Melanie Deutsch

Immune thrombocytopenia and α-interferon therapy

Abstract Thrombocytopenia is often found in patients with liver diseases, especially due to congestive splenomegaly caused by portal hypertension. Immune thrombocytopenia has been described rarely, and it seems to be especially associated with hepatitis C virus, which has been described as having a particular interaction with the immune system contributing to the induction of autoimmunity. Interferons, on the other hand, because of their immunomodulatory properties, are able to induce or exacerbate autoimmune diseases. Mild thrombocytopenia is a common adverse effect of interferon therapy. Severe life-threatening thrombocytopenia is extremely rare. We report two cases of severe immune thrombocytopenia in patients with chronic hepatitis C, probably induced by α-interferon. Bone marrow aspirate and elevated platelet-associated IgG antibodies, determined by indirect immunofluorescence, were suggestive of immune thrombocytopenia. None of the patients had any clinical sign of autoimmune syndrome, including arthritis, serositis, Sicca syndrome, vasculitis, thyroid abnormalities and others. Cryoglobulins and rheumatoid factors were tested and were undetectable. The patients histories of exposure to α-interferon and the exclusion of other causes are most consistent with drug-induced immune thrombocytopenia. After α-interferon withdrawal, thrombocytopenia was treated successfully with prednisolone and immunoglobulins. Response to treatment was consistent with the diagnosis of α-interferon-induced immune thrombocytopenia and peripheral consumption of platelets.

Fulminant hepatic failure as a presenting paraneoplastic manifestation of Hodgkin's disease.

Malignancies may uncommonly present as fulminant hepatic failure and, due to the rarity of such an occurrence, they may easily be overlooked as one of its possible causes. An unusual case of Hodgkins disease presenting as a fulminant hepatic failure is reported. A 34-year-old man presented with an acute onset of liver failure characterized by jaundice, ascites, encephalopathy and bleeding diathesis. Chemotherapy was initiated, resulting in a dramatic improvement not only in the patients level of consciousness, but also in prothrombin time. Unfortunately, he succumbed shortly after to disseminated candidiasis. A post-mortem needle liver sample revealed massive hepatocellular necrosis, but no liver infiltration by the neoplastic disease. We conclude that in Hodgkins disease, involvement of the liver can be manifested as a syndrome of paraneoplastic fulminant hepatic failure. In such cases, liver transplantation is an absolute contraindication but urgent chemotherapy under antifungal surveillance can be life saving.

Cholestatic jaundice as a paraneoplastic manifestation of renal cell carcinoma

Malignant diseases may cause cholestatic jaundice through either main bile duct obstruction or widespread hepatic metastasis. Renal cell carcinoma (hypernephroma, RCC) can cause a variety of paraneoplastic manifestations which can be the main presenting symptoms. Cholestasis, as a paraneoplastic syndrome, has been well described in patients with malignant lymphohyperplastic diseases. Non-metastatic nephrogenic hepatic dysfunction syndrome without jaundice has often been described in patients with hypernephroma (Stauffers syndrome). Paraneoplastic cholestatic jaundice has not yet been described. We report, for the first time, two patients who presented with pruritus and cholestatic jaundice. During the diagnostic work-up, RCC was diagnosed. The renal tumour was an unexpected finding during computed tomographic (CT) scan. No clinical manifestations of hypernephroma, short of microscopic haematuria, were detected. Conjugated bilirubin, alkaline phosphatase and gamma-glutamyltranspeptidase were markedly increased. No hepatic metastasis or main bile duct obstruction were detected by appropriate investigations. After radical nephrectomy, liver abnormalities disappeared rapidly. We conclude that RCC should be included among neoplasms causing not only anicteric intrahepatic cholestasis but also frank jaundice as part of a paraneoplastic syndrome. The differential diagnosis from hepatic metastasis, main bile duct obstruction or other causes of jaundice is of clinical importance and of prognostic value. Patients with unexplained cholestasis should be investigated for malignant diseases including hypernephroma.

Hepatitis C Virus (HCV)-Related Cryoglobulinemia: Cryoglobulin Type and Anti-HCV Profile

