A histologically proven case of progressive liver sarcoidosis with variceal rupture

Sarcoidosis is a chronic multi-systemic granulomatous disease,and liver involvement frequently occurs.in most cases,no evidence of liver dysfunction is ob-served,and portal hypertension due to sarcoid liver diseases is a rareoccurrence.Moreover,no case of liver sarcoidosis has ever been reported with confirma-tion of the disease progression.Herein we describe a patient having hepatic sarcoidosis with severe portal hypertension and liver dysfunction.The diagnosis was histologically confirmed from granulomatous status to established liver cirrhosis over 10 years.A 46-year-old woman developed massive hematemesis due to the rupture of gastric cardial varices.She underwent emer-gency endoscopic injection sclerotherapy,and clear evi-dence of chronic hepatic failure.Twelve years ago,she was diagnosed as having sarcoidosis with respiratoryclinicalsymptoms.Liver biopsy revealed asymptomatic incidental granulomas without fibrosis development.After a couple of years,features of liver dysfunction were manifest and progressed.Ten years after the first biopsy,a second liver biopsy was performed,and well established dense fibrosis was revealed.Although significant liver dysfunction with portal hypertension is rarely seen in sarcoidosis,this case indicates that we have to consider the possibility that sarcoidosis may cause end-stage liver cirrhosis.     

Endoscopically proven case of rapid esophagogastric variceal progression and rupture as a result of portal hypertension with liver sarcoidosis

Sarcoidosis is a multi‐systemic disease of unknown etiology that results in the development of non‐caseating epithelioid granulomas. The liver is the third most frequently involved organ after the lymph nodes and the lungs. Most cases of liver sarcoidosis do not present with symptoms and involve minimal liver dysfunction, but some cases display progression to portal hypertension and liver cirrhosis, and finally to liver failure. The mechanism and the risk of progression in liver sarcoidosis are still unknown because of the diagnostic difficulty associated with this condition, and because follow‐up examinations can only be done in an invasive manner. Here, we present an informative case of liver sarcoidosis with rapid progression of esophagogastric varices. Four months prior to the definitive diagnosis, no signs of varices were observed on endoscopy, and developmentof esophagogastric varices, rapid progression, and eventual rupture occurred in a short period of time. A liver biopsy, carried out after endoscopic sclerotherapy, revealed that granulomas primarily affected the portal area without fibrotic and cirrhotic changes, which is considered a primary cause of portal hypertension and esophagogastric varices. Following the liver biopsy, the patient was given systemic steroids and is currently receiving outpatient care. Thus, we should consider the possibility that liver sarcoidosis, even in the absence of cirrhotic changes, can cause serious events such as esophagogastric variceal rupture following rapid progression as a result of portal hypertension.     

Role of liver function tests in detecting methotrexate-induced liver damage in sarcoidosis

BACKGROUND: Methotrexate has become a standard second-line agent for the treatment of sarcoidosis. Because sarcoidosis has a high frequency of liver involvement, we routinely perform a liver biopsy after each cumulative gram of methotrexate therapy in patients with sarcoidosis in whom we plan to continue therapy. METHODS: Following a previously described protocol for methotrexate therapy, we have performed 100 liver biopsies on 68 patients with chronic sarcoidosis at our institution. On the basis of the liver biopsy results, we identified the following 4 groups: sarcoidosis (47 cases), toxic effects of methotrexate (14 cases), hepatitis C (2 cases), and normal liver tissue (37 cases). RESULTS: We found no difference among the groups in terms of age, weight at time of biopsy, the number of patients receiving corticosteroids at the time of biopsy, cumulative dose of methotrexate, race, or sex. The 14 cases of toxic reactions to methotrexate included 5 patients who had undergone 1 or more previous liver biopsies in which the results did not show toxic effects. We found a significant difference between groups for levels of alkaline phosphatase and asparate aminotransferase at the time of starting (or restarting) methotrexate therapy (analysis of variance, P<.05). This finding was also true for the liver function tests performed at the time of the biopsy (analysis of variance, P<.05). The highest values were for those whose biopsy findings showed sarcoidosis. CONCLUSIONS: Toxic reactions to methotrexate eventually occurred in more than 10% of patients with sarcoidosis treated for more than 2 years with methotrexate. Because of hepatic involvement owing to sarcoidosis, results of serial liver function tests were not useful in determining which patients would have this reaction to methotrexate.     

