Chronic Idiopathic Jaundice Research Articles

A Case of Sustained Cholestasis Caused by Acute A Viral Hepatitis in Dubin-Johnson Syndrome

Dubin-Johnson syndrome is a rare clinical entity. It shows intermittent symptoms such as chronic or intermittent jaundice, abdominal pain, weakness, nausea, vomiting, anorexia and diarrhea. Symptoms are precipitated or aggravated by pregnancy, alcoholism, surgical procedures and intercurrent disease. Chronic idiopathic jaundice is typical of Dubin-Johnson syndrome and its prognosis is good. We describe a case of prolonged cholestasis for more than 10 months caused by acute A viral hepatitis in a patient with Dubin-Johnson syndrome. It is a first report of cholestasis complicated by acute A viral hepatitis in a patient with Dubin-Johnson syndrome.

Pathophysiology of cholestasis

Cholestasis is postulated to be a disturbance of the secretion of micelles of bile salts mixed with other solids. This disturbance results in alteration of bile canalicular microvilli, canalicular dilatation, whidening of the pericanalicular ectoplasm, enlargement of the Golgi zone, and increase in smooth endoplasmic reticulum. Cholestasis is perpetuated by the effects of retained bile on the hepatocyte. This nonmechanical theory excludes from the category of cholestatasis other types of direct reacting hyperbilirubinemia, such as early primary biliary cirrhosis and chronic idiopathic jaundice, but includes the cholestatic component found in many liver diseases of established cause.

Chronic idiopathic jaundice in Papua and New Guinea: A report of nine patients with Dubin-Johnson's or rotor's syndrome

9 patients with chronic idiopathic jaundice are described. 7 had Dubin-Johnson's syndrome, and 2 Rotor's syndrome. 6 of those with Dubin-Johnson's syndrome were from the Madang District of New Guinea and were all diagnosed within one year. Mechanisms are proposed by which this high local incidence may have arisen, but further genetic studies would be needed to decide the most likely one. This high incidence is contrasted with the apparent absence of these syndromes in the Highlands people of Papua and New Guinea.

Isolement et propriétés d'une mélanine obtenue à partir de mélanogènes urinaires dans un cas de maladie de dubinjohnson

The authors report on the clinical history of a patient having the features of the chronic idiopathic jaundice of Dubin-Johnson disease, in whom a dark pigment was recovered from the urines. This pigment had several properties (solubility, U.V. and I.R. absorption spectra, electrophoretic mobility in agar gel), quite similar to those of melanin obtained from various human materials (hair, choroid, urine from a melanoma patient), or synthesized from adrenochrome. These data suggest strongly that the pigment under study is a true melanin resulting from the oxidation of unidentified precursors or melanogens excreted by the patient.

Chronic Familial Hyperbilirubinemia

Summary A patient is presented who exhibits Rotor's syndrome of chronic idiopathic jaundice with direct hyperbilirubinemia, Bromsulphalein (BSP) retention, and normal liver histology. He also has a slightly shortened red blood cell survival. The apparent onset of jaundice was coincident with a well documented episode of viral hepatitis. Studies of the patient's bilirubin metabolism and BSP excretion are presented and compared with findings in previously reported cases. Three of the patient's 5 children were found to have slight shortening of red blood cell survival, indirect-reacting hyperbilirubinemia out of proportion to the degree of hemolysis, and elevated BSP retention. It is postulated that the patient's defects in bilirubin and BSP uptake, as well as the low grade hemolytic process, were transmitted to the children, probably as an autosomal dominant. At the present time the children do not show an excretory defect.

Studies of Chronic Idiopathic Jaundice (Dubin-Johnson Syndrome) : II. Evaluation of a large family with the trait

Studies of Chronic Idiopathic Jaundice (Dubin-Johnson Syndrome) : II. Evaluation of a large family with the trait

Chronic idiopathic jaundice (Dubin-Johnson's syndrome) in three sisters.

