Hodgkin's disease presenting as a cholestatic febrile illness: incidence and main characteristics in a series of 421 patients

Abstract

In order to determine the frequency and characteristics of patients with liver abnormalities as the presenting manifestation of Hodgkin's disease (HD), 421 consecutive HD patients were studied. Six patients in the series (1.4%) presented with liver abnormalities that led to of a liver biopsy and the subsequent diagnosis of HD. All had fever prior to HD diagnosis, four frank jaundice, and one hepatic failure. No patient had pruritus. Moderate hepatomegaly was present in four patients. Cholestasis was observed in all cases; in most patients a moderate increase in the transaminase activity was also seen. Two patients had a mild rise in the serum LDH, four had leukopenia, and one eosinophilia. At liver histologic study, Reed-Sternberg cells were demonstrated in four patients; in the remaining two, the presence of atypical histiocytes, lymphocytes, and eosinophils was highly suggestive of HD, the latter diagnosis being confirmed by subsequent study of bone marrow and/or retroperitoneal lymphadenopathies. In three of the six patients, HD was not demonstrated in sites other than the liver. Three patients older than 60 years died shortly after HD diagnosis. By contrast, three patients younger than 40 years showed a dramatic response to chemotherapy: two of them had a further relapse, and one is considered cured after 14 years of continuous remission. Liver disease constitutes an infrequent form of HD presentation which must be included in the differential diagnosis of any patient with fever of unknown origin.

Macrophage activating syndrome is associated with lobular hepatitis and severe bile duct injury with cholestasis

“…Intriguingly, lymphomas are not only a common underlying disorder of MAS in adults, but also rarely accompanied by cholestasis, particularly related to HL. Generally, jaundice in HL is due to hepatic infiltration or extrahepatic biliary obstruction; seldom, cholestasis remains idiopathic [9]. Hubscher et al described three cases of idiopathic intrahepatic cholestasis in HL with progressive small bile duct destruction defining the vanishing bile duct syndrome (VBDS) [10].…”

Febrile cholestatic disease as an initial presentation of nodular lymphocyte-predominant Hodgkin lymphoma

“…In the only published series of 421 HL patients, 1.4% of patients initially had cholestasis and fever with no peripheral adenopathies [1] . Liver involvement of any kind at the time of presentation of HL is infrequent and ranges from 5-14%, but increases with advanced stages of the disease up to 60% postmortem [3] .…”

“…The prognosis for patients with liver disease as the initial manifestation of HL is generally poor [1,[15][16][17] , but not the rule, since some case reports show favorable response to chemotherapy [18][19][20][21][22] . Unfortunately, this was not the case with our patient where 3 mo after the appearance of symptoms, ABVD chemotherapy resulted in a poor therapeutic response.…”

“…Febrile cholestatic disease is a rare initial presentation of Hodgkin lymphoma (HL) [1] . Initial liver involvement is extremely rare in indolent types of HL and more frequent in aggressive types of HL such as mixed cellularity and lymphocytic depletion [2] .…”

Extrahepatic Hodgkin’s Disease with Intrahepatic Cholestasis: Report of Two Cases

“…However, the incidence of hepatic involvement varies according to the diagnostic method used and is reported to be 50–60% in postmortem studies. Only a small proportion of patients (3–13%) become clinically jaundiced [1, 2, 3, 4]. There are several possible causes of cholestasis in HD; hepatocellular infiltration, biliary obstruction, hemolysis, viral hepatitis or drug toxicity [2, 3, 5].…”