Sarcoidosis and chronic hepatitis C: A case report

Several case reports deal with the relationship between hepatitis C virus (HCV) infection and pulmonary or hepatic sarcoidosis. Most publications describe interferon α-induced sarcoidosis. However, HCV infection per se is also suggested to cause sarcoidosis. The present case report describes a case of biopsy-verified lung and liver sarcoidosis and HCV infection, and the outcome of antiviral therapy. In March 2009, a 25-year-old man presented with moderately elevated liver enzymes without any clinical symptoms. The patient was positive for HCV antibodies and HCV RNA of genotype 1b. Four months later the patient became dyspnoic and pulmonary sarcoidosis was diagnosed by lung biopsy and radiography. A short course of corticosteroid treatment relieved symptoms. Three months later, liver biopsy showed noncaseating granulomas consisting of epithelioid histiocytes and giant cells with a small amount of peripheral lymphocyte infiltration, without any signs of fibrosis. Chronic HCV infection with coexistence of pulmonary and hepatic sarcoidosis was diagnosed. Antiviral therapy with peginterferon α and ribavirin at standard doses was started, which lasted 48 wk, and sustained viral response was achieved. A second liver biopsy showed disappearance of granulomas and chest radiography revealed normalization of mediastinal and perihilar glands. The hypothesis that HCV infection per se may have triggered systemic sarcoidosis was proposed. Successful treatment of HCV infection led to continuous remission of pulmonary and hepatic sarcoidosis. Further studies are required to understand the relationship between systemic sarcoidosis and HCV infection.     

Pulmonary sarcoidosis and antiphospholipid syndrome

Various autoimmune diseases have been reported to occur in patients with sarcoidosis. However, coexistence of sarcoidosis and antiphospholipid syndrome (APS) is extremely rare. We describe a 59-year-old female patient with pulmonary sarcoidosis who had preceding APS. Her previous medical history consisted of a miscarriage and ischemic colitis. She was diagnosed as APS during the onset of a brainstem infarction with positive reaction to beta2-glycoprotein I-dependent anticardiolipin antibody. Two years later, chest CT revealed enlargement of the hilar and mediastinal lymph nodes and small nodules in the lung fields. Transbronchial lung biopsy demonstrated non-caseating epithelioid cell granuloma leading to the diagnosis of definite pulmonary sarcoidosis. This is the first APS case where pulmonary involvement with sarcoidosis has been confirmed through lung biopsy. Our case report suggests that APS should be recognized as an accompanying disorder of sarcoidosis.     

Epithelioid Hemangioendothelioma of the Liver Diagnosed by Liver Biopsy under Laparoscopy

We report a case of primary epithelioid hemangioendothelioma arising in the liver. There were no specific findings or signs except for the deformity and multiple lesions of the liver at imaging procedures, which included magnetic resonance imaging. The key to the diagnosis was histological examination of liver biopsy specimens obtained under laparoscopy. Plasma factor VIII activity was elevated, which was also helpful in the diagnosis.     

HEPATOBILIARY SARCOIDOSIS: TYPICAL APPEARANCE IN LAPAROSCOPY

We present a case of systemic sarcoidosis. A 72‐year‐old Japanese woman, who was diagnosed with asymptomatic enlarged abdominal para‐aortic lymph nodes in April 2000, was admitted to our hospital in December 2003 because of multiple mass lesions of the liver and spleen. She had hepatosplenomegaly and asymptomatic pulmonary fibrosis. Blood examination revealed cholestasis and progressing liver synthetic dysfunction. In laparoscopic photographs, various sizes of whitish flat lesions were scattered on the surface of the liver. Liver biopsy showed non‐caseating epithelioid cell granulomas. These lesions of the spleen disappeared on contrast‐enhanced computed tomography imaging, and serum liver dysfunction was improved rapidly after steroid therapy. Laparoscopy may be useful for the diagnosis of granulomatous liver disease, such as hepatobiliary sarcoidosis.     

The association of Sweet's syndrome with sarcoidosis.

We report a 43-year-old woman with biopsy proven Sweet's syndrome with massive mediastinal lymphadenopathy. No other clinical signs compatible with sarcoidosis were present. Mediastinoscopy was performed to establish a diagnosis. Histological evaluation revealed non-caseating granulomas compatible with sarcoidosis. We review the association of Sweet's syndrome and (haematological) malignancies, and eight other cases of Sweet's syndrome and sarcoidosis. All but one presented with erythema nodosum, making the diagnosis of acute sarcoidosis (L?fgren's syndrome) more likely than malignancy.     

