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JADA Specialty Scan - O & M Pathology
JADA Specialty Scan

Clonazepam for burning mouth syndrome

Patients who have the chronic pain condition known as “burning mouth syndrome” (BMS) are frequently underserved by both medical and dental practitioners, research shows. Enduring an unremitting burning sensation in the mouth, usually without any visible abnormalities or unusual laboratory findings, patients are in need of effective medication that can alleviate their symptoms. Some 2.5% to 5.1% of people in the general population and 14% of postmenopausal women have BMS, which is also known as “stomatodynia,” “stomatopyrosis,” “glossopyrosis,” or “glossodynia.” The syndrome is classified into 2 major types: primary BMS, which lacks an identifiable organic systemic cause, and secondary BMS, which relates to local or systemic pathologic conditions.

Although several controlled studies have examined the therapeutic efficacy of the benzodiazepine clonazepam in the treatment of BMS, scientists in China could find no evidence-based studies evaluating the drug’s effect on symptom remission. Noting that duration, administration mode, and dosage of clonazepam for treatment of BMS is inconsistent between existing studies, they conducted their own research, and their review article was published online December 17 in Oral Diseases. Their primary aim was to elucidate the effect of clonazepam on BMS, according to evidence-based criteria. Secondarily, they wanted to learn whether the effect was influenced by treatment duration, administration mode, or dosage.

To explore, they searched PubMed, MEDLINE, Embase, Web of Science, and Cochrane Library databases for relevant studies through September 22, 2015. Of the 249 studies identified, scientists ultimately discovered 5 trials that were eligible for analysis. Published between 1998 and 2012, 2 of the studies were case-control and 3 were randomized clinical trials (RCTs). The quality values of all studies analyzed was higher than moderate, indicating to scientists that the findings generated by the meta-analyses were reliable.

Participants totaled 195, and the duration of clonazepam usage varied from 2 weeks to 29 months. Scientists divided the studies’ participants into 2 groups: those who were treated on a short-term basis (10 weeks or less) and those treated on a long-term basis (longer than 10 weeks). The included studies used 2 forms of administration: systemic, which means the patients swallowed the tablet, and topical, which means the participants sucked on the tablet near the pain sites, retaining saliva without swallowing for 3 minutes before expectorating.

Scientists found that burning mouth sensation scores by patients using a 0 through 10 visual analog scale were lower in the clonazepam group than in the placebo group for participants in 3 RCTs receiving short-term treatment. Also, clonazepam tended to alleviate BMS symptoms among long-term clonazepam users in 2 case-control studies and 1 RCT, indicating a positive therapeutic effect was demonstrated for both short-term and long-term use.
Scientists analyzed participants in the 2 RCT studies in which participants used topical clonazepam and found they demonstrated BMS symptom remission. Scientists’ analysis of 1 case-control study and 1 RCT using systemic administration of clonazepam also demonstrated a significant reduction in burning sensation after administration, indicating that both topical and systemic administration were effective.

“Our meta-analyses of these studies demonstrated that clonazepam treatment can lead to successful pain relief in BMS patients,” authors said in the discussion. They commented that “Benzodiazepines are known GABAA receptor agonists that bind to both peripheral and central receptor sites, promote brain stem serotonergic descending pain inhibition, and suppress spontaneous central neuronal hyperactivity occurring postdifferentiation.

 “In summary, the results of this meta-analysis of 195 participants show that clonazepam is effective for symptom remission in patients with BMS both in short-term and long-term application and with topical and systemic administration” the scientists concluded.

Read the original article.


Consulting Editor: Paul C. Edwards MSc, DDS, FRCD(C)
Editor, American Academy of Oral and Maxillofacial Pathology
Professor, Dept. of Oral Pathology, Medicine, Radiology
Indiana University School of Dentistry

Associate Consulting Editor: Lynn W. Solomon DDS, MS
Chair, Research and Scientific Affairs Committee, American Academy of
Oral and Maxillofacial Pathology
Associate Professor, Dept. of Oral Diagnostic Sciences,
Nova Southeastern University College of Dental Medicine

Nevoid basal cell carcinoma syndrome highlights common molecular pathways involved in basal cell carcinoma, keratocystic odontogenic tumor

Research elucidating the origins of nevoid basal cell carcinoma syndrome (NBCCS) has considerable promise for treatment of basal cell carcinoma (BCC)—the most common human malignancy—as well as the treatment of human malignancy in general, authors publishing in the June issue of Head and Neck Pathology reported.