ABSTRACT Cryoglobulin characteristics in chronic hepatitis C (CHC) might be of importance for knowing more about the pathogenesis and treatment of the disease. We aimed to investigate the relationship between cryoglobulin types and their specificity against hepatitis C virus (HCV) antigenic epitopes in CHC patients. We analyzed samples from 43 patients with HCV-associated cryoglobulinemia, of whom 4 had concomitant lymphoma. Cryoglobulins were measured, purified, typed by immunofixation electrophoresis, and tested for IgG and IgM anti-HCV antibodies by immunoblot analysis and an enzyme-linked immunosorbent assay (ELISA). Clinical and other laboratory data were recorded. The median cryocrit level of the tested samples was 6%. Type I cryoglobulins were detected in 9.3% (4/43) of the cryoprecipitates, and type II cryoglobulins were detected in 48.8% (21/43) of the cryoprecipitates. IgM monoclonal protein, mainly IgM(κ), was found in 92% (23/25) of type I and II cryoprecipitates. Type III cryoglobulins were identified in 41.9% (18/43) of the patients and were associated with high blood serum IgG levels. In 81.3% (13/16) of type II and 92.3% (12/13) of type III cryoglobulins, there was IgG reactivity against the viral core region. Ninety-two percent and 32% of IgG anti-HCV core-positive cryoprecipitates had additional specificities against the NS3 and NS4 regions, respectively. Also, IgM anti-HCV antibodies were detected in 31% of the cryoprecipitates. In conclusion, all types of cryoglobulins were found in patients with HCV-associated cryoglobulinemia, with type II being the most frequently identified. Type III cryoglobulins were common and were associated with high serum IgG levels. HCV-related cryoglobulins demonstrated IgM, and particularly IgG, anti-HCV specificities, mainly against the core and NS3 epitopes.

Post-Infantile Giant Cell Hepatitis Associated with Autoimmune Hepatitis and Polyarteritis Nodosa

We report the case of a patient with corticosteroid-responsive giant cell hepatitis associated with typical manifestations and changes of polyarteritis nodosa from the kidney and central nervous system. Initially, the patient presented with transient right hemiparesis, followed by spontaneous remission without any abnormalities on computed tomography scan, magnetic resonance imaging and cerebrospinal fluid examination. A few months later he was admitted to our clinic because of icterus, peripheral oedema and abdominal distension. He was found to have clinical signs of active cirrhosis. Serological tests for hepatitis B, C and HIV virus were negative. Serum ceruloplasmin, a 1 -AT and ferritin levels were within normal limits. Antinuclear antibodies were positive (1:160). Liver biopsy showed micronodular cirrhosis with many eosinophils in the portal tracts and giant hepatocytes with multiple nucleoli in the lobule. Fulfilling the diagnostic criteria for autoimmune hepatitis, he was started on treatment with prednisolone and azathioprine, resulting in both clinical and biochemical responses. Four years later he presented with severe pain at the right costovertebral angle. Ultrasonography revealed a haematoma at the right kidney, and selective angiography of the abdominal aorta, renal arteries and hepatic artery documented microaneurysms in both kidney and liver arteries. Because of severe haemorrhage, right nephrectomy was performed. Histology of kidney specimen showed characteristic lesions of polyarteritis nodosa. Several months later, while on treatment with prednisolone and cyclophosphamide, the patient experienced a fatal episode of brain haemorrhage. An association between autoimmune hepatitis, polyarteritis nodosa and postinfantile giant cell hepatitis has not been reported previously.

Unusual combination of paraneoplastic manifestations in a patient with metastatic gastrointestinal stromal tumor (GIST)

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Activating mutations in tyrosine kinase receptors KIT or platelet-derived growth factor receptor alpha (PDGFRA) are the main mechanisms causing the disease. Patients generally present with non-specific symptoms, while a number of tumors are discovered incidentally and may be metastatic at the time of diagnosis. Aggressive GISTs have a defined pattern of metastasis to the liver or throughout the abdomen, or both. Though GISTs rarely present systemic or isolated paraneoplastic reactions, a few cases have been reported in the literature. We present the case of a 54-year-old patient with metastatic GIST at diagnosis and the emergence of paraneoplastic manifestations during follow-up.

Hepatitis B s antigen kinetics during treatment with nucleos(t)ides analogues in patients with hepatitis B e antigen‐negative chronic hepatitis B

Serum hepatitis B s antigen (HBsAg) levels might be used as a predictor of virological breakthrough or of sustained off‐treatment virological response in hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B (CHB) patients. We evaluated the changes of HBsAg in those patients under nucleos(t)ide analogue(s) [NA(s)] therapy for ≥12 months.

Polymorphisms of the CD14 Genes are Associated with Susceptibility to Alcoholic Liver Disease in Greek Patients

