Pediatric Sialadenosis Due to Valproic Acid.

Sialadenosis is a rare entity characterized by bilateral diffuse, painless swelling of the parotid glands. Its etiology is not clear; however, it may occur due to adverse effects of some drugs. To our knowledge, sialadenosis due to valproic acid has not been reported in the literature up to date in any child. In this article, the authors presented a child who developed sialadenosis due to valproic acid, and improved after stopping use of the drug.

World Workshop on Oral Medicine VI: clinical implications of medication-induced salivary gland dysfunction.

OBJECTIVE: This study aimed to systematically review the available literature on the clinical implications of medication-induced salivary gland dysfunction (MISGD). STUDY DESIGN: The systematic review was performed using PubMed, Embase, and Web of Science (through June 2013). Studies were assessed for degree of relevance and strength of evidence, based on whether clinical implications of MISGD were the primary study outcomes, as well as on the appropriateness of study design and sample size. RESULTS: For most purported xerogenic medications, xerostomia was the most frequent adverse effect. In the majority of the 129 reviewed papers, it was not documented whether xerostomia was accompanied by decreased salivary flow. Incidence and prevalence of medication-induced xerostomia varied widely and was often associated with number and dose of medications. Xerostomia was most frequently reported to be mild-to-moderate in severity. Its onset occurred usually in the first weeks of treatment. There was selected evidence that medication-induced xerostomia occurs more frequently in women and older adults and that MISGD may be associated with other clinical implications, such as caries or oral mucosal alterations. CONCLUSIONS: The systematic review showed that MISGD constitutes a significant burden in many patients and may be associated with important negative implications for oral health.

[Side effects of drugs on the oral cavity]. / Reacciones adversas a medicamentos en la cavidad oral.

Although drugs are the most powerful therapeutic tools we have for improving the quality of life of the population, their use is not free of adverse effects. Today there are many polymedicated patients, and it is difficult to find the cause of their adverse effects that increase exponentially when more than 4 drugs are combined. There are a large number of drugs that can result in numerous adverse effects in the oral cavity. The most common are xerostomia, altered taste, gingival enlargement and mucositis caused by cancer treatment. We also review other disorders of the salivary glands, oral mucosal changes, pigmentations, halitosis, osteonecrosis, opportunistic infections and bleeding diathesis.

Association of cyclophosphamide use with dental developmental defects and salivary gland dysfunction in recipients of childhood antineoplastic therapy.

BACKGROUND: The aim of this study was to examine the effect of antineoplastic therapy on dental development and saliva function in recipients of childhood antineoplastic therapy. METHODS: Patients attending the long-term follow-up clinic at Children's Hospital at Westmead, NSW, Australia, were included if they had received treatment prior to 16 years of age and were in remission for more than 5 years. A dental examination and saliva test were performed for each participant. Holtta's Defect Index (HDI) was used to assess tooth aplasia, microdontia, and root-crown ratio on an orthopantomogram (OPG). Multivariable-adjusted regression analyses were used to estimate the association of patient characteristics and treatment modalities with dental outcomes. RESULTS: One hundred six participants (61% male) were recruited (response rate = 88%). The mean HDI score was 24.7 ± 17.8. A cumulative dose of cyclophosphamide >7500 mg/m(2) increased the HDI score by 13.06 (P = .01). Recipients of cyclophosphamide also had significantly increased odds of exhibiting very low saliva flow (<0.7 mL/min) (odds ratio = 12.43; 95% confidence interval, 2.08-74.35; P = .006). CONCLUSIONS: Children and adolescents who received high doses of cyclophosphamide were at increased risk of dental disturbances. Cyclophosphamide recipients were also at greater risk of exhibiting very low saliva flow. This study applied the HDI to patients receiving all forms of antineoplastic treatment and highlights the dose-dependent relation between cumulative dose of cyclophosphamide and dental disturbances.

Oral signs of intravenous chemotherapy with 5-Fluorouracil and Leucovorin calcium in colon cancer treatment.

