September 2016 Systemic Diseases Mucocutaneous Diseases Less Common Oral Diseases Acromegaly JournaCALIFORNIA DENTAL ASSOCIATION

Oral and Systemic Diseases You May Encounter Throughout Your Career

Joel M. Laudenbach, DMD You are not a statistic.

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DEPARTMENTS 533 The Editor/The Study of Suff ering

534 Letters

537 Impressions

545 Table Clinic Winners

583 RM Matters/Hiring Done Right: License Verifi cation and Background Checks

589 Regulatory Compliance/HIPAA Privacy Tips and Reminders 594 Tech Trends 537

FEATURES 551 Oral and Systemic Diseases You May Encounter Throughout Your Career An introduction to the issue. Joel M. Laudenbach, DMD

553 Common Oral Manifestations of Select Systemic Diseases: , Diabetes Mellitus and HIV This article discusses several common abnormal signs and symptoms that may present in the oral cavity initially with or without any systemic symptoms at a typical dental practice. Sahar Mirfarsi, DDS; Eric T. Stoopler, DMD; Ho-Hyun (Brian) Sun, MS; and Jeffrey A. Elo, DDS, MS

561 Mucocutaneous Diseases: Oral , Mucous Membrane and Vulgaris This review describes the clinical features, epidemiology, etiology, pathogenesis and management for each condition. Seena Patel, DMD, MPH; Satish Kumar, DDS, MDSc, MS; Joel M. Laudenbach, DMD; and Antonia Teruel, DDS, MS, PhD

571 Less Common Oral Diseases of Medical Significance This article reviews four less common oral diseases of medical significance. Scott S. De Rossi, DMD, and Katharine Ciarrocca, DMD, MSEd

577 Acromegaly: A Dental Disease? This article describes the disease and the dental implications for patients who have it. Gil Ivry, DDS, MD, and Alan L. Felsenfeld, MA, DDS

SEPTEMBER 2016 531 CDA JOURNAL, VOL 44, Nº9

Volume 44, Number 9 JournaCALIFORNIA DENTAL ASSOCIATION September 2016 CDA Classifieds.

Free postings. published by the Editorial Upcoming Topics Letters to the Editor California Kerry K. Carney, DDS, CDE October/Sugar www.editorialmanager. EDITOR-IN-CHIEF Priceless results. Dental Association November/Regulatory com/jcaldentassoc 1201 K St., 14th Floor [email protected] Issues Sacramento, CA 95814 Ruchi K. Sahota, DDS, CDE December/General Topics Subscriptions 800.232.7645 ASSOCIATE EDITOR Subscriptions are available cda.org Advertising only to active members of Brian K. Shue, DDS, CDE the Association. The CDA Offi cers ASSOCIATE EDITOR Doug Brown subscription rate is $18 and ADVERTISING SALES is included in membership Kenneth G. Wallis, DDS [email protected] PRESIDENT Joel M. Laudenbach, DMD dues. Nonmembers can GUEST EDITOR 916.554.7312 [email protected] view the publication online at cda.org/journal. Clelan G. Ehrler, DDS Andrea LaMattina Permission and SENIOR PUBLICATIONS Manage your subscription PRESIDENT-ELECT Reprints [email protected] SPECIALIST online: go to cda.org, log in Andrea LaMattina and update any changes to SENIOR PUBLICATIONS Blake Ellington your mailing information. Natasha A. Lee, DDS SPECIALIST VICE PRESIDENT TECH TRENDS EDITOR Email questions or other [email protected] changes to membership@ [email protected] 916.554.5950 Courtney Grant cda.org. COMMUNICATIONS R. Del Brunner, DDS SECRETARY SPECIALIST Manuscript [email protected] Jack F. Conley, DDS Submissions EDITOR EMERITUS www.editorialmanager. Kevin M. Keating, DDS, MS TREASURER com/jcaldentassoc [email protected] Robert E. Horseman, DDS CDA classifiedsclassifieds wworkork harder to HUMORIST EMERITUS Stay Connected cda.org/journal bbringring you resuresults.lts. SeSellinglling a practice Craig S. Yarborough, DDS, MBA Production or a piece ooff equipment? Now you SPEAKER OF THE HOUSE [email protected] Val B. Mina can include photos to help buyers SENIOR GRAPHIC DESIGNER Walter G. Weber, DDS Go Digital cda.org/apps see the potential. IMMEDIATE PAST PRESIDENT Randi Taylor SENIOR GRAPHIC DESIGNER Look for this symbol, noting additional video [email protected] content in the ePub version of the Journal. And if you’re hiring, candidates anywhere can apply right from Management Peter A. DuBois the site. Looking for a job? You can EXECUTIVE DIRECTOR Journal of the California Dental Association (ISSN 1043–2256) is published monthly by the post that, too. And the best part— Jennifer George California Dental Association, 1201 K St., 14th Floor, Sacramento, CA 95814, 916.554.5950. it’s free to all CDA members. CHIEF MARKETING OFFICER Periodicals postage paid at Sacramento, Calif. Postmaster: Send address changes to Journal of the California Dental Association, P.O. Box 13749, Sacramento, CA 95853. Carrie E. Gordon The California Dental Association holds the copyright for all articles and artwork published All of these features are designed to CHIEF STRATEGY OFFICER herein. The Journal of the California Dental Association is published under the supervision of help you get the results you need, CDA’s editorial staff . Neither the editorial staff , the editor, nor the association are responsible for Alicia Malaby any expression of opinion or statement of fact, all of which are published solely on the authority COMMUNICATIONS faster than ever. Check it out for of the author whose name is indicated. The association reserves the right to illustrate, reduce, DIRECTOR revise or reject any manuscript submitted. Articles are considered for publication on condition yourself at cda.org/classifieds. that they are contributed solely to the Journal. Copyright 2016 by the California Dental Association. All rights reserved.

532 SEPTEMBER 2016 Editor CDA JOURNAL, VOL 44, Nº9

The Study of Suff ering Kerry K. Carney, DDS, CDE

he origin of the word “pathology” comes from the Greek roots, When you look at a slide of small cell pathos (suffering) and logia (study). It is a pretty good term. carcinoma, you do not see the mother of six A population may consist of the who has dedicated her life to her family’s welfare Tsuffering and the nonsuffering (not to and now fi nds herself in a battle for her life. be confused with the insufferable. That is a subject for a different editorial.) In dental school, pathology classes were simple, you either liked them or abnormal autopsy results. His work gave As dentists, we do not experience you hated them. Regardless of your a fuller picture of the disease progression. that depersonalization with our patients’ predisposition, the fact that they were The microscope became a signifi cant suffering. We rely on our knowledge always scheduled right after lunch tool for furthering the study of pathology. and understanding of pathology made it diffi cult not to succumb to Rudolph Virchow is credited with every day in the dental practice. postprandial somnolence while trying emphasizing the need to study the We listen to complaints, we gather to follow one slide after another. process of disease on a cellular level. medical history data and we perform Pathology is the nexus of microbiology, The microscope made evident what was gross observational examination. biochemistry, anatomy, physiology, invisible to the naked eye. The disease There are some pathological genetics, the environment and the process in the cellular building blocks of fi ndings you will see every month human organism. It is fascinating. It is the body could be documented. Since or so. There are some pathological a puzzle and it is an old fi eld of study. then, pathology has become an important fi ndings you will see every year or Its history follows the history of the part of every aspect of modern medicine. so, and there are some pathological scientifi c method. Its advances have been I had a friend who wanted to be a fi ndings you hope to only hear about tied to the advances of technological aids. pathologist. He did not want to deal with from a colleague over coffee. We Before the scientifi c method, suffering patients directly. He found relating to gather specimens for cytological and death of the nonviolent kind might patients diffi cult and thought he could exams, order biopsies and consult have been attributed to “imbalances” in be more useful if he helped the attending with oral pathologists. But for the humors or the result of witchcraft. physician fi gure out what was wrong us, there is no separation of the The fi rst steps in the study of and let the attending physician convey suffering from the sufferer. suffering had to come from the questions, that information to the patient and We have to explain to the patient “Why did an individual suffer? Why devise the therapeutic intervention. what we think is going on or why we did some suffer and recover while And therein lies the problem with the need to take a biopsy or consult with others suffered and succumbed?” study of suffering: It separates the suffering a specialist. We have to recognize a The early investigators would have from the sufferer. When you look at a potential or actual problem and we have relied on noninvasive, gross observational slide of small cell carcinoma, you do not to be able to convey the signifi cance examination. But by the 15th century, the see the mother of six who has dedicated of our fi ndings to our patient and Italian physician Antonio Benivieni used her life to her family’s welfare and now still empathize with that individual postmortem dissection and examination fi nds herself in a battle for her life. and his or her family. We have to to determine cause of death. By 1761, When you see the slide of the misshapen do the tough job of communicating Giovanni Morgagni published a work red blood cells indicative of sickle cell pathological fi ndings, confi rming the that described more than 600 autopsies. anemia, you do not see the family that patient’s understanding and comforting Though normal anatomy had been has had to deal with lifelong infection the person who is our patient. well-established by this time, Morgangi’s precautions and medication regimens. Pathology is not a procedure; work was groundbreaking because he Pathology takes something so it is a tool. A tool we have to keep organized his fi ndings to correlate patient intimate as personal suffering and sharp and up to date in order to help symptoms or clinical fi ndings with renders it a slide or statistic. us take care of our patients. ■

SEPTEMBER 2016 533 Letters CDA JOURNAL, VOL 44, Nº9

More on Laser Treatment of

Regarding the laser study published in MVP-7, with a variable pulse duration the May 2016 issue of the Journal related that is designed specifi cally to accomplish to the possible roles of laser technology all the steps of the LANAP protocol for in treating periodontal disease, we the treatment of periodontal disease. respectfully offer these observations: The LANAP protocol is a multistep, First, while the authors rightfully minimally invasive surgical treatment acknowledge the growing trend that combines the use of this digitally among clinicians in the use of — and pulsed PerioLase MVP-7 Nd:YAG laser realization of benefi ts from — diode, with conventional instrumentation Er:YAG and Er,Cr:YSGG lasers, the to achieve an unprecedented level of researchers neglected to mention the success in treating moderate to severe pulsed Nd:YAG laser, the laser type periodontal disease, even in cases deemed with the longest history of clinical use hopeless by conventional standards. in treating periodontal disease.1-2 Not only is this laser-based protocol the Concerning periodontitis therapy, only one to have two human histological the tissue-conserving characteristics studies attesting to its clinical safety of the 1064-nm Nd:YAG laser and effi cacy, it is the only one to have wavelength, its bactericidal and anti- demonstrated periodontal regeneration of fi rst line of management.” They further infl ammatory capabilities, and its apparent all the critical periodontal tissues — the stated, “This technique is intriguing in photobiostimulative and growth factor ultimate proof of fi broblast proliferation on that it is another approach to minimally upregulating capacities all may be seen and around the root surface. Signifi cantly, invasive surgical therapies … A minimally to contribute to successful treatment and the LANAP protocol histological invasive surgical approach may offer management of periodontal disease. studies revealed new , new advantages in regeneration of defects With respect to fi broblast attachment periodontal ligament and new alveolar in the esthetic zone in which minimal to the root surface, Negi et al.3 noted in bone, even in teeth presenting with loss soft tissue change is required.”6 their in vitro study that root surfaces of of attachment within furcations.4-5 In conclusion, the substantial periodontally diseased teeth treated with Earlier this year, based on the human scientifi c and clinical evidence base for pulsed Nd:YAG laser irradiation followed histological evidence, the U.S. Food the LANAP laser-assisted periodontal by scaling with ultrasonic instruments and Drug Administration cleared the treatment that already exists in support of and root planing with hand curettes PerioLase MVP-7 for “periodontal successful clinical outcomes for periodontal showed the highest number of fi broblasts regeneration — true regeneration of the patients should not be overlooked. — statistically signifi cantly greater than attachment apparatus (new cementum, those surfaces treated with scaling and root new periodontal ligament and new alveolar DAWN M . GREGG, DDS planing only — as a relative measure of bone) on a previously diseased root surface CEO and training director, biocompatibility of the treated surfaces. when used specifi cally in the LANAP The Institute for Advanced Laser Dentistry, Second, we wholeheartedly agree with Protocol” (510(k) K151763), affi rming and vice president of operations, the authors’ contention that stated, “Laser the positive fi ndings of the thousands of Millennium Dental Technologies Inc. protocol and confi guration can signifi cantly clinicians trained in the LANAP technique Cerritos, Calif. affect the clinical outcomes …” In our since it was developed two decades ago. JON B. SUZUKI, DDS, PHD, MBA experience, scrupulous adherence to In the 2014 American Academy Professor of microbiology and immunology, one such well-defi ned laser protocol of Periodontology’s Regeneration School of Medicine, and professor of “guarantees” (to use a word chosen by the Workshop, participants acknowledged periodontology and oral implantology, authors) successful clinical outcomes. that the published histological evidence School of Dentistry, Temple University Specifi cally, the laser-assisted new provided proof of principle that the Philadelphia attachment procedure (LANAP) protocol LANAP protocol can induce periodontal REFERENCES 1. Neill ME, Mellonig JT. Clinical effi cacy of the Nd:YAG laser for capitalizes on the unique capabilities of regeneration and that “this approach may combination periodontitis therapy. Pract Periodontics Aesthet Dent one particular Nd:YAG laser, the PerioLase be appropriate for multiple defects as a 1997;9(6 Suppl):1–5.

534 SEPTEMBER 2016 CDA JOURNAL, VOL 44, Nº9

2. Harris DM, Gregg RH 2nd, McCarthy DK, et al. Laser-assisted treated 12 teeth that were predetermined In conclusion, the authors cannot new attachment procedure in private practice. Gen Dent to be surgically extracted and consented support or oppose potential clinical use 2004;52(5):396–403. 3. Negi S, Krishnamurthy M, Ganji KK, et al. Modulatory to treatment with full-mouth LANAP of Nd:YAG or diode laser based on the eff ects by neodymium-doped yttrium aluminum garnet laser on therapy. After nine months of healing, en previously published study, but strongly fi broblast attachment to single rooted tooth surfaces following bloc biopsy extractions were provided. Ten suggest that well-designed randomized ultrasonic scaling and root planning: An in vitro study. J Indian Soc Periodontol 2015;19(1):25–31. out of 12 teeth were analyzed histologically clinical trials with a large number of 4. Yukna RA, Carr RL, Evans GH. Histologic evaluation of an to assess the periodontal wound healing. patients be conducted to spotlight the Nd:YAG laser-assisted new attachment procedure in humans. Int J Five teeth evidenced a degree of periodontal exact clinical benefi ts of such protocol. Periodontics Restorative Dent 2007;27(6):577–587. 5. Nevins ML, Camelo M, Schupbach P, et al. Human clinical and regeneration with new cementum, SAJJAD ASHNAGAR, DDS histologic evidence of laser-assisted new attachment procedure. Int periodontal ligament and alveolar bone. J Periodontics Restorative Dent 2012;32(5):497–507. One tooth had new attachment with Ann Arbor, Mich. 6. Kao RT, Nares S, Reynolds MA. Periodontal regeneration — intrabony defects: A systematic review from the AAP Regeneration new cementum and inserting collagen REZA AMID, DDS, MSC Workshop. J Periodontol 2015;86(2 Suppl):S77–S104. fi bers, and four teeth healed via a long Tehran, Iran junctional epithelium. Negi et al.3 provided REFERENCES 1. Yukna RA, Carr RL, Evans GH. Histologic evaluation of an Nd: The Authors Respond the only in vitro study in the fi eld of root YAG laser-assisted new attachment procedure in humans. Int J With regard to the letter to the conditioning with Nd:YAG laser. Although Periodontics Restorative Dent 2007;27(6):577. editor from Dawn M. Gregg, DDS, they reported signifi cant improvement 2. Nevins ML, Camelo M, Schupbach P, Kim S-W, Kim DM, Nevins M. Human clinical and histologic evaluation of laser-assisted and Jon B. Suzuki, DDS, PhD, MBA, in cell attachment after laser irradiation new attachment procedure. Int J Periodontics Restorative Dent we would like to respond as follows: compared to the control group, they used an 2012;32(5). We would like to emphasize that our ultrasonic device after laser conditioning. 3. Negi S, Krishnamurthy M, Ganji KK, Pendor S. Modulatory eff ects by neodymium-doped yttrium aluminum garnet laser on study focused on the effect of Er,Cr:YSGG Therefore, it is not clear that the improved fi broblast attachment to single rooted tooth surfaces following with suggested irradiation protocol of 120 result comes from laser irradiation and/ ultrasonic scaling and root planning: An in vitro study. J Indian Soc and 160 mj. The laboratory results ascribed or ultrasonic scaling. Low number of cases Periodontol 2015;19(1):25. 4. K151763. www.accessdata.fda.gov/cdrh_docs/pdf15/ to the effect of that specifi c laser wavelength is one of main challenges they all face. K151763.pdf. Accessed June 30, 2016. (Er,Cr:YSGG 2.78 μm) on fi broblasts. Other There seems to be a misunderstanding 5. 510(k) Clearances, US Food and Drug Administration. www.fda. protocols, lasers or products are defi nitely regarding FDA approval versus FDA gov/MedicalDevices/ProductsandMedicalProcedures/DeviceAppr ovalsandClearances/510kClearances. Accessed June 30, 2016. not discussed in this paper and cannot be clearance. Briefl y, FDA approval is 6. Cobb CM. Is There Clinical Benefi t From Using a Diode or supported or opposed based on our data. given through the premarket approval Nd: YAG Laser in the Treatment of Periodontitis? J Periodontol Regarding Drs. Gregg and Suzuki’s fi rst application (PMA) process. Using the 2016(0):1–18. point that we neglected to mention the 510(k) process (Section 510(k) of the Nd:YAG laser, we would like to refer to Food, Drug and Cosmetic Act), dental The Journal welcomes letters the introduction of the published paper lasers including PerioLase Nd:YAG pulsed We reserve the right to edit all that clearly mentions Nd:YAG as one type dental laser system4 are substantially communications. Letters should discuss an item of laser that “clearly exemplifi es the deep equivalent to other legally marketed published in the Journal within the last two focus of both researchers and clinicians dental lasers with the same application months or matters of general interest to our on the utilization of lasers in dentistry.” and technology.5 This process does readership. Letters must be no more than 500 Referring to the cited literature by Drs. not require any published clinical trial words and cite no more than fi ve references. Gregg and Suzuki, we realized the necessity or study, but safety-of-use data.6 The No illustrations will be accepted. Letters of cautious analysis. Yukna et al.,1 in a FDA clearance means that the laser is should be submitted at editorialmanager.com/ case series study on only six pairs of teeth, “cleared” for sale on the open market, jcaldentassoc. By sending the letter, the author reported that LANAP-treated specimens based on safety and nothing more. certifi es that neither the letter nor one with showed new cementum and new connective Recent systematic review of the substantially similar content under the writer’s tissue attachment in and occasionally literature6 reveals little evidence on the authorship has been published or is being coronal to the notch, whereas fi ve of the added clinical value of using diode or considered for publication elsewhere, and the six control teeth had a long junctional Nd:YAG laser, either as a solo therapy author acknowledges and agrees that the letter epithelium with no evidence of new or as an adjunct, over SRP and/or and all rights with regard to the letter become attachment or regeneration. Nevins et al.2 conventional surgical treatment. the property of CDA.

