Concurrent Hepatic Tuberculosis and Hepatic Graft-versus-host Disease in an Allogeneic Hematopoietic Stem Cell Transplant Recipient: A Case Report.

BACKGROUND: Infection and graft-versus-host disease (GVHD) are among the most common complications after hematopoietic stem cell transplantation (HSCT). With well-known risk factors including allogeneic HSCT and GVHD, tuberculosis (TB) has a higher incidence and shorter survival rate in HSCT recipients than in the general population. CASE REPORT: A 55-year-old Indonesian female with a history of latent TB was found to have acute myeloid leukemia 3 months after allogeneic HSCT. She presented with fever, abdominal pain, and predominant cholestatic-type liver function tests derangement. Computed tomography scans showed a relatively unremarkable liver. Liver biopsy specimens revealed multiple necrotizing granulomas with numerous acid-fast bacilli shown using Ziehl-Neelsen histochemical stain. No fungal organisms are detected by Grocott's methenamine silver and periodic acid-Schiff stains. There was also mild portal hepatitis with prominent bile duct injury and scattered apoptotic bodies, compatible with GVHD. In addition, the patient was also discovered to have cutaneous and intestinal TB as well as cutaneous and colonic GVHD during investigation. She was started on anti-TB treatment and adjusted immunosuppression scheme accordingly. Unfortunately, our patient died of spontaneous intracranial haemorrhage approximately 2 months after the diagnosis of post-transplantation TB and GVHD. CONCLUSION: We report a case of concurrent hepatic TB and GVHD in an allogeneic HSCT recipient. Recognition of the dual pathology in the biopsy results aids proper treatment.

Tuberculous hepatitis in renal transplant recipients following alemtuzumab induction therapy.

Mycobacterium tuberculosis infection is one of many opportunistic infections in renal transplant recipients, arising either from reactivation of latent infection or de novo infection, occasionally donor derived. M. tuberculosis hepatitis has never been reported in patients who have received alemtuzumab as part of their renal transplant management. We describe 2 patients who underwent deceased-donor renal transplantation following alemtuzumab induction therapy and presented with a febrile syndrome, subsequently diagnosed as tuberculous hepatitis, one with disseminated disease. Both responded well to treatment without significant side effects, resulting in excellent graft function. The importance of chemoprophylaxis should be emphasized to minimize the risk of developing active tuberculosis in patients with latent tuberculosis infection undergoing solid organ transplantation.

Isolated tuberculous liver abscess in a patient with asymptomatic stage I sarcoidosis.

Sarcoidosis is a multi-system disorder characterized by non-caseating granulomas. Depressed cellular immunity predisposes patients to infections with certain intracellular organisms, mostly fungi, Mycobacterium tuberculosis, and Nocardia species. Isolated liver tuberculosis is a rare condition, and atypical clinical presentation challenges the clinical acumen of the treating physician. Liver sarcoidosis is usually unsuspected and confused with primary or metastatic liver carcinoma. We describe a case of isolated tuberculous liver abscess without pulmonary spread in a patient with asymptomatic stage I sarcoidosis.

Leflunomide-associated infections in rheumatoid arthritis.

OBJECTIVE: To determine the prevalence of severe infections in patients with rheumatoid arthritis (RA) prescribed leflunomide in North Canterbury, New Zealand. METHODS: A case-note audit of all Christchurch Hospital patients with RA prescribed leflunomide between 2002 and 2006 was performed. The criterion for severe infection was inpatient hospitalization. Relevant reports to the national Pharmacovigilance Centre were also examined. RESULTS: Since January 2002, 171 patients with RA have commenced taking leflunomide. Ninety-nine of 171 (57.9%) patients were also prescribed prednisone. Combination disease modifying antirheumatic drug therapy was common, with 82/171 (48.0%) taking methotrexate (MTX), 15/171 (8.8%) hydroxy-chloroquine, 11/171 (6.4%) sulfasalazine, and 8/171 (4.7%) anti-tumor necrosis factor therapy. Eleven patients developed infection requiring hospitalization while taking leflunomide including: lower respiratory tract infections (3), cellulitis (2), disseminated herpes zoster (2), probable TB liver (1), abdominal sepsis (1), mycotic aneurysm (1) and gastroenteritis (1). Nine of the 11 patients were also taking corticosteroids or corticosteroids with MTX. The 171 patients were treated for a total of 4005 months, giving an incidence for severe infection of 3.30/100 patient-years (95% CI 1.65-5.90). Patients at increased risk were those with severe disease and taking concomitant MTX and corticosteroids. The NZ Pharmacovigilance Centre has received 7 additional reports of severe infections in patients with RA taking leflunomide. Reported cases include probable pulmonary TB (1), pneumocystis pneumonia (1), other pulmonary infection (2), and septicemia (3) including a case of infective endocarditis. Four occurred in combination with MTX, one with adalimumab. All 5 patients were also taking -corticosteroids. CONCLUSION: We believe this observed rate of serious infection is acceptable in the context of optimally treating active RA. Patients with severe disease and taking combination MTX and corticosteroids are at greatest risk. In our experience, once established, infections may rapidly progress in patients with RA taking leflunomide, and early cholestyramine washout is strongly recommended.

Intestinal tuberculosis and secondary liver abscess.

