Granulomatous Hepatitis Research Articles

Enhanced inducible nitric oxide synthase expression and nitrotyrosine accumulation in experimental granulomatous hepatitis caused by Toxocara canis in mice

The involvement of inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT) in pathogenesis of toxocaral granulomatous hepatitis (TGH) in a murine host was quantitatively determined by biochemical, parasitological, pathological, and immunohistochemical assessments in a 42-week investigation. Mice were sacrificed for serum collection and histological processing as well as acid-pepsin digestion of the liver in a larval recovery study. Significantly increased levels of total serum NO were found in the trial, indirectly suggesting iNOS activation in the liver. iNOS reactivity was predominantly observed in infiltrating leucocytes in lesions and normal and apocrine-like cholangiocytes; in contrast, hepatocytes and multinucleated giant cells showed negative cytoplasmic staining in TGH. Strong iNOS-like reactivity was also detected on the body wall of larvae. The locations of NT reactivity were nearly identical to those of iNOS expression; infiltrating leucocytes or cholangiocytes stained for iNOS were also stained for NT in TGH. Enhanced iNOS expression, but not invading larvae (r = 0.256, P = 0.211), seemed to play a certain role in pathological damage in TGH due to a significant correlation between iNOS expression and serum alanine aminotransferase (ALT) levels (r =0.593, P = 0.021) in the trial. Our present results indicate a potential therapeutic strategy for treatment of GH caused by other nematodes through manipulation of iNOS expression.

Maladie des griffes du chat et syndrome oculo-glandulaire de Parinaud

By presenting this case report describing Parinaud's oculoglandular syndrome, we review the medical literature on its most frequent etiology: catscratch disease, a self-limited, systemic illness caused by a Gram-negative bacillus, Bartonella henselae, principally affecting children under 15 years of age. Typical symptoms include regional lymphadenopathy, fever, malaise, and fatigue, possibly with more severe complications such as splenomegaly, granulomatous hepatitis, and encephalopathy. Ocular manifestations may include follicular conjunctivitis, Parinaud's oculoglandular syndrome, neuroretinitis, optic neuritis, and chorioretinitis. Diagnosis is based on serologic tests, and when necessary, antimicrobial treatment can be considered.

Brucellosis

Brucellosis

Fever of unknown origin in Turkey: evaluation of 87 cases during a nine-year-period of study.

To investigate fever of unknown origin (FUO) in 87 patients. We investigated 87 (61 male) patients with FUO using the criteria of Petersdorf and Beeson [Medicine 40 (1961) 1] hospitalized between January 1994 and August 2002 at Cukurova University Hospital. The median age of the patients was 38.5 years (range: 14-80 years). Eleven patients (12.6%) were over 65. The mean duration of hospitalization was 22.5+/-13 days. Infectious diseases were the most common causes of FUO. Tuberculosis (n=15, 17.2%), infective endocarditis (n=6), abdominal abscess (n=6), brucellosis (n=5), urinary tract infection (n=5), visceral leishmaniasis (n=4), salmonellosis (n=3), rhinocerebral mucormycosis (n=4), atypical pneumonia, cerebral toxoplasmosis, Cytomegalovirus infection or encephalitis were diagnosed in 51 (58.6%) patients. The second most common causes of FUO were collagen vascular diseases (n=16, 18.3%) determined as vasculitis syndrome, adult Still's disease (n=4), systemic lupus erythematosus, Behçet's disease, juvenile ankylosing spondylitis. Neoplasm was found in 12 (13.7%) patients; (non-Hodgkin lymphoma, Hodgkin lymphoma, chronic myeloid leukemia, gastrointestinal tract carcinoma, glioma). Miscellaneous diseases thyroiditis, granulomatous hepatitis were diagnosed in two (2.2%) patients. On admission, six patients (6.8%) were neutropenic. Infectious diseases, especially tuberculosis, were the leading diagnostic category of FUO in this study. Adult Still's disease was more common than expected. An aetiological diagnosis could not be reached in six (7%) patients who were followed for 1 year. Five of these patients completely recovered, and one patient died.