UNLABELLED: Several studies have shown how cytostatics may cause hypofunction of salivary glands but failed to elucidate any potentially related side effects. Keeping in mind the sialochemical assistance and the role of saliva on the homeostasis of the stomatognathic system, the aim of this study was to establish potential gland disorders in patients submitted to 5- Fluorouracil (5-Fu) and Leucovorin calcium (LV) as well as their correlation with certain oral health disorders that diminish the quality of life. MATERIALS AND METHODS: the focus of this research was observational and longitudinal. Twenty-five patients diagnosed with colon cancer at an initial, intermediate and late phase submitted to specifically devised therapy were assessed. Clinical history, oral health indexes and basal or stimulated saliva samples were recorded. RESULTS: Basal and stimulated flow dropped in the intermediate stage. Stimulated saliva pH decreased during treatment. On basal saliva, urea, sodium and potassium rose during the intermediate phase. Löe and Silness rates as well as simplified bleeding increased during therapy but reverted by the end of the treatment. Depth index of the vestibular gingival sulcus rose during the intermediate phase but did not return. CONCLUSION: This treatment caused functional salivary gland disorders as evidenced by basal and stimulated hyposialia, and acidification of stimulated saliva pH during the intermediate phase. Increase in basal urea may be due to proteic catabolism arising from plasma or glands. Variation in Na+ and K+ of basal saliva concentrates might be assumed as a possible duct disorder. Recovery of bleeding and Löe and Silness rates may point to a transient inflammatory effect associated to a decrease in salivary flow. Increase in the depth rates of the periodontal vestibular sulcus could be correlated with a higher risk of periodontal disease.

Oral pilocarpine (5mg t.i.d.) used for xerostomia causes adverse effects in Japanese.

OBJECTIVE: To evaluate Japanese tolerability to pilocarpine of 5 mg t.i.d. METHODS: From January 2006 to July 2006, 39 patients with xerostomia received 5 mg t.i.d. pilocarpine for at least for 12 weeks unless they had experienced unacceptable adverse effects. All patients received radiotherapy that included the parotid glands in the radiation field >50 Gy. The body weights of the patients ranged from 42 to 73 kg (median 60 kg). RESULTS: Thirty-six of the 39 patients were evaluable. The tolerated rate was only 47%. Of the 25 patients whose body weights were less than 65 kg, the tolerated rate was 36%, whereas the rate of the 11 patients whose body weights were 65 kg or above was 72% (p=0.050). The most common adverse effect was sweating with an incidence of 64%. Response rate, which was defined as the total number of patients with an increase of at least 25 mm from the baseline in the VAS score divided by the number of maintaining patients among those who started pilocarpine after more than 4 months from the start of radiotherapy, was 40% at 12 weeks (n=15). CONCLUSION: For Japanese, 5mg t.i.d. pilocarpine caused a high incidence of unacceptable adverse effects. A lower dose of pilocarpine needs to be considered.

[Implications of antiretroviral therapy in oral medicine--a review of literature]. / Implikationen der antiretroviralen Therapie in der Oralmedizin. Eine Literaturübersicht.

The success of antiretroviral therapy leads to a chronification of HIV-infection resulting in a decline of lethality. The lifelong intake of antiinfectives, though, may result in drug side effects with clinical dental implications. Despite fundamental cellular alterations, including prolonged hemorrhage following surgical interventions, antiretrovirals of all classes, of protease inhibitors, (non-nucleoside) reverse transcriptase inhibitors and of fusion inhibitors may promote oral manifestions like oral ulcera, dysgeusia, salivary gland disorders, papilloma, (peri)oral paresthesia or aphtous stomatitis. Due to inhibitory effects especially of protease inhibitors of cy tochrome P450-isoenzyme CYP3A4 therapeutical interactions with psychotropics/sedatives, antifungal agents, corticoids and intiinfectives, particularly metronidazole, may raise. The application and prescription of systemically metabolized adjuvant drugs as well as the monitoring of the possible progression of HIV infection is a key task in the oral health care of HIV-seropositive patients calling for a close medical coordination of therapeutical interventions.

Non-neoplastic salivary gland diseases.

A wide range of non neoplastic disorders can affect the salivary glands, although the more common are: mumps, acute suppurative sialadenitis, Sjögren's syndrome and drug-induced xerostomia. Salivary dysfunction is not a normal consequence of old age, and can be due to systemic diseases, medications or head and neck radiotherapy. Diagnosis of salivary disorders begins with a careful medical history, followed by a cautious examination. While complaints of xerostomia may be indicative of a salivary gland disorder, salivary diseases can present without symptoms. Therefore, routine examination of salivary function must be part of any head, neck, and oral examination. Health-care professionals can play a vital role in identifying patients at risk for developing salivary dysfunction, and should provide appropriate preventive and interventive techniques that will help to preserving a person's health, function, and quality of life. The present work provides an overview of most of the non neoplastic disorders of the salivary glands, in which the general presentation, pathology, and treatments are discussed.

Oral lesions of HIV disease and HAART in industrialized countries.