SEPTEMBER 2016 535 You are the protector of the smile. You enable people to laugh without shame, eat their favorite foods and experience the dignity of aging with grace. That’s why this association tirelessly advocates for the profession and stands up for those in need of care. Because the world is a better place when people are smiling, and that’s thanks to you.

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® Impressions CDA JOURNAL, VOL 44, Nº9

Informed Consent

David W. Chambers, EdM, MBA, PhD Informed consent now comes in three fl avors: legal, ethical and moral. For many, informed consent means getting signatures on documents no one reads but everyone understands are meant to protect the service provider. This is legal CYA, strongly endorsed by the insurance industry and sometimes nimbly stepped around by the legal profession. Staff has been delegated to “get” consent, and computers have made this as easy as a click here and a click there. As patients are assumed to be identical, one form fi ts all. When I last had oral surgery, I was placed in front of a computer, everyone left the room and I emerged 20 minutes later with a list of questions that troubled the staff. Chief among my concerns was the phrase “patients may use various functions of the clinic . . .” The problem was that the word “use,” although it had the right letters, had been jumbled in an unfortunate manner. The ethical approach to informed consent is grounded in the principle of individual self- determination. Patients should be allowed to freely choose The nub: what happens to their bodies, time and wallets. The problem is that there is a wide discrepancy between what dentists 1. Because people want to know and patients know about biology and dental procedures. what will happen to them, they So the patient has to be “informed.” There is equally a demand more pieces of paper: gap between what dentists and patients know about what patients fear and value. So the dentist has to be informed. because CYA does not satisfy this The usual standard is the “reasonable person.” Ultimately, need, more paper will be needed those who stand in for a reasonable person are 12 lay in the future. individuals guided by attorneys. The research evidence is overwhelming that patients can accurately recall only a 2. Ethical informed consent is for fraction of what they have been told, even a short time standardized, “reasonable” patients later. There is also good evidence that practitioners “steer” patients toward treatments the practitioner prefers by following theoretical principles. selective emphasis or omission of information. There 3. Moral informed consent takes has been little attention paid to whether patients are providing all the information needed for safe treatment. place between two individuals The moral approach to informed consent is built on mutually satisfi ed that additional mutual commitments. A person consents to an informed information is unlikely to change decision when no reasonable new information is likely to change the decision. A dentist is about to start an extensive the course of action they have reconstruction case. Is there anything the patient might say decided on. that would change the treatment plan or the approach? “I am hypertensive and hemophiliac.” “I have left my last three dentists after two appointments each.” “I have no money.” The same calculus is appropriate for the patients. “You should David W. Chambers, EdM, MBA, PhD, is professor of dental education at the University of the Pacifi c, Arthur know the success rate for this procedure is about 90 percent, A. Dugoni School of Dentistry, San Francisco, and editor but I have never done one myself.” “Yours is a very extreme of the Journal of the American College of Dentists. case of this condition.” ■

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CDA JOURNAL, VOL 44, Nº9

Making a Titanium Surface Biologically Active Titanium is utilized in artifi cial joints and dental implants, but it isn’t known for its benefi cial attributes biologically. Scientists at RIKEN may have found a way to make titanium more benefi cial, however. Mussels, which can attach to metallic surfaces, have helped provide insight into connecting a biologically active molecule to a titanium surface. Mussels have the ability to attach to these surfaces because of the protein L-DOPA. Researchers created a hybrid protein featuring the piece of L-DOPA that creates growth. The tests resulted in evidence of L-DOPA folding and functioning properly, as well as binding to the titanium surface. Study Aims to Reduce Pain for Chen Zhang is with the RIKEN Nano Medical Engineering Laboratory, and Patients was the fi rst author of the paper published in Angewandte Chemie. “We thought it would be interesting to try to use various techniques to Oral cancer can be one of the most attach a biologically active protein — in our case we chose insulin-like growth painful types of cancer for people to live with. factor-1, a promoter of cell proliferation — to a titanium surface like those Two dentists have been awarded a three- used in implants,” Zhang said. year, $1.2 million grant to test whether a Yoshihiro Ito is the team leader of the Emergent Bioengineering Research nonviral gene delivery method can treat pain from oral cancer effectively and safely. The Team of the RIKEN Center for Emergent Matter Science. grant money has been awarded to Brian L. “We are very excited by this fi nding, because the modifi cation process is Schmidt, DDS, MD, PhD, professor in the a universal one that could be used with other proteins. It could allow us to department of oral and maxillofacial surgery prepare new cell-growth enhancing materials, with potential applications in at New York University College of Dentistry cell culture systems and regenerative medicine,” Ito said. “And it is particularly (NYU Dentistry) and director of NYU’s interesting that this is an example of biomimetics, where nature can teach us Bluestone Center for Clinical Research new ways to do things. The mussel has and of the NYU Oral Cancer Center, and given us insights that could be used to Seiichi Yamano, DDS, PhD, DMD, MMSc, allow us to live healthier lives.” associate professor in the department of prosthodontics at NYU Dentistry. Schematic showing the composition and Mussel “The clinical challenge of treating structure of the mussel. Byssal oral cancer pain is then compounded thread by the off-target effects produced by Adhesive plaque pharmacological agents, which lack anatomical specifi city,” Schmidt said. “Since high opioid doses generate unwanted side effects that create additional cells,” Yamano said. “Transfection effi ciency “I found that delivery of the OPRM1 unintended suffering for the patient.” using the nonviral vector in oral cancer gene into the cancer reversed cancer pain. Yamano has created two “nonviral cells showed eightfold more gene transfer I just needed a safe method to deliver hybrid vectors: a cell-permeable peptide than normal cells and higher expression the gene. Dr. Yamano’s nonviral method (CPP) combined with either a cationic lipid than that for an adenoviral vector.” is ideal. Our previously awarded bridge (CPP/lipid) or a cationic polymer (CPP/ Yamano and Schmidt have been working funding allowed us to develop preliminary polymer).” The vectors are effi cient when on this for the last fi ve years. Schmidt has data for the application. Our long-term goal it comes to transfection and have a little already proved that OPRM1 (the gene is to develop an effective and safe treatment cytotoxicity in different types of cancer cells. for the μ-opioid receptor) is “methylated for oral cancer pain. These studies are a “In addition to their transfection and down regulated in oral cancer tumors” signifi cant step toward that goal. We foresee effi ciency, my nonviral vectors preferentially and that OPRM1 re-expression after viral clinicians directly inoculating our nonviral transfect oral cancer cells compared to normal gene transduction lowered cancer pain. vector into oral cancers,” Schmidt said.

538 SEPTEMBER 2016 CDA JOURNAL, VOL 44, Nº9

Study Links Vaping to Use in Teens A new USC study has found Jessica Barrington-Trimis is the vaping among teens to be a lead author and a postdoctoral scholar possible gateway to other tobacco research associate in the department products. The study, published in of preventive medicine at the Keck the journal Pediatrics, shows that School of Medicine of USC. vaping isn’t just a replacement for “If teenagers who vape are using cigarettes, as widely suggested. e-cigarettes instead of cigarettes, we E-cigarettes work by heating up would have expected to see the decline liquid nicotine, the neurotoxin derived in smoking rates continue through from tobacco that is as addictive as 2014,” Barrington-Trimis said in a cocaine, producing a vapor that users USC press release. “But what we’ve decrease in cigarette smoking rates in inhale. For the study, researchers seen is a downward trend in cigarette 2014. The combined e-cigarette and followed fi ve groups of high schoolers. use from 1995 to 2004 but no further cigarette use in 2014 far exceeded what we would have expected if teens were simply substituting cigarettes with e-cigarettes. The data suggest that at least some of the teens who are vaping Cost Estimates Show Bleak Outlook for Teaching would not have smoked cigarettes.” According to the press release Health Center Program about the study, in 2011, around 1.5 The estimated cost to train a resident at a Teaching Health Center is now percent of high schoolers had vaped $157,602 per year, according to a new study titled “The Cost of Residency in the past 30 days. Four years later, Training in Teaching Health Centers.” Created in 2010, the Teaching Health that number jumped to 16 percent. Center Graduate Medical Education program was a fi ve-year initiative created E-cigarettes are sometimes touted as by the Aff ordable Care Act to increase the number of primary care residents and the healthy alternative to traditional dentists trained in community-based settings. The program has brought health care cigarettes, but some reports have cited negative effects to the vapors. services to people who are geographically isolated, economically or medically E-cigarettes carry a variety of health vulnerable. Teaching Health Centers are located in a variety of settings, including risks for users and those around urban, rural and tribal communities, and serve populations such as veterans and them. E-cigarette aerosol contains their families, minority communities, older adults, children and adolescents. formaldehyde and lead, as well as at In 2015, the program was extended by two years at nearly a 40 percent budget least 10 toxic chemicals on California’s reduction leaving programs running at $95,000 per resident (it was $150,000 at Proposition 65 list of chemicals known one point). This gap in funding has left the program reeling and “Many programs that to cause cancer and birth defects. are withstanding the loss have agreed they cannot continue with the reduced funding “Because e-cigarettes are perceived level in perpetuity, but are hopeful that this as less harmful and less dangerous report illustrates the true cost of producing the than combustible cigarettes, another next generation of primary care physicians,” concern is that teens may be introduced according to a press release. to nicotine use via e-cigarettes,” Barrington-Trimis said. “In California, The study, published in the New England where smoking rates are among the Journal of Medicine, was released a year lowest in the country, the increase in before the September 2017 date when vaping, possibly followed by increases the program extension is set to end. in smoking, could erode the progress that has been made over the last several decades in tobacco control.”

SEPTEMBER 2016 539

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CDA JOURNAL, VOL 44, Nº9

Extrafamilial, Interfamilial Transmission of S. mutans Research presented at the ASM Microbe research meeting provides compelling evidence that children acquire mutans from intra- and extrafamilial sources besides their mother. Children typically have more than one strain (i.e., genotype) of S. mutans and most share at least one strain with their mother or a family member. However, 72 percent of children in this study had one or more S. mutans strains not found in participating household family members indicating these strains likely came from outside the home (extrafamilial transmission), possibly from other children in the population. “While the prevailing theory on S. mutans transmission suggests mother- to-child transmission as the primary route of infection, in this study 40 percent of children shared no strains with their mothers,” said Stephanie Momeni, a doctoral candidate in the department of biology at the Drinking Sugary Sports Drinks University of Alabama at Birmingham, in a news release. Interestingly, 22.8 a Social Activity for Teens percent shared 37 strains only with another child in the household (siblings or cousins), demonstrating another dimension to interfamilial transmission. Drinking sugary sports drinks may be a social thing for teenagers. “While the data support that S. mutans is often acquired through mother- According to a Cardiff University to-child interactions, the current study illuminates the importance of child-to- study published in the British Dental child acquisition of S. mutans strains and the need to consider these routes Journal, half of the 12- to-14-year-olds of transmission in dental caries risk assessments, prevention and treatment surveyed said they consume these strategies,” said Momeni. drinks for social reasons. What’s more Further analysis with an alternate bacterial typing method is needed staggering is that 89 percent of school to confi rm these fi ndings and it is important children consume these drinks and to note that not all household family 68 percent drink them one to seven members chose to participate in the study. times per week. The study included 160 children in four schools in South Wales. Aside from the social aspect Image of S. mutans colony morphology. of the drinks, kids like the taste, low price and availability of the drinks. Maria Morgan is a senior lecturer in dental public health at Cardiff University. According to the California Center and rinse away food particles that “The purpose of sports drinks for Public Health Advocacy, the would otherwise remain in the are being misunderstood and this average American consumes 50 gallons mouth and promote bacterial growth study clearly shows evidence of high of soda and other sweetened beverages that causes . CDA also school age children being attracted each year. What’s more, according to suggests loading up on fruits and to these high sugar and low pH level 2005-07 and 2011-12 California Health vegetables as these foods promote drinks, leading to an increased risk Interview Surveys, 32 percent of 6- to- fl ow, helping to neutralize of dental cavities, enamel erosion 11-year-olds drink a sugar-sweetened acids that attack . and obesity,” Morgan said. “Dental beverage each day, and that increases Most important, protect teeth health professionals should be aware to 65 percent of the 12- to 17-year-olds. throughout the year by brushing of the popularity of sports drinks Dentists can remind their patients for two minutes, twice a day with a with children when giving health to stay away from sugar-laden sodas fl uoride , fl ossing regularly education or advice or designing and drink plenty of water, especially and visiting a dentist for a complete health promotion initiatives.” after meals, to keep hydrated dental checkup on a regular basis.

542 SEPTEMBER 2016 CDA JOURNAL, VOL 44, Nº9

ADA President Calls on Dentists to Help Curb Opioid Abuse ADA President Carol Summerhays, This comes on the heels of a recent DDS, has called on dentists across the study published in The Journal of country to take steps to help prevent the the American Dental Association that widespread abuse of opioid pain medications. found “A notable minority of dental “Patients have a responsibility to use patients had incidents of multiple opioid painkillers only as prescribed and preexisting opioid prescriptions, a to keep their unused medications from factor implicated in patient misuse, getting into the wrong hands. We can abuse, overdose and diversion.” empower them by being more judicious Researchers reviewed South Carolina combination products were in our prescribing when less aggressive prescription drug monitoring dispensed in the 2013-14 fi scal year, treatments are indicated. We can also program data representing dispensed according to the state’s Controlled make sure patients leave our offi ces medication for patients prescribed at Substance Utilization Review and knowing about their abuse potential least one opioid by a dentist during Evaluation System (CURES). and how to safely secure, monitor and a two-year time frame (2012-2013). In her letter, Summerhays laid discard them at home,” Summerhays In California, more than 1 out several steps dentists can take said in a letter published by ADA News. billion dosage units of hydrocodone to help prevent opioid abuse: ■ Register for the next ADA Continuing Education Recognition Program webinar on model opioid prescribing in the context of New Reliever of Jaw Pain Discovered modern drug-seeking behavior. A new fi nding in the treatment of pain could lead to better ways to treat ■ Use your state’s prescription jaw pain, as well as skin irritation, headaches and abdominal pain. A study drug monitoring program. completed by Duke University has discovered a small-molecule drug known ■ Review the “ADA Practical as 16-8 blocked TRPV1. TRPV1 has been researched for pain and itching. The Guide to Substance Use researchers discovered that 16-8 decreased pain in animals, including pancreas Disorders and Safe Prescribing.” infl ammation. Study co-author Rodger Liddle, MD, is with the Duke University ■ Visit the ADA Center for School of Medicine and a member of the Duke Institute for Brain Sciences. Professional Success to review ADA resources and previous Liddle said, “So-called pancreatitis is extremely painful and diffi cult to treat, webinars on opioid prescribing and new cases are on the rise globally,” in a press release. and abuse prevention topics. “As a physician, I soon realized the enormous potential that these ■ Tell your patients to visit compounds might have, given how benefi cial dual-target molecules can be in MouthHealthy.org/meds, where clinical medicine,” said Wolfgang Liedtke, MD, PhD, a professor of , they can learn about the dangers anesthesiology and neurobiology at Duke University School of Medicine. of using opioid pain medications Chronic pain is a problem for more than 100 million people in the for nonmedical purposes. U.S., according to the Institute of Medicine. ■ Urge your patients, especially The study, which was published in Scientifi c Reports, is intended to be the parents, to sign the Medicine “fi rst chapter” of a story that helps develop Abuse Project pledge to safeguard compounds for clinical use in humans or animals, their medicines and talk with their according to the researchers. One of the next families about medicine abuse. ■ Participate in (or possibly steps will be to examine the topical applications host) a National Recovery to mucous membranes in the body and skin. Month event in September. CDA also has a “Controlled Substances Prescribing and Dispensing” resource available on cda.org.

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Saliva May Have Disease-Detecting ‘Fingerprints’ Saliva may have the “fi ngerprints” to test for disease. A recent study, published in ACS’ Journal of Proteome Research, may help off er an Nanoparticles Help Break alternative to the use of needles or other invasive measures that can cause Up Plaque, Prevent Cavities apprehension in patients. The study looked at saliva as a disease-detecting agent. Saliva contains a mixture of analytes that could create a “characteristic The that live in dental plaque individual signature.” Metabolic aspects of urine can change when there is and contribute to tooth decay often resist a health issue, but diet and environment can play a factor. The researchers traditional antimicrobial treatment, as state that saliva may not be as aff ected by diet and environment, however. they can “hide” within a sticky biofi lm The study took place over 10 days and included 23 healthy people. In those matrix, a glue-like polymer scaffold. people, their saliva changed less than urine did as a result of dietary changes. University of Pennsylvania researchers recently discovered a new strategy that “Although longer-term research would be needed, this initial work on takes advantage of the pH-sensitive and saliva fi ngerprints suggests that they could be useful in searching for signs enzyme-like properties of iron-containing of disease,” the researchers stated in a press release. nanoparticles to catalyze the activity Around six saliva samples were collected each day from each of the of hydrogen peroxide, according to a participants for 10 consecutive days — seven days in a “real-life” situation news release. The activated hydrogen and three days under a standardized diet. (A physical exercise program peroxide produced free radicals that took place at day 10.) were able to simultaneously degrade The study did fi nd that the individual phenotype in saliva is slightly weaker the biofi lm matrix and kill the bacteria than that in urine. Researchers from within, signifi cantly reducing plaque and the Medical University of Graz, FiorGen preventing tooth decay in an animal model. Foundation, University of Florence, FH “Even using a very low concentration Joanneum University of Applied Sciences of hydrogen peroxide, the process was incredibly effective at disrupting and Karl-Franzens-University participated the biofi lm,” said Hyun (Michel) in the study. Koo, senior author of the study, in the news release. “Adding nanoparticles increased the effi ciency of bacterial killing more than fi ve-thousandfold.” Beginning with in vitro studies, than 99.9 percent of the S. mutans in just as humans do. Twice-a-day, one- which involved growing a biofi lm the biofi lm within fi ve minutes. The minute treatments for three weeks containing the cavity-causing bacteria researchers also showed that the signifi cantly reduced the onset and Streptococcus mutans on a tooth-enamel- treatment regimen, involving a 30-second severity of carious lesions compared to like surface and then exposing it to topical treatment of the nanoparticles the control or treatment with hydrogen sugar, the researchers confi rmed that followed by a 30-second treatment with peroxide alone. The researchers nanoparticles adhered to biofi lm, were hydrogen peroxide, could break down the observed no adverse effects on the gum retained even after treatment stopped biofi lm matrix components, essentially or oral soft tissues from the treatment. and could effectively catalyze hydrogen removing the protective sticky scaffold. “It’s very promising,” said Koo. peroxide in acidic conditions. Moving to an animal model, the “The effi cacy and toxicity need to They also showed that the researchers applied the nanoparticles be validated in clinical studies, but nanoparticles’ reaction with a 1% or and hydrogen peroxide topically to the I think the potential is there.” less hydrogen peroxide solution was teeth of rats, which can develop tooth For more, see the study in the journal remarkably effective — killing more decay when infected with S. mutans Biomaterials, vol. 101, pp. 272-284.