Caused by defects in the hedgehog (HH) signaling pathway, NBCCS causes tumor cell proliferation, among other abnormalities. Characterized by development of numerous cutaneous BCCs at an early age—most commonly around the time of puberty—an affected person may have up to 500 BCCs in a lifetime, most commonly on the face but also on the trunk and limbs. Owing to the large number of tumors, the number of excisions performed may be extensive, and significant disfigurement may occur, the authors said in the report. They also discussed the clinical features, molecular pathogenesis, diagnostic criteria and differential diagnosis, and histopathology of NBCCS, as well as screening and treatment for it.

BCC is by far the most common cancer in fair-skinned people and makes up some 80% of nonmelanoma skin cancers. “As in cases of NBCCS, sporadic BCCs that arise due to [ultraviolet] exposure in non-NBCCS patients also frequently harbor aberrations in the hedgehog signaling pathway… ,” the authors reported. In addition to genetic syndromes, multiple BCCs in a young person may develop largely due to environmental factors, such as excessive ultraviolet light exposure from indoor tanning. They said a histologic clue that is suggestive of NBCCS is the presence of multiple incidental minute buds of early superficial BCC in otherwise unremarkable skin of an excision for BCC.

A well-recognized clinical feature of NBCCS called “keratocystic odontogenic tumor” that the authors discussed typically occurs in the posterior mandible and is recognized radiographically by an area of radiolucency often associated with the crown of an unerupted tooth.

In conclusion, the authors reported that understanding the underlying pathogenesis of NBCCS has led to greater knowledge of the HH signaling pathway and to the development of targeted therapeutics for BCC.

“Additionally, the development of HH-targeted agents has served as a model for use of targeted therapy in the treatment of human malignancy in general.”

Read the original article.


AAOMP at ADA 2016 October 22, 2016
At ADA 2016 you will have a chance to learn from and network with specialists from the AAOMP, during a free course in the Exhibit Hall. Speakers will present a lecture followed by an extended conversation hour where attendees can ask questions of the speakers, engage in peer-to-peer discussion and network. Participants who register for this free course will earn 2.0 CE credits for the course and 1.0 additional credit for the extended conversation.


Protecting infants from oral mutilation

Dentists aiming to raise awareness about the practice of gouging out an infant’s tooth germs based on the belief that the gingival swelling of unerupted teeth causes a variety of illnesses published an article in the April 2016 issue of British Dental Journal.

Infant oral mutilation (IOM) is prevalent in many countries in sub-Saharan Africa, but also occurs in western countries, according to the article. Increased immigration from Africa to developed countries during the past 20 years means the United Kingdom, the United States, Israel, Sweden, Norway, France, Australia, and New Zealand have all reported cases of IOM. “In the west, cultural and deep-rooted beliefs are challenging to address, particularly in migrant communities,” the authors said. “IOM will continue outside of the native settlements if the healthcare professionals in high income countries are not aware of its existence.”

Believed to be an outgrowth of an 18th century European practice of incising the gingiva over an erupting tooth as a means of decreasing pain, the practice was first reported in the 1930s among tribes in Sudan, where primary canines of infants were enucleated with a piece of iron, the authors reported. Now, IOM is typically carried out by a village healer without formal medical training who is recognized in the community as competent to provide health care. These healers are often respected older women, family members, priests, teachers, religious healers, or tribal heads who make a living from such ritualistic practice. Performed in nonsterile conditions, sharp instruments such as razor blades, bicycle spokes, fingernails, and knives are used.

Developing mandibular primary canines are the most commonly affected teeth, because they are easily noticed as whitish bulges, and healers believe the pale mandibular canine swelling to be abnormal and a cause of illness. The tooth follicles resemble worms to some village healers because on excision they are soft, partially mineralized masses of tissue. The authors outline the history of IOM; its etiology, prevalence, and practice; the affected teeth; complications from IOM; and child protection efforts against IOM globally and in the United Kingdom.

“We should recognize the odontogenic sequelae and complications of IOM, particularly among those who are African refugees or migrants,” the authors noted in their conclusions. “A sensitive approach and communication from clinicians is essential in educating the parents and carers, as they often hold deep seated core values and cultural traditions.”

