Steroids and immunosuppressants are indicated to treat systemic vasculitides. However, the therapeutic strategy is different from one disease to the other. Treatment choice should be adapted to the predictable outcome, severity, pathogenic mechanisms and patient's general condition. In polyarteritis nodosa, Churg Strauss syndrome, and microscopic polyangiitis we have demonstrated that immunosuppressants should not be systematically prescribed. Immunosuppressants should be only prescribed in the most severe patients, when factors of poor prognosis are present. In Wegener's granulomatosis, immunosuppressants should be systematically prescribed together with steroids. The optimal treatment duration is of 12 months for polyarteritis nodosa and Churg-Strauss syndrome. A more prolonged treatment is mandatory in Wegener's granulomatosis, at least 18 months. The new therapeutic strategies comprise also new immunosuppressants and new immunomodulating agents which could replace or be associated to the "older drugs"
(Internal Medicine 42: 313-317, 2003)

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Objective The aim of this study was to investigate the efficacy of metronidazole plus ciprofloxacin for the treatment of Japanese patients with active Crohn's disease.
Methods and Patients Seven patients (counting one patient twice with 2 enrollments at a 5-month interval) with a flare-up of Crohn's disease were enrolled. While continuing the baseline treatment under which the patients relapsed, they received metronidazole 250 mg twice (4 patients) or three times (3 patients) daily plus ciprofloxacin 200 mg three times daily for 4 weeks. The efficacy was evaluated by the changes in the assessment score of IOIBD, the International Organization for the Study of Inflammatory Bowel Disease, and the inflammation markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count.
Results Metronidazole plus ciprofloxacin decreased the CRP in seven patients and the IOIBD score in six patients. Significant differences were detected in these parameters at weeks 2 and 4 compared with baseline. Five of the patients achieved normalization of CRP and a reduction of the IOIBD score to zero or one. Although one patient complained of taste disturbance, no other adverse events occurred and all patients completed the 4 weeks of study medication.
Conclusion The addition of metronidazole plus ciprofloxacin could be a useful intervention for the treatment of Japanese patients with active Crohn's disease.
(Internal Medicine 42: 318-321, 2003)

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Objective Most hepatocellular carcinoma (HCC) in Japan is caused by chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). HBV DNA has been detected in the serum and liver tissue of some proportion of those patients who are HBs antigen-negative and HCV antibody-negative; i.e., non-B, non-C (NBNC) patients with HCC. We sought to detect HBV DNA in the serum from NBNC HCC cases and to investigate genomic mutations of HBV in seronegative cases.
Patients and Methods The sera from 26 NBNC HCC patients were examined by polymerase chain reaction (PCR) followed by southern blotting for existence of HBV DNA. The precore/core and polymerase regions of the HBV genome in the sera from five seronegative cases were analyzed by direct sequence.
Results HBV DNA was detected in 17 of 26 patients (65.4%). Demographic factors such as age, gender, anti-HBs positivity, anti-HBc positivity, complication with cirrhosis, and excessive alcohol intake did not affect circulating HBV positivity. Genomic mutations with ammo acid substitutions were detected in the polymerase and the precore regions from one of the five cases, and in the core region from four of the five cases.
Conclusions PCR-based HBV screening is necessary in patients suffering from liver diseases of unknown etiology, although its etiological importance and benefit of viral elimination have not been established. Genomic mutations in the precore/core and the polymerase region detected in this study might be involved in the lack of HBsAg in NBNC HCC cases.
(Internal Medicine 42: 322-330, 2003)

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A 31-year-old woman with Graves' disease with a 12-month-history of propylthiouracil intake and autoantibodies in the sera was admitted to our hospital. The differential diagnosis between autoimmune hepatitis and propylthiouracil-induced hepatitis was intractable. Steroid therapy was started and she showed a complete response to the treatment. Liver biopsy demonstrated acute hepatitis and plasma cell infiltration. A second liver biopsy, which was performed 10 months after starting steroid therapy, showed some inflammatory cells in the portal tracts. These findings suggest that she had been suffering from autoimmune hepatitis.
(Internal Medicine 42: 331-335, 2003)

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A 74-year-old man was referred to us for evaluation of a tumor in the right atrium (RA). Transesophageal echocardiography (TEE) showed an unmovable 50×60 mm mass in the RA. Based on histological findings of subcutaneous tumors in the right abdominal wall, he was diagnosed as malignant lymphoma (ML), and treated with a THP-COP regimen. Upon completion of first THO-COP therapy, TEE showed marked regression of the mass and division into 3 masses, one of which showed marked floating movement with a small stalk. To prevent the risk of embolic events, surgical resection was performed. Resected tumors were necrotic tissues. Serial imaging of cardiac tumor and surgical resection is desirable to decrease the possibility of embolic complication.
(Internal Medicine 42: 336-339, 2003)