544 SEPTEMBER 2016 Abstracts CDA JOURNAL, VOL 44, Nº9

Winners of the 2016 Table Clinic Competition

The California Dental Association hosted the annual Table Clinic Competition May 12–14 during CDA Presents in Anaheim. Dental, dental hygiene and dental assistant students and military/residents from across the state are encouraged to enter each year. First-place winners from the contests were invited to submit abstracts of their work, which appear in this section. CDA continues to collaborate with the California Dental Hygienists’ Association for the RDH portion of the competition.

SCIENTIFIC DENTAL STUDENT WINNER

Drew Roberts (middle) Purpose: We hypothesized that the and Weston Grimes MSC niche identifi ed in the incisor (not pictured) were would also express H3K27me3, and the the winners in the bivalent domain of H3K4. Furthermore, scientifi c dental student we hypothesized that the enzymatic category. The award process of methylating H3K27me3 was presented by Drs. governed by EZH2 would provide an Ken Wallis (left) and Gary Ackerman (right). “on-or-off” switch type mechanism for expressing specifi c stem cell DNA that leads to MSC differentiation into tooth mesenchyme. The H3K4 and H3K27 chromatin “switch” will be identifi able around this niche and demonstrate potential ways the NVB dictates MSC differentiation. Results: Our data show H3K27me3, H3K4 and EZH2 activity within the Bivalent Epigenetic Control of MSC niche near the NVB in the incisor. Mesenchymal Stem Cells in the Conclusion: Our data validate Mouse Incisor research establishing the cervical loop Drew Roberts and Weston Grimes, of the incisor as an MSC niche. We Herman Ostrow School of Dentistry of USC have shown that the epigenetic switch Background: Lineage tracing in a mouse pathway of stem cell differentiation incisor model identifi ed the neurovascular involving H3K27me3, EZH2 and H3K4 bundle (NVB) as a mesenchymal stem as a potential bivalent domain repressor, cell (MSC) niche. EZH2 affects regulatory is active within the stem cell niche.

genes involved in an epigenetic switch, THE CORRESPONDING AUTHOR, Weston Grimes, can be centered on H3K27me3. reached at [email protected].

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CLINICAL DENTAL STUDENT WINNER

Dentoskeletal Eff ects of Micro-Implant- compared using pre- and posttreatment Assisted Rapid Palatal Expansion posteroanterior cephalograms. (MARPE) in Adolescents and Adults Results: MARPE therapy signifi cantly Eric Chen, University of California, increased skeletal parameters with Los Angeles, School of Dentistry no signifi cant changes in dental side Introduction: Skeletally anchored effects. Signifi cant increases in linear micro-implant-assisted rapid palatal measurements included the maxillary expansion (MARPE) has recently gained basal bone width, nasal fl oor width, traction as a nonsurgical therapy for intermolar distance and central incisor transverse maxillary defi ciency. This interapex distance. Signifi cant increases retrospective clinical study evaluates the in angular measurements included the dentoskeletal effects of a new MARPE inter-maxillary-wall, interalveolar, inter- design in adolescents (age range: 12–15) nasal-wall and interincisal angles. and adults (age range: 18–60). Conclusion: MARPE successfully Eric Chen (middle) was the winner in the Methods: Thirteen MARPE achieved maxillary expansion (6 mm clinical dental student category. He was patients were selected from a 35-patient average) with minimal dentoalveolar presented with his award by Drs. Ken Wallis database treated by a single practitioner side effects in adolescents and (left) and Gary Ackerman (right). based on the quality of comparable middle-aged adults alike.

records. Six linear and six angular THE AUTHOR, Eric Chen, can be reached at dental and skeletal measurements were [email protected].

COMMUNITY/EDUCATION DENTAL STUDENT WINNER

Cavitation Reduction Using Medicine (WUCDM) students, primary Quality Improvement Drivers and care, mental health and social workers Interprofessional Collaborative collaborate to ensure care is received by Practice in Underserved Communities the children in the community. Through Jessica Vergel de Dios, Western implementation of quality improvement University of Health Sciences drivers, such as three- or six-month Comprehensive health homes recalls based on caries risk assessment located within school-based and school- and reinforcement from on-campus linked settings effectively reduce health programs, 55.41 percent and 60.64 percent disparities within the community by of JSFC patients ages 0 to 17 returned improving access to health care. The with no new cavitations at the fi rst and Jeff Seymour Family Center (JSFC) was second recall appointments, respectively. established to provide holistic health This demonstrates an effective care to children and families living in El interprofessional collaborative practice Monte, Calif. Specifi cally, the JSFC dental model for providing quality oral care for Drs. Ken Wallis (left) and Gary Ackerman (right) congratulate the community/education dental clinic was established as a comprehensive children in underserved communities. student winner, Jessica Vergel de Dios (middle). oral clinic where Western University THE AUTHOR, Jessica Vergel de Dios, can be reached at of Health Sciences College of Dental [email protected].

546 SEPTEMBER 2016 CDA JOURNAL, VOL 44, Nº9

RDH INFORMATIONAL STUDENT WINNERS (CDA IN COLLABORATION WITH CDHA)

Angela-Sue Yeaton demonstrates that using yoga therapy and Simon Weber for the dental professional may show off their award- have a benefi cial impact on many winning display. areas of strain, especially that of musculoskeletal disorders commonly experienced in the dental fi eld. Methods: Literature and peer- reviewed journals for this study were obtained through the utilization of an online academic research library. Results: An overwhelming amount of dental professionals report an increase in job satisfaction, longevity and a decrease in work-related pain. Yoga Flow for the Dental Pro Conclusion: Yoga therapy can be Simon Weber and Angela-Sue Yeaton, incorporated into daily life, chairside Cerritos College and education for the dental professional Background: Yoga is an ancient to lay down the foundation of a yet emerging practice that is fi nding healthy body, mind and spirit.

its way into bettering our health, both THE CORRESPONDING AUTHOR, Simon Weber, can be physically and mentally. Research reached at [email protected].

RDH RESEARCH STUDENT WINNERS (CDA IN COLLABORATION WITH CDHA)

Jason Abellera (left) capacity and fl ow rate to determine if the and Remy Grace Ramos vapors are a risk factor for dental caries. (right) researched Methods: Saliva of 10 volunteer vaping and oral health. EC users was tested to observe changes in saliva quality before and after stimulation by EC vapors. Results: The pH of the participants’ saliva was signifi cantly affected by the vapors from EC use (p=0.01). Participants’ resting fl ow rate was within normal range (mean = 0.45 ml/min) and stimulated saliva was below normal range (mean = 0.44 ml/ min). Buffering capacity showed little to no improvement after EC use. Vaping and Oral Health Conclusion: Electronic cigarettes Jason Abellera and Remy Grace Ramos, have a signifi cant effect on saliva pH, Cerritos College buffering capacity and fl ow rate. However, Background: One of the most common further studies may be necessary to reported side effects of electronic cigarette determine whether or not these effects (EC) use is dryness of the mouth. pose as a risk for caries development.

Purpose: To observe the effects that THE CORRESPONDING AUTHOR, Jason Abellera, can be EC vapors have on saliva pH, buffering reached at [email protected].

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RDA STUDENT WINNERS

Jemma Lipperd and does not receive adequate stimulation the Christina Seto were body registers the bone as unnecessary, the winners in the RDA therefore it begins to resorb. In cases of student category.They disease, the infection of the tissue begins were presented their to cause the level of bone to dissipate. If award by Drs. Ken Wallis (left) and Gary treatment for bone loss is not sought, the Ackerman (right). condition will worsen. It is important to have a healthy level of bone in order to maintain proper stability and function in the oral cavity. In this project, we examined the various surgical, nonsurgical, biological and regenerative treatments for correcting bone loss. With our focus placed on autografting, allografting and xenografting, we explored the Bone Loss in the Oral Cavity procedures for repairing bone to normal Jemma Lipperd and Christina functioning levels with an emphasis Seto, Citrus College on grafting for arch reconstruction and People experience bone loss in the implant placement for individual teeth oral cavity for several reasons including as well as full arch and partial dentures.

disease, , dentures, bridgework, THE CORRESPONDING AUTHOR, Jemma Lipperd, can be medications and drug habits. When bone reached at [email protected].

MILITARY/RESIDENT WINNER

Fighting Caries With a Silver Bullet greater than the disadvantage of color Capt. Eileen Welch, AEGD, Travis AFB change in the lesion. Introduction: Dental caries remains Conclusion: SDF proves to be a one of the most prevalent chronic therapeutic agent to add to our toolbox infections, even though it is largely that will change the way we treat certain preventable. An agent that arrests caries patient populations. It has applications by targeting the bacteria that are at for those at high caries risk, with access the nidus of the infection would be an to care issues, of young or uncooperative invaluable tool to the fi eld of dentistry. behavior or as holding care for caries Background: Silver is antibacterial that are very diffi cult to restore. by way of its interaction with DNA and Additionally, I foresee great uses for this sulfhydryl groups of proteins. Fluoride product in our armed forces. In the military, Drs. Ken Wallis (left) and Gary Ackerman (right) has garnered a proven name for caries our patients are special because they may be congratulate military/resident winner Capt. Eileen prevention and remineralization. The called upon to deploy at a moment’s notice. Welch, AEGD. combination of properties of fl uoride SDF can be an effective agent to arrest and silver in silver diamine fl uoride small caries and to prevent caries before or (SDF) enable it to arrest caries and during a deployment, where care may be protect against future caries. More limited or non-existent. Its easy application research is to come, but the results of process means it can be utilized in the SDF have been supported by many fi eld for dentinal sensitivity or developing studies to date. Even though SDF leaves lesions that cannot be treated immediately. arrested caries black in color, the lesion SDF has potential to become part of the can be removed and restored later or care we provide for those patients with noninvasively restored with glass ionomer duties that come before routine dental care.

cement. In some cases, the benefi ts of THE AUTHOR, Capt. Eileen Welch, can be reached at nonsurgical arrest of caries may be much [email protected].

548 SEPTEMBER 2016 CDA JOURNAL, VOL 44, Nº9

Thank you to the following judges for the annual Table Clinic Competition held May 12–14 at CDA Presents in Anaheim.

RDA Competition Patricia Alvarez, RDA Izabella Ambartsumyan, RDA Shari Becker, RDA Lina Bocanegra, RDA Maleah Brooks, RDA Benson Dimaranan, RDA Evangeline Enriquez, RDA Melrose Nabua, RDA Karen Schroeder, RDA Manolita Teh, RDA Tobi Trotta, RDA Georgie Vargas-Burket, RDA

RDH Competition Ramesh Gowda, DDS Howard Richmond, DDS David Rothman, DDS Arnold Valdez, DDS

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SEPTEMBER 2016 549 introduction

CDA JOURNAL, VOL 44, Nº9

Oral and Systemic Diseases You May Encounter Throughout Your Career

Joel M. Laudenbach, DMD

GUEST EDITOR

Joel M. Laudenbach, he practice of dentistry practicing oral health care provider, it DMD, is an assistant involves intense clinical is reasonable to anticipate examining professor of oral medicine patient care that is balanced patients who present with oral cavity and geriatric dentistry and the coordinator of the with rewarding patient and/or maxillofacial signs and/or Advanced Oral Diagnosis interactions — both personal symptoms that are true manifestations Workgroup at Western Tand professional. Clinical oral of underlying systemic disease(s). University of Health health care team members, including This issue of the Journal provides Sciences, College of Dental dentists, dental hygienists and dental four clinically relevant articles that Medicine in Pomona, Calif. Dr. Laudenbach is a assistants, are committed to helping highlight selected systemic diseases diplomate of the American all patients seeking oral and dental with oral signs and/or symptoms Board of Oral Medicine. examination, diagnosis and treatment. that oral health care providers may Confl ict of Interest Our patients seek out and follow up encounter throughout a dental career. Disclosure: None reported. with oral health care providers for In the fi rst article, Jeffrey A. Elo, various reasons, not the least of which DDS, et al. provide a focused review is to ensure screening, diagnosis and of three systemic diseases with oral treatment of oral and dental diseases. manifestations that an oral health In preparation for patient care and care provider will likely encounter licensure examinations, all oral health throughout the clinical practice care providers are taught extensively career. It quickly becomes clear from how to screen, recognize, diagnose reviewing this article that oral health and manage a vast array of oral and care providers have many clinical maxillofacial pathologies. Throughout signs and symptoms to assess that may the clinical dental career, oral raise suspicion for the presence of an health care providers will encounter underlying systemic disease. The three pathologies that are solely limited to diseases presented here — anemia, the oral cavity and/or the maxillofacial diabetes mellitus and HIV — have oral region, with no underlying relation manifestations that should be readily to systemic disease(s). As we consider recognized by oral health care providers the long-term clinical career of the and lead to a medical referral in an

SEPTEMBER 2016 551 introduction

effort to rule out undiagnosed and/ planus, mucous membrane pemphigoid update on various therapeutic options. or uncontrolled systemic disease(s). and pemphigus vulgaris. It is crucial for The last two articles are highly The second article in this issue patients with these diseases to have an focused on selected diseases that we focuses on a set of mucocutaneous early diagnosis in an effort to minimize/ feel oral health providers rarely, if ever, diseases that oral health care providers manage potential complications, may encounter throughout the clinical will less commonly encounter over disease progression and neoplastic dental career. It is critical that providers a clinical dental career, yet will still risks. Throughout the clinical dental be able to effectively recognize, likely confront the challenges of disease career, it is reasonable for an oral health synthesize and combine various oral recognition, differential diagnosis provider to be confronted occasionally clinical signs and symptoms, which formulation and appropriate referral/ with one or two of these diseases and help to generate a differential diagnosis management. Seena Patel, DMD, they need to be able to recognize, of commonly, infrequently and rarely MPH, et al. have reviewed selected oral diagnose and/or make appropriate encountered oral, maxillofacial and diseases that are potentially malignant referral(s). The authors also share lesion systemic diseases. The detailed articles and/or have signifi cant morbidity and/ management strategies for these less by Scott S. De Rossi, DMD, et al. and or possible mortality associated with the commonly encountered oral diseases Alan L. Felsenfeld, MA, DDS, et al. underlying systemic diseases — lichen so oral health care providers have an present rarely encountered systemic diseases with oral manifestations that would normally generate quite a discussion among our dental and medical colleagues. A review of these diseases, perhaps last seen in the Our archive is available 24/7. classroom and/or clinical educational setting, will help oral health clinicians Our extensive publication archive is online for your research. Access to refi ne medical and dental history every issue of the Journal from the past 17 years at cda.org/journal. taking skills, oral and maxillofacial pathology recognition skills, as well as the differential diagnosis formulation process. Our patients rely on us to have and continually refi ne these critical recognition and diagnostic skills. It is my hope that your review of these articles and diseases will help you to make better patient care decisions, especially when it comes to exploring the potential for underlying systemic disease(s) in your patients throughout your clinical oral health care career. ■ systemic diseases

CDA JOURNAL, VOL 44, Nº9

Common Oral Manifestations of Select Systemic Diseases: Anemia, Diabetes Mellitus and HIV

Sahar Mirfarsi, DDS; Eric T. Stoopler, DMD; Ho-Hyun (Brian) Sun, MS; and Jeff rey A. Elo, DDS, MS

ABSTRACT In this article, we discuss several common abnormal signs and symptoms that may be present in the oral cavity initially with or without any systemic symptoms at a typical dental practice. The purpose of this discussion is to increase clinical awareness for establishing differential diagnoses so that patients may obtain appropriate referrals for appropriate medical treatment.

AUTHORS

Sahar Mirfarsi, DDS, is a Eric T. Stoopler, DMD, education lectures; is paid Jeff rey A. Elo, DDS, MS, n 2015, the American Dental resident in the department is an associate professor for preparing educational is an associate professor Association Health Policy Institute of oral medicine at the of oral medicine and the material — Coursera; in the division of oral and published the Survey of Dental Practice. University of Pennsylvania, director of the postdoctoral payment received from maxillofacial surgery at School of Dental Medicine in oral medicine program at the WebMD for expert opinion; Western University of Health The report analyzed data from 2009 Philadelphia. University of Pennsylvania, and payment received Sciences College of Dental and stated there were approximately Confl ict of Interest Disclosure: School of Dental Medicine from Elsevier Inc. for book Medicine in Pomona, Calif. I3,640 patient visits per offi ce to None reported. in Philadelphia. He has a preparation. He is also an assistant general practitioners and an additional fellowship in Dental Surgery, professor in the department 4,599 patient visits to specialists. In The Royal College of Ho-Hyun (Brian) Sun, MS, of oral and maxillofacial Surgeons and a fellowship is a dental student at Western surgery at the Loma Linda consideration of the many thousands in Dental Surgery, The Royal University of Health Sciences University Medical Center in of patients seen in dental offi ces each College of Physicians and College of Dental Medicine Loma Linda, Calif. year, it is critical that oral health care Surgeons. in Pomona, Calif. Confl ict of Interest Disclosure: providers maintain current awareness, Confl ict of Interest Disclosure: Confl ict of Interest Disclosure: None reported. knowledge and vigilance toward Dr. Stoopler is a member None reported. of the executive committee recognizing any changes present in their and board of trustees for patients’ oral cavities and maxillofacial the American Academy regions. Though some of these changes of Oral Medicine; is a site are nonspecifi c in nature, many remain visitor consultant for the pathognomonic of their associated, and Commission on Dental 1 Accreditation; is paid for often undiagnosed, systemic diseases. expert testimony from legal Previous studies have demonstrated fi rms; has received payment initial or primary manifestations of many and honoraria for continuing systemic conditions in the oral cavity,

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MCV

Low Normal High and early recognition of these signs is an important fi rst step toward diagnosis Microcytic Normocytic Macrocytic and management of the systemic disease.2,3 Despite the comprehensive nature of dental school training, the RBC curriculum often does not allow for Low or normal full understanding of the variety of High systemic diseases, their relationships ■ Iron-defi ciency anemia ■ Hemolytic ■ B12 defi ciency with the orofacial region and the ■ Lead poisoning ■ Bone marrow disorders ■ Folic acid defi ciency attainment of skills necessary to make ■ Anemia of chronic ■ Hypersplenism ■ Liver disease the proper diagnoses.4 Clinicians must infl ammation ■ Acute blood loss ■ Hypothryroidism ■ Sideroblastic anemia ■ ■ develop the skills necessary to become Anemias of chronic disease Reticulocytosis profi cient in taking thorough medical histories and be able to appreciate oral fi ndings that may originate ■ Thalassemias (alpha and from a systemic disease process.4 beta thalassemias or There are multiple anatomic combination with other hemoglobin abnormalities) structures in the oral cavity that may be involved in systemic pathoses.3 For instance, the periodontium often demonstrates a strong association with FIGURE 1. Diagnostic fl owchart demonstrating the utility of the mean corpuscular volume (MCV) value in the the hematopoietic and endocrine complete blood count (CBC) for diagnostic and classifi cation of anemias. systems such that prolonged gingival swelling, bleeding and/or infl ammation could be a manifestation not only of These are conditions commonly FIGURE 1 illustrates the diagnostic localized periodontal disease, but also of encountered on a routine basis in our utility of the mean corpuscular volume hematological malignancies () university-based dental/surgery clinics (MCV) value in the CBC for diagnostic or diabetes mellitus.3-6 Patients infected and whose oral manifestations are readily and classifi cation of anemias. with HIV could also present with initial detectable by dental professionals. In the U.S., 5-11 percent of women or recurrent mucosal signs and symptoms and 1-4 percent of men are iron defi cient, despite effective medical care.7 Any Anemia of which 5 percent and 2 percent exhibit multitude of locations, including the oral According to the American Society symptoms of anemia, respectively.2,8 In mucosa, , gingiva and alveolar of Hematology, anemia is the most fact, the Centers for Disease Control bone, may exhibit unusual changes and common blood disorder and is caused and Prevention (CDC) attributed 4,894 should be investigated and monitored.2 by a decrease in the amount or quality deaths to anemia in 2013, accounting In this article, we discuss several of the hemoglobin in circulating blood.8 for approximately 1.5 deaths per 100,000 common abnormal signs and symptoms There are several causes and types of Americans.9 Anemia is associated with that may be present in the oral cavity anemia, and laboratory evaluation is several different oral presentations, such initially with or without any systemic essential for evaluation. A complete as mucosal , atrophic glossitis and symptoms at a typical dental practice. blood count (CBC) is often the fi rst , although pallor in the oral The purpose of this discussion is to diagnostic laboratory test performed for cavity may be diffi cult to appreciate in increase clinical awareness for establishing evaluation of hemoglobin, hematocrit all cases (FIGURE 2).2,3 However, if a differential diagnoses so that patients and red blood cell indices that will similar absence of color is also observed may obtain referrals for appropriate aid in diagnosis of specifi c anemias. A in nail beds and the conjunctiva, or medical treatment. In particular, three discussion on the pathophysiology and if the fi ngernails exhibit koilonychias conditions — anemia, diabetes mellitus classifi cation of anemias are beyond or spoon-like anatomy, then the and HIV — were selected for discussion. the scope of this manuscript. However, index of suspicion may be raised.8

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FIGURE 2. Pallor of the gingiva and oral mucosae in a patient with iron-defi ciency anemia. (Courtesy of Sahar Mirfarsi, DDS, Philadelphia.) FIGURE 3. Atrophic glossitis in a patient with FIGURE 4. Angular in a patient with vitamin pernicious anemia. (Courtesy of Eric T. Stoopler, DMD, B12 defi ciency. (Courtesy of Eric T. Stoopler, DMD, Philadelphia.) Philadelphia.)

