Heterogeneous characteristics of lymphatic microvasculatures associated with pulmonary sarcoid granulomas.

RATIONALE: Pulmonary sarcoidosis is a disorder characterized by noncaseating epithelioid granulomas that are anatomically distributed along lymphogenous routes. Currently, limited information is available about lymphangiogenesis in pulmonary sarcoidosis. OBJECTIVE: To clarify the characteristics of lymphangiogenesis in pulmonary sarcoidosis. METHODS: The concentrations of vascular endothelial growth factor (VEGF), VEGF-C, and VEGF-D in serum and bronchoalveolar lavage fluid from 65 patients with pulmonary sarcoidosis, 10 with idiopathic pulmonary fibrosis, and 29 healthy volunteers were measured by ELISA. Paraffin-embedded lung tissues obtained from 19 patients were used for immunohistochemical analyses, using primary antibodies against VEGF, VEGF-C, VEGF-D, podoplanin, VEGF receptor (VEGFR)-2, VEGFR-3, and CD73. RESULTS: The serum and bronchoalveolar lavage fluid concentrations of VEGF and VEGF-C were significantly increased in patients with pulmonary sarcoidosis. Immunohistochemical analysis showed that VEGF and VEGF-C were expressed in sarcoid granulomas. Immunostaining with anti-podoplanin antibody for the detection of lymphatic vasculatures showed the presence of usual lymphatics and atypical tubular structures around sarcoid granulomas. Atypical tubular structures were characterized by a thin membrane, with weak expression of podoplanin and a membrane deficit in a part of the borderline. The structures were observed in around 58.6% of the total of 193 granulomas, whereas usual lymphatics were limited in 15.6%. Atypical tubular structures were coexpressed with VEGFR-2, but not VEGFR-3, whereas VEGFR-3 was expressed in usual lymphatics. Part of the tubular structures was connected to CD73(+) afferent lymphatics. CONCLUSION: These results indicate the presence and the importance of heterogeneous lymphatic microvasculature around sarcoid granulomas in pulmonary sarcoidosis.

[Case of systemic lupus erythematosus occurring after induced abortion and drug eruption].

We describe a19 year-old woman who was diagnosed as systemic lupus erythematosus (SLE) after abortion. She had taken anti-convulsants for epilepsy since she was 8 years old. Induced abortion surgery was performed at six weeks in her pregnancy. She showed pyrexia and a general rash 2 days after the abortion. She was introduced to our hospital because the administration of antibiotics was not effective. Since the anti-convulsants had been changed after pregnancy, we returned to those administered before pregnancy and followed her up. Her eruption improved, but she became aware of thirstiness and dry eye. She was diagnosed as Sjögren syndrome by ophthalmologic examination, lip biopsy, and elevation of an anti-SS-A antibody and an anti-SS-B antibody in the serum. Since we could not rule out SLE because of the low concentration of complement activity in blood, we followed her up carefully by checking serum markers of SLE. Protein urine developed after the improvement of the eruption 2 weeks later. Low complement activity was recognized and double stranded (ds)-DNA antibody became positive. In addition to these findings, she had an episode of hypersensitivity to sunlight and was therefore diagnosed as SLE. Since induced abortion and drug eruption might be associated with the onset of SLE, the case is thought to be a valuable from the view point of understanding the mechanism of SLE onset.