The incidence of intestinal tuberculosis (ITB) has been increasing in the West, due to the AIDS epidemic, transglobal immigration, IV drug abuse, an aging population, and an increase in the number of immunocompromised patients. Obstruction and perforation of the intestine are the most common and serious complications of ITB. Another complication, tuberculous liver abscess (TLA), is rare and usually associated with foci of infection in the lung or gastrointestinal tract. We report a case of a 17-year-old boy with Down syndrome who presented with multiple TLAs secondary to obstructive and multiple perforated ileal tuberculosis.

Fatal Mycobacterium bovis BCG infection in TNF-LT-alpha-deficient mice.

Neutralization of TNF or disruption of TNF-R1 leads to fatal Mycobacterium bovis BCG infection. Here we used TNF-LT-alpha-deficient mice to test whether a complete disruption of TNF and LT-alpha reduces further host resistance to BCG infection. The bacterial burden especially in the lungs of TNF-LT-alpha-deficient mice was significantly increased and the mice succumbed to infection between 8 and 10 weeks. In the absence of TNF-LT-alpha the granulomatous response was severely impaired and delayed. The cells in the granulomas of TNF-LT-alpha-deficient mice expressed low levels of MHC class II and ICAM-1. They contained a few T cells and F4/80-positive macrophages expressing little iNOS and acid phosphatase activity. By contrast, the lethal action of endotoxin was dramatically reduced in BCG-infected TNF-LT-alpha-deficient mice. In summary, in the absence of TNF-LT-alpha the recruitment and activation of mononuclear cells in response to BCG infection were significantly delayed and reduced resulting in immature granulomas allowing uncontrolled fatal infection.

[A case of AIDS complicated with liver tuberculosis].

We experienced a double infection of tuberculosis and amebiasis of the liver. A 28 year old male with AIDS was admitted to our hospital because of severe diarrhea and liver abscess by Entamoeba histolytica. In spite of improvement of the diarrhea and liver abscess by the therapy against E. historicica, serum levels of gamma-GTP and ALP remained high and hepatosplenomegaly gradually increased. A liver biopsy was performed. Pathology showed a granulomatous lesion with Langhans' giant cells. From this specimen, IS6110 gene, a specific DNA for Mycobacterium tuberculosis was detected by PCR method. After anti-tuberculosis treatment was given for 6 months the increased serum gamma-GTP, ALP decreased and hepatosplenomegaly diminished.

[Disseminated tuberculosis in non-immunocompromised host: three case reports]. / Tuberculose disséminée sur terrain non immunodéprimé: à propos de trois cas.

INTRODUCTION: Disseminated tuberculosis, i.e., tuberculosis involving lung, liver, spleen, bone marrow and lymph nodes is rare (2.8%), particularly when immunocompromised diathesis is lacking. EXEGESIS: We report three cases of disseminated tuberculosis confirmed by bacteriology or histology, which occurred in non-immunocompromised patients. Disease evolution under antituberculous treatment was favorable in two cases and fatal in the third one. CONCLUSION: Disseminated tuberculosis must be suspected when miliary pulmonary lesions are associated with hematologic abnormalities, even in non-immunocompromised host. Early treatment is mandatory to avoid fatal outcome.

[The treatment of pulmonary tuberculosis patients with liver involvement]. / Likuvannia khvorykh na tuberkul'oz leheniv z urazhenniam pechinky.

It has been ascertained both in an experimental and clinical setting that of all the pathogenetic means of treatment pulmonary tuberculosis tocoferolum acetatum is a preparation of choice for PT patients presenting with concurrent hepatic pathology. This drug preparation has hepatoprotective immunomodulating effect. Shown for the first time is surfactant-correcting action of the drug. In a clinical setting, in a series of a total of 118 patients with pulmonary tuberculosis presenting with hepatic pathology the efficacy of tocoferolum acetatum was found to be superior to that of other hepatoprotectors. Tocoferolum acetatum eliminates the hepatotoxic reactions 2.5-3.5 times as often as hepatoprotectors and vitamins group B, ascorbic acid and bioflavonoids.

[Disseminated extrapulmonary tuberculosis in idiopathic CD4-lymphocytopenia]. / Disseminierte extrapulmonale Tuberkulose bei idiopathischer CD4-Lymphozytopenie.

A previously healthy, now 42-year-old man suddenly fell ill with bouts of septic fever up to 39.5 degrees C, sweats and weight loss without any demonstrable organ involvement. Physical examination on hospitalization 3 weeks after onset of the illness was unremarkable. Blood sedimentation rate at one hour was 123 mm. There was also a moderate increase in gamma-GT and alkaline phosphatase. Routine bacteriological and serological tests failed to discover a causative microorganism. After imaging tests had provided first indication of splenic and hepatic involvement, biopsies of these two organs demonstrated disseminated epithelioid granulomas and Langhans giant cells. Staining and culturing of pelvic crest biopsy tissue showed evidence of Mycobacterium tuberculosis, but there was no evidence of pulmonary involvement. In addition to four-drug tuberculostatic treatment the patient was given glucocorticoids for several weeks to control the fever bouts. Persistent CD4+ T-lymphocytopenia was demonstrated as the cause of the entirely extrapulmonary tuberculosis in this HIV-negative patient. This is an only recently described and so far unexplained syndrome.