Atrophic glossitis is a common condition that is also associated with heart disease, cancer and stroke. manifestation of anemia that may be vitamin B12 defi ciency.3 It typically presents In 2014, the American Diabetes readily detected by a dental professional. as dryness, erythematous cracking, pain Association (cdc.gov/diabetes/data/ It often manifests as a smooth tongue, and sores of the commissures of the and statistics/2014statisticsreport.html) the result of depapillation of the fi liform often co-presents with candidiasis caused reported 29.1 million Americans with and fungiform that may by C. albicans in particular (FIGURE 4).12 diabetes mellitus — 9.3 percent of the be accompanied by burning or painful Unlike magenta tongue, is U.S. population. The number of patients sensations (FIGURE 3).2,3,10 Atrophic nonspecifi c and should not be used alone as with diabetes is expected to increase by glossitis is a relatively nonspecifi c oral a defi nitive sign for diagnosis.2,3 In contrast, 1.4 million per year (cdc.gov/diabetes/ manifestation and may indicate a number accompanying , pdfs/data/2014-report-national-diabetes- of different types of anemia, including and koilonychias may be representative statistics-report-data-sources.pdf). iron defi ciency anemia (IDA), pernicious of Plummer-Vinson syndrome (PVS) DM is classifi ed into several types, anemia or other vitamin B complex and an iron-defi ciency etiology of including type 1, type 2, gestational, defi ciencies.3 Partial depapillation, with anemia, especially in postmenopausal genetic, infectious and those caused or without pain, could mimic benign women or women of Northern European by pancreatic injury, though it is migratory glossitis (BMG) or geographic descent.8,11,48 Dysphagia, in particular, is worth noting that even nondiabetic tongue, which is usually asymptomatic. likely caused by an or hyperglycemia could damage organs such It may be prudent to investigate abnormal bands in the esophagus that as the kidneys, eyes and blood vessels.15 patients with reported symptoms of causes esophageal stenosis.8,13 These Peripheral vascular damage, along with lingual neuropathy, pain and/or signs of epithelial protrusions are premalignant and hypertension, are particularly correlated erythematous areas to rule out conditions may undergo transformation to oral and with DM and contribute to kidney failure, such as .2,11 A dark red esophageal squamous cell carcinoma.11,13 ischemia and diabetic gangrene, as well and swollen tongue is consistent with Suspected cases of PVS must be followed as neuropathy.12,15 Neuropathy in DM is a descriptions of “magenta tongue” and is a closely to prevent the development of common manifestation of microvascular particularly strong indicator of inadequate oral-gastrointestinal malignancies.8 dysfunction.17 There are many systemic vitamin B12 intake.2 Because these signs and symptoms that are associated lingual presentations are rarely associated Diabetes Mellitus with undiagnosed DM and persistent with other premalignant diseases, The most common group of hyperglycemia, such as unusual excessive they may be correlated with other carbohydrate metabolic disorders hunger (polyphagia), thirst (polydipsia) reported symptoms, such as , characterized by hyperglycemia and diluted urination (polyuria).15 constipation, and fever, to aid in is diabetes mellitus (DM).11,14 Poorly controlled blood glucose in DM the detection of more complex illnesses, Hyperglycemia is an abnormal elevation type 1, in particular, will present with such as irritable bowel syndrome, that of blood glucose levels owing to a lack a variety of oral manifestations.11 often lead to pernicious anemia.11 of insulin production and/or tissue Chronic hyperglycemia also causes There are additional accompanying insensitivity to insulin.14-16 According delayed postsurgical wound healing, in signs that may allow the dentist to to the 2014 National Diabetes Statistics addition to many systemic defi ciencies.14,18 determine the exact etiology of anemia. Report, diabetes is the seventh leading Unfortunately, many patients are unaware Angular cheilitis is a readily visible oral cause of death, after conditions like of this fact until their fi rst surgical

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FIGURE 6. in a patient with diabetes mellitus. encounter, and any dental surgeries (Courtesy should be well-planned and potential of Sahar complications explained to patients in Mirfarsi, DDS, Philadelphia.) a detailed manner.18 Oral health care professionals must remain vigilant of any perioperative complications in patients at FIGURE 5. Poor oral health in a patient with risk for diabetes or those with extensive diabetes mellitus. (Courtesy of Alina Krivitsky Aalam, DDS, Los Angeles.) family histories of the disease. The patient’s own experiences with wound healing may be deemed insignifi cant and otherwise remain unreported.17 to periodontal bone loss. As a result, HIV Approximately one-third of diabetic attachment loss is more frequent and HIV is an RNA lentivirus patients complain of xerostomia or progresses at a much faster rate in patients (subclass of retroviruses) that can hyposalivation.17,19 While hyposalivation who present with poorly controlled cause infection and lead to the refers to objectively low amounts of DM.23,24,25 Conversely, periodontal disease development of AIDS.15 HIV targets unstimulated salivary fl ow and may could increase infl ammatory reactions T lymphocytes — specifically CD4 be measured, xerostomia indicates and contribute to an increase in the blood cells — and increases the chance a subjective sensation of dry mouth glucose level.26 Several studies have shown of opportunistic infections from and is commonly diagnosed according support for this notion by demonstrating , bacteria, protozoa and fungi to patient complaints.17,20 Diffuse, that regular dental prophylaxis and/or deep by weakening the immune system.30 nontender, bilateral and noninfl ammatory cleaning may help in decreasing the blood The CDC reports 1.2 million HIV- enlargement of the glands may be glucose levels of type 2 DM patients.3,27 positive individuals currently residing associated with salivary defi ciencies, While it is common for patients with DM in the U.S., including 12.8 percent though diabetic sialadenosis is most to lose both dentition and attachment, the of those who remain unaware of commonly exclusive to the parotid reciprocity of this relationship is subject their infection. This number is glands.19 Lack of saliva and its protective to further investigation, which may or augmented by approximately 50,000 factors have been associated with may not confi rm a signifi cant “cycle” of new HIV infection cases each year.12 the development of carious lesions bidirectional positive feedback between There are multiple orofacial and other microbial processes such periodontal disease and DM.3,17,25 manifestations associated with as .17 Because salivary Diabetic patients could also present HIV-infected patients. glucose levels are also elevated in with patient-reported symptoms such as Though seemingly random, ulceration persons with both uncontrolled and dorsum of the tongue papillae atrophy, is a common presentation. Establishing controlled diabetes, the risk of carious taste changes (dysgeusia) and burning an association with HIV is diffi cult lesions increases and notable decay mouth syndrome (glossodynia).3,11,17 because such lesions could be caused is often encountered in patients Glossodynia and dysgeusia could by an interaction of multiple factors, with this metabolic disorder.11,19,21 present as an uncomfortable pain, such as aphthous ulcers and herpetic Gingival tissue bleeding, infl ammation tingling or soreness of the mouth sores.1 Regardless, oral manifestations and periodontitis constitute another set without any organically identifi able may be signifi cant as the initial of interrelated oral manifestations in cause in poorly controlled cases.11,17 presentation of HIV infection in patients with DM (FIGURES 5 and 6).2,3,22 Patients could also present with undiagnosed patients or as an indication These symptoms are sometimes associated gingival , which contributes of failing highly active antiretroviral with recurrent aphthous ulcers as well.22 to plaque accumulation and risk of therapy (HAART) regimen,30 more Interestingly, DM and periodontitis often periodontal disease.28 Benign migratory recently recognized as combined demonstrate an extensive bidirectional glossitis (BMG) is commonly reported antiretroviral therapy (cART).30 relationship that is well-documented in in type 1 DM, although this reported Patients initiating treatment with the literature.14,17 Diabetes can reduce fi nding has not yet been investigated or viable cART often report decreased bone formation and predispose a patient confi rmed by any previous studies.11,29 oral manifestations of many lesions

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FIGURE 7. Necrotizing ulcerative (NUG) FIGURE 8. Pseudomembranous candidiasis in an HIV- FIGURE 9. Erythematous candidiasis in an HIV- in an HIV-positive patient. (Courtesy of Eric T. Stoopler, positive patient. (Courtesy of Shelley Miyasaki, DDS, positive patient. (Courtesy of Eric T. Stoopler, DMD, DMD, Philadelphia.) PhD, and Michael Jacobs, DDS, MS, San Francisco.) Philadelphia.)

including those from Kaposi’s sarcoma Despite their lifesaving effects, variant, in particular, may be mistaken (KS), oral hairy (OHL), cART medications may increase the for angular cheilitis but may be major aphthous ulcers, HIV-related presentations of several other oral HIV distinguished by a lack of cracking and periodontal disease such as linear symptoms. Features like oral and of the lip commissures.7,30 gingival erythema (LGE), necrotizing salivary gland defi ciencies have been This distinction is critical as it may ulcerative gingivitis (NUG) and noted for their predilection toward help differentiate between the initial necrotizing ulcerative periodontitis HIV patients specifi cally undergoing presentation of a viral disease as opposed (NUP).15,30 LGE is a form of gingivitis pharmacologic treatment.32,33 to a metabolic or nutritional disease. that is associated with HIV-infected Salivary gland defi ciencies have also HIV infection is rarely associated individuals. It is clinically described been reported in conjunction with with hyperplastic candidiasis, which as a well-defi ned erythematous band parotid swelling with or without tends to present more commonly in along the gingival tissue without xerostomia.7,45,46 cART medications tissues under constant contact with resolution even after removal of like zidovudine were themselves overlying prostheses or dentures.7 More usual causative local factors such as linked to brown, fl at pigmented recent reports indicate that oral ulcers calculus and plaque.7,44 Decreased lesions, though the pathologic nature in HIV patients may occasionally CD4 counts have demonstrated an of such lesions is questionable.7,47 In indicate other fungal infections, such inversely correlated relationship with turn, fungal and some opportunistic as histoplasmosis, cryptococcosis, oral manifestations of OHL, such infections like oropharyngeal candidiasis aspergillosis and even penicilliosis.7,41 as more prominent elongations of have exhibited indifference toward Secondary viral infections make the papillae.1,31 In contrast, minor HIV therapy and were shown to up the second group of opportunistic aphthous ulcers (less than 1 cm in mount equal rates of recurrence.30 infections in HIV-infected patients. diameter) may present even in those remains a Historically, AIDS studies have with a functioning population of CD4 particularly common infectious agent. demonstrated associations between cells, though major and nonspecifi c The pseudomembranous form, thrush, HIV and the different variants of the ulcers are more common in those is considered the most prevalent human herpesvirus (HHV) and human with notable immune suppression.30 infectious agent in HIV patients.7,34 papillomavirus (HPV) (FIGURE 10).30 Aphthous ulcers typically occur on In fact, several studies have indicated Epstein-Barr infections may occur nonkeratinized tissue away from the that fungal infection of the oropharynx during HIV-induced and keratinized gingiva.30 is the most common sign of disease in as well, with bilateral, painless, fl at or Similarly, NUG and NUP present in HIV-positive patients regardless of age, corrugated whitish patches (leukoplakia) low-CD4 patients as painful necrotic, race or gender.35-39 Pseudomembranous on the lateral tongue or buccal mucosa ulcerated and hemorrhagic gingival candidiasis manifests as a superfi cial (FIGURE 11).42,43 virus papillae (FIGURE 7).3 NUP, however, leukoplakic coating that is easily nonetheless remains the most prevalent differs from NUG in that patients removed (FIGURE 8). This remains in viral agent in HIV-positive patients develop rapid periodontal attachment contrast to erythematous candidiasis, and causes symptomatic ulceration loss and gingival swelling in addition which presents as an erythematous following vesicles. Fever and perioral skin to the aforementioned symptoms.3 patch (FIGURE 9).1 The erythematous involvement (vermillion borders of the

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FIGURE 10. Human papilloma virus (HPV) lesions FIGURE 11. Leukoplakia in an HIV-positive patient. FIGURE 12. Kaposi’s sarcoma in a patient with in an HIV-positive patient. (Courtesy of Eric T. Stoopler, (Courtesy of Shelley Miyasaki, DDS, PhD San AIDS. (Courtesy of Shelley Miyasaki, DDS, PhD San DMD, Philadelphia.) Francisco.) Francisco.)

) is also seen.42 Herpetic ulcerations 12).30 NHL presents as a supple and REFERENCES 1. Parks ET, Lancaster H. Oral manifestations of systemic involving the lips, gingiva, palate and fi rm swelling of reddish-pink coloration disease. Dermatol Clin 2003;21(1):171–82, viii. the dorsum of the tongue are typically that may or may not be accompanied 2. Urse GN. Systemic disease manifestations in the oral painless, but will take up to 10 to 14 days by ulceration and lymphadenopathy.30 cavity. Osteopathic Family Physician 2014;6(3):16–21. 30 3. Chi AC, Neville BW, Krayer JW, et al. Oral to heal. Infections by varicella-zoster More advanced stages of HIV infection manifestations of systemic disease. Am Fam Physician virus (VZV), a member of the herpesvirus are associated with additional symptoms 2010;82(11):1381–8. family, are also commonly seen in in both of the neoplasms as their 4. Lockhart PB, Hong CH, van Diermen DE. The influence 7 of systemic diseases on the diagnosis of oral diseases: immunocompromised patients. Vesicle- growths begin impinging on vital A problem-based approach. Dent Clin North Am 30 like lesions of VZV manifest specifi cally structures such as nerve bundles. 2011;55(1):15–28. along the trigeminal nerve dermatomes Bacterial infection is also among the 5. Gallipoli P, Leach M. Gingival infiltration in acute monoblastic leukaemia. Br Dent J 2007;203:507–9. (ophthalmic, maxillary and mandibular opportunistic infections in HIV patients. 6. Kinane DF, Marshall GJ. Periodontal manifestations of branches) and are accompanied by While NUP is a well-established oral systemic disease. Aust Dent J 2001;46(1):2–12. tingling, burning or painful sensations.7 sign of an HIV-associated bacterial 7. Phelan JA. Oral manifestations of human immunodefi ciency virus infection. Med Clin North Am 1997;81(2):511–31. The pebbly like lesions could present infection, other bacterial agents also 8. Derossi SS, Raghavendra S. Anemia. Oral Surg Oral as papillary hyperplasia (usually of tend to exhibit persistent infection Med Oral Pathol Oral Radiol Endod 2003;95(2):131–41. the palate), condyloma acuminataum followed by rapid spread. Still, bacterial 9. Xu J, Murphy SL, Kochanek KD, et al. Deaths: Final data for 2013. Natl Vital Stat Rep 2016;64:1–119. (asymptomatic papillary lesions that are complications in AIDS tend to be more 10. Wu YC, Wang YP, Yu J, et al. Oral manifestations and rare in the oral cavity but remain the generalized in nature and are less likely to blood profile in patients with iron deficiency anemia. J same color as their surrounding mucosa), present without more profound systemic Formos Med Assoc 2014;113(2):83–87. 7 11. Islam NM, Bhattacharyya I, Cohen DM. Common oral verruca vulgaris (asymptomatic papillary symptoms such as fever and malaise. manifestations of systemic disease. Otolaryngol Clin North lesions with white exterior protrusions Am 2011;44(1):161,82, vi. that are also rare in the oral cavity) or Summary 12. Neville BW, Damm DD, Allen CM, et al. Oral and Maxillofacial Pathology. 4th ed. St. Louis: Elsevier; 2016. focal epithelial hyperplasia (primary in Because the oral cavity is a direct 13. Zimmer V, Buecker A, Lammert F. Sideropenic 42,43 children as papulonodular lesions). inlet of the gastrointestinal system and dysphagia. 2009;137(6):e1–2. While the advent of cART has the rest of the viscera, it represents a 14. Lima SM, Grisi DC, Kogawa EM, et al. Diabetes mellitus and inflammatory pulpal and periapical disease: A drastically decreased the incidence potentially invaluable tool in establishing review. Int Endod J 2013;46(8):700–9. of developmental neoplasms, several the initial diagnosis of myriad systemic 15. Glick M. Burket’s Oral Medicine. 12th ed. Shelton, malignancies, including KS and diseases and conditions. Several Conn.: People’s Medical Publishing House USA; 2015. 16. Bender IB, Bender AB. Diabetes mellitus and the dental non-Hodgkin’s (NHL), pathoses have established associations pulp. J Endod 2003;29(6):383–9. remain closely associated with AIDS. with various oral structures and several 17. Borgnakke WS, Anderson PF, Shannon C, et al. Is KS is attributed to Kaposi’s sarcoma were found to have initial or primary there a relationship between oral health and diabetic neuropathy? Curr Diab Rep 2015;15(11):93. herpesvirus (KSHV) and is considered a presentations in the orofacial area. 18. Miley DD, Terezhalmy GT. The patient with diabetes pathognomonic sign of HIV infection, Dental professionals must recognize the mellitus: Etiology, epidemiology, principles of medical which presents as painless, purple to diagnostic utility of the oral cavity in order management, oral disease burden and principles of dental management. Quintessence Int 2005;36(10):779–95. red, fl at, focal or multiple lesions on to potentially detect systemic diseases 19. Mandel L, Patel S. Sialadenosis associated with surfaces such as the gingiva, palate, and contribute to the comprehensive diabetes mellitus: A case report. J Oral Maxillofac Surg alveolar bone or other mucosae (FIGURE health care of their patients. ■ 2002;60(6):696–8.

