In this report, we described the case of dacryocystitis containing concretions. Our case had a history of using ROS. The histological study showed a crystal-like structure in specimens. It was assumed these substances formed crystal-like structure contained unbiological materials that caused the concretions. Therefore, we considered the possibility that the white substance found in the lacrimal path and/or sacs of the patient was formed or developed by accumulation of rebamipide. Results of the chemical analysis of the specimen did in fact reveal that the concretion contained rebamipide.
Dacryocystitis is inflammation of the lacrimal sac. The causes of csytitis vary and include infection, autoimmune diseases, and malignant diseases12. The majority is induced by infection. In our study, all three cases showed colonies of acetinomysis. Acetinomysis is a type of indigenous bacterium in the mouth, and is frequently found in dacryocystitis. The histological study in our case showed granular tissues and crystal-like structures. In the granulation tissue area, non-uniform patterns were found through Alcian blue staining. It is difficult to confirm whether the positive staining was caused by rebamipide application or responses to inflammation. The screening of other dacryocystitis specimens without rebamipide application is required to answer this question. There was a faint stain at the marginal region by Kossa staining. However, at the crystal-like structure area, there was prominent staining by Alcian blue and Kossa. It is likely that the positive staining by Alcian blue reflects the mucin augmentation.
Previously, we had experienced other 2 cases of dacryocystitis after showing a poor response to treatment with antibiotic agents 13. A head CT scan revealed ductal high-density deposits along bilateral lacrimal sac. Both cases had medical history of rheumatoid arthritis with Sjögren syndrome and had been applied ROS for dry eye treatment. Dacryocystotomy was performed and the contents were extracted. Histological study showed granulation tissues with actinomyces colonies and crystal-like structure. Interestingly, all three cases were incidentally affected by rheumatoid arthritis. It is difficult to ascertain whether this systemic background had any influence on the patients contracting dacryocystitis with concretions. It can be speculated that an aggressive autoimmune response following rheumatoid arthritis leads to inflammation and granular tissue formation in the lacrimal pathway. Another possibility is that the immunosuppressive state for the rheumatoid arthritis treatment precedes susceptibility to infections such as actinomyces. We conjecture that the low tear secretion results in a disturbance of the washout system to remove unnecessary substances in the lacrimal pathway.
The content of dacryoliths was found to be organic material with minerals such as calcium and magnesium 14. In addition, Mano et al. reported that the protein profiles of dacryoliths were different between ROS and non-ROS group 15. However, the exact composition of organic material is unclear in either with or without ROS application.
The chemical analysis of the specimen in our case revealed that the water-insoluble ingredient contained rebamipide. It is assumed that the crystal-like structure found during histological examination included rebamipide. Rebamipide is water insoluble. When there is stenosis of the lacrimal pathway, the aggregation of rebamipide can obstruct the lacrimal pathway. Then, dacryocystitis can be induced at this site following infection of such as actinomyces.
In light of these results, it can be inferred that the accumulation of rebamipide particles leads to congestion of the lacrimal pathway and complications of actinomycosis can result in the formation of dacryocystitis. In addition, immunosuppressive disorders such as rheumatoid arthritis and Sjögren syndrome may increase the risk of dacryocystitis under ROS application.
Our results suggest that the ROS should be carefully applied to any patient with rheumatoid arthritis and/or Sjögren syndrome. The ROS application to these patients may result in concretions on the lacrimal pathway and induce dacryocystitis.