Read the original article.


Therapies for oral lichen planus

Scientists in China interested in possible therapeutic strategies effective in treating steroid-resistant oral lichen planus (OLP) conducted a systematic review of the literature to provide an overview of nonsteroidal therapies. They published their findings in the May issue of Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.

In summarizing various treatment modalities, study design, clinical type of OLP, dosage regimen, and treatment protocol, results and adverse effects were discussed.

The review presented the strength of the evidence found in support of the following therapies:

  • topical agents (macrolide immunosuppressants)—tacrolimus, pimecrolimus, cyclosporine A, rapamycin, and etanercept;
  • systemic agents—thalidomide, mycophenolate (Mofetil), tetracycline, retinoids, curcumin, and glycyrrhizin;
  • phototherapy;
  • laser therapy—low-level therapy; carbon dioxide; yttrium aluminum garnet, and Excimer;
  • photodynamic therapy;
  • ultraviolet therapy—psoralen and ultraviolet A (long-wave); photopheresis and ultraviolet B (short-wave);
  • traditional surgery;
  • other surgeries—cryosurgery and autogenous palatal grafts.

Within their conclusions, the authors called for further studies, especially randomized controlled trials with strict inclusion and exclusion criteria and larger sample sizes for the evaluation of long-term safety and efficacy of these therapies.

Read the original article.

Resources on enrolling in, opting out of Medicare available

If you send biopsies to an oral pathology laboratory for a Medicare-eligible patient, you must register with the Centers for Medicare & Medicaid Services (CMS) using Form 855I or Form 855O or formally opt out of Medicare for the oral pathologist to get paid for his or her services.

The easiest of these options is to register with CMS as an ordering and referring provider using Form 855O. It is a much shorter and easier form to complete, and doing so will also allow your patients enrolled in Medicare to get any drugs you have prescribed that are covered under Medicare Part D paid for by Medicare. Medicare will not pay for these drugs if you fail to register by June 1, 2016. This will also allow you to submit claims to Medicare Advantage plans, some of which do cover dental services. If you formally opt out of Medicare, Medicare will not cover oral pathology services, but there are still forms that will need to be filled out and you will not be able to submit claims to Medicare Advantage plans.

Please remember, opting out of Medicare is not the same as doing nothing. A decision tree, frequently asked questions and a tutorial video can be found at

Get the ADA Oral Pathologist App

The ADA Oral Pathologist App helps dentists diagnose oral pathology conditions such as lesions, papules, nodules, ulcers, vesicles, and many others. Over 200 conditions can be searched by name or by entering clinical observations. The app is for Android or Apple mobile devices.

To see product details or place an order, click here. Save 15% on the Oral Pathologist app and all ADA Catalog products by using promo code 16408E at checkout before June 17, 2016.


AAOMP at ADA October 22, 2016
At ADA 2016 you will have a chance to learn from and network with specialists from the AAOMP, during a free course in the Exhibit Hall. Speakers will present a lecture followed by an extended conversation hour where attendees can ask questions of the speakers, engage in peer-to-peer discussion and network. Participants who register for this free course will earn 2.0 CE credits for the course and 1.0 additional credit for the extended conversation.


What is Specialty Scan?

This is one in a series of quarterly newsletters updating dentists on selected specialties in dentistry. Information presented is aggregated and summarized from previously published materials, each item attributed to its publication of origin. This issue of JADA Specialty Scan focuses on oral pathology, the second in the series on this topic for 2016. Other Specialty Scan issues are devoted to endodontics, oral and maxillofacial radiology, orthodontics, periodontics and prosthodontics. The ADA has engaged the specialty organizations in these areas as well as its own Science Institute and Division of Legal Affairs to assist with these newsletters. We welcome feedback on this and all Specialty Scan issues.

Editorial and Advertising Policies

Any statements of opinion or fact are those of the authors and do not necessarily reflect the views of the American Dental Association. Neither the ADA nor any of its subsidiaries have any financial interest in any products mentioned in this publication. Any reference to a product or service, whether in advertisements or otherwise, is not intended as an endorsement or as approval by the ADA or any of its affiliated organizations unless accompanied by an authorized statement that such approval or endorsement has been granted.

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