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20. Wiener RC, Wu B, Crout R, et al. Hyposalivation oral lesions among HIV-infected intravenous drug abusers 1992;73(2):142–4. and xerostomia in dentate older adults. J Am Dent Assoc and other risk groups. Oral Surg Oral Med Oral Pathol 45. Glick M. Dental Management of Patients With HIV. 2010;141(3):279–84. 1990;69(2):169–73. Chicago: Quintessence; 1994:319. 21. Cao X, Wang D, Zhou J, et al. The relationship between 40. Tamí-Maury IM, Willig JH, Jolly PE, et al. Prevalence, 46. Sroussi HY, Epstein JB. Changes in the pattern of oral dental caries and metabolic syndrome among 13,998 incidence and recurrence of oral lesions among HIV- lesions associated with HIV infection: Implications for middle-aged urban Chinese. J Diabetes 2016. infected patients on cART in Alabama: A two-year dentists. J Can Dent Assoc 2007;73(10):949–952. 22. Mays JW, Sarmadi M, Moutsopoulos NM. Oral longitudinal study. South Med J 2011;104(8):561–6. 47. Singh SK, Rai T. A case of zidovudine induced manifestations of systemic autoimmune and inflammatory 41. Tong AC, Wong MH, Smith NJ. Penicillium marneffei pigmentation on palms and soles. Indian Dermatol Online J diseases: Diagnosis and clinical management. J Evid Based infection presenting as oral ulcerations in a patient infected 2014 Jan-Mar; 5(1): 98–99. Dent Pract 2012;12(3 Suppl):265–82. with human immunodeficiency virus. J Oral Maxillofac Surg 48. Samad A, Mohan N, Balaji RV, et al. Oral manifestations 23. Kaye EK, Chen N, Cabral HJ, et al. Metabolic 2001;59(8):953–956. of Plummer-Vinson syndrome: A classic report with literature Syndrome and Periodontal Disease Progression in Men. J 42. Regezi JA, Sciubba JJ, Jordan RCK, Rosengarten Family review. J Int Oral Health 2015;7:68–71. Dent Res 2016. 2016 Jul;95(7):822–8. Fund. Oral Pathology: Clinical Pathologic Correlations 4th 24. Taylor GW, Burt BA, Becker MP, et al. Non-insulin ed. St. Louis: Saunders; 2003:448. THE CORRESPONDING AUTHOR, Jeffrey A. Elo, DDS, can be dependent diabetes mellitus and alveolar bone loss 43. Patton LL. Oral lesions associated with human reached at [email protected]. progression over two years. J Periodontol 1998;69(1):76–83. immunodeficiency virus disease. Dent Clin North Am 25. Moore PA, Weyant RJ, Mongelluzzo MB, et al. Type 1 2013;57(4):673–98. diabetes mellitus and oral health: assessment of periodontal 44. Greenspan JS, Barr CE, Sciubba JJ, et al. Oral disease. J Periodontol 1999;70(4):409–17. manifestations of HIV infection. Definitions, diagnostic 26. Lamster IB, Lalla E, Borgnakke WS, et al. The criteria and principles of therapy. The USA Oral AIDS relationship between oral health and diabetes mellitus. J Collaborative Group. Oral Surg Oral Med Oral Pathol Am Dent Assoc 2008;139 Suppl:19S–24S. 27. Borgnakke WS. Does treatment of periodontal disease influence systemic disease? Dent Clin North Am 2015;59(4):885–917. 28. Mealey BL, Oates TW. American Academy of Periodontology. Diabetes mellitus and periodontal diseases. J Periodontol 2006;77(8):1289–303. 29. Wysocki GP, Daley TD. Benign migratory glossitis in patients with juvenile diabetes. Oral Surg Oral Med Oral Pathol 1987;63(1):68–70. 30. Patton LL, Phelan JA, Ramos-Gomez FJ, et al. Prevalence and classification of HIV-associated oral lesions. Oral Dis 2002;8 Suppl 2:98–109. 31. Greenspan D, Greenspan JS. HIV-related oral disease. Lancet 1996;348(9029):729–33. 32. Patton LL, McKaig R, Strauss R, et al. Changing prevalence of oral manifestations of human immunodeficiency virus in the era of protease inhibitor therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;89(3):299–304. 33. Greenspan D, Canchola AJ, MacPhail LA, et al. Effect of highly active antiretroviral therapy on frequency of oral warts. Lancet 2001;357(9266):1411–2. 34. Nittayananta W. Oral fungi in HIV: Challenges MAKE SURE YOUR in therapies. Oral Dis 2016;22 (October REPUTATION IS PROTECTED 2015):107–113. 35. Tukutuku K, Muyembe-Tamfum L, Kayembe K, et al. WITH MALPRACTICE Oral manifestations of AIDS in a heterosexual population in a Zaire hospital. J Oral Pathol Med 1990;19(5):232–4. INSURANCE FROM PSIC. 36. Klein IP, Martins MA, Martins MD, et al. Diagnosis of HIV infection on the basis of histoplasmosis-related oral ulceration. Spec Care Dent 2016;36(2):99–103. Get a quick rate quote at 37. Feigal DW, Katz MH, Greenspan D, Carrard VC. The www.psicinsurance.com/dentists prevalence of oral lesions in HIV-infected homosexual and Scan or visit www.psicinsurance.com/ bisexual men: Three San Francisco epidemiological cohorts. dentists to learn AIDS 1991;5(5):519–25. more about PSIC. Call 1-800-718-1007, ext. 9191 38. Maheshwari M, Kaur R, Chadha S. Candida Species www.psicinsurance.com/dentists Prevalence Profile in HIV Seropositive Patients From a Major Tertiary Care Hospital in New Delhi, India. J Pathog Malpractice insurance is underwritten by Professional Solutions Insurance Company. 2016;2016:1–8. 14001 University Avenue | Clive, Iowa 50325-8258 ©2016 PSIC NFL 9663 39. Barone R, Ficarra G, Gaglioti D, et al. Prevalence of

SEPTEMBER 2016 559 Free eDelivery.

Available for iPhone, Android or Kindledle Fire. Check it out at cda.org/apps. mucocutaneous diseases

CDA JOURNAL, VOL 44, Nº9

Mucocutaneous Diseases: Oral Lichen Planus, Mucous Membrane Pemphigoid and Pemphigus Vulgaris

Seena Patel, DMD, MPH; Satish Kumar, DDS, MDSc, MS; Joel M. Laudenbach, DMD; and Antonia Teruel, DDS, MS, PhD

ABSTRACT Mucocutaneous diseases affect the oral cavity and can present a diagnostic challenge. They can have systemic involvement, necessitating multidisciplinary management. Frequently, patients will see their general dentists initially for evaluation. A better understanding of mucocutaneous diseases can prevent delay in appropriate diagnosis and treatment. Oral lichen planus, mucous membrane pemphigoid and pemphigus vulgaris are three mucocutaneous diseases that affect the . This review describes the clinical features, epidemiology, etiology, pathogenesis and management for each condition.

AUTHORS ucocutaneous diseases are Seena Patel, DMD, MPH, Satish Kumar, DDS, Joel M. Laudenbach, Antonia Teruel, DDS, systemic, autoimmune is an assistant professor MDSc, MS, is an assistant DMD, is an assistant MS, PhD, is a clinical and associate director professor in the department professor of oral medicine assistant professor in the disorders that can affect of oral medicine at the of periodontics and and geriatric dentistry department of diagnostic the oral cavity. In fact, Arizona School of Dentistry preventive dentistry at the and the coordinator of the sciences at the University of many patients present and Oral Health, A.T. Still University of Pittsburgh, Advanced Oral Diagnosis Pittsburgh, School of Dental Mwith oral manifestations as the initial sign. University, in Mesa, Ariz. School of Dental Medicine Workgroup at Western Medicine, in Pittsburgh. When these diseases cause oral pain and/ Dr. Patel is a diplomate in Pittsburgh. Dr. Kumar is a University of Health Confl ict of Interest of the American Board diplomate of the American Sciences, College of Dental Disclosure: None reported. or discomfort, patients tend to fi rst consult of Orofacial Pain and Board of Orofacial Pain Medicine in Pomona, with their own general dentist. Therefore, American Board of Oral and American Board of Calif. Dr. Laudenbach is a dentists need to be aware of these diseases Medicine. Oral Medicine. diplomate of the American and recognize when a specialist referral is Confl ict of Interest Confl ict of Interest Board of Oral Medicine. indicated. Early diagnosis and management is Disclosure: None reported. Disclosure: None reported. Confl ict of Interest Disclosure: None reported. critical to prevent systemic progression. Oral lichen planus (OLP), mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV) are three mucocutaneous diseases that present with oral manifestations. This review describes the clinical features, epidemiology, etiology, pathogenesis, diagnosis and management for each of these conditions.

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FIGURE 1A. FIGURE 1B. FIGURE 1C.

FIGURE 1D.

FIGURE 1E. FIGURE 1F.

FIGURES 1. Types of oral lichen planus. Reticular and erosive type, right buccal mucosa (1A). Plaque type: right lateral border of the tongue (1B). Plaque type: dorsum of the tongue (1C). Erosive type, , front view (1D). Erosive type, desquamative gingivitis, left side (1E). Erosive type, desquamative gingivitis, right side (1F). Erosive type, right buccal vestibule, right buccal mucosa (1G). Bullous type, left labial surface of the lower lip (1H).

FIGURE 1G. FIGURE 1H.

Oral Lichen Planus mucosa is the most common site. Lesions of the tongue and fl oor of mouth. They are usually bilateral and symmetric.3 usually present as a unilateral, isolated and Clinical Features OLP has been categorized into several keratotic plaque. A biopsy is also necessary Lichen planus is a chronic, types: reticular/plaque-like, erosive and to differentiate these two conditions. The infl ammatory disorder that affects bullous (FIGURE 1). The reticular/plaque- reticular/plaque-like lesions associated the skin and mucous membranes. It like type is the most common presentation with OLP are often asymptomatic. The often affects the oral mucosa.1 In fact, and is characterized by bilateral, white, erosive type has lesions that erode the patients with OLP frequently have interlacing linear keratosis (Wickham mucosa, resulting in erythematous and oral manifestations only,1 but about 25 striae).2 Sometimes, the white areas appear ulcerated areas that are often painful percent of OLP patients present with more like plaques, making it diffi cult to and devoid of epithelium with areas of lesions affecting the vulva and vagina.2 differentiate from leukoplakia.4 Plaque- Wickham striae and erythema. These Other sites of involvement include type lichen planus will usually present ulcerations can contract a superimposed the nails, scalp, esophagus and eyes.2 with bilateral, multifocal involvement. candida infection. When the gingiva The majority of patients with OLP are Lesions can also migrate. Leukoplakic is affected, the lesions are described as asymptomatic. Oral lesions can affect lesions have a tendency to occur on desquamative gingivitis. Atrophic, erosive any part of the mouth, but the buccal high-risk sites, such as the lateral border and ulcerative lesions are the most painful

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TABLE 1 Differential Diagnoses of Mucocutaneous Disorders17,24,25,39-42,59

Diff erential Diagnoses Clinical Characteristics Autoantibody Specifi cities Oral lichen planus White, lacy, striations (Wickham’s striae), erosion, ulceration, desquamative gingivitis Basement membrane zone fi nding(s) is/are possible Lichenoid mucositis White, lacy, striations (Wickham’s striae), erosion, ulceration, desquamative gingivitis Basement membrane zone In cases of contact , may be unilateral, localized to the site of irritation fi nding(s) is/are possible Mucous membrane pemphigoid Ulceration, bullae formation, desquamative gingivitis, ocular involvement (symblepharon, BP180, laminin 332 BP230, ankyloblepharon) α6β4 integrin, laminin 311, type VII collagen Pemphigus Ulceration, bullae formation, desquamative gingivitis Autoantibodies against desmoglein 1 and 3 Bullous pemphigoid Multiple, tense bullae on the skin; oral mucosal involvement is rare but can present BP180 NC16A domain with bullae formation and ulceration BP230 Epidermolysis bullosa acquisita Bullous lesions on the skin and mucosa occurring with minimal trauma Type VII collagen Bullous systemic Ulceration with radiating keratotic striae; rarely scars Type VII collagen Linear IgA disease Tense blisters, erosions without signifi cant mucosal involvement LAD-1, BP230 (IgA reactivity) Generalized erythema, crusting of the lips, target/bull’s eye skin lesions None Graft versus host disease White striated lesions resembling lichen planus, oral ulcerations, erosions None Chronic hyperplastic candidiasis Ill-defi ned keratotic lesions, usually on the buccal mucosa (bilateral) extending to the commissures None Frictional keratosis Ill-defi ned keratosis usually adjacent to an irritant (i.e., sharp/fractured tooth) None

and require treatment. Lastly, the bullous Etiology and Pathogenesis Diagnosis type presents with fl uid-fi lled vesicles The etiology of OLP is unknown and OLP has a distinct, clinical appearance and is considered a rare form of OLP.1 the exact mechanisms for the pathogenesis in the majority of cases, especially when Malignant transformation of of OLP are not fully understood. OLP patients present with the reticular/ OLP to squamous cell carcinoma has appears to be associated with an immune- plaque-like type bilaterally. Oral biopsy been reported in the literature but mediated reaction against an exogenous is indicated to confi rm the clinical is controversial because of clinical antigen or an autoantigen expressed diagnosis, while it also helps to rule out and histological overlap of OLP with by the epithelial cells. This immune other similar appearing diseases, including potentially malignant oral lesions, such reaction is mediated by T lymphocytes, dysplasia and neoplasia. Atrophic/erosive, as leukoplakia and .2,5 results in a cytotoxic reaction and leads ulcerative and bullous types can appear Some authors believe that lichenoid to apoptosis of epithelial basal cells. to be similar to oral MMP, PV and lupus lesions with dysplasia are an entirely Cytotoxic T lymphocytes (CD8+) are erythematosus (LE). A histopathological different pathology.6,7 However, others primarily responsible for the sustained analysis can help to differentiate between feel that lichenoid dysplasia may be part infl ammation and destruction of epithelial these conditions.3 However, studies of the lichen planus disease process.8 cells although helper T lymphocytes have shown differences in interobserver OLP lesions carry an estimated risk of (CD4+) are also activated in OLP.14,15 and intraobserver reliability in the 0.5 percent to 2 percent for malignant Several etiological factors have been histological assessment of OLP and a transformation.9 Hence, periodic implicated in the development of oral lack of a clinicopathologic correlation observation is recommended.8 lichenoid lesions (OLL, described in the in the diagnostic assessment of OLP.1,16 diagnosis section below), such as dental A biopsy is the recommended Epidemiology restorations, medications, trauma and viral diagnostic technique.6 Specifi cally, an OLP has a worldwide prevalence rate infections, even though a causative role incisional biopsy of the lesion is obtained of 0.2 percent to 2 percent.10,11 Women for these factors in the development of and transferred to a 10% buffered formalin are affected more than men.10 Patients OLP has yet to be confi rmed.12 To date, the solution, which is then sent to an oral between the ages of 30 and 60 are at strongest evidence suggests an association pathologist for microscopic examination the highest risk for developing OLP.2 between the hepatitis C virus and OLP.13 using conventional hematoxylin and

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TABLE 2 Topical for the Management of Mucocutaneous Diseases

Topical Potency Dosage Frequency Triamcinolone (0.1% paste) Mid-strength potency 4 times daily Fluocinonide (0.05% gel) High potency 4 times daily eosin (H&E) staining. Specimens will Dexamethasone (0.5mg/5mL elixir) High potency Swish with 1 teaspoon for 2 show a lymphocytic infi ltrate at the minutes and expectorate 4 times superfi cial lamina propria and liquefaction daily degeneration in the basal cell layer. Fluticasone propionate (50 μg) Upper mid-strength potency Apply 2 puff s to lesion 4 times “Saw-toothed” rete ridges may be present. daily There will be no evidence of dysplasia.6 Immunofl uorescence is an advanced Clobetasol (0.025% to 0.05% gel) Super potent 4 times daily histopathologic diagnostic technique Betamethasone (0.05% gel) Super potent 4 times daily that detects the presence and location of Jacob SE, Steele T. Corticosteroid classes: A quick reference guide including patch test substances and cross-reactivity. J Am Acad autoantibodies in the biopsy specimen. For Dermatol 2006;54(4):723-727. this, the specimen must be transferred in Michel’s solution. It is usually reserved for oral hypoglycemic agents, angiotensin- them to tailor the treatment regimen to the autoimmune vesiculobullous conditions converting enzyme inhibitors or severity of the disease. Topical medications like MMP and PV and is described nonsteroidal anti-infl ammatory drugs.1 are the preferred treatment modality. further in later sections. However, when A thorough history helps differentiate However, in severe cases with multiple OLP presents atypically or with bullous oral lichenoid lesions from OLP. areas of mucocutaneous involvement, features, immunofl uorescence may be both topical and systemic medications useful. A recent retrospective study Management may be used. Medications can be divided evaluating 82 samples analyzed under The management of OLP is driven into several categories: corticosteroids, direct immunofl uorescence (DIF) showed by symptom severity and the extent of calcineurin inhibitors, retinoids and other that 68 had positive fi ndings.3 All lesions mucosal involvement (FIGURE 2). Medical “steroid-sparing” systemic medications.1 were of the atrophic type. The DIF fi ndings consultation with a dermatologist and/or Corticosteroids have been shown to included fi brinogen, immunoglobulin a gynecologist is indicated if the patient be the most effective and are considered M (IgM) and complement component reports lesions and/or symptoms of the the fi rst line of treatment.4,18-21 Topical 3 (C3) deposition at the basement skin and/or genital areas. In addition, corticosteroids are typically applied as a membrane zone.3 While DIF studies can a screening for the hepatitis C virus is gel or used as a mouth rinse. The gel is be useful for diagnosing OLP, clinicians recommended. The patient can be referred recommended for localized lesions, while may want to utilize this technique to his or her physician for an evaluation.2 the rinse is prescribed for widespread for patients who do not present with Because of its pathogenesis, the goal involvement. Topical corticosteroids are characteristic clinical features of OLP and of OLP treatment is immunomodulatory available in different dosages and potencies cannot be differentiated from other oral and immunosuppressive.4 In the majority (TABLE 2). For erosive lichen planus, a mucocutaneous diseases such as MMP. of cases, patients are asymptomatic and high- to super-potent medication is needed, The differential diagnosis of OLP is periodic observation is recommended. such as fl uocinonide gel, clobetasol gel, extensive and includes frictional keratosis, Patient education about the malignant betamethasone gel, fl uticasone propionate chronic hyperplastic candidiasis, oral potential, need for long-term follow-up spray or dexamethasone elixir.1 Clobetasol MMP, oral PV and oral LE (TABLE 1).2,3,17 and periodic rebiopsy is paramount. For gel has been shown to be the most effective There are other lesions that resemble OLP symptomatic cases, patients fi rst need and studied.22-24 It is advisable to apply the both clinically and histopathologically. to identify any external factors that medications for a short-term duration. For These are termed oral lichenoid lesions trigger or exacerbate their condition. severe cases, patients may need to apply and are divided into three diagnoses: oral These factors may include acidic or spicy the medication up to four times a day over lichenoid contact lesions, oral lichenoid foods, sharp or rough cusps on teeth a period of one to two months.1 They may drug reactions and oral lichenoid lesions or existing restorations, heavy plaque/ then gradually taper off. In some cases, of graft versus host disease. Contact calculus accumulation, ill-fi tting dental however, the patient may always have to lesions are typically a hypersensitivity prostheses or even stressful life events. apply the medication one to two times a to dental restorative materials (usually Patient education is, therefore, critical.1 day to maintain comfort, while reducing amalgam) or food fl avorings (usually When managing OLP, clinicians the severity of and potential for fl are- cinnamon). Drug reactions can be from follow a stratifi ed-care approach, allowing ups. For gingival involvement, occlusive

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Management considerations for active/symptomatic OLP, MMP and PV

Avoidance of Topical Intralesional Systemic precipitating factors medications injection medications

Need medical consultation Dietary Corticosteroids Corticosteroids with a dermatologist (PV, MMP) modifi cations and ophthalmologist (MMP)

Adjust ill-fi tting Calcineurin restorations and Corticosteroids prostheses inhibitors

Stress Steroid-sparing Retinoids management medications

Abbreviations: MMP, mucous membrane pemphigoid; OLP, oral lichen planus; PV, pemphigus vulgaris.