Scleral nodule associated with sarcoidosis

Purpose To describe an unusual case of an inflammatory scleral nodule associated with systemic sarcoidosis. Design Observational case report. Methods A patient presented with a red, painful, elevated scleral nodule on the left eye that was unresponsive to nonsteroidal anti-inflammatory drugs and topical corticosteroids. Results Laboratory evaluation was normal with the exception of elevated liver function tests. Further evaluation by a gastroenterologist revealed a granulomatous hepatitis secondary to sarcoidosis, which was confirmed by liver biopsy. Treatment with oral prednisone resulted in resolution of the hepatitis and scleral nodule. The patient has been recurrence-free over 7 months of follow-up. Conclusion Although rare, scleral disease may be associated with sarcoidosis.

P362 Azathioprine and methylprednisolone for the treatment of idiopathic granulomatous hepatitis

P362 Azathioprine and methylprednisolone for the treatment of idiopathic granulomatous hepatitis

Hepatitis granulomatosa idiopática con orquiepididimitis bilateral y erupción cutánea

We report a 52 years old male admitted for fever lasting one month, dry cough, headache and malaise. Initial laboratory work up showed an AST of 172 U/l, and ALT of 252 U/l, a GGT of 353 U/l and alkaline phosphatases of 952 U/l. An abdominal CAT scan disclosed a mild hepatosplenomegaly. A liver biopsy showed a granulomatous hepatitis. During the evolution, the patient had a left testicle swelling with darkening of the surrounding skin. A testicular ultrasound showed a bilateral orchiepidydimitis. The patient was treated with non steroidal anti-inflammatory drugs and fever subsided. Three months later, these drugs were discontinued and the patient remained asymptomatic and with normal laboratory values until 36 months of follow up.

Drug-induced MPO-ANCA-positive necrotizing crescentic glomerulonephritis preceded by granulomatous hepatitis

A 67-year-old man being treated with allopurinol, furosemide, digoxin, and tamocapril for congestive heart failure and paroxysmal atrial fibrillation was admitted to our hospital because of intermittent fever, general fatigue, and liver dysfunction. On admission, myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, and the titer was high. Discontinuation of all four drugs led to improvement of the symptoms, but the patient's renal function deteriorated. Liver biopsy showed granulomatous hepatitis (GH), and renal biopsy findings led to a diagnosis of pauci-immune necrotizing crescentic glomerulonephritis (CGN). The patient's renal function spontaneously improved without immunosuppressive therapy, and the MPO-ANCA titer decreased. We speculate that some common pathway induced by the drugs, possibly allopurinol, led to the two different clinical diseases, GH and CGN.

Allopurinol Hypersensitivity Syndrome Associated With Pancreatic Exocrine Abnormalities and New-Onset Diabetes Mellitus

Allopurinol, a xanthine oxidase inhibitor, has been in use since 1963 as an effective treatment to lower uric acid levels in patients with gout. 1 Severe and occasionally fatal adverse reactions have been attributed to allopurinol use in 1 of 260 patients and include agranulocytosis, granulomatous hepatitis, and a systemic hypersensitivity syndrome known as the allopurinol hypersensitivity syndrome (AHS), 2 which most frequently develops within days to weeks after initiating allopurinol therapy. 3 The syndrome initially manifests with a rash, ranging from an intensely pruritic maculopapular rash to toxic epidermal necrolysis. 3 Associated with rash are fever, leukocytosis, eosinophilia, evidence of acute hepatic injury, and renal dysfunction. 1 , 3 , 4 We describe for the first time a patient with AHS who, along with having the common features of AHS, developed concurrent elevations in pancreatic exocrine enzyme level and new-onset type 1 diabetes mellitus.

Lentiviral vectors for the gene therapy of lympho-hematological disorders.