BACKGROUNDnThe incidence and severity of alcoholic liver disease (ALD) in chronic drinkers has been found to correlate with some environmental factors and especially with the dose of alcohol consumption, but it is obvious that other parameters clearly contribute to individual alcohol susceptibility. Chronic ethanol exposure leads to continuous endotoxin-mediated Toll-like receptor-4 (TLR-4) and CD14 activation and subsequent cytokine release resulting in chronic inflammation with continued hepatocellular damage. Therefore, genetic studies of polymorphism in TLR-4 and CD14 genes seem to be appropriate in determining genetic susceptibility to ALD. Our aim is to evaluate in a series of Greek drinkers, the possible association of polymorphisms in the TLR-4 and CD14 genes with ALD.nnnMETHODSnIn 96 patients with ALD polymorphism of TLR-4 and CD14 genes were studied compared with 104 patients with cirrhosis of other etiology, 100 healthy subjects, and 50 patients with a history of alcohol abuse but without liver disease.nnnRESULTSnNo association between ALD and the presence of the Asp299Gly and Thr399Ile polymorphisms in the TLR-4 gene could be documented in our patients. Regarding the CD14 -159 (C/T) genotypes, TT genotype and T allele were found to be overrepresented in alcoholic patients compared with patients with nonalcohol-induced liver disease and healthy controls. On the other side, when compared patients with ALD and patients with alcohol abuse and no liver disease, TT genotype was found to be significantly less frequent. There is no statistically significant association with the presence of the T allele and the severity of ALD, suggesting that CD14 polymorphism does not influence disease severity in advanced stages of the disease.nnnCONCLUSIONSnIn our series in Greek patients with alcohol abuse and alcoholic cirrhosis, a significant negative association with the CD14 endotoxin receptor gene polymorphism (TT genotype) but not with the TLR-4 gene polymorphism was documented.

Acute neutrophilic meningitis treated successfully with corticosteroids.

This report describes a cocaine user who presented with polymorphonuclear pleocytosis in cerebrospinal fluid mimicking bacterial meningitis. Thorough investigation of the cerebrospinal fluid did not reveal evidence of bacteria or fungi. Clinical deterioration was observed in spite of empiric treatment with antibiotics. The patient had a favorable outcome after corticosteroid treatment.

Acute splenic sequestration crisis (ASSC) in an adult patient with β-thalassemia sickle cell disease: a life-threatening complication

Dear Editor, We present a case of an adult patient with sickle cell βthalassemia and a severe episode of recurrent acute splenic sequestration crisis (ASSC). A 21-year-old white man with sickle cell β-thalassemia was admitted to our hospital with headache and abdominal pain. At the age of six, he had an acute thrombotic cerebrovascular event, and since then, he was placed on repeated sessions of exchange transfusion. At the age of seven, he had suffered an episode of ASSC that was treated conservatively. Since then, the patient presented frequent pain crises that did not respond to hydroxyurea treatment. At admission, his blood pressure was 140/70 mmHg, body temperature was 38°C, and heart rate was 105 beats/min. He had hepatomegaly and splenomegaly (4 cm under the left costal margin). Hemoglobin (Hb) was 9.4 g/dl, hematocrit 29.8%, MCV 75.8 fl, white blood cell count 4,500/μl, platelet count 206,000/μl, LDH 372 U/l, and total bilirubin 2.21 mg/dl/ indirect 0.78mg/dl. HbSwas 71%. An abdominal ultrasound at admission showed an enlarged spleen (19 cm). Intravenous fluids and pain relief medications were started and the patient initially improved. On the third hospital day, the patient was suddenly found tachycardic (125 beats/min), confused, short of breath with significant hypoxemia (SatO2=80%). His Hb and platelet count dropped to 3.5 g/dl and 52,000/μl, respectively, while his LDH (1,368 U/l) and total bilirubin (3.70 mg/dl) were increased. A urinalysis was negative for Hb. A repeated abdominal ultrasound revealed an increase in the size of spleen (21 cm) with new peripheral hypoechoic areas. Intravenous fluids, oxygen, and emergency transfusion with four packed RBC units and fresh frozen plasma (FFP) were promptly administered. The patient rapidly improved and a progressive rise in Hb and SatO2 was documented. An abdominal computed tomography scan confirmed the U/S findings (see Fig. 1). The patient was transfused with two more RBC units and was discharged on the tenth hospital day with a Hb of 9.2 g/dl. An elective splenectomy was scheduled. ASSC represents a rare complication of sickle cell disease and its variants with increased mortality during the first decade of life [1–6, 14, 15]. This adult patient with sickle cell β-thalassemia presented with an acute, life-threatening, and recurrent episode of ASSC. The diagnosis was established by the acute splenic enlargement, the severe and rapid drop of Hb, and the accompanying new onset thrombocytopenia. Because his Hb decreased to 3 g/dl, this episode is considered as major by definition [8]. A minor episode is defined as a drop in Hb levels but with an Hb level >6 g/dl. Ten cases of ASSC in adults with sickle cell βthalassemia have been reported in the English literature [7–10, 14]. Of these, nine were men (90%) with a mean age of 36 years. Three of these episodes could be classified as major. The lowest Hb level recorded was 3.5 g/dl, and it was reported in our case. The mortality rate in these patients was high (50%). Four of the five (80%) surviving patients experienced recurrent ASSC [7–10, 14]. Ann Hematol (2008) 87:499–500 DOI 10.1007/s00277-007-0422-3