FIGURE 2. Management considerations for active/symptomatic oral lichen planus, mucous membrane pemphigoid and pemphigus vulgaris.19,20,25,28,30,34,44,46,50,54-56

trays can be fabricated. These trays can an initial treatment option. Other dermatitis.26 In symptomatic cases of OLP hold the medication in place over the medications for systemic management that are refractory to topical steroids, affected tissue more effectively when of OLP include steroid-sparing agents calcineurin inhibitors can be used as a the tray borders are extended beyond and anti-infl ammatory agents.1 Indolent, second-line treatment.27 Examples of these the marginal gingiva (FIGURE 3). nonresponsive lesions should undergo medications include 0.1% tacrolimus For localized lesions that do not respond rebiopsy to confi rm the clinical diagnosis, ointment and 1% pimecrolimus cream.28 to the gels or mouth rinses, intralesional while helping to rule out other diagnoses Common adverse effects of calcineurin corticosteroid injections (ICIs) can be such as epithelial dysplasia and neoplasia. inhibitors include mild burning of the considered the next treatment option. Topical corticosteroids are generally oral mucosa and increased levels of the Triamcinolone (10 mg/mL) can be well tolerated and few adverse effects have medication in the blood, which may lead to administered by injecting 0.1 mg/cm3 into/ been reported, the most common of which systemic side effects. In addition, mucosal surrounding the lesion base.25 ICIs may is oral candidiasis. A recent retrospective staining, sore throat and taste disturbance result in localized pain, bleeding, swelling review reported a 13.6 percent prevalence are other reported oral adverse effects. and/or, rarely, infection. For severe, rate of oral candidiasis in 315 patients Most of these resolve with continued recalcitrant cases or diffuse mucocutaneous diagnosed with OLP who were treated with application and healing of the lesions. involvement, short-term systemic therapy corticosteroids, the majority of which were Topical tacrolimus and pimecrolimus may be indicated initially. Corticosteroids topical, for two weeks.19 Systemic absorption also have a black box warning that are the fi rst-line medication in this is considered to be clinically insignifi cant states rare cases of malignancies have instance. They are usually prescribed at when using topical corticosteroids.22 been reported in patients treated with a high dose of prednisone, such as 0.5-1 Calcineurin inhibitors are medications topical calcineurin inhibitors. This mg/kg/day for a short duration and then typically used to prevent organ transplant outcome is extremely rare, but caution tapered off.18,25 A methylprednisolone rejection. However, topical formulations should be used when prescribing these dose pack may also be considered as were developed to treat atopic medications for long-term use.29

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FIGURE 3C.

FIGURE 3A. FIGURE 3B. FIGURES 3. Occlusive trays used to hold the topical corticosteroid gel over the aff ected gingiva. Maxillary occlusive tray (3A–B). Intraoral placement of the maxillary occlusive tray (3C).

Topical retinoids may be another The ocular mucosa is the next most Epidemiology alternative to corticosteroid therapy in commonly affected site, followed by While the overall incidence of MMP the management of OLP.30 The more involvement of the skin, nasal cavity, is not clear, it is estimated to be 1.3 to 2.0 widely known retinoid medications anogenital area, pharynx, larynx and, per million people per year.25,36,38 MMP are retinol, tretinoin and isotretinoin. rarely, the esophagus.25,33,36 The severity usually affects people aged 60 to 80 years Common side effects reported with of symptoms of MMP varies considerably. and is more prevalent in females.25,33 topical retinoid treatment are transient Some cases present with mild oral burning of the mucosa and taste lesions while others exhibit severe and Etiology and Pathogenesis disturbance. These medications should pervasive systemic involvement.36 The subepithelial blisters seen be avoided in pregnant women. Based Clinical signs affecting the oral mucosa in MMP result from the binding of on the existing literature, topical include bullae formation, which rupture and autoantibodies to target antigens in the retinoids should only be considered result in ulceration. A positive Nikolsky sign epithelial basement membrane zone.25 as a second- or third-line option.30 may also be seen and presents as epithelial This autoantibody-antigen interaction Lastly, because the atrophic/ sloughing upon pressure from manipulating triggers a complement-mediated erosive type of OLP can compromise the affected tissue. In addition, patients response in which infl ammatory cells are , effective plaque control can present with desquamative gingivitis recruited. As a result, this destructive can reduce symptoms. Studies have and mucosal scarring.25,33 Symptoms infl ammatory process is responsible for shown improvement in OLP symptoms of MMP can include pain, dysphagia, the detachment of the epithelial layer when patients follow a meticulous diffi culty eating, erythematous from the basement membrane.25 oral hygiene protocol and have gingiva that bleed easily and diffi culty Even though the exact frequent professional cleanings. The maintaining appropriate oral hygiene. mechanisms of MMP are not fully best results are usually achieved when Ocular symptoms may initially present as understood, evidence suggests a role good oral hygiene is combined with chronic conjunctivitis, burning, irritation, of against specifi c topical corticosteroid therapy.31,32 photophobia and excessive tearing.34 antigens.36 The target antigens Mucosal scarring from MMP can result associated with MMP include laminin Mucous Membrane Pemphigoid in severe consequences. In the ocular 332, laminin 311, α6β4 integrin, mucosa, MMP may lead to blindness due type VII collagen and BP230 and Clinical Features to symblepharon or ankyloblepharon BP180. BP180 is most frequently MMP, formerly known as cicatricial because of fusion of the scleral and palpebral targeted in cases of MMP.25,36 The pemphigoid, is a rare, heterogeneous conjunctiva and of the superior and inferior different clinical presentations seen group of chronic infl ammatory and palpebrae, respectively (FIGURE 4).25,33,34,36 in MMP are dependent on the specifi c immune-mediated, subepithelial blistering Other ocular effects of MMP include antibody-antigen complex location diseases that largely affect the mucous entropion (eyelids turn inward) and (TABLE 3). In addition, a genetic role membranes.33,34 MMP commonly affects trichiasis (eyelashes are misdirected toward has been suggested for MMP because the oral mucosa with predominantly the eye surface).34 The risk of developing of the increased prevalence of certain gingival involvement.33 When only ocular lesions is 5 percent over the initial human leukocyte antigen (HLA) oral lesions are present, the condition is fi ve years.36 In the esophagus and larynx, alleles such as the HLA-DQB1*0301 referred to as oral MMP (FIGURE 4).35 scarring can lead to stenosis and strictures.37 reported in several studies.39-42

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must be placed in Michel’s solution or snap-frozen in liquid nitrogen.17,30,34 It is then incubated with these antihuman antibodies, which bind to any site where the immunoglobulin is present.17 FIGURE 4A. FIGURE 4B. Under DIF, the affected tissue will show linear deposition of IgG, IgA and/or C3 at the basement membrane zone.25 IIF is a technique used to detect antibodies circulating in the blood. A section of tissue similar to human oral mucosa, such as monkey esophagus, is incubated with the patient’s serum. Autoantibodies, if present, will attach to structures within the epithelium of the tissue. A fl uorescein-conjugated goat FIGURE 4C. FIGURE 4D. antihuman antibody is incubated with FIGURES 4. Clinical images of mucous membrane pemphigoid. Oral involvement: desquamative gingivitis and this tissue and examined under UV light ulceration (4A–C). Ocular: Symblepharon formation in the right eye (4D). for the presence of autoantibodies.17,25 MMP that only affects the oral mucosa TABLE 3 has been shown to have a lower incidence Clinical Presentation and Antigen Location of Mucous Membrane Pemphigoid of autoantibody detection with IIF.34 Antigen Clinical Presentation Management Laminin 332 Increased risk for malignancy Managing MMP follows a similar α6β4 integrin α6 subunit Appearance of oral lesions course as that of OLP (FIGURE 2). More specifi cally, there is no curative treatment, similar medications are used Diagnosis condition.25,33 Lesional biopsy specimens and management is often needed for MMP is diagnosed by the clinical placed in 10% buffered formalin the long term. Topical, intralesional or presentation, routine histopathology solution are evaluated under routine systemic immunomodulating agents are and DIF. It must be differentiated from histopathology (H&E). Findings will show utilized (TABLE 2). These medications the other pemphigoid disorders (bullous a subepithelial split and infl ammatory can control ulcer and scar formation pemphigoid and pemphigoid gestationis), infi ltrate comprised of eosinophils, and alleviate symptoms, thereby dermatitis herpetiformis and linear neutrophils and lymphocytes.25,35 improving the patient’s ability to eat, IgA disease.34 Other conditions in the Biopsies of chronic ulcerative diseases speak and maintain oral hygiene.25 differential diagnoses include OLP, involving the oral mucosa should Once a patient is diagnosed with pemphigus, epidermolysis acquisita, include immunofl uorescence analysis. MMP, referrals to a dermatologist and bullous systemic lupus erythematosus Two types of immunofl uorescence ophthalmologist are necessary to evaluate and erythema multiforme (TABLE 1).25,43 can be implemented: DIF or indirect for mucosal involvement beyond the oral Biopsy is a critical part of this process. immunofl uorescence (IIF). DIF is a cavity.25 Patients with MMP who have oral Two biopsy specimens should be taken technique used to detect autoantibodies mucosal involvement only have a more from lesional and intact tissue. If biopsies bound to the patient’s tissue. Antibodies benign course of the disease compared are taken within the ulcerated tissue, formed against human immunoglobulins to the other variants.30,34 Patients with they will show nonspecifi c infl ammatory are tagged with fl uorescein dye that MMP who have skin and other mucosal changes, and the pathologist will not can be viewed with ultraviolet light involvement are at an increased risk for be able to accurately diagnose the (UV). The perilesional biopsy specimen scarring. Early intervention and systemic

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FIGURE 5B. FIGURE 5C. FIGURE 5A. FIGURES 5. Clinical images of pemphigus vulgaris. Oral involvement (5A–B). Oropharyngeal involvement (5C). therapy is critical for this group, so a Pemphigus Vulgaris those of Mediterranean and Ashkenazi medical consultation and multidisciplinary Jewish decent.50 PV normally manifests management is warranted. Clinical Features between the ages of 40 and 60.49,50 Topical medications are the fi rst line PV describes a group of autoimmune, Unlike OLP and MMP, however, PV of treatment, and they include high- and intraepithelial blistering diseases. Lesions affects men and women equally.49 super-potent corticosteroids or calcineurin affect any mucosal surface lined by inhibitors, which are available in gels, stratifi ed epithelium and/or the skin. Etiology and Pathogenesis ointments or mouth rinses. Occlusive Mucosal sites of involvement include Acantholysis is the main mechanism trays may also be fabricated for generalized the oral, nasal, laryngeal, esophageal, involved in the development of lesions gingival involvement.25 Intralesional genital and conjunctival mucosa. For most in PV and is defi ned by disruption of corticosteroid injections can also be patients, the oral mucosa is the fi rst site the cell-to-cell adhesion within the performed and should be considered as a of involvement. In the mouth, lesions epithelial layer. IgG targets intercellular second-line treatment. Triamcinolone (5- commonly occur on the buccal mucosa, adhesion molecules, ultimately producing 10 mg/mL suspension) is usually used and palate and gingiva. They present as blisters blisters above the basal layer.51 The most administered in a dosage of 0.1 mg/cm3.25,44 that easily rupture into diffuse erosions important adhesion molecules of the Systemic medications for the and ulcerations (FIGURE 5). A positive desmosome affected in PV are desmogleins management of MMP include Nikolsky sign can be elicited, similar to 1 (Dsg1) and desmogleins 3 (Dsg3). corticosteroids, dapsone, minocycline, MMP. Skin lesions present with fl accid Patients with oral involvement of PV mycophenolate mofetil, azathioprine, blisters that rupture into large, painful have antibodies against Dsg3, because cyclophosphamide, tumor necrosis erosions.10,49,50 Aggravating or precipitating Dsg3 is found in greater concentrations factor-alpha inhibitors, colchicine and factors may include medications, pesticide in the mucosa than Dsg1.25,51 A genetic rituximab.25,34,36,45-47 For progressive exposure, malignancies, diet and stress.10 role has also been suggested for PV. In a disease, patients are usually started on PV can have a severe systemic course that recent meta-analysis, it was reported that 1-2 mg/kg/day of prednisone combined can be life threatening when untreated.49,50 specifi c HLA-DRB1 allele types were with cyclophosphamide, azathioprine or Recognition and prompt referral to a responsible for increased susceptibility methotrexate. Dapsone has been found practitioner with advanced training and resistance to developing PV.52 to be more effective in patients with mild and expertise in clinical oral medicine/ to moderate MMP, and minocycline has oral pathology can prevent delay of Diagnosis shown effi cacy for oral but not ocular appropriate diagnosis and management. The diagnosis of PV is similar to disease. These medications can have that of MMP in that it is based on severe adverse effects, such as systemic Epidemiology the clinical features combined with immunosuppression, hematologic Pemphigus describes a group of histopathology, immunopathology abnormalities, hematuria and hair loss.46 diseases divided into four classifi cations: and/or serology. Biopsies should be Frequent professional dental PV, pemphigus foliaceus, IgA pemphigus performed under routine histopathology cleanings have also been shown to reduce and paraneoplastic pemphigus or and DIF (see diagnosis section of gingival infl ammation, bleeding and pemphigus autoimmune multiorgan MMP). Features of histopathology in pain resulting from MMP.25,48 Patients syndrome. Of these, PV is the most PV include suprabasal cleavage with should also see their dentists regularly common with an incidence of 0.1 to 0.5 acantholysis. DIF shows intercellular for professional dental cleanings, as an per 100,000 patients per year. Patients deposition of IgG and C3. Serological important part of MMP management. particularly at risk for PV include tests include IIF and enzyme-linked

