The efficacy of mizoribine for the treatment of rheumatoid arthritis and its correlation with renal function.

OBJECTIVES: To evaluate the correlation between the efficacy of mizoribine (MZR) and the factors that might effect MZR concentration: renal function and dosage and administration of MZR in patients with rheumatoid arthritis (RA). METHODS: The efficacy of MZR treatment was prospectively evaluated in 97 RA regardless of dosage, at the 14 participated institutions. The Disease Activity Score 28-CRP3 was used to assess RA activity. The renal function was evaluated based on the serum creatinine and serum cystatin-C (Cys-C). The patients were followed up for 24 weeks. RESULTS: The patients with a mean age 66.2 years included 18 male. The renal function assessment showed increased creatinine in 16.4% of patients and increased Cys-C in 54.5%, suggesting the higher sensitivity of Cys-C to detect impaired renal function than creatinine. In patients with good or moderate response according to the European League against Rheumatism classification criteria, the Cys-C was significantly higher compared with those with no response. MZR treatment was significantly more effective in patients with an arithmetic product of the single MZR dose used and Cys-C of 179 or more. CONCLUSIONS: The efficacy of MZR may increase in proportion to its single dose, or increased Cys-C level in patients with impaired renal function.

Association of an overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis with cytomegalovirus infection.

A 63-year-old woman, who presented with severe jaundice and elevated serum conjugated bilirubin level, denied alcohol and drug use and showed no evidence of viral hepatitis. Based on clinical and laboratory features, she was diagnosed with autoimmune hepatitis with primary biliary cirrhosis. Hematological and immunochemical assays, radiographic imaging, clinical examination, and liver biopsy were conducted. Laboratory results were the following: negative for fluorescence antinuclear antibody, negative for antismooth muscle antibodies but positive for antinuclear antibody (enzyme-linked immunosorbent assay) and antimitochondrial M2 antibody, high titers of serum globulin, and positive for cytomegalovirus IgM. Liver biopsy showed submassive lobular necrosis, inflammation with broad areas of parenchymal collapse, and chronic nonsuppurative destructive cholangitis. The patient responded well to corticosteroid therapy. This case might illustrate an association between cytomegalovirus infection and the occurrence of autoimmune hepatitis.

Acute intrahepatic cholestasis accompanied with Chlamydophila pneumoniae infection.

We report a case of Chlamydophila (C.) pneumoniae infection presenting with fever and rapid intrahepatic cholestasis. A 63-year-old man had a week-long history of intermittent high fever and rapidly progressive jaundice with atypical erythema. The results of liver function tests were recorded. The results of all serological tests were negative; the IgM, IgG, and IgA titers for C. pneumoniae had increased, which indicates a C. pneumoniae infection. The patient's fever and liver dysfunction improved upon administration of minocycline. Light microscopic findings showed the presence of enlarged liver cells with clear cytoplasm, a few mitotic figures, multinucleated cells, and bile cholestasis. The electron microscopic appearance of liver biopsy showed that bile canaliculi exhibited intrahepatic forms of cholestasis. From the results of light and electron microscopy, we inferred atypical intrahepatic cholestasis, probably resulting from the C. pneumoniae infection.

Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome concomitant with systemic sclerosis, immune thrombocytopenic purpura.

A 58-year-old Japanese woman presented with chronic fluctuating liver dysfunction with purpura. Raynaud's phenomenon had been diagnosed 4 years previously. At the initial examination, skin biopsy showed limited cutaneous systemic sclerosis (SSc). Laboratory investigations revealed liver dysfunction. Anti-nuclear antibodies, anti-mitochondria M2 antibody, anti-thyroglobulin antibody, and platelet-associated IgG were positive. Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) were diagnosed serologically, clinically and histologically. Immune thrombocytopenic purpura (ITP) was diagnosed by bone marrow puncture, clinical and laboratory findings, and Helicobacter pylori IgG was positive. She was treated with prednisolone 30 mg/day, ursodeoxycholic acid 600 mg/day, and a 7-day course of lansoprazole plus amoxicillin and clarithromycin. Thrombocytes increased rapidly and transaminase improved at day 7. We report a rare case of PBC-AIH overlap syndrome with concurrent ITP and SSc which suggest the presence of shared genetic susceptibility factors in multiple autoimmune conditions including PBC, AIH, ITP and SSc.