Sarcoid myopathy with elevated creatine phosphokinase

Acute inflammatory myopathy complicating sarcoidosis is rare, and its prognosis and appropriate therapy have not been defined well. We describe a patient with chronic sarcoidosis who, during a 3-month period, developed an acute proximal myopathy associated with marked elevations in creatine phosphokinase (CPK) and extensive granulomatous inflammation on muscle biopsy. High-dose corticosteroids were dramatically effective in inducing remission, with resolution of all signs and symptoms of the myopathy and normalization of CPK.     

Osseous infiltration in a patient with sarcoidosis

A man with lumbar back pain underwent magnetic resonance imaging that showed vertebral and iliac bone lesions. A vertebral biopsy was performed in order to rule out malignancy. Pathology showed non-necrotizing granulomas. The patient had been diagnosed with pulmonary sarcoidosis 20 years earlier and this time the diagnosis made was vertebral sarcoidosis. Osseous infiltration is seen in 13% of patients with sarcoidosis, most of them with long-term disease. Iliac sarcoidosis has seldom been reported, and there are no cases of both iliac and vertebral sarcoidosis in the literature.     

Clinical and magnetic resonance imaging manifestations of neurosarcoidosis

OBJECTIVES: To describe clinical and neuroimaging manifestations of neurosarcoidosis in a cohort of 21 patients. PATIENTS AND METHODS: We reviewed records of 21 patients with sarcoidosis and central nervous system (CNS) manifestations referred to Cooper University Hospital, with emphasis on neuroimaging findings and associated clinical and laboratory evidence of sarcoidosis. Nineteen patients were categorized as having "definite," "probable," or "possible" neurosarcoidosis, while 1 had associated CNS vasculitis and another had Hodgkins lymphoma with cauda equina syndrome. RESULTS: The most common manifestations included myelopathy, cranial neuropathies, and encephalopathy. In 6 patients, CNS biopsy showed sterile, noncaseating granuloma (NCG), while in the remainder, the diagnosis was established through a combination of clinical, radiographic, and laboratory findings. Notably, 10 patients developed acute neurological emergencies, including seizures, spinal cord compression, and increased intracranial pressure. Findings on magnetic resonance imaging (MRI) included a variety of manifestations, including isolated mass lesion, diffuse intraparenchymal inflammatory lesions in the brain and spinal cord, leptomeningeal enhancement, hydrocephalus, and intracranial hemorrhage. CONCLUSIONS: Sarcoidosis is associated with diverse neurological manifestations and neuroimaging findings. The diagnosis of isolated CNS sarcoidosis requires a biopsy to document the presence of sterile NCG and to exclude neoplasms and other granulomatous diseases. When a biopsy of the CNS is not possible, a diagnosis of neurosarcoidosis can reasonably be supported in many patients by MRI findings and exclusion of other disorders. RELEVANCE: Optimum management of patients with neurosarcoidosis relies on the ability of clinicians to recognize the broad spectrum of clinical and neuroimaging manifestations of the disorder.     

A case of cardiac sarcoidosis associated with various clinical symptoms and thrombocytopenia]

A 29-year-old man presented with acute onset of high fever, chest pain and dyspnea. Chest X-ray film showed diffuse interstitial shadows, a cavitary lesion in the left upper lung field and cardiomegaly, but no lymphadenopathy. Abdominal CT scan showed hepatosplenomegaly and multiple small low density areas in the liver and spleen. Electrocardiogram demonstrated multifocal ventricular premature beats and ventricular tachycardia. Cardiac catheterization revealed left ventricular aneurysms. Sarcoidosis was confirmed by lung and liver biopsy. Drug therapy of prednisolone and mexiletine resulted in clinical improvement of symptoms, signs and chest X-ray film, but platelet count decreased gradually. It is suggested that an immune mechanism of sarcoidosis may have been the cause of this thrombocytopenia.     