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comparative study with long-term follow-up. J Oral Pathol Med membrane pemphigoid. Br J Oral Maxillofac Surg 51. Lanza A, Cirillo N, Femiano F, Gombos F. How does 2003;32(6):323–329. 2008;46(5):358–366. acantholysis occur in pemphigus vulgaris: A critical review. J 19. Marable DR, Bowers LM, Stout TL, et al. Oral candidiasis 35. Petruzzi M. Mucous membrane pemphigoid aff ecting Cutan Pathol 2006;33(6):401–412. following steroid therapy for oral lichen planus. Oral Dis the oral cavity: Short review on etiopathogenesis, diagnosis 52. Yan L, Wang JM, Zeng K. Association between HLA-DRB1 2016;22(2):140–147. and treatment. Immunopharmacol Immunotoxicol polymorphisms and pemphigus vulgaris: A meta-analysis. Br J 20. Thongprasom K, Carrozzo M, Furness S, Lodi G. 2012;34(3):363–7. Dermatol 2012;167(4):768–777. Interventions for treating oral lichen planus. Cochrane 36. Schmidt E, Zillikens D. Pemphigoid diseases. Lancet 53. Giurdanella F, Diercks GF, Jonkman MF, Pas HH. Database Syst Rev 2011;(7):CD001168. 2013;381(9863):320–332. Laboratory diagnosis of pemphigus: Direct immunofl uorescence 21. Zakrzewska JM, Chan ES, Thornhill MH. A systematic 37. Murrell DF, Marinovic B, Caux F, et al. Defi nitions and remains the gold standard. Br J Dermatol 2016 (in press). review of placebo-controlled randomized clinical trials outcome measures for mucous membrane pemphigoid: 54. Martin LK, Werth V, Villanueva E, Segall J, Murrell DF. of treatments used in oral lichen planus. Br J Dermatol Recommendations of an international panel of experts. J Am Interventions for pemphigus vulgaris and pemphigus foliaceus. 2005;153(2):336–341. Acad Dermatol 2015;72(1):168–174. Cochrane Database Syst Rev 2009;(1):CD006263. 22. Carbone M, Arduino PG, Carrozzo M, et al. Topical 38. Bertram F, Brocker EB, Zillikens D, Schmidt E. Prospective 55. Dumas V, Roujeau JC, Wolkenstein P, Revuz J, Cosnes clobetasol in the treatment of atrophic-erosive oral lichen analysis of the incidence of autoimmune bullous disorders A. The treatment of mild pemphigus vulgaris and pemphigus planus: A randomized controlled trial to compare two in Lower Franconia, Germany. J Dtsch Dermatol Ges foliaceus with a topical corticosteroid. Br J Dermatol preparations with diff erent concentrations. J Oral Pathol Med 2009;7(5):434–440. 1999;140(6):1127–1129. 2009;38(2):227–233. 39. Carrozzo M, Fasano ME, Broccoletti R, et al. HLA-DQB1 56. Atzmony L, Hodak E, Leshem YA, et al. The role of adjuvant 23. Carbone M, Conrotto D, Carrozzo M, Broccoletti R, alleles in Italian patients with mucous membrane pemphigoid therapy in pemphigus: A systematic review and meta-analysis. J Gandolfo S, Scully C. Topical corticosteroids in association with predominantly aff ecting the oral cavity. Br J Dermatol Am Acad Dermatol 2015;73(2):264–271. miconazole and chlorhexidine in the long-term management of 2001;145(5):805–808. 57. Ingen-Housz-Oro S, Valeyrie-Allanore L, Cosnes A, et al. atrophic-erosive oral lichen planus: A placebo-controlled and 40. Delgado JC, Turbay D, Yunis EJ, et al. A common major First-line treatment of pemphigus vulgaris with a combination comparative study between clobetasol and fl uocinonide. Oral histocompatibility complex class II allele HLA-DQB1* 0301 is of rituximab and high-potency topical corticosteroids. JAMA Dis 1999;5(1):44–49. present in clinical variants of pemphigoid. Proc Natl Acad Sci Dermatol 2015;151(2):200–203. 24. Eisen D, Carrozzo M, Bagan Sebastian JV, Thongprasom U S A 1996;93(16):8569–8571. 58. Gambino A, Carbone M, Arduino P, Carcieri P, et K. Number V Oral lichen planus: Clinical features and 41. Mostafa MI, Zarouk WA, El-Kamah GY. Class II alleles al. Conservative approach in patients with pemphigus management. Oral Dis 2005;11(6):338–349. HLA-DQB1* 0301 among a seven-membered Egyptian gingival vulgaris: A pilot study of fi ve cases. Int J Dent 25. Stoopler ET, Sollecito TP. Oral mucosal diseases: Evaluation family of a child with oral pemphigoid. Bratisl Lek Listy 2014;2014:747506. and management. Med Clin North Am 2014;98(6):1323– 2011;112(10):591–594. 59. Neville B, Damm DD, Allen C, Chi A. Oral and 1352. 42. Setterfi eld J, Theron J, Vaughan RW, et al. Mucous Maxillofacial Pathology. 4th ed. St. Louis: Elsevier; 2016:709– 26. Azizi A, Lawaf S. The comparison of effi cacy of adcortyl membrane pemphigoid: HLA-DQB1*0301 is associated 23,729–734, 736–739, 740–744. ointment and topical tacrolimus in treatment of erosive with all clinical sites of involvement and may be linked to oral lichen planus. J Dent Res Dent Clin Dent Prospects antibasement membrane IgG production. Br J Dermatol THE CORRESPONDING AUTHOR, Seena Patel, DMD, MPH, can be 2007;1(3):99–102. 2001;145(3):406–414. reached at [email protected]. 27. Shichinohe R, Shibaki A, Nishie W, Tateishi Y, Shimizu H. 43. Carvalho CH, Santos BR, Vieira Cde C, Lima E, Santos PP, Successful treatment of severe recalcitrant erosive oral lichen Freitas Rde A. An epidemiological study of immune-mediated planus with topical tacrolimus. J Eur Acad Dermatol Venereol skin diseases aff ecting the oral cavity. An Bras Dermatol 2006;20(1):66–68. 2011;86(5):905–909. 28. Arduino PG, Carbone M, Della Ferrera F, Elia A, 44. Kalinska-Bienias A, Kalowska M, Kwiek B, et al. Effi cacy Conrotto D, Gambino A, Comba A, Calogiuri PL, Broccoletti and safety of perilesional/intralesional triamcinolone injections R. Pimecrolimus versus tacrolimus for the topical treatment in oral mucous membrane pemphigoid. Br J Dermatol of unresponsive oral erosive lichen planus: An eight-week 2016;174(2):436–438. randomized double-blind controlled study. J Eur Acad 45. Chaidemenos G, Sidiropoulos T, Katsioula P, Koussidou- Dermatol Venereol 2014;28(4):475–482. Eremondi T. Colchicine in the management of mucous 29. Al Johani KA, Hegarty AM, Porter SR, Fedele S. membrane pemphigoid. Dermatol Ther 2011;24(4):443–445. Calcineurin inhibitors in oral medicine. J Am Acad Dermatol 46. Kirtschig G, Murrell D, Wojnarowska F, Khumalo N. 2009;61(5):829–840. Interventions for mucous membrane pemphigoid/cicatricial 30. Petruzzi M, Lucchese A, Lajolo C, Campus G, Lauritano D, pemphigoid and epidermolysis bullosa acquisita: A systematic Serpico R. Topical retinoids in oral lichen planus treatment: An literature review. Arch Dermatol 2002;138(3):380–384. overview. Dermatology 2013;226(1):61–67. 47. Lee HY, Blazek C, Beltraminelli H, Borradori L. Oral 31. Salgado DS, Jeremias F, Capela MV, Onofre MA, mucous membrane pemphigoid: Complete response to topical Massucato EM, Orrico SR. Plaque control improves the painful tacrolimus. Acta Derm Venereol 2011;91(5):604–605. symptoms of oral lichen planus gingival lesions. A short-term 48. Arduino PG, Lopetuso E, Carcieri P, et al. Professional study. J Oral Pathol Med 2013;42(10):728–732. oral hygiene treatment and detailed oral hygiene instructions 32. Stone SJ, McCracken GI, Heasman PA, Staines KS, in patients aff ected by mucous membrane pemphigoid with Pennington M. Cost-eff ectiveness of personalized plaque specifi c gingival localization: A pilot study in 12 patients. Int J control for managing the gingival manifestations of oral lichen Dent Hyg 2012;10(2):138–141. planus: A randomized controlled study. J Clin Periodontol 49. Kershenovich R, Hodak E, Mimouni D. Diagnosis and 2013;40(9):859–867. classifi cation of pemphigus and bullous pemphigoid. 33. Chan LS, Ahmed AR, Anhalt GJ, et al. The fi rst international Autoimmun Rev 2014;13(4–5):477–481. consensus on mucous membrane pemphigoid: Defi nition, 50. McMillan R, Taylor J, Shephard M, et al. World Workshop diagnostic criteria, pathogenic factors, medical treatment and on Oral Medicine VI: A systematic review of the treatment of prognostic indicators. Arch Dermatol 2002;138(3):370–379. mucocutaneous pemphigus vulgaris. Oral Surg Oral Med Oral 34. Scully C, Lo Muzio L. Oral mucosal diseases: Mucous Pathol Oral Radiol 2015;120(2):132–142.e161.

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Less Common Oral Diseases of Medical Signifi cance

Scott S. De Rossi, DMD, and Katharine Ciarrocca, DMD, MSEd

ABSTRACT The oral cavity is frequently involved in conditions that affect the skin or other multi-organ diseases. In many instances, oral involvement precedes the appearance of other symptoms or lesions at other locations. Anatomically, the mouth is easily accessible. An astute dental provider has the opportunity to observe physical and oral conditions that might include undiagnosed or poorly managed systemic disease. This article reviews four less common oral diseases of medical signifi cance.

AUTHORS

Scott S. De Rossi, DMD, is Katharine Ciarrocca, he oral cavity is frequently in 75 percent of a professor of oral medicine DMD, MSEd, is an involved in conditions that affect cases.1-6 Often, bowel disease precedes the and chairman of oral health assistant professor in the the skin or other multi-organ onset of oral lesions by months or years.1 department of oral health and diagnostic sciences diseases. In many instances, Males are affected by PV nearly twice at The Dental College and diagnostic sciences of Georgia at Augusta at The Dental College oral involvement precedes the as often as females. The peak age range University in Augusta, Ga. of Georgia at Augusta Tappearance of other symptoms or lesions is between the third and sixth decades. Confl ict of Interest University in Augusta, Ga. at other locations. Anatomically, the Laboratory values are generally within Disclosure: None reported. She is a diplomate of the mouth is easily accessible. An astute normal limits, although many patients American Board of Oral 4 Medicine. dental provider has the opportunity to may have a mild anemia, zinc defi ciency 5 Confl ict of Interest observe physical and oral conditions or peripheral eosinophilia. A search for Disclosure: None reported. that might include undiagnosed or an infectious etiology has persistently poorly managed systemic disease. This yielded negative or inconsistent results. article reviews four less common oral diseases of medical signifi cance. Pathogenesis The pathogenesis is unknown although immunological and microbial factors have been suggested as possible etiological Introduction and Epidemiology factors. The association of PV with Pyostomatitis vegetans (PV) is a infl ammatory bowel disease, particularly relatively rare, chronic, non-neoplastic ulcerative colitis, is well-known and in disorder of unknown etiology. The most cases, bowel disease precedes the signifi cance of PV lies in its association onset of oral lesions by months or years.7 A with infl ammatory disease of the bowel, peripheral eosinophilia has been observed including ulcerative colitis, Crohn’s in most reported cases.8 Histologically, disease, spastic colitis and chronic diarrhea. it is characterized by intraepithelial and/ Several case reports and literature reviews or subepithelial abscesses containing have estimated that PV is associated with large numbers of eosinophils.

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Clinical Features Clinically, PV characterized by miliary pustules, erosions and a vegetating dermatosis of skin and mucous membranes.9 Oral lesions typically involve the anterior attached gingiva and the labial and buccal mucosa and FIGURE 1A. FIGURE 1B. are distinct in character. Hard and soft FIGURES 1. Gingival (A) and buccal mucosa lesions (B) associated with pyostomatitis vegetans. palate and tonsillar areas may also be affected. Multiple small, superfi cial, yellowish pustules (2-3 mm in diameter) symptomatic lesions in the oral cavity Hereditary Hemorrhagic Telangiectasia may be present on an erythematous recalcitrant to topical therapy. Some base that can coalesce forming necrotic patients have reported benefi t from Introduction and Epidemiology lesions with a typical “snail tracks” zinc supplementation, and lesions Hereditary hemorrhagic telangiectasia appearance.7 Deep folds in the buccal can resolve following colectomy.10 (HHT) is a genetic disorder of the blood mucosa are common, and small vegetating vessels that affects approximately one papillary projections may be seen over Clinical Signifi cance in 5,000 people. It affects males and the surface of friable mucosa. Patients The relationship between PV females from all racial and ethnic groups. usually describe only mild to moderate and granulomatous diseases of the The disorder is also referred to as Osler- soreness or discomfort despite the gastrointestinal tract, such as Crohn’s Weber-Rendu (OWR) syndrome after extensive involvement9 (FIGURE 1). disease (CD), are of paramount the doctors who studied HHT about 100 importance. Oral lesions, including years ago.13 In 1896, Henri Rendu fi rst Diagnosis and Management PV, can occur in up to 40 percent of described HHT as a hereditary disorder Management of PV consists mainly children with CD and may include involving nosebleeds and characteristic of immunosuppression using topical mucogingivitis, aphthous ulcers or red spots that were distinctly different or systemic corticosteroids with swellings. Occasionally, oral and from hemophilia.14 Before Dr. Rendu’s medical and/or surgical treatment of perianal disease occurs in the absence work, doctors did not understand that any underlying infl ammatory bowel of signifi cant intestinal disease. In individuals with what we now call disease. Identifying and/or controlling one study, oral lesions were reported HHT have abnormalities of their blood associated bowel disease must be the in at least 10 percent of children vessels, not a clotting problem in the primary objective in the management with CD.11 However, when rigorously blood itself. Frederick Weber and Sir of PV. Lesions frequently improve evaluated by a dentist, oral involvement William Osler reported on additional when the colitis is controlled; an was noted in 42 percent of children features of HHT in the early 1900s. exacerbation of colitis is usually followed with CD.11,12 The dentist detected More than a hundred years later, HHT by a similar fl are in oral lesions. Diet oral manifestations of CD in 20 of is still often misdiagnosed in affected modifi cation and systemic medications 48 children, which included: individuals and many doctors do not like antispasmodics, antibiotics, ■ Mucogingivitis (12 patients). understand all of its manifestations. aminosalicylates (e.g., sulfasalazine ■ Mucosal tags (four patients). and mesalamine), corticosteroids, ■ Deep ulceration (four patients). Pathogenesis azathioprine and dapsone may be ■ Cobblestoning (three patients). Mutations in at least fi ve genes are used to treat the bowel disease.6 Oral ■ Lip swelling (three patients). thought to result in HHT, but mutations lesions are often effectively managed ■ Pyostomatitis vegetans in two genes, ENG and ACVRL1/ with topical corticosteroids in a gel (one patient). ALK1, cause approximately 85 percent or formulation. However, Oral lesions in the presence of cases. The frequency of arteriovenous systemic corticosteroids, dapsone and of a positive review of system for malformations (AVMs) in particular organs other immunosuppressive therapy may gastrointestinal problems should warrant and the occurrence of certain rare symptoms be indicated for moderate to severe a biopsy for histologic diagnosis. are dependent on the gene involved.15

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TABLE 1 TABLE 2 FIGURE 2. Multiple oral Other Common Signs and Symptoms of Diagnosing HHT hereditary Hereditary Hemorrhagic Telangiectasia The diagnosis of HHT is defi nite if three of hemorrhagic ■ Abdominal pain the following criteria are present, possible or telangiectasia ■ Anemia suspected if two are present and unlikely if lesions on the ■ Arteriovenous malformations fewer than two are present: dorsum of the tongue. ■ Exercise intolerance ■ Epistaxis (spontaneous, recurrent ■ Fatigue nosebleeds) ■ Intestinal bleeding ■ Telangiectasias (multiple on lips, oral ■ Leg swelling cavity, fi ngers and nose) ■ Migraine headaches ■ Visceral lesions (gastrointestinal ■ Nosebleeds telangiectasias and arteriovenous ■ Seizures malformations) ■ Shortness of breath ■ Family history (fi rst-degree relative ■ Telangiectasias with HHT)

Clinical Features Manifestations of HHT are not generally present at birth, but develop and usually affect the face, lips, tongue, ■ Relatives of patients with HHT with increasing age. About 95 percent oral mucosa, gingiva, conjunctiva, should be screened for the condition. of people with the gene for HHT will trunk, arms and fi ngers.18 Lesions tend Optimal medical management for eventually develop signs or symptoms to occur at a young age and progress as HHT requires distinguishing between of HHT, most often by the age of 40. the patient ages. Bleeding from these organ locations where telangiectasias and However, just because a person reaches the sites is usually mild and easily contained. AVMs are best managed symptomatically/ age of 50 without HHT symptoms does Laser ablation can be used as needed.19 expectantly, versus those in which not mean that he or she is not affected.16 lesions should be detected and treated He or she may have very subtle signs on Diagnosis and Management before the onset of symptoms. physical exam and lab testing that only a Patients can present with a wide clinician well-familiar with HHT might spectrum of clinical problems, such as Clinical Signifi cance detect. However, most patients are unaware telangiectasias and AVMs, caused by Bleeding from oral AVM can occur but of their diagnoses. If the oral health abnormal vascular structures. They is rarely clinically important. The main professional suspects HHT, the patient may also have a family history of HHT. concern is often cosmetic; short-term benefi ts should be referred for screening and be Molecular genetic testing is used to may be obtained via laser or other ablation queried if there is a fi rst-degree relative establish the genetic subtype of HHT therapies. Care should be taken by the oral with HHT. The earliest symptom of HHT in a clinically affected individual health professional to avoid traumatic injury is usually epistaxis, often developing in and family and for early diagnosis to to oral AVMs. Chemical and laser cautery adolescence. Patients also start to develop allow for appropriate screening and is often effective in controlling bleeding small telangiectasias on the face, lips, preventive treatment20 (TABLE 2). associated with oral lesions.21 Oral health palate, fi ngers and along the gastrointestinal care providers who recognize key features tract. A large number of HHT patients Key Features of HHT and work to establish the diagnosis will also have or develop AVMs in one or ■ HHT is underrecognized and signs with a physician can help to minimize more visceral organs. Complications of and symptoms may be identifi ed the potentially hemorrhagic effects and/or AVMs in the lungs and liver are generally by oral health professionals. AVMs discovered beyond the oral cavity. the consequence of blood shunting through ■ Patients with HHT require annual these abnormal blood vessels, which monitoring for new telangiectasias Granulomatosis With Polyangiitis lack a capillary bed and thus result in a and AVMs and for complications direct artery-to-vein connection.17 These related to existing lesions. Introduction and Epidemiology AVMs can cause mild to life-threatening ■ Treatments such as embolization, Granulomatosis with polyangiitis (GPA), complications and, because they are hidden, laser therapy or surgery may be formerly called Wegener’s granulomatosis, make HHT one of the most challenging required for oral telangiectasias was fi rst described by Friedrich Wegener diseases to diagnose17 (FIGURE 2, TABLE 1). or visceral lesions. in 1936. It is a multisystem granulomatous Telangiectasias of the skin and mucosa ■ Many patients will require regular disease and necrotizing vasculitis of unknown are common among patients with HHT replenishment of iron stores. etiology.22 However, it is thought that GPA

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may be related to unregulated cell-mediated immunologic mechanisms. This is based on its resemblance to the systemic vasculitis of polyarthritis nodosa, serum sickness, the presence of immune complexes in FIGURE 3. Strawberry gingivitis associated FIGURE 4. Aphthous-like lesions associated with glomeruli of some of the affected patients with granulomatosis with polyangiitis. Behçet’s disease. and the presence of sterile granulomas in tissue sections.23 Accordingly, it is interactions. The initiating event is with GPA.30 SG initially manifests in the suggested that GPA may represent some ANCA-induced leukocyte activation, interdental papillae, spreads to involve form of hypersensitivity to an unknown in which PMN-derived mediators wider zones and usually leads to gingival inhaled infectious or environmental (e.g., cytokines, lipid metabolites, etc.) enlargement.31 This distinct gingival agent, combined with genetic factors.24 are intimately involved. The result is alteration eventually gives rise to short, necrotizing infl ammation of blood vessel bulbous and fragile granular hemorrhagic Pathogenesis walls. The causative agent(s) leading to lesions (FIGURE 3). In contrast to the Although a single disease entity, GPA granuloma formation, predominantly in characteristic gingival lesions, oral displays a set of clinical manifestations, each the respiratory tract, is still unknown.26 ulcerations can be seen later in the course of with a different immunopathogenesis.24 disease and usually appear after development Granuloma formation, vasculitis and Clinical Features of renal and lung involvement. glomerulonephritis are the histologic Clinically, GPA has a predilection to hallmarks of GPA, which can occur males and affects people of all ages, with a Diagnosis and Management together in full-blown disease or mean age of 40 years.27 In its classic form, Laboratory investigations reveal separately in “initial-phase” disease. the disease is characterized by the triad of specifi c fi ndings in GPA, which include The American College of acute necrotizing granulomas of the upper elevated ANCA with two distinct cellular Rheumatology’s criteria for GPA respiratory tract (ear, nose, sinuses, throat), patterns. The more common is known include the following: the lower respiratory tract (lung) or both; as “cytoplasmic” (C-ANCA), and less ■ Nasal or oral infl ammation (painful necrotizing or granulomatous vasculitis frequently “perinuclear” (P-ANCA).32 or painless oral ulcers, or purulent affecting small- to medium-sized vessels, Additionally, a signifi cantly higher or bloody nasal discharge). most prominent in the lungs and upper percentage of serine protease 3 (PR-3) is ■ Abnormal chest radiograph showing airways, but affecting other sites as well; found in GPA patients when compared nodules, fi xed infi ltrates or cavities. and renal disease in the form of segmental to normal controls or other patients with ■ Abnormal urinary sediment necrotizing glomerulonephritis and renal unrelated immune disorders. PR-3 is a (microscopic hematuria with papillary necrosis.28 The typical history is neutral serine protease in azurophil granules or without red cell casts). that of granulomatous disease presenting of human polymorphonuclear leukocytes ■ Granulomatous infl ammation initially in the upper respiratory tract with and monocyte lysosomal granules.33 on biopsy of an artery or sinusitis, nasal discharge, serous otitis media, Leukocytosis, elevated sedimentation perivascular area. hemoptysis and pleurisy. Involvement of rate and anemia may also be found. The different clinical manifestations other systems, particularly the kidneys, At present, despite the increasingly are characterized by multiple immune usually ensues. Nevertheless, limited wide range of potential therapies, abnormalities that culminate in the and superfi cial GPA are also reported cyclophosphamide plus corticosteroids overproduction of autoantibodies directed when only respiratory disease or skin and remain the most recognized and effective mainly against proteinase 3 (PR3- mucosal lesions are seen, respectively.29 means of inducing and sustaining antineutrophil cytoplasmic antibodies Oral lesions are noted only in a remission of GPA.24 With additional (ANCA)).25 The most common hypothesis minority of cases and rarely are the initial research, the use of specifi c mediators for ANCA-mediated vasculitis involves presentation of disease. Localized or diffuse (e.g., cytokines, adhesions molecule the interaction of polymorphonuclear “strawberry gingivitis” (SG) is the most antagonists, anti-id ANCA, etc.) to neutrophils (PMN) and endothelial characteristic oral lesion that usually modulate the infl ammatory response may cells (EC) via cell adhesion molecule appears before the patient is diagnosed prove benefi cial in the therapy of GPA.