Hepatic granulomas as primary presentation of Mycobacterium avium infection in an HIV-negative, nonimmunosuppressed patient.

Nontuberculous hepatic granuloma in patients not infected by human immunodeficiency virus (HIV) is rare. We report an 89-year-old woman who presented with hepatic granuloma without lung involvement. Ultrasonography and computed tomography (CT) of the abdomen showed low-density lesions in the liver. Histopathological examination of a liver biopsy revealed florid, caseating granulomatous reaction with aggregates of epithelioid histiocytes and Langerhans-type giant cells in a predominantly portal and periportal distribution. Gastric juice cultures were positive for Mycobacterium avium. The patient was treated with antimycobacterial therapy. Her clinical condition improved dramatically within 1 month of starting therapy, with marked reduction in hepatomegaly together with normalization of liver biochemistry and CT findings.

Autoimmune hepatitis associated with pulmonary arterial hypertension.

A 46-year-old woman presented with arthralgia. She had a history of fluctuating liver function impairment for 6 months. Laboratory investigations revealed elevated liver function test results, positive antinuclear antibodies and elevated serum IgG. The histological findings of a liver biopsy were interface hepatitis accompanied by plasmocytic infiltration with bridging fibrosis. There was no evidence of cirrhosis on pathological examination and no portal hypertension on endoscopic and radiographic studies. Autoimmune hepatitis was diagnosed, and treatment with prednisolone improved the liver dysfunction. After 6 months, she complained of dyspnea. Doppler echocardiography showed a dilated right ventricle, severe tricuspid insufficiency, and systolic pulmonary arterial pressure indicative of pulmonary arterial hypertension. We report this rare case of autoimmune hepatitis with pulmonary arterial hypertension.

Recurrent paralytic ileus associated with strongyloidiasis in a patient with systemic lupus erythematosus.

We present an interesting case of recurrent paralytic ileus due to strongyloidiasis in a woman who was being treated with corticosteroids and immunosuppressants for systemic lupus erythematosus (SLE). She was also a carrier of human T-cell leukemia virus type I. She had a history of strongyloidiasis 8 years earlier. Recurrent episodes of paralytic ileus due to strongyloidiasis occurred during treatment of her SLE with corticosteroids. Ivermectin was given and improved the symptoms. This case shows that symptomatic strongyloidiasis can be induced in immunocompromised hosts by immunosuppressive therapy. It is important to rule out strongyloidiasis prior to starting immunosuppressive therapy in patients from endemic areas.

[Combined effect of micafangin and itraconazole on severe aspergillosis of the bilateral pleural cavities in a patient with Wegener's granulomatosis].

Visceral fungal infections are difficult to manage in patients with collagen diseases and immunocompromised hosts. In particular aspergillosis can be a life-threatening complication in these patients. Here we report that combined use of two antifungal agents (micafangin and itraconazole) was effective against severe aspergillosis of the bilateral pleural cavities in a 48-year old male patient diagnosed with Wegener's granulomatosis. Immunosuppressive therapy with corticosteroids and cyclophosphamides improved his nasal and pulmonary symptoms, but inflammation of the bilateral pleural cavities caused bronchial fistulas. Aspergillus fumigatus then infected the bilateral pulmonary cavities through these fistulas. This patient was treated with combined therapy of ITCZ and MCFG was given to this patient because of the risk of renal dysfunction associated with AMPH-B. After 5 weeks of treatment his clinical findings had improved and the fungus was suppressed.