Diagnosing isolated cardiac sarcoidosis

Abstract. Kandolin R, Lehtonen J, Graner M, Schildt J, Salmenkivi K, Kivistö SM, Kupari M (Helsinki University Central Hospital, Helsinki, Finland). Diagnosing isolated cardiac sarcoidosis. J Intern Med 2011; 270 : 461–468. Objectives. Cardiac sarcoidosis (CS) without clinically apparent extracardiac disease may escape detection because of the poor sensitivity of endomyocardial biopsy (EMB). We set out to analyse our experience of repeated and imaging‐guided biopsies in clinically isolated CS. Methods. We retrospectively reviewed the medical records, laboratory test results, imaging studies and pathological analyses of 74 patients with either histologically proven or clinically probable CS at our institution between January 2000 and December 2010. Results. Fifty‐two patients had histologically proven CS, of whom 33 (26 women) had disease that was clinically isolated to the heart. Sarcoidosis was detected in the first EMB in 10 of the 31 patients who underwent biopsy. CS was found by repeated EMBs, targeted by cardiac imaging, in seven additional patients, and 11 patients were diagnosed by sampling 18‐F‐fluorodeoxyglucose position emission tomography‐positive mediastinal lymph nodes at mediastinoscopy. Together, the first biopsy (cardiac or mediastinal lymph node) provided the diagnosis in 34%, the second biopsy in 31% and the third in 22% of biopsied patients with isolated CS. Four (13%) of the remaining diagnosis were made after cardiac transplantation and one in a patient who did not undergo biopsy) at autopsy after sudden cardiac death. Conclusions. Cardiac sarcoidosis may present without clinically apparent disease in other organs. At least two‐thirds of patients remain undiagnosed after a single EMB session. The detection rate can be improved by repeated and imaging‐guided cardiac or mediastinal lymph‐node biopsies. Nevertheless, false‐negative biopsy results remain a problem in CS patients with no apparent extracardiac disease.     

Extrapulmonary sarcoidosis primarily diagnosed in the liver

Sarcoidosis is a relatively common, chronic, multisystem disease of unknown origin characterized by the presence of noncaseating epithelioid granulomas. Although an array of organs may be affected by the disease, the commonest site of affection is the lung. We describe a 73-year-old patient admitted to our hospital because of fatigue, weight loss, and an increased alkaline phosphatase level. In conjunction with clinical presentation, laboratory variables, and imaging analysis, a liver biopsy finally confirmed the diagnosis of a systemic sarcoidosis without affection of the lung or mediastinal lymph nodes. Treatment with ursodeoxycholic acid before diagnosis did not improve clinical symptoms and cholestasis indicators. After prednisone treatment, liver enzyme values normalized and remained normal during follow-up for 2 years after diagnosis. The literature on hepatic manifestation of sarcoidosis, its diagnosis, treatment, and prognosis is reviewed. This single case of sarcoidosis presented to the clinician almost exclusively with liver enzyme abnormalities. The consideration of sarcoidosis in such cases is of utmost importance, since the differential diagnosis of hepatic granulomas includes infectious diseases in which treatment with corticosteroids could be fatal.     

Extrapulmonary Sarcoidosis Primarily Diagnosed in the Liver

Sarcoidosis is a relatively common, chronic, multisystem disease of unknown origin characterized by the presence of noncaseating epithelioid granulomas. Although an array of organs may be affected by the disease, the commonest site of affection is the lung. We describe a 73-year-old patient admitted to our hospital because of fatigue, weight loss, and an increased alkaline phosphatase level. In conjunction with clinical presentation, laboratory variables, and imaging analysis, a liver biopsy finally confirmed the diagnosis of a systemic sarcoidosis without affection of the lung or mediastinal lymph nodes. Treatment with ursodeoxycholic acid before diagnosis did not improve clinical symptoms and cholestasis indicators. After prednisone treatment, liver enzyme values normalized and remained normal during follow-up for 2 years after diagnosis. The literature on hepatic manifestation of sarcoidosis, its diagnosis, treatment, and prognosis is reviewed. This single case of sarcoidosis presented to the clinician almost exclusively with liver enzyme abnormalities. The consideration of sarcoidosis in such cases is of utmost importance, since the differential diagnosis of hepatic granulomas includes infectious diseases in which treatment with corticosteroids could be fatal.     

A case of cardiac sarcoidosis with advanced atrioventricular block. Failure of endomyocardial biopsy diagnosis and success in detecting