AbstractPerhaps no clinical field stands to gain more from gene therapy than that of lympho-hematological disorders. First, blood cells are the site of manifestation of a large number of well-characterized monogenic hereditary defects, the correction of which would eliminate all symptoms in affected individuals (Table 1). Second, adding a genetic component to currently used drug-based approaches could facilitate the control of several acquired diseases of the immuno-hematological system including leukemia and AIDS, and could be used to provide blood precursors with an increased resistance against the toxicity of chemotherapy used in cancer treatment. Third, most of the cellular components of this tissue are renewed throughout life and derived from a single progenitor, the so-called human hematopoietic stem cell (hHSC). Fourth, not only is this common precursor currently the best characterized of all stem cells, but it is also relatively easy to isolate, it can be manipulated ex vivo, and it can be reintroduced into the body with an efficacy high enough to reconstitute a functional organ. Finally, the recently discovered plasticity of stem cells, with hematopoietic progenitors capable of contributing to the regeneration of tissues such as muscle (FERRARI et al. 1998; GUSSONI et al. 1999) or liver (LAGASSE et al. 2000), indicates that gene therapy through the modification of hHSC may open truly vertiginous therapeutic perspectives extending well beyond the lympho-hematopoietic system.KeywordsLong Terminal RepeatChronic Granulomatous DiseasePurine Nucleoside PhosphorylaseWoodchuck Hepatitis VirusHuman Hematopoietic Stem CellThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Granulomatous hepatitis: MRI findings

The purpose of this study was to describe the magnetic resonance imaging findings of granulomatous hepatitis on T1-weighted, T2-weighted and postgadolinium images. Eight patients with histopathological diagnosis of granulomatous hepatitis were evaluated in this study. MRI examinations included precontrast T1-weighted breath-hold spoiled gradient echo, breathing independent STIR sequences, and T1-weighted breath-hold spoiled gradient-echo sequence following after i.v. gadolinium administration in arterial, intermediate and late phases. Diffuse nodular liver involvement was visualized in all patients. Nodules were consistent with granulomas and were 0.5–4.5 cm in diameter. Caseating granulomas were intermediate and high signal on T2-weighted, low signal on T1-weighted images. They revealed no enhancement in two patients, and enhanced in one patient. Noncaseating granulomas revealed intermediate signal on T1, and T2-weighted images and increased enhancement on arterial phase images with persisting enhancement in late phase images. Portal lymph nodes were visible in five patients. Splenomegaly was present in five patients. Granulomatous hepatitis has spectrum of MRI features, to be considered in differential diagnosis with other diffuse nodular liver pathologies.

Bartonella henselae-specific cell-mediated immune responses display a predominantly Th1 phenotype in experimentally infected C57BL/6 mice.

Immune responses of the immunocompetent host to Bartonella henselae infection were investigated in the murine infection model using C57BL/6 mice. Following intraperitoneal infection with human-derived B. henselae strain Berlin-1, viable bacteria could be recovered from livers and spleens during the first week postinfection, while Bartonella DNA remained detectable by PCR in the liver for up to 12 weeks after infection. Granulomatous lesions developed in livers of infected mice, reached maximal density at 12 weeks after infection, and persisted for up to 20 weeks, indicating that B. henselae induced a chronic granulomatous hepatitis in the immunocompetent murine host. T-cell-mediated immune responses were analyzed in vitro by means of spleen cell proliferation and cytokine release assays as well as analysis of immunoglobulin G (IgG) isotypes. Spleen cells from infected mice proliferated specifically upon stimulation with heat-killed Bartonella antigen. Proliferative responses were mainly mediated by CD4+ T cells, increased during the course of infection, peaked at 8 weeks postinfection, and decreased thereafter. Gamma interferon, but not interleukin-4, was produced in vitro by spleen cells from infected animals upon stimulation with Bartonella antigens. Bartonella-specific IgG was detectable in serum of infected mice by 2 weeks, and the antibody concentration peaked at 12 weeks postinfection. IgG2b was the prominent isotype among the Bartonella-specific serum IgG antibodies. These data indicate that B. henselae induces cell-mediated immune responses with a Th1 phenotype in immunocompetent C57BL/6 mice.