SummaryThree sisters, aged 18, 16 and 11 years, were suffering from familial jaundice with elevated direct bilirubin. Two of them had a brown pigmentation of the liver cells and had slight, diffuse gastrointestinal symptoms. They meet the criteria for Dubin‐Johnson's syndrome. The third, suffering from a very mild form of familial jaundice, had very little pigment in the liver cells. This case is difficult to classify, being either a Dubin‐Johnson's syndrome, a Rotor's syndrome, or a condition intermediate between these two. Attempts to characterize the hepatic pigment with histochemical methods were made and seem to indicate that the pigment belongs to the lipofuscins.

Fine Structure of the Liver of Constitutional Hyperbilirubinemia

Constitutional hepatic dysfunction showing an increase in the free form of the plasma bilirubin, was first reported by Gilbert1) under the term of cholemie simple familiale in 1901. Similarly in 1948, Rotor2) reported the other type of constitutional hepatic disorder which showed mainly an increase in the conjugated form of the plasma bilirubin. However, histological examination of the liver in these two types of diseases has been reported to be within normal limits. In 1954, Dubin and Johnson3) described another type of the disorder under the term of chronic idiopathic jaundice with unidentified pigment in the liver which showed characteristic pigment in the liver cells and an increase in the conjugated form of the plasma bilirubin. These three disorders have many problems yet to be dissolved. In Rotor syndrome, despite of quite similarities to Dubin-Johnson syndrome in clinical and laboratory findings, there has been no report in which the confirmation of the pigment in the liver was made. These made us to study the two conditions with an use of electronmicroscope to find whether they are the same or different in their etiology and to delineate the particular pigmentation in the liver of Dubin-Johnson syndrome, as to its origin or nature and difference from ordinary brown colored pigmentation in the liver seeing in cases of cirrhosis, hepatitis or even in normal cases. In addition, we studied the cases of Gilbert's disease under the same circumstances.

Rotor's Syndrome and Chronic Idiopathic Jaundice

During the past decade increasing attention has been paid to a group of congenital or familial diseases of bilirubin metabolism, prompted largely by the hope that these diseases might provide some clues to the mysteries of bilirubin uptake, conjugation, and excretion by the liver cell. Among these diseases are two conditions characterized by jaundice and an increase in serum levels of both the conjugated and unconjugated fractions of bilirubin. These are Rotor's syndrome 1,2 and chronic idiopathic jaundice. 3-5 Some workers have suggested that these two conditions are close relatives, or even variants of a single disease. Others have scrapped the original criteria set down for these entities and have instituted radical changes in established terminology. Because such premature breaches in nomenclature may lead to obfuscation, I believe it desirable to reexamine the current status of these conditions. In our present state of knowledge, the major differences between these two

Chronic idiopathic jaundice with normal liver histology. A report of a case and review of the literature.

In recent years there have been numerous reports and reviews of the various kinds of familial, nonhemolytic and nonobstructive hyperbilirubinemia in the adult. Basically, these cases can be divided into two main categories. The first group is made up of those cases in whom the elevated bilirubin is mainly unconjugated (indirect), and they, consequently, have no bile in the urine. Gilbert et al. 1-3 described a group of patients in this category, and since then there have been numerous reviews of this syndrome published under a variety of names. 4-8 The second group is composed of patients who have elevated levels of both conjugated (direct) and unconjugated (indirect) bilirubin in their serum. These patients frequently have bilirubinuria. Patients of this variety were first described by Dubin and Johnson 9 and Sprinz and Nelson, 10 and a rather extensive review of this syndrome (chronic idiopathic jaundice or the Dubin-Johnson syndrome) appeared

Constitutional hyperbilirubinemia with unconjugated bilirubin in the serum and lipochrome-like pigment granules in the liver.

