Although bullous pemphigoid and cicatricial pemphigoid are sometimes associated with malignancy, it remains uncertain whether such an association is pathogenetically related or just a coincidence attributable to the advanced age of the patients. We report a 61-year-old patient with antiepiligrin (laminin 5) cicatricial pemphigoid (AeCP) associated with an advanced gastric carcinoma. The gastric carcinoma cells in this patient were shown to produce laminin 5 by immunofluorescence microscopy, and the patient's serum contained autoantibodies directed against laminin 5 on immunoprecipitation. Furthermore, the blistering symptoms and the titre of antibasement membrane zone antibodies coordinately changed with the resection and subsequent relapse of the gastric cancer. These observations suggest that the gastric carcinoma producing laminin 5 may have induced the production of autoantibodies to this laminin, which were pathogenic to the skin and mucous membranes in this patient. This report demonstrates a link between this autoimmune subepithelial blistering disease and malignancy. It is of interest and potential great importance to examine other cases of AeCP for such a potential association.

Teratogenic effects of azosemide, a loop diuretic, were investigated in rats, mice and rabbits. Azosemide was given orally to pregnant rats, mice and rabbits during organogenesis. The pregnant animals were killed at term and their fetuses were examined for external, visceral and skeletal abnormalities. In rats, azosemide at 10-30 mg/kg/day did not affect intrauterine growth, resorptions and rates of external and visceral malformations. Treatment with 90 mg/kg/day resulted in a significant increase in skeletal abnormalities such as wavy ribs, bent scapula and bent humerus. However, the skeletal abnormalities observed in term fetuses could not be found in adult offspring, indicating that they were temporary. In mice, 1250 mg/kg/day of azosemide caused maternal death, abortion, and retarded maternal and fetal weight. Treatment with 200-500 mg/kg/day did not induce fetal mortalities, external and visceral malformations. Skeletal abnormalities increased in dose-dependent fashion. The type of abnormalities was identical to that encountered in rat fetuses. Furosemide as a positive control also produced similar types of skeletal abnormalities in mouse fetuses. In rabbits, azosemide did not have embryolethal or teratogenic effects even at the highest dose (6 mg/kg/ day), which caused maternal death.Treatment for a different 3-day period and then a different day during organogenesis in rats and mice showed that the sensitive period was days 15-17 of gestation with a peak on day 16 in rats, and days 12-15 with a peak on day 13 in mice.

Azosemide produced bent long bones such as wavy ribs in rat fetuses, but these abnormalities could not be found in the adult offspring. In the present study, the morphological sequence from appearance to disappearance of wavy ribs was examined in cartilage‐bone double stained specimens of fetuses and pups from mothers treated with azosemide on day 16 of gestation. The first detected change of the skeletal abnormalities was inhibition of bone deposition in the ossification centers of fetuses on day 17 of gestation. A bend first appeared on day 18 of gestation, and consisted of cartilage and portion stained neither alcian blue nor alizarin red S. Ossification began at this stage. From day 19 of gestation onward, ossification progressed toward the ends of the cartilage model including the bent region. The bend disappeared in most pups as bone in the bent region grew on days 10–14 postpartum. The present findings imply that the bend may be caused by difference in growth between cartilaginous and unstained portions, and a surface remodeling of bones may straighten the bend in the subsequent bone growth.

The present case differed from past cases by lacking inferior conjunctival sac shortening and by showing erosive lesions solely at the mucocutaneous junctions. The ocular involvement in this case correlated very well with the severity of gastric carcinoma.

In vivo corneal confocal microscopy is useful for observing stromal abnormalities in cornea farinata. Further investigation of posterior stromal opacities using confocal microscopy may be useful to understand and differentiate various corneal conditions involving primarily deep stromal layers.