Valproic acid-associated sialadenosis of the parotid and submandibular glands: diagnostic and therapeutic aspects

Abstract

Sialadenosis has been defined as a non-inflammatory, parenchymatous salivary gland disease causing recurrent, bilateral swelling of the salivary glands. As an adverse drug reaction of valproic acid, sialadenosis is very rare. To our knowledge, it has been reported only once in the world literature to date. We present herein the case of a patient with valproic acid-associated sialadenosis of both the parotid and submandibular glands. This appears to be the first published case of a patient who received surgical treatment. On light and electron microscopy of all the affected salivary glands, granular sialadenosis with predominantly moderate electron-dense secretory cytoplasmatic granules was observed. No relevant degenerative alterations were seen. There was no histological evidence of peripheral neuropathy of the nerve supply, leading to disordered activity of acinar cells by loss of neurosecretory granules. Lateral parotidectomy, performed under neuromonitoring control for safety reasons, is the treatment of choice for chronic recurrent parotitis that does not respond to conservative therapy, particularly if the cosmetic deformity is unacceptable to the patient. If the submandibular glands are involved, partial removal is recommended.

Reversal of Valproate‐Induced Major Salivary Gland Changes By Moringa Oleifera Extract in Rats

“…Although it has been reported to prevent the growth of salivary gland tumors, [5] VA has some clinical side effects including sialadenosis and dry mouth. [4,9] It has been observed to cause oxidative stress in tissues by oxidant/antioxidant imbalance, trigger inflammatory reactions, and autoimmune reactions. [2,10] Therefore, conducting research on compounds that can counteract the adverse effects of VA has become important.…”

“…VA is widely used as an antiepileptic and mood‐stabilizing drug and also inhibits histone deacetylase activity. Although it has been reported to prevent the growth of salivary gland tumors, [5] VA has some clinical side effects including sialadenosis and dry mouth [4,9] . It has been observed to cause oxidative stress in tissues by oxidant/antioxidant imbalance, trigger inflammatory reactions, and autoimmune reactions [2,10] .…”

“…It was observed that sympathetic nerve excitation was related to the loss of acinar granules which contain α‐amylase [57] . Findings indicates that a relationship exist between sympathetic/parasympathetic activity and VA administration [9] Once α‐amylase hydrolyzes α‐1,4 linkages of starch, glucose, and maltose are formed. Thus, elevated maltase activity might have been induced by the increased levels of maltose as a result of increased α‐amylase action.…”

A Review and Assessment of Drug-Induced Parotitis

“…5- 65 For a medication to be definitely associated with drug-induced parotitis, it must meet the following conditions: medications must have been implicated in at least 5 patients by 3 or more investigators and a minimum of 1 case must have a modified Naranjo score associated with probable causality. These strategies to determine causality have been adapted from a previous study.…”