Case Reports1 February 1962Constitutional Hyperbilirubinemia with Unconjugated Bilirubin in the Serum and Lipochrome-like Pigment Granules in the LiverUFFE SAGILD, M.D., OLE Z. DALGAARD, M.D., NIELS TYGSTRUP, M.D.UFFE SAGILD, M.D.Search for more papers by this author, OLE Z. DALGAARD, M.D.Search for more papers by this author, NIELS TYGSTRUP, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-2-308 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSeveral syndromes of constitutional hyperbilirubinemia, caused by deficiencies in the elimination of bilirubin by the liver, have been described (1). Some of these may be diagnosed from their clinical course (2-4), while others can be differentiated only on the basis of laboratory findings. Thus the Gilbert-Meulengracht syndrome (5) [constitutional hepatic dysfunction], the Dubin-Johnson syndrome (6) [chronic idiopathic jaundice], and the Rotor syndrome (7) [chronic familial non-hemolytic jaundice with conjugated bilirubin in the serum] may appear to be identical clinically.The case presented here demonstrates that pathologic findings considered to be typical of different syndromes may be found in the same...

Electron-Microscopic Findings in Parenchymal Liver-Cells of Chronic Idiopathic Jaundice (Dubin-Johnson's Syndrome)

Electron-Microscopic Findings in Parenchymal Liver-Cells of Chronic Idiopathic Jaundice (Dubin-Johnson's Syndrome)

Human hepatocellular pigments and lysosomes

The fine structure of human hepatocellular granules containing lipofuscin, the pigment of chronic idiopathic jaundice (Dubin-Johnson), or bile pigment (obstructive jaundice) are described. Because of their fine structure and acid phosphatase activities all these granules are considered to be altered lysosomes. Iron-containing granules in human liver cells are also considered to be derived from lysosomes. This is based on their pericanalicular arrangement, size, and acid phosphatase activity. Parallel studies in spleen macrophages of the rat are referred to. Our findings provide evidence for the suggestion that the pericanalicular dense bodies are the lysosomes of the hepatic cell. Of special interest to pathologists are: (a) the unique structure of bile pigment deposits found within the cells, bile canaliculi, and sinusoids of the obstructed liver; (b) the differences in fine structure and distribution of acid phosphatase activity between the pigment of chronic idiopathic jaundice (Dubin-Johnson) and hepatocellular lipofuscin; (c) the fine structure of lipofuscin granules; and (d) the general roles suggested for lysosomes in the physiology and pathology of cells, including a role in the intracellular transport of bile.

Chronic idiopathic jaundice

A case of chronic idiopathic jaundice, a disease only recently recognized, is presented in detail. The disorder, usually found in young people, is manifested by chronic or intermittent fluctuating jaundice influenced by physiologic stress, with elevation of both the direct and indirect serum bilirubin, abdominal pain, and failure of the gallbladder dye to visualize on x-ray film. It differs from constitutional hyperbilirubinemia or Gilbert's disease in several respects, and is characterized by abnormal amounts of coarsely granular, brown pigment in the parenchymal cells of the liver, which is predominant in the centrolobular zones. This clinicopathologic entity probably represents an inborn deficiency in the liver's ability to excrete various substances. The liver can conjugate indirect bilirubin with glucuronic acid but then has difficulty excreting the conjugated bilirubin; hence, direct reacting bilirubin accumulates in the serum and spills over into the urine. It is unable to excrete adequately the dye used in cholecystography and cholangiography, the lipofuscin pigment which accumulates in the liver cells, and urobilinogen which may spill over into the urine. Undoubtedly many more cases will be recognized in the future. For a detailed review of the subject the reader is referred to Dubin's recent excellent comprehensive paper [ 3]. We wish to stress its importance in the differential diagnosis of jaundice and the resulting therapeutic and surgical implications.

Chronic idiopathic jaundice: A study of two afflicted families

Two Puerto Rican families are described, eight members of which were found to have varying amounts of hepatic cellular pigment on liver biopsy. Ten members were found to have hyperbilirubinemia. The microscopic appearance of the liver in one instance, and in another family member examined in another hospital, presented the fully developed picture of chronic idiopathic jaundice. In four instances a mild degree of pigment deposition was found and in two a borderline increase of the same pigment was noted. In one anicteric member the amount and distribution of pigment varied only slightly from the normal. It would therefore appear that some members of families with chronic idiopathic jaundice may have only a borderline increase in pigment. The conspicuous hepatic pigment demonstrated in chronic idiopathic jaundice results from accumulation of a pigment present in small amount in the centrolobular zone of normal livers. Bromsulphalein retention and oral cholecystography are not necessarily abnormal where accumulation of the pigment characteristic of chronic idiopathic jaundice is not greatly in excess, even in the presence of jaundice. Hepatic and pancreatic function tests may be entirely normal.