The epidemiology of HIV-related oral disease in industrialized nations has evolved following the initial manifestations described in 1982. Studies from both the Americas and Europe report a decreased frequency of HIV-related oral manifestations of 10-50% following the introduction of HAART (highly active antiretroviral therapy). Evidence suggests that HAART plays an important role in controlling the occurrence of oral candidosis. The effect of HAART on reducing the incidence of oral lesions, other than oral candidosis, does not appear as significant, possibly as a result of low lesion prevalence in industrialized countries. In contrast to other oral manifestations of HIV, an increased prevalence of oral warts in patients on HAART has been reported from the USA and the UK. HIV-related salivary gland disease may show a trend of rising prevalence in the USA and Europe. The re-emergence of HIV-related oral disease may be indicative of failing therapy. A range of orofacial iatrogenic consequences of HAART has been reported, and it is often difficult to distinguish between true HIV-related oral disease manifestations and the adverse effects of HAART. A possible association between an increased risk of oral squamous cell carcinoma and HIV infection has been suggested by at least three epidemiological studies, with reference to the lip and tongue. These substantial and intensive research efforts directed toward enhancing knowledge regarding the orofacial consequences of HIV infection in the industrialized nations require dissemination in the wider health care environment.

A review of drug-induced oral reactions.

Every drug can produce untoward consequences, even when used according to standard or recommended methods of administration. Adverse drug reactions can involve every organ and system of the body and are frequently mistaken for signs of underlying disease. Similarly, the mouth and associated structures can be affected by many drugs or chemicals. Good oral health, including salivary function, is very important in maintaining whole body health. Regarding different parts of the oral system, these reactions can be categorized to oral mucosa and tongue, periodontal tissues, dental structures, salivary glands, cleft lip and palate, muscular and neurological disorders, taste disturbances, drug-induced oral infection, and facial edema. In this article, the drugs that may cause adverse effects in the mouth and related structures are reviewed. The knowledge about drug-induced oral adverse effects helps health professionals to better diagnose oral disease, administer drugs, improve patient compliance during drug therapy, and may influence a more rational use of drugs.

The role of radioactive iodine in salivary gland dysfunction.

The use of radioactive iodine has become an important adjunct to the treatment of thyroid cancer. Many normal tissues--including salivary glands, gastrointestinal mucosa, gonads, and lactating breast tissue--have the ability to concentrate radioactive iodine under normal circumstances. Although the mechanism is just beginning to be elucidated, it is this ability that might contribute to the immediate and long-term complications associated with radioactive iodine treatment. In some patients, the salivary complications can be permanent and might compromise daily functioning. In this article, we examine the salivary gland complications associated with radioactive iodine therapy, and we suggest potential protective mechanisms to circumvent these problems.

Oral, perioral and systemic pathosis in HgCl2-induced autoimmunity in the BN rat.

Male BN rats were repeatedly skin-injected with HgCl2 solution and sacrificed after 6, 9, 14, 21, 28 or 24 days. Mononuclear cell infiltrates were observed in the oral mucosa and in lacrimal, salivary and thyroid glands from 6-9 days onwards, with a peak at 14-21 days. Immunohistochemistry identified these cells as predominantly T cells with some NK cells but very few B cells. Reversible parenchymal changes were observed but there was no obvious persistent tissue destruction. Serum titers of IgE, IgG1, anti-laminin and anti-DNP, but not IgG2a antibodies, were raised and peaked at 14-21 days. However, there was no correlation, within animals, between these titers and the extent of mononuclear cell infiltration. Mercury was histochemically detected within dendritic cells/macrophages in the connective tissue stroma of the glands and in the oral mucosa, but no correlation was found between the distribution of mercury and the degree of inflammation. We conclude that the accumulation of mononuclear cells in oral and perioral tissues of HgCl2-treated BN rats does not represent a local immune response to tissue-retained Hg. Instead, we propose that the extravasation represents an epiphenomenon that is not necessarily deleterious to the infiltrated organ.

Iodide mumps after contrast enhanced CT with iopamidol: a case report.

We have experienced a case of iodide mumps after CT examination with 100 ml of iopamidol. The patient was a 70-year-old woman with a history of right nephrectomy due to right renal cancer. She underwent CT examination to explore local recurrence and abdominal metastases including lymph node and liver metastases. Three hours after the CT examination, she complained of nausea, vomiting, facial flushing, bilateral jaw pain, and fever. The laboratory findings 12 hours after CT examination showed increased white blood cells and elevated serum amylase enzyme. Analysis of the amylase fraction showed that 86% originated from the salivary glands. She was admitted to the hospital, and the symptoms continued for four days, with decreasing severity. Anti-inflammatory therapy was performed, and the patient was discharged six days after the event.

Repetitive weekly cycles of 4-day continuous infusion of recombinant interleukin-2: a phase I study.

