Pleural Effusion
  • Autopsy revealed a black liver, atrophy of fat tissue on the mesentery, and pneumonia with bilateral pleural effusion.[ncbi.nlm.nih.gov]

Treatment

Dubin-Johnson syndrome is a benign disorder which usually does not require any specific treatment.

Prognosis

The outlook is very positive for Dubin-Johnson syndrome and other conditions that lead to conjugated hyperbilirubinemia and generally the condition does not shorten the lifespan of the individual.

Etiology

The condition develops as a result of reduced secretion of conjugated bilirubin into the bile and is often present in patients with hepatitis.

It can equally be seen with patients with biliary obstruction, where there is an impaired flow of bile into the intestine [5]. The formation of bile is very sensitive and thus can be affected by various conditions like high levels of inflammatory cytokines, etc.

Epidemiology

In the United States, conjugated hyperbilirubinemia is commonly seen among patients with other biliary or notable liver diseases. It is equally common seen in patients with sepsis, cardiogenic shock and other systemic illnesses. Dubin-Johnson syndrome however, is very rare [3].

Internationally, ascariasis, clonorchiasis, and other parasistic diseases commonly lead to biliary obstruction especially in lesser-developed countries. Malaria and other haemolytic differences can equally make patients susceptible to biliary obstruction due to the formation of gallstone pigments. Dubin- Johnson syndrome equally occurs rarely.

Regarding racial differences, conjugated hyperbilirubinemia will only reflect the differences noted for the underlying disease condition. No difference is recorded for Dubin Johnson syndrome. The situation is the same for sex related differences in occurrence. [4]

The age at which conjugated hyperbilirubinemia is reflected is also dependent on the disease state. Biliary artesia leads to conjuhated bilirubinemia within the first month of life, the occurrence is more frequent within midlife for patients with primary biliary cirrhosis or viral hepatitis to senescence as is the case with malignancies and biliary stones.

Sex distribution
Age distribution

Pathophysiology

Dubin-Johnson syndrome or high levels of conjugated bilirubin often secondarily increase the level of unconjugated bilirubin.

The mechanism behind this is not clearly defined but one possible cause is the reduced hepatic clearance of unconjugated bilirubin. This is due to competition with conjugated bilirubin for excretion or uptake [6].

Prevention

There are no guidelines for prevention of Dubin-Johnson syndrome.

Summary

Dubin-Johnson syndrome is a disorder that brings about an increase in levels of conjugated bilirubin found in the serum [1]. When the increase occurs, there is no elevation of ALT, AST and other liver enzymes.

The syndrome is an autosomal recessive disorder. Dubin-Johnson syndrome has similarities with the Rotor syndrome as it is a defect in the ability of hepatocytes to disseminate bilirubin into the bile.

The condition is generally asymptomatic but it can be diagnosed early in infants with the aid of laboratory tests.

Before being eliminated from the body, bilirubin must be converted into a soluble conjugate since it is not soluble in water. Uridine diphosphate (UDP)-glucuronyl transferase is the compound which converts bilirubin to a mixture of monoglucuronides and diglucuronides (conjugate bilirubin) in the liver. An ATP-dependent transporter disseminates the conjugate bilirubin into the bile. Under normal conditions, this process is very efficient leading to low concentration levels of plasma unconjugated bilirubin [2].

Apart from the Dubin-Johnson syndrome, there are many conditions that lead to the accumulation of bilirubin in the plasma. Conditions like hemolysis which bring about an increase in the bilirubin formation or conditions like Gilbert syndrome which reduce the rate of bilirubin conjugation bring about unconjugated hyperbilirunemia.

If the disease reduces the flow of bile into the intestine or the secretion of conjugated bilirubin into the bile conjugated hyperbilirunemia sets in. This is because of the reflux of conjugates into the plasma. Hepatobiliary diseases lead to elevated conjugated bilirubin levels.

Patient Information

The patients need to be reassured that no treatment is required if only Dubin-Johnson syndrome is diagnosed. Again, there is typically no reduction in life expectancy [10].

References

Article

  1. Westwood A. The analysis of bilirubin in serum. Ann Clin Biochem. Mar 1991;28 ( Pt 2):119-30.
  2. Iyanagi T, Emi Y, Ikushiro S. Biochemical and molecular aspects of genetic disorders of bilirubin metabolism. Biochim Biophys Acta. Sep 30 1998;1407(3):173-84.
  3. Klein CJ, Revenis M, Kusenda C, Scavo L. Parenteral nutrition-associated conjugated hyperbilirubinemia in hospitalized infants. J Am Diet Assoc. Nov 2010;110(11):1684-95.
  4. Johnston DE. Special considerations in interpreting liver function tests. Am Fam Physician. Apr 15 1999;59(8):2223-30.
  5. Shani M, Seligsohn U, Gilon E, et al. Dubin-Johnson syndrome in Israel. I. Clinical, laboratory, and genetic aspects of 101 cases. Q J Med 1970; 39:549.
  6. Dittrich H, Seifert E. On the behavior of pigment and biligraffin excretion in a patient with Dubin-Johnson syndrome. Acta Hepatosplenol 1962; 9:45.
  7. Morita M, Kihara T. Intravenous cholecystography and metabolism of meglumine iodipamide (Biligrafin) in Dubin-Johnson syndrome. Radiology 1971; 99:57.
  8. Essner E, Novikoff AB. Human hepatocellular pigments and lysosomes. J Ultrastruct Res 1960; 3:374.
  9. Swartz HM, Sarna T, Varma RR. On the natural and excretion of the hepatic pigment in the Dubin-Johnson syndrome. Gastroenterology 1979; 76:958.
  10. Nisa AU, Ahmad Z; Dubin-Johnson syndrome. J Coll Physicians Surg Pak. 2008 Mar;18(3):188-9.

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Last updated: 2019-06-28 09:56