Familial chronic idiopathic jaundice (Dubin-Sprinz disease), with a note on bromsulphalein metabolism in this disease

This paper deals with five cases of chronic idiopathic jaundice (Dubin-Sprinz disease); four patients were siblings. In two patients concomitant cholelithiasis was observed. In two patients without cholelithiasis, the gallbladder could be well visualized after intravenous contrast dye was given, but only after a delay of five hours. Biliary excretion of conjugated bromsulphalein is impaired in Dubin-Sprinz disease. This results in re-entry of some of the conjugated bromsulphalein from the liver cells into the blood stream and excretion of an excess of conjugated bromsulphalein by the kidneys. These abnormalities in bromsulphalein metabolism, together with a familial occurrence, may be useful in establishing the correct diagnosis.

Electron Microscopic Study of Human Cholestasis.

SummaryIn both extrahepatic biliary obstruction and intrahepatic cholestasis, alteration of the bile canalicular wall of liver cells and distortion of normally present microvilli can be demonstrated by electron microscopy. The functional defect is localized into membrane of liver cells, the more so since cytoplasm of liver cells does not necessarily show significant alterations. It is assumed that the lesion in extrahepatic biliary obstruction results from increased hydrostatic pressure while it cannot be decided whether in intrahepatic cholestasis it is primary or also secondary to increased pressure. Microvillous changes are not found in chronic idiopathic jaundice and only focally in viral hepatitis with liver cell injury possibly as the result of intrahepatic cholestatic component. In both types of cholestasis, communication between dilated bile canaliculi and perisinusoidal tissue spaces may account by regurgitation for at least part of the jaundice.

The Cholecystogram in Chronic Idiopathic Jaundice.

The Cholecystogram in Chronic Idiopathic Jaundice.

Chronic idiopathic jaundice with unidentified pigment in liver cells.

In 1954 Dubin and Johnson 1 reported 12 cases of idiopathic jaundice with an unidentified pigment in the centrilobular liver cells. Clinically, these patients could have been classified as cases of familial hyperbilirubinemia or chronic hepatitis. However, with the unusual liver biopsy finding of a previously undescribed pigment, a new clinical entity was suggested. Since the original description, four additional cases have been recorded. 2-5 It is our purpose to record an additional case of this entity. Clinically, in addition to mild recurring icterus of unexplainable cause, these cases are characterized by (1) vague abdominal discomfort, (2) dark urine which is positive for bilirubin, (3) hepatomegaly, (4) poor visualization of the gall bladder by oral dye methods, (5) one-minute bilirubin values which are elevated to at least 50% of the total bilirubin and an otherwise benign course with a good prognosis for life. The diagnosis of these cases can only

Constitutional non-hemolytic jaundice with “lipochrome” hepatosis (Dubin-Sprinz disease)

An additional case is reported of a new clinicopathologic entity which has recently been described by Dubin and Johnson, and Sprinz and Nelson as “chronic idiopathic jaundice with unidentified pigment in liver cells.” The evolution of the literature on the subject is traced, and a comparison with Gilbert's disease is offered. The disorder is attributed to an error in liver metabolism. Alcoholism and intercurrent illness may act as precipitating or aggravating factors. Clinical features include persistent, low grade, non-hemolytic jaundice, lassitude, upper abdominal pain and slight enlargement and tenderness of the liver. Direct reacting bilirubin is elevated and forms a major portion of the total. Bilirubinuria, abnormal serocoagulation tests, delayed bromsulphthalein excretion and failure to see the gallbladder on cholecystography may be demonstrated on occasion. The patient's general health is not impaired, and prognosis appears to be good. A constant and diagnostic histologie finding is the presence of coarse, brown lipofuscin pigment within pericentrally placed liver cells. Histochemical reactions which permit characterization of this pigment are outlined and discussed.