Rosiglitazone induced granulomatous hepatitis

Rosiglitazone induced granulomatous hepatitis

Spindle-cell lesions of the liver: diagnosis by fine-needle aspiration biopsy.

Rarely, spindle-cell lesions in liver fine-needle aspiration biopsies (FNABs) are encountered. A retrospective review of our experience with lesions that are mesenchymal in origin or appearance was undertaken to elucidate the frequency and spectrum of these lesions. Image-guided liver FNABs performed over a 3-year period (n = 585) at our institution (1996-1998) were retrospectively evaluated. Cytologic smears, cell block preparations, and clinical follow-up of lesions with spindle-cell morphology were reviewed. Twenty-nine of 585 cases were of spindle-cell morphology (5%). Hemangiomas (n = 12, 41%) and metastatic sarcomas (n = 6, 21%) comprised the largest categories, followed by granulomatous inflammation (n = 3, 10%). Other cases included primary angiosarcoma and fibrolamellar hepatocellular carcinoma. The most frequent spindle-cell liver lesion encountered is hemangioma, followed by metastatic leiomyosarcoma and granulomatous hepatitis. Awareness of diagnostic possibilities, special attention to specimen adequacy, and use of ancillary procedures can maximize diagnostic yield.

Epidemiologic and clinical characteristics of Bartonella quintana and Bartonella henselae endocarditis: a study of 48 patients.

Epidemiologic and clinical characteristics of Bartonella quintana and Bartonella henselae endocarditis: a study of 48 patients.

An unusual case of sarcoidosis

A 34-year-old woman was referred to the department of internal medicine in June, 1999, for the treatment of hepatic sarcoidosis. She had no symptoms. Her medical history was remarkable for suspected tuberculosis and possible sarcoidosis at the age of 4 years, Klebsiella pneumoniae pneumonia at the age of 20 years, a perianal granuloma diagnosed as Crohn’s disease at 26 years, and a severe pneumonia of unknown aetiology at 27 years. At the age of 33 years in July, 1998, she gave birth to healthy twins. Hepatomegaly, splenomegaly, and abdominal lymphadenopathy were discovered on ultrasound examination for abdominal swelling in March, 1999. Investigations showed marked cholestasis and hypergammaglobulinaemia. Examination of liver biopsy samples in April, 1999, showed a granulomatous hepatitis with cholangitis compatible with sarcoidosis. At that time, her chest radiograph was normal. Shortly after having been referred to us in June, 1999, she complained of left-sided chest pain, without cough or fever, and a chest radiograph showed an alveolar infiltrate in the left lung. A bronchoalveolar lavage was done; the findings were compatible with sarcoidosis (CD4+ lymphocytosis) and showed neither bacteria, fungi nor Pneumocystis carinii. Corticosteroid therapy was started. 6 weeks later, she was admitted with a high fever, cough, and chest pain; chest radiograph showed a large infiltrate in the left inferior pulmonary lobe. A diagnosis of invasive aspergillosis was made on the basis of microscopy of broncho-alveolar lavage which showed absence of bacterial pathogens, presence of septate hyphae, and positive aspergillosis antigenaemia. Serum antibodies to Aspergillus spp were positive. Computed tomography scan of her chest showed an alveolar infiltrate and subpleural nodules (figure). Fungal cultures, however, remained negative. Liposomal amphotericin B was given, and itraconazole was added after 2 weeks.

BCG: Granulomatous hepatitis, mycotic aneurysm of the abdominal aorta and systemic BCG infection: case report

BCG: Granulomatous hepatitis, mycotic aneurysm of the abdominal aorta and systemic BCG infection: case report

BCG immunotherapy: be cautious of granulomas: Disseminated BCG infection and mycotic aneurysm as late complications of intravesical BCG instillations

We describe a 65-year-old man with a granulomatous hepatitis and a progressive mycotic aneurysm of the abdominal aorta. One year before he received intravesical bacillus Calmette–Guérin (BCG) for carcinoma of the bladder without any complaints. Only post-mortem investigations could confirm that he suffered from a systemic BCG infection. Literature is reviewed for this rare complication.

