Dubin-Johnson syndrome is a chronic hereditary disease characterized by a violation of the release of bilirubin from hepatocytes into bile. The main clinical manifestation is intermittent jaundice. The disease is also characterized by dyspeptic disorders, decreased appetite and deterioration of general well-being. Diagnosis includes biochemical blood and urine tests, bromsulfalein assay, instrumental techniques (ultrasound, laparoscopy, liver biopsy). Treatment involves lifestyle correction, the appointment of a sparing diet. If necessary, choleretic drugs and other medications are used.
E80.6 Other disorders of bilirubin metabolism
The syndrome has several synonyms — enzymopathic jaundice, genetically determined pigmented hepatosis. The nosological form is named after two American scientists, I.N. Dubin and F.B. Johnson, who described the syndrome in 1954. This is a rare disease that manifests itself in 70% at a young age. Basically, Dubin-Johnson syndrome is observed in residents of the Middle East. The highest frequency of occurrence among Iranian Jews is 1 case per 1300 population. In 60% of patients, pathology is accompanied by a decrease in the activity of coagulation factors and bleeding. The incidence does not depend on gender.
The syndrome has a genetic nature, characterized by an autosomal recessive way of inheritance. Among relatives, the disease can manifest itself in both men and women, it repeats after 1-2 generations. The hereditary defect is represented by a mutation in the nucleotide sequence that provides encoding of the MRP2 protein. This protein is responsible for the excretion (release) of conjugated bilirubin and organic anions into the bile ducts.
Due to the dysfunction of the ATP-dependent transport system of the tubules, bile does not pass into the bile capillaries, which is why bilirubin accumulates in hepatic tissues. The long-existing syndrome is accompanied by reverse biochemical reactions: an excessive amount of direct bilirubin is released from glucuronic acid. The resulting indirect bilirubin also penetrates into the bloodstream, causing a toxic effect on the nervous system.
The release of active metabolites of epinephrine (tryptophan, tyrosine) is disrupted. As a result, melanin-like pigments located in the lysosomes of hepatocytes accumulate in the liver. During macroscopic examination, multiple dark spots are visible in the hepatic parenchyma — the so-called “chocolate liver”. When examining samples under a microscope, clusters of pigment grains are observed, mostly in the center of the lobules.
Usually, the manifestation of Dubin-Johnson syndrome occurs at the age of 20-30, although the first characteristic signs appear already in adolescents. Extremely rarely, the disease is detected in children. In women with an asymptomatic course of enzymopathic jaundice, the clinical debut of the disease can provoke the onset of pregnancy or the use of contraceptives.
The main symptom of the disease is jaundice, not accompanied by skin itching. First, there is jaundice of the sclera and mucous membranes, then the skin also acquires a jaundice shade. Jaundice can be aggravated by debilitating physical exertion, stressful situations, intercurrent infections. As a rule, jaundice periods are replaced by jaundice-free periods, although in a number of patients, icteric skin persists constantly.
The syndrome periodically worsens. The patient complains of severe pain on the right side of the hypochondrium, less often in the umbilical region. Sometimes the pain goes to the right shoulder or shoulder blade. The pain syndrome can be so intense that it resembles hepatic colic. Simultaneously with the pain, nausea and bitterness in the mouth bother. Occasionally there is vomiting, which does not bring relief. General intoxication is manifested by increased fatigue, drowsiness, decreased appetite.
Dubin-Johnson syndrome is characterized by a benign course and, with proper treatment, does not cause unpleasant consequences. A frequent complication with a long—term disease is inflammatory processes in the gallbladder and ducts. Inflammation can also spread to the hepatic parenchyma, causing cholestatic hepatitis. In the presence of these pathologies, jaundice in patients with Dubin-Johnson syndrome becomes permanent.
When a bacterial infection is attached, empyema of the gallbladder and purulent cholangitis may occur, which, under unfavorable conditions, transform into limited peritonitis. In elderly people, hereditary pigment syndrome provokes the appearance of fibrous changes in the liver lobules. As a result, the functional activity of the liver decreases. Due to a violation of the synthesis of blood clotting factors, the risk of bleeding increases.
During the physical examination of patients, a gastroenterologist or hepatologist palpates the edge of the liver protruding a few centimeters from under the costal arch. The syndrome is differentiated with Rotor disease, hepatitis, cancer metastases to the liver. Symptoms of gallbladder lesion (Mussi, Ortner, Ker) are negative. The following laboratory and instrumental studies are used to confirm the disease:
- Blood test. The main diagnostic criterion of the syndrome is an increase in the level of total bilirubin of more than 85 mmol / l, while the mass fraction of direct bilirubin exceeds 15%. When performing a coagulogram, 60% of patients show a decrease in prothrombin activity and a decrease in prothrombin time.
- Urine analysis. Elevated levels of bilirubin are detected in the urine. For differential diagnosis with similar clinical symptoms of Rotor syndrome, the ratio of type I and type III coproporphyrins in urine is evaluated. With Dubin-Johnson hepatosis, the amount of coproporphyrin type 1 is 80%, and type 3 is 20%.
- Bromosulfalein test. The analysis is most sensitive for the assessment of hepatic functions. With Dubin-Johnson syndrome, after 45 minutes, the concentration in the blood of a special dye, which was previously injected intravenously, is more than 6%. Such a test is considered positive and indicates a decrease in the absorption and excretory function of the liver.
- Abdominal ultrasound. With sonography, the syndrome is manifested by an increase in the liver by 1-2 cm, in middle-aged and elderly patients, foci of fibrosis are often found. The dimensions and contours of the gallbladder are not changed, concretions are not visualized. Simultaneous enlargement of the spleen is characteristic.
- Invasive methods. In doubtful situations, diagnostic laparoscopy is indicated, which allows the doctor to examine the outer surface of the liver and identify characteristic brown spots. To confirm the diagnosis, a percutaneous biopsy of liver tissue is prescribed, followed by examination of biopsies under an electron microscope.
Etiopathogenetic treatment of the disease has not been developed. The main role in preventing the deterioration of the condition of patients belongs to non-drug measures. To prevent exacerbations of Dubin-Johnson syndrome, patients are advised to avoid physical fatigue and stress as much as possible. The main directions of treatment used in modern gastroenterology to improve the quality of human life:
- Diet. The diet limits the consumption of refractory fats and products containing preservatives. Completely exclude the use of alcoholic beverages. A fortified diet with sufficient calories is shown.
- Drugs with choleretic effect. Synthetic or herbal medicines are prescribed that either increase the concentration of bile acids or increase the content of the aqueous component of bile. Experts prefer soft herbal preparations.
- Sanitation of foci of infection. The most common chronic sources of infection — dental caries and chronic tonsillitis – are being identified and treated. If concomitant pathology of the biliary tract is detected, appropriate pathogenetic therapy is selected.
Prognosis and prevention
The presence of Dubin-Johnson disease does not affect life expectancy and performance, so the prognosis is favorable. The syndrome is not progressing. If medical recommendations are followed, patients feel well. Patients should refrain from alcohol and taking contraceptives. Specific prevention has not been developed. Families with Dubin-Johnson syndrome should consult with a geneticist before planning a pregnancy.