[Cyclophosphamide-responsive subclinical Sjögren's syndrome in a patient with initial peripheral and central nervous system involvement].

A 36-year old woman was admitted because of painful dysesthesia of her extremities, suggesting the presence of mononeuritis multiplex. Laboratory data was almost within normal limits, with the exception of lupus anticoagulant positivity and increase of IgM level. We considered the possibility of connective tissue diseases and examined the patient accordingly. Keratoconjunctivitis sicca without dry eye symptoms, identified by rose-bengal and fluorescence testing, was the only recognizable abnormality. Oral sicca symptoms were not revealed although lip biopsy showed infiltration by a moderate number of plasma cells and lymphocytes. Under the diagnosis of subclinical Sjögren's syndrome, the following examination was carried out. Sural nerve biopsy specimens revealed wallerian degeneration and perivascular mononuclear cell infiltration of the vasa nervorum. We therefore concluded that the peripheral neuropathy was caused by subclinical Sjögren's syndrome. Magnetic resonance imaging (MRI) of the brain demonstrated multiple small lesions with increased spin echo images (T2 weighted) in the white matter. So, this patient was suffered from not only peripheral but also central nervous system complications. The mechanism of nervous system involvement was considered to be mononuclear cell-dependent ischemic damage caused by infiltration of the vasa nervorum. Both steroid pulse therapy and oral corticosteroid administration were ineffective in treatment of the peripheral neuropathy. Alternative use of cyclophosphamide (75 mg per day) was dramatically effective in relieving peripheral nervous system disorders. This was evident in the remarkable improvement of painful dysesthesia, grip strength and motor nerve conduction velocities. This case could be considered valuable for understanding the pathophysiology of Sjögren's syndrome and associated nervous system complications.

[Protein-losing enteropathy and cerebral infarction associated with systemic lupus erythematosus].

A 26-year old woman, who was diagnosed as having systemic lupus erythematosus at the age of 23 year old, presented diarrhea and headache. She showed severe hypoproteinemia (serum total protein 3.7 g/dl, serum albumin 1.4 g/dl) and hyperlipidemia. She revealed to have protein-losing enteropathy with the result of alpha-1-antitrypsin clearance test using stool. Increase of prednisolone improved the loss of albumin into the bowel and abnormal laboratory findings. She also showed watershed infarction in the area of middle cerebral artery and posterior cerebral artery. Protein-losing enteropathy is a rare complication of SLE, only 18 cases are available on literature. No case is found to have cerebral infarction in patients with protein-losing enteropathy associated with SLE. It is known that blood levels of anticoagulation factors decrease in protein-losing enteropathy due to the leakage of plasma protein into intestinal lumen. Serum antithrombin III was decreased in this case. Hyperlipidemia found in this case seems to be caused by same mechanism in nephrotic syndrome. Lupus anticoagulant was also positive in this patient. These factors seems to be related to the occurrence of cerebral infarction. This case suggests the possibility of cerebral infarction in patients with protein-losing enteropathy in SLE.

[Two cases of RA-like and SLE-like features similar to remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome)].

In 1985, McCarty et al reported 10 patients with a symmetrical synovitis affecting predominately the wrists and flexor digitorum tendon sheaths associated with marked pitting edema of the dorsum of both hands and both feet. It was insisted on the clinical entity as remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome). These patients were mostly elderly men whose sera revealed negative rheumatoid factor and had a benign clinical course. Patients with RS3PE syndrome remitted completely within 3-36 months and the remission was maintained even after all medications were discontinued. We experienced 2 interesting cases which were similar to RS3PE syndrome. One case with SLE-like conditions evolved into RA-like conditions. On the contrary, the other which had been effectively treated as RA developed into SLE-like conditions. Both cases were seronegative and had the characteristic pitting edema of both hands and feet demonstrating the symmetrical synovitis without bony erosions. They went into complete remission by corticosteroid therapy, although it did not continue for a long time. We should consider that such cases are similar to RS3PE syndrome and must be distinct from it.

[A case of cyclosporin A-induced myopathy].