 We present a case of cardiac sarcoidosis with advanced atrioventricular (AV) block in a 45-year-old female patient. Although endomyocardial biopsy and other diagnostic findings were inconclusive, gastrocnemial muscle biopsy indicated a definitive diagnosis of sarcoidosis. Whole-body gallium-67 scintigraphy was useful to confirm the suspicion of the presence of sarcoidosis. Thereafter, magnetic resonance imaging (MRI) was successful in detecting the space-occupying lesion in the skeletal muscle, leading to a positive diagnosis of sarcoidosis. It is concluded that the presence of myocardial disease, such as cardiac sarcoidosis, should be considered when advanced AV block is encountered. Even if endomyocardial biopsy and other conventional diagnostic approaches are inconclusive, the possibility of cardiac involvement in sarcoidosis cannot be denied. This case report stresses the importance of more advanced diagnostic approaches, such as whole-body gallium scanning and MRI, in clarifying the etiology of AV block. Establishing the diagnosis of cardiac sarcoidosis is important in determining whether or not to begin effective long-term treatment with corticosteroids. Received: February 2, 2002 / Accepted: October 12, 2002 Correspondence to M. Sekiguchi     

Extrapulmonary sarcoidosis with chronic renal failure

We present a young woman with extrapulmonary sarcoidosis who had been treated for tuberculosis 15 years earlier. The initial diagnosis had been made on the basis of liver biopsy. The patient later developed bilateral visual loss secondary to uveitis. We identified noncaseating granulomatous lesions in the kidney, intra-abdominal lymph node, and previous liver biopsy specimens. Although rare, renal sarcoidosis can manifest itself as hypercalcemic nephropathy, granulomatous interstitial nephritis, renal tubular dysfunction, or glomerulonephritis. Corticosteroids are the treatment of choice.     

Encephalopathy and neuropathy in end-stage liver disease before and after liver transplantation.

The nervous system involvement of 8 patients with end-stage liver disease was evaluated by means of clinical neurological, neuropsychological, neurophysiological and neuroradiological investigation before and 6-12 months after a successful liver transplantation. Preoperatively, all subjects (7 women, 1 man; mean age 40 years, range 30-54 years) exhibited decreased muscle strength and 2 patients manifested clinical signs of polyneuropathy. In neuropsychological tests, slight visuoconstructive apraxia, and disturbances of verbal memory and cognitive function were observed. Magnetic resonance imaging (MRI) revealed cerebral lesions in two patients. After transplantation, muscle strength reverted to normal in all patients, polyneuropathy improved and in all but 2 patients recovery of neuropsychological functioning was observed. Clinical signs of encephalopathy had disappeared. All patients were emotionally better adjusted after transplantation. Four subjects showed new, albeit mild changes in neurophysiological and neuropsychological tests postoperatively. We conclude that the majority of neurological impairment disappeared after liver transplantation. We want to stress that evaluation of neurological sequelae of liver transplantation needs to be based on assessments both before and after liver transplantation.     

Focal neurological signs in hepatic encephalopathy in cirrhotic patients: an underestimated entity?

OBJECTIVES: Focal neurological signs have been poorly documented in the course of hepatic encephalopathy in cirrhotic patients because they are not mentioned in any textbooks of liver diseases. Having the opportunity to observe such cases, we underwent a prospective study to determine incidence, characteristics, associated factors, prognostic significance, and outcome of this rare form of hepatic encephalopathy. METHODS: Over a 12-month period, all cirrhotic patients hospitalized in the intensive care unit of our department for hepatic encephalopathy were prospectively studied. Patients with clinical and electroencephalogram evidences of hepatic encephalopathy were examined by a senior physician and, in cases of focal neurological signs, underwent examination by a neurologist, CT scan, lumbar punction, and cerebral magnetic resonance imaging and echo Doppler examination of neck and head vessels. Clinical and biological parameters were compared in patients during episodes with and without focal neurological signs, and outcome was noted. RESULTS: Thirty-four cirrhotic patients were hospitalized for 48 episodes of hepatic encephalopathy; two of these patients with cerebral hematoma were excluded. Twenty-four patients exhibited 38 hepatic encephalopathy episodes without focal neurological signs (82.6%), and eight patients exhibited eight hepatic encephalopathy episodes with focal neurological signs (17.4%) that were hemiplegia and hemiparesia in six patients (75%). In all patients, cerebral CT scan and cerebrospinal fluid examination disclosed no abnormalities, as neither did cerebral magnetic resonance imaging (n = 5) and echo Doppler examination of neck and head vessels (n = 5). Except for female sex, which was more often encountered in patients with focal neurological signs (p < 0.05), there were no differences between episodes with and without focal neurological signs for any of the parameters studied. In surviving patients who recovered from hepatic encephalopathy (7/8), focal neurological signs disappeared without recurrences after follow up of 6 months (3-12). CONCLUSIONS: Hepatic encephalopathy with focal neurological signs when carefully searched is not uncommon. It could be more frequent in cirrhotic females, is reversible, and has no prognostic significance.