Methotrexate in Crohn’s disease: long-term efficacy and toxicity

OBJECTIVE: A 16-wk, placebo-controlled trial has recently shown weekly low-dose methotrexate to be an effective treatment for patients with chronically active Crohn’s disease. The long-term efficacy and safety of this antimetabolite drug, however, are not yet well established and are assessed in this study. METHODS: A total of 49 patients with Crohn’s disease who were treated with methotrexate for ≥6 months were studied. All patients had been chronically treated with steroids; but at the time of initiation, only 27 were still on steroids. Of the 49 patients, 42 had previously taken azathioprine but were no longer on this drug because of intolerance or failure. Clinical remission was defined as a Harvey-Bradshaw index of <4. RESULTS: In all, 41 patients achieved complete clinical remission and were maintained on methotrexate for a median of 18 months (range, 7–59 months). In these patients the probabilities of relapse were 29%, 41%, and 48% at 1, 2, and 3 yr, respectively. A higher rate of relapse was observed in women and in patients with ileocolitis. Adverse reactions were recorded in 24 patients, requiring discontinuation of methotrexate in five. A liver biopsy was performed in 11 patients; a mild steatosis was found in five, a slight dilation of the sinusoids in one, a granulomatous hepatitis with a mild portal fibrosis in one, and a slight periportal fibrosis in one patient. CONCLUSIONS: This study suggests a long-term benefit of maintenance treatment with methotrexate in patients with chronically active Crohn’s disease, with side effects that are usually only moderate.

Pet-, animal-, and vector-borne infections.

1. Carol Glaser, DVM, MD* 2. Paul Lewis, MD† 3. Stephanie Wong, DVM‡ 1. 2. *Viral and Rickettsial Disease Laboratory, California Department of Health Services, Berkeley, CA. 3. 4. †Assistant Professor of Pediatrics, Division of Infectious Diseases, Oregon Health Sciences University, Portland, OR. 5. ‡Tufts University School of Veterinary Medicine, Grafton, MA. Zoonoses are diseases that can be transmitted from animals to humans. They can be acquired via insect vectors, food, and direct or indirect contact with animals. More than 250 zoonoses have been described, and they are caused by a wide variety of pathogens, including viruses, rickettsia, bacteria, fungi, and parasites. Some of the diseases are rare, such as rabies and plague; others, such as cat-scratch disease, are common. The transmission of zoonotic diseases is both diverse and dynamic. Although illnesses such as salmonellosis and campylobacteriosis are by far the most common zoonotic infections in humans and are transmitted most often by food, there is a small risk of acquiring illness from pets and wildlife. Because many pet- and wildlife-related zoonoses are acquired via fecal-oral or direct contact routes, the inquisitive nature of children puts them at a higher risk for infection than adolescents and adults. It is important for pediatricians to be aware of zoonoses, especially those related to direct pet contact, because approximately 56% of United States households contain at least one pet. Pet ownership has many psychological and social benefits and should not be discouraged, with the exception of households that contain immunocompromised individuals or children younger than age 5 years, which should not have reptiles because of the risk of salmonellosis. This review discusses the epidemiology, animal reservoirs, transmission, clinical syndromes, laboratory features, treatment, and prevention of toxoplasmosis, rabies, cat-scratch disease, Lyme disease, and rat-bite fever. Additionally, brief overviews of animal bites and enteric infections are presented, as are tables on zoonoses related to dogs, cats, rodents, birds, and exotic pets (Table 1⇓ ); animal bite-related zoonoses (Table 2⇓ ); and vector-borne diseases (Table 3⇓ ). View this table: Table 1. Pet-related Zoonoses View this table: Table 2. Animal Bite-related Zoonoses View this table: Table 3. Vector-borne Diseases ### EPIDEMIOLOGY/ETIOLOGY Toxoplasmosis has a worldwide distribution. The seroprevalence in women of childbearing …