A 40-year old man with Behçet's disease was admitted for severe decrease of visual acuity. Since 1987, he had suffered from oral aphtha, retinitis, erythema nodosum, genital ulcer and epididymitis. He was diagnosed as complete Behçet's disease and has been administered cyclosporin A (CYA) and colchicine (Col). Because of repeated ocular attacks and reduced visual acuity, CYA was increased from 3.49 mg/kg/day (220 mg/day) to 6.35 mg/kg/day (400 mg/day) and Col, 0.5 mg/day to 1.0 mg/day. 2 weeks later, he revealed fever, generalized myalgia, muscle weakness and general fatigue, accompanying marked elevation of creatine kinase (4962 IU/l). CYA was discontinued and Col was diminished to 0.5 mg/day. The myalgia disappeared in 4 days and general conditions including creatine kinase were normalized within 2 weeks. We concluded that CYA was highly suspected of the cause of myopathy considering his clinical course.

A monoclonal antibody (OPT1) to T cells which is available for paraffin-embedded materials.

A monoclonal antibody (MAb), OPT1, reactive with T cells in formalin-fixed, paraffin-embedded tissue sections, has been identified through immunization with activated T cells from peripheral blood lymphocytes (PBL). The antibody is an IgG1 antibody as demonstrated by the Ouchterlony technique. By cytofluorometric analysis, almost all CD3+ lymphocytes and only a few CD20+ lymphocytes of peripheral blood expressed the OPT1 antigen. Nonhematolymphoid cell lines were negative for OPT1 by the immunoperoxidase staining using acetone-fixed cell lines. On the contrary, peripheral T cells, cells of two T cell lines out of four and a part of the cells of one B cell line out of two were positive for OPT1. The immunoperoxidase staining of paraffin-embedded tissue sections revealed that most of lymphocytes in T cell areas of lymph nodes expressed OPT1 antigen. Some lymphocytes in both cortex and medulla of the thymus and erythroid precursors of the bone marrow were OPT1+. In the malignant lymphoma series, approximately 90% of T cell lymphomas and 6% of B cell lymphomas reacted with OPT1. None of the Reed-Sternberg cells nor Hodgkin cells in Hodgkin's disease were positive. Consequently, OPT1 may be useful for the diagnosis and study of malignant lymphomas and other related lesions.

A novel monoclonal antibody (OPD4) recognizing a helper/inducer T cell subset. Its application to paraffin-embedded tissues.

A novel monoclonal antibody (MAb), OPD4, reactive with a helper/inducer (H/I) subset of T cells in formalin-fixed, paraffin-embedded tissue sections, has been identified through immunization with an activated H/I T cell line, namely DL40. The antibody is an IgG1 antibody and it recognizes an antigen with a molecular weight of 200 kd, corresponding to that of leukocyte common antigen. OPD4+/CD4+ T cells provided better help for pokeweed mitogen-stimulated polyclonal IgG production than OPD4-/CD4+ T cells. OPD4 recognized the H/I T cell subset even in paraffin-embedded tissue sections, but did not recognize nonhematopoietic cells, suppressor/cytotoxic T cells, B cells, monocytes in the peripheral blood, or other normal hematopoietic cells as examined by the flow cytometric and immunoperoxidase methods. Besides the lymphoid cells, OPD4 reacted with a number of histiocytes (epithelioid cells) in tissues from sarcoidosis and tuberculosis. For the neoplastic lesions, OPD4 reacted with approximately half of the cases of T cell lymphomas. Consequently, OPD4 may be useful for the diagnosis and study of malignant lymphomas and other related lesions.

A case of complete atrioventricular block due to malignant lymphoma.

A case of malignant lymphoma associated with complete heart block in a 30-year-old woman is reported. The patient progressively deteriorated despite temporary pacing and died 24 days after being admitted. Microscopic examination of the heart revealed marked infiltration by lymphoma cells in the atrioventricular node and the bundle of His. A diffuse lymphoma (large cell type, B cell) was diagnosed. This case is considered to be rare, since complete heart block was the first and only manifestation of the malignant lymphoma.