A phase I trial was performed with a new interleukin-2 (IL-2) given as a continuous intravenous infusion in patients with solid tumors. The objectives of the study were to examine the feasibility of administering IL-2 in 4-day cycles for 4 consecutive weeks, and to investigate the response pattern of peripheral blood lymphocytes. Tumor necrosis factor (TNF) and IL-2 serum concentrations were also measured. Prior to this study, IL-2 had been tested at increasing dosages during one 4-day cycle, and it appeared that a dose of 1300 mcg/m2/day was tolerated. However, when this treatment schedule was maintained for 4 consecutive weeks, the maximum tolerated dose was 430 mcg/m2/day. In this schedule, a dose-dependent progressive increase in rebound lymphocyte count occurred after each weekly cycle, resulting in a 5-70-fold increase after the 4th cycle. Serum TNF peak concentrations also showed a tendency to increase during each subsequent cycle, while serum IL-2 peak concentrations showed a paradoxical decrease. Clinical toxicity comprised several events, which, possibly, could be ascribed to autoimmune phenomena. Myocardial infarction as a late toxicity of IL-2 is suggested. One complete response (renal carcinoma) and two partial responses (renal and breast carcinoma) were documented, one of these occurring in a patient who previously had shown a transient response on interferon therapy.

Estrogen induces the development of autoantibodies and promotes salivary gland lymphoid infiltrates in normal mice.

There are important bidirectional interactions between the immune and the endocrine system. Sex hormones influence the immune system throughout life including postnatal and prenatal stages. For example, we find that administration of estrogen to normal mice markedly augments the ability of CD5+ B cells to express their autoimmune potential by producing increased numbers of plaque-forming cells (APFC) to bromelain-treated mouse erythrocytes (Br-ME). The effect of sex hormones on immune function at the most critical stage of development, the prenatal period, remains unstudied. We hypothesize that an imbalance of the in utero sex hormone microenvironment critically influences the fetal immune system. We have termed this influence immunological imprinting. After birth this imprinting could contribute to immune-mediated disorders. To test this hypothesis, we developed a mouse model in which normal mice were prenatally exposed to estrogens. In preliminary experiments, these mice produced higher numbers of APFC to Br-ME, particularly in the peritoneal cavity cell exudates. Furthermore, mice prenatally exposed to estrogens had accelerated development of autoimmune salivary gland lesions indistinguishable from Sjögren's syndrome (SS) in humans. Further experiments are warranted to confirm these findings. The prenatal effects of estrogen may have relevance for familial and neonatal autoimmune syndromes.

Iatrogenic causes of salivary gland dysfunction.

Saliva is important for maintaining oral health and function. There are instances when medical therapy is intended to decrease salivary flow, such as during general anesthesia, but most instances of iatrogenic salivary gland dysfunction represent untoward or unavoidable side-effects. The clinical expression of the salivary dysfunction can range from very minor transient alteration in saliva flow to a total loss of salivary function. The most common forms of therapy that interfere with salivation are drug therapies, cancer therapies (radiation or chemotherapy), and surgical therapy. These therapies can affect salivation by a number of different mechanisms that include: disruption of autonomic nerve function related to salivation, interference with acinar or ductal cell functions related to salivation, cytotoxicity, indirect effects (vasoconstriction/dilation, fluid and electrolyte balance, etc.), and physical trauma to salivary glands and nerves. A wide variety of drugs is capable of increasing or decreasing salivary flow by mimicking autonomic nervous system actions or by directly acting on cellular processes necessary for salivation: drugs can also indirectly affect salivation by altering fluid and electrolyte balance or by affecting blood flow to the glands. Ionizing radiation can cause permanent damage to salivary glands, damage that is manifest as acinar cell destruction with subsequent atrophy and fibrosis of the glands. Cancer chemotherapy can cause changes in salivation, but the changes are usually much less severe and only transient. Finally, surgical and traumatic injuries interfere with salivation because of either disruption of gland innervation or gross physical damage (or removal) of glandular tissue (including ducts).

Acute transient sialadenopathy associated with anesthesia.

Five cases of acute transient sialadenopathy associated with the administration of anesthesia are described in this article. In each case, the patient's straining on the endotracheal tube was followed immediately by firm swelling of one or more of the salivary glands. The facial swelling was resolved within 24-four hours without treatment.

Oral manifestations of drug reactions.

The clinical manifestations of oral reactions to the more commonly prescribed drugs have been presented. These reactions include the following conditions: stomatitis, ulceration and necrosis, opportunistic infections, hemorrhage, gingival hyperplasia, pigmentation, altered salivary function, and altered taste sensation. A patient who complains of any of these signs and symptoms should be thoroughly questioned regarding medication. If an offending drug can be identified, its alteration or elimination, in consultation with the prescribing clinician, will often result in resolution of the clinical problem.