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We report a case of hypercalcemia in an elderly patient due to vitamin D intoxication with clinical features and electrocardiogram (ECG) findings mimicking acute myocardial infarction. A 78-year-old man was referred to our department with symptoms of general fatigue, anorexia and chest pain. The ECG demonstrated ST elevation in leads V₁ to V₃ and diffuse T wave flattening, resulting in myocardial infarction being suspected. However, his symptoms, including chest pain, gradually improved and the ECG returned to normal in accordance with a fall in his serum calcium level. We introduce the use of QaTc interval shortening in differentiating ST-T changes of hypercalcemia from those of true myocardial ischemia.
(Internal Medicine 42: 340-344, 2003)

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We treated a patient with an unusual bone disease at least partly associated with Chinese herbs. Seven years after 65-year-old man had begun to consume Chinese herbs, multifocal osteoarthralgias were noted, and the patient was hospitalized for renal dysfunction (serum creatinine, 2.8 mg/dl; urea nitrogen, 19 mg/dl). Fanconi syndrome also was apparent. A renal biopsy specimen showed tubulo-interstitial fibrosis. Chinese herbs were discontinued and prednisolone was started, but bone and joint pain as well as renal function gradually worsened. Four years later, creatinine was 9.0 mg/dl and alkaline phosphatase was 571 IU/l. As bone scintigraphy revealed localized asymmetric lesions, Paget's disease of bone was suspected at first. However, neither osteosclerosis nor hypertrophy was seen in radiographs. Based on a bone specimen histology we diagnosed as mixed-type renal osteodystrophy including osteomalacia and osteitis fibrosa. Mosaic pattern of cement lines was not present. This case was not compatible with either Paget's disease or typical renal osteodystrophy as seen in dialysis patients. Etidronate disodium was effective in alleviating bone symptoms. The patient's bone disorder may be a new disease at least partly related to Chinese herbs independently of nephropathy.
(Internal Medicine 42: 345-350, 2003)

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A 51-year-old man without human immunodeficiency virus, hepatitis B virus or hepatitis C virus was admitted with left scrotum swelling and hydrocele. The cytological finding of fluid in the left scrotum revealed malignant lymphoma, and the immunophenotypic analysis and monoclonal rearrangement of immunoglobulin heavy chain demonstrated B-cell lymphoma. However, no solid tumor of lymphoma was identified in the specimen following a left orchiectomy, or in any other body site and genomic human herpes virus-8 and Epstein-Barr virus were not detected in the lymphoma cells. So we interpreted this as a primary effusion lymphoma without any ethological viral infection. Subsequently, he underwent chemo-radiation therapy and has remained in remission.
(Internal Medicine 42: 351-353, 2003)

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An 80-year-old woman was diagnosed with primary cutaneous B cell lymphoma. She had multifocal cutaneous tumors, but no nodal lymphadenopathy or bone marrow involvement. Histopathological examination of a biopsy specimen showed diffuse large B cell lymphoma without a bc1-2 expression. Complete resolution of hypercalcemia and disappearance of tumors were achieved with CHOP therapy, but a rapidly progressive skin lesion was observed soon after the completion of the therapy. The clinical manifestation of primary cutaneous diffuse large B cell lymphoma is diverse and the treatment strategy is not entirely clarified. This case represents another example of this rare lymphoma.
(Internal Medicine 42: 354-357, 2003)

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Antiphospholipid syndrome (APS) is defined as the occurrence of thrombosis, recurrent miscarriage, or both in association with laboratory evidence of persistent antiphospholipid antibodies. Owing to protean manifestations and laboratory studies, the diagnosis may be difficult. Because the other signs and symptoms of thrombosis are predominant, prolonged fever is not usually the main clinical finding. We describe a patient who presented with fever of unknown origin (FUO) and was found to have thromboses of the splenic vein, the superior mesenteric vein, and the portal vein due to the primary antiphospholipid syndrome. We also reviewed the medical literature (Medline 1966-2001), including the main FUO series of the previous 40 years, and laparotomy series for FUO. We conclude that although very rare, primary APS and thrombosis may present with FUO. APS should be considered in the differential diagnosis of prolonged fever associated with thrombosis.
(Internal Medicine 42: 358-361, 2003)

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We report a woman with lupus nephritis complicated with lupus peritonitis and cytomegalovirus (CMV) colitis. Diagnosis of lupus peritonitis was made by abdominal computed tomography scan, colonoscopy, and ascitic fluid analysis. Steroid and cyclophosphamide therapy resulted in the improvement of severe lupus nephritis and peritonitis. Thereafter, she developed multiple colonic ulcers as diagnosed by colonoscopy and positive CMV antigenemia assay. Treatment with ganciclovir resulted in the disappearance of colonic lesions. The low cluster of differentiation (CD)4+ lymphocyte count (41/mm³) suggested that the cell-mediated immunity of this patient was comparable to that seen in patients with acquired immunodeficiency syndrome (AIDS).
(Internal Medicine 42: 362-366, 2003)

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We report the first case of an elderly patient suffering from Norwegian scabies who died after treatment with γBHC. γBHC (60 mg) was applied over the entire body except for the head of a 91-year-old female in our geriatric ward. This chemical was used in a smaller dose than previously reported, and it proved to be effective except for its effect on the head. Six days after the initial application, γBHC (40 mg) was also applied to the patient's head, but she died 5 days later. We propose that application of γBHC to the head of such patients should be done with great caution.
(Internal Medicine 42: 367-369, 2003)

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