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TABLE 3 Criteria For Diagnosis Of Behçet’s Disease Recurrent oral ulceration Minor/major aphthous or herpetiform ulcer observed by the physician or patient that number of other systemic manifestations proposed in 1990, the presence of oral recurred at least three times in one 12-month may be seen due to necrotizing vasculitis. aphthous ulcerations (FIGURE 4) and two period plus two of the following: The onset of the disease is usually between of the following clinical manifestations Recurrent genital ulceration the ages of 20 and 30 and affects men are required for the diagnosis of BD: Aphthous ulcer or scarring observed by the twice as often as women. The disease is ■ Recurrent genital ulcerations. physician or patient seen worldwide, but is more common in ■ Skin lesions such as erythema Eye lesions Mediterranean and Asian populations. nodosum-like lesions. Anterior/posterior uveitis, cells in the vitreous ■ Papulopustular lesions. on slit-lamp examination or retinal vasculitis Pathogenesis ■ Ocular involvement. observed by an ophthalmologist Although the pathogenesis of ■ Positive pathergy test. Cutaneous lesions BD remains unknown, as with other The diagnostic criteria are Erythema nodosum observed by physician or autoimmune diseases, the disorder may summarized in TABLE 3.36 patient, pseudofolliculitis or papulopustular represent aberrant immune activity lesions, or acneiform nodules observed by triggered by exposure to an agent, perhaps Diagnosis and Management physician in postadolescent patients not infectious, in patients with a genetic There are no specifi c diagnostic receiving corticosteroids predisposition to develop the disease.34 laboratory tests or histopathologic fi ndings Positive pathergy test Major disease mechanisms in Behçet’s for BD. Therefore, the diagnosis of BD Interpreted by the physician at 24 to 48 hours syndrome include increased neutrophil relies on clinical criteria and often takes functions, such as chemotaxis and several years to establish a defi nitive Source: International Study Group for Behçet’s Disease. phagocytosis, and excessive production diagnosis after the appearance of the initial Criteria for diagnosis of Behcet’s disease. The Lancet 1990;335(8697):1078–1080. of reactive oxygen species (ROS), manifestations. Findings of HLA-B5101, including superoxide anion, which may raised serum immunoglobulin D (IgD) and be responsible for oxidative tissue damage antibodies to cardiolipin are supportive Clinical Signifi cance seen in BD, and immunological alterations of the diagnosis. Disease activity may be Prompt diagnosis of GPA or including T lymphocyte abnormalities in assessed by serum levels of acute phase microscopic polyangiitis is important both subpopulation and function have reactants, such as C-reactive protein to permit initiation of therapy that may been considered to be correlated with and erythrocyte sedimentation rate.37 be lifesaving and organ-sparing. This BD. There is some anecdotal evidence Treatment of BD is primarily may be diffi cult because presenting suggesting that emotional stress and symptomatic, focusing on reducing signs and symptoms are hard to hormonal alterations may infl uence the discomfort and preventing serious distinguish from those of a patient course and disease activity of BD. complications.38 Most often, patients with nonvasculitic processes, such as are managed by a rheumatologist in infection or malignancy. Oral lesions Clinical Features consultation with various other specialists should be biopsied for histologic Manifestations of BD are not consistent including oral health professionals. diagnosis. A positive ANCA test strongly among patients. Clinical presentations Treatment of oral ulcerations associated suggests the diagnosis of vasculitis, but are very heterogeneous and evolution with BD is identical to the treatment both diagnostically false-positive and of the disease varies due to ethnic, of major aphthae and includes the use false-negative results may be seen. geographical and individual differences. of topical glucocorticoids.39 Treatment The most common presenting symptoms for the mucocutaneous manifestations Behçet’s Disease are recurrent oral aphthous ulcerations of BD are summarized in TABLE 4. and genital ulcerations.35 Oral lesions are Introduction and Epidemiology seen in nearly 100 percent of cases and Clinical Signifi cance Behçet’s disease (BD) is a rare condition are commonly the initial manifestation BD is not a contagious disease, and characterized by a triad of symptoms of the disease. Oral lesions may precede symptoms vary from person to person. The including aphthous-like oral ulcerations the diagnosis by up to 10 years. most common symptoms and signs include along with genital ulceration and eye According to the criteria of the oral and genital ulcers, infl ammation of the disease, namely iridocyclitis. However, a International Study Group, which was eye, skin lesions and arthritis. Associated

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TABLE 4 Treatment of Mucocutaneous Manifestations

Mild to Moderate Severity Moderate to Severe Severity Oral ulceration — examples include topical Thalidomide corticosteroid and palliative rinses (i.e., Azathioprine 17. de Gussem EM, Faughnan ME. Pulmonary Vascular Manifestations of Hereditary Hemorrhagic Telangiectasia. Orphan Lung Diseases. viscous lidocaine) Infl iximab/etanercept Springer London, 2015. 191–200. Topical steroids 18. Nada S, Bhatt SP. Hereditary hemorrhagic telangiectasia: Epistaxis and hemoptysis. CMAJ 2009;180:838. Genital ulceration Topical steroids Colchicine in females 19. Irani F, Kasmani R. Hereditary hemorrhagic telangiectasia: Fatigue Thalidomide and dyspnea. CMAJ 2009;180:839. Manawadu D, Vethanayagam Azathioprine D, Ahmed SN. Hereditary hemorrhagic telangiectasia: Transient Infl iximab ischemic attacks. CMAJ 2009;180:836–7. 20. Latino GA, et al. Targeting underdiagnosis in hereditary Erythema nodosum Colchicine hemorrhagic telangiectasia: A model approach for rare diseases? Corticosteroids Orphanet J Rare Dis 9.1 (2014): 1–10. 21. Karnezis TT, Davidson TM. Treatment of hereditary hemorrhagic Acne Local corticosteroid/antibiotic telangiectasia with submucosal and topical bevacizumab therapy. applications (in combination) Laryngoscope 122.3 (2012): 495–497. 22. Wegener F. Uber generalisierte, septische Gefaesserkrankungen. Verh Dtsch Ges Pathol 29:202–27, 1936. 23. Kumar V, Abbas A, Fausto N. Pathologic Basis of Disease. 7th ed. Philadelphia: Elsevier Saunders 2005. p. 541. anterior or posterior uveitis, retinitis and REFERENCES 24. Almouhawis HA, et al. Wegener’s granulomatosis: A review of iritis seen in BD may be serious and lead to 1. Hansen LS, Silverman S Jr., Daniels TE. The diff erential diagnosis of clinical features and an update in diagnosis and treatment. J Oral pyostomatitis vegetans and its relation to bowel disease. Oral Surg Pathol Med 42.7 (2013): 507–516. loss of vision if untreated. The oral health Oral Med Oral Pathol 1983; 55 (4): 363–73. 25. Gross WL, Trabandt A, Csernok E. Pathogenesis of Wegener’s professional suspicious of BD should refer 2. Neville BW, Smith SE, Maize, JC, Laden SA, Denton WT. granulomatosis. Ann Med Interne (Paris). 1998 Sep;149(5):280–6. the patient to an ophthalmologist for a Pyostomatitis vegetans. Am J Dermatopathol 1985; 7 (1); 69–77. 26. Lutalo PMK, D’Cruz DP. Diagnosis and classifi cation of 3. Sollecito TP, Stoopler Et, Rangarajan S, Pinto A. Pyostomatitis granulomatosis with polyangiitis (aka Wegener’s granulomatosis). J complete eye exam if ocular manifestations vegetans and : A case report and review of Autoimmun 48 (2014): 94–98. are present. Other more serious symptoms the literature. Int J Gastroenterol 2003; 2: 2. 27. Yi ES, Colby TV. Wegener’s granulomatosis. Semen Diagn Pathol of the disease may include blood clots, 4. Ficarra G, Cicchi P, Amorosis A, Piluso S. Oral Crohn’s disease and 18:34–46, 2001. pyostomatitis vegetans. An unusual association. Oral Surg Oral Med 28. Comarmond C, Cacoub P. Granulomatosis with polyangiitis infl ammation in the central nervous Oral Pathol 1993; 75 (2): 220–24. (Wegener): Clinical aspects and treatment. Autoimmun Rev 13.11 system, symptoms of the digestive tract 5. Soriano Ml, Martinez N, Grilli R, Farina MC, Martin L, Requena (2014): 1121–1125. and, occasionally, involvement of the L. Pyodermatitis-pyostomatitis vegetans. Oral Surg Oral Med Oral 29. Patten SF and Tomecki JT. Wegener’s granulomatosis: Cutaneous Pathol 1999; 87: 322–26. and oral mucosal disease. J Am Acad Dermatol 28: 710-718, 1993. kidneys. Treatment of BD is symptomatic 6. Ballo FS, Camisa C, Allen CM. Pyostomatitis vegetans. Report of 30. De Rossi SS, Abdelsayed R, Ciarrocca K. Gingival lesions in a and aimed at reducing symptoms and a case and review of the literature. J Am Acad Dermatol 1989; 21 21-year-old man. J Am Dent Assoc 143.3 (2012): 253–258. preventing complications. Prognosis varies (2); 381–7. 31. Eufi nger H, Machtens E and Akuamoa-Boateng E. Oral 7. Shah S, Cotliar J. Pyostomatitis Vegetans. N Engl J Med 368.20 manifestations of Wegener’s granulomatosis: Review of the literature based on the organ systems involved. (2013): 1918–1918. A peripheral eosinophilia has been observed and report of a case. Int Oral Maxillofac Surg 21:50–53, 1992. in most reported cases. 32. Nolle B, Specks U, Ludemann J, et al. Anticytoplasmic Summary 8. Shephard M, Venda Nova C, Hodgson TA. Eosinophilia associated autoantibodies: Their immunodiagnostic value in Wegener’s with disease exacerbations in a patient with pyostomatitis vegetans. Br granulomatosis. Ann Intern Med 111:28–40, 1989. Careful examination of the oral J Dermatol 173.6 (2015): 1556–1557. 33. Yang T, et al. Inhibition of T Cell Proliferation by Granulocyte cavity may reveal fi ndings indicative of 9. DeRossi SS, et al. Chronic lesions of the gingiva and mucosa. J Am Membrane-Associated Proteinase 3 Is Reversed by Blocking the an underlying systemic condition and Dent Assoc 138.12 (2007): 1589–1592. Interaction of Calreticulin With LRP on T Cells. Blood 124.21 (2014): 10. Nico MM, et al. Pyostomatitis vegetans and its relation to 4110–4110. allow for early diagnosis and medical infl ammatory bowel disease, pyoderma gangrenosum, pyodermatitis 34. de Chambrun MP, et al. New insights into the pathogenesis of treatment. It is imperative that oral vegetans and pemphigus. J Oral Pathol Med 41.8 (2012): Behçet’s disease. Autoimmun Rev 11.10 (2012): 687–698. health professionals carefully evaluate 584–588. 35. Alpsoy E, Zouboulis C, Ehrlich GE. Mucocutaneous lesions of 11. Harty S, et al. A prospective study of the oral manifestations of Behçet’s disease. Yonsei Med J 2007;48(4):573–585. patients in the context of a comprehensive Crohn’s disease. Clin Gastroenterol Hepatol 3.9 (2005): 886–891. 36. Yazici H, Yazici Y. Criteria for Behçet’s disease with refl ections on health history and review of systems. 12. Pittock S, et al. The oral cavity in Crohn’s disease. J Pediatr 138.5 all disease criteria. J Autoimmun 48 (2014): 104–107. The oral cavity is a vital anatomical (2001): 767–771. 37. DavatchiF, et al. Impact of the positive pathergy test on the 13. McDonald J, Pyeritz RE. Hereditary Hemorrhagic Telangiectasia. performance of classifi cation/diagnosis criteria for Behçet’s disease. location involved in various critical (2014). Mod Rheumatol 23.1 (2013): 125–132. physiologic processes, such as digestion, 14. Rimmer J, Lund VJ. Hereditary haemorrhagic telangiectasia. 38. Davatchi F, et al. Treatment of Behçet’s disease. J Chronic Dis 1.1 respiration and speech. Because the mouth is Rhinology 53.2 (2015): 129–134. (2013): 42–54. 15. Garrido-Martin EM, et al. Common and distinctive pathogenetic 39. Katsanos KH, et al. Review article: nonmalignant oral frequently involved in conditions that affect features of arteriovenous malformations in hereditary hemorrhagic manifestations in infl ammatory bowel diseases. Aliment Pharmacol the skin or other multi-organ diseases such telangiectasia 1 and hereditary hemorrhagic telangiectasia 2 animal Ther 42.1 (2015): 40-60. Treatment for the mucocutaneous as those discussed in this article, the oral models — brief report. Arterioscler Thromb Vasc Biol 34.10 (2014): manifestations of BD are summarized. 2232–2236. health professional can play a vital role in 16. Kamath N, et al. Hereditary hemorrhagic telangiectasia. North THE CORRESPONDING AUTHOR, Scott S. De Rossi, DMD, can be promoting health and preventing disease. ■ Am J Med Sci 7.3 (2015): 125. reached at [email protected].

576 SEPTEMBER 2016 acromegaly

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Acromegaly: A Dental Disease?

Gil Ivry, DDS, MD, and Alan L. Felsenfeld, MA, DDS

ABSTRACT Acromegaly is a serious disease that affects the pituitary gland causing unusual growth in patients. There are various dental manifestation of the condition and it is plausible that a dentist will be the fi rst to recognize the problem. This article describes the disease and the dental implications for patients who have it.

AUTHORS

Gil Ivry, DDS, MD, Alan L. Felsenfeld, MA, t is a quiet Thursday morning in your the term “acromegaly” and developed a trained at the University of DDS, is a professor of practice and a new patient, who is a set of criteria for the clinical diagnosis of California, Los Angeles, clinical dentistry at the 56-year-old male, presents for an initial the problem.2 It was not until 1909 when School of Dentistry for University of California, Los his predoctoral education Angeles, School of Dentistry consultation and dental evaluation. Harvey Cushing, through multiple autopsies, and the UCLA School of in the section of oral and He states that he noted a change in his correlated acromegaly with pituitary Medicine for his medical maxillofacial surgery. He is Ibite in the past year along with increasing enlargement. Current literature shows males degree. He completed a a board-certifi ed oral and spacing between his front teeth, and is and females are equally affected, and the UCLA School of Dentistry maxillofacial surgeon and asking about orthodontics and veneers for average age of presentation is 44 years.3 residency in oral and former editor-in-chief of the maxillofacial surgery and is Journal of the California cosmetic reasons. Further discussion of his Under normal conditions, signaling in private practice in Santa Dental Association. medical history elicits a recent diagnosis of from the hypothalamus by growth hormone Monica, Calif. Confl ict of Interest hypertension and prediabetes. Examination releasing hormone (GHRH) stimulates Confl ict of Interest Disclosure: None reported. of the patient shows a well-developed male the anterior pituitary to secrete growth Disclosure: None reported. with a prognathic resulting in a hormone (GH), which has direct effects class III , interproximal spacing on tissue as well as stimulating the liver between the mandibular and maxillary to produce insulin-like growth factor-1 anterior teeth, and forehead (IGF-1). There is a control mechanism built enlargement. He has a deep voice and large in with GH and IGF-1 negative feedback hands. Given the recent changes in his loops to the pituitary and hypothalamus bite with an otherwise normal TMJ exam (FIGURE 1). Unregulated overproduction and development of high blood pressure of GH is what leads to acromegaly. and diabetes, you suspect a systemic disease The diagnosis of acromegaly requires process. As you question the patient further, demonstration of increased GH secretion he reveals that he underwent a neurosurgical as well as elevated IGF-1 levels. Random procedure a few months ago to remove a and fasting GH and IGF-1 levels brain tumor. Your patient has acromegaly. facilitate making a defi nitive diagnosis, and a gadolinium-enhanced MRI of the Pathophysiology of Acromegaly pituitary gland is used to evaluate for Acromegaly is a rare disease fi rst an adenoma. Random GH levels less described by Andrea Verga in 1864 as than 0.04 μg/l excludes a diagnosis of “prosopectasia,” or enlarged face, with acromegaly. Additionally, the inability to an incidence of two to three per million appropriately suppress GH secretion with per year, most frequently due to a growth an oral glucose challenge is used as an hormone secreting pituitary adenoma.1 important diagnostic tool. After the patient In 1886, Pierre Marie fi rst established is given an oral glucose load of 75 grams

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TABLE

Stress Systemic and Orofacial Presentation of Excessive GH Production

Exercise Systemic Orofacial Sleep rhythms Headaches Visual changes (bitemporal Macroglossia β-Adrenergic − hemianopsia) Frontal bossing -Adrenergic + α Obstructive sleep apnea Class III malocclusion Dopaminergic + − Gastroesophageal refl ux disease Spacing between mandibular teeth − (GERD) Anterior open bite Peptidergic Arthritis Major salivary gland enlargement neurons Carpal tunnel syndrome Thickened lips GHRH + − Somatostatin Hypertension, cardiomegaly, arrhythmias, heart failure, valvulopathy Pituitary Skin tags, excessive perspiration Growth hormone Bone and Diabetes, insulin resistance tissue Renal failure growth IGF-1 Hypogonadism, erectile dysfunction Direct Dyslipidemia eff ects on Colon polyps tissues Liver Osteopenia Large hands

FIGURE 1. Hypothalamic-pituitary axis. and demonstrates the inability to suppress the pituitary gland from the tumor or indicated, similar radiographic signs, as GH secretion to less than 1 μg/l within two other sources. As indicated, there are well as other diagnostic indicators, can hours, a diagnosis of acromegaly is likely.4 numerous dental manifestations of this be seen on the lateral cephalometric The most common cause of acromegaly disease that can be evaluated easily by fi lm or image as shown in FIGURE 4.6,7 is a pituitary adenoma, a benign expansile dentists. The TABLE is a listing of most tumor of the gland. Other causes, although of the presenting signs and symptoms of Management of Acromegaly very rare, can include adrenal, thyroid, the disease. See FIGURES 2A and 2B for a The treatment of patients with brain, pancreas or lung tumors that cause clinical view of a patient with acromegaly. acromegaly has numerous considerations a section of GH in a manner similar to the depending on co-morbidities, patient pituitary adenomas. Radiographic Evaluation desires and responses to treatment. Acromegaly in a growing child is called When a patient presents with the FIGURE 5 represents an algorithmic approach gigantism and is related to signifi cant potential diagnosis of untreated acromegaly, to the management of acromegaly. activity of IGF-1 while the child is still he or she should be referred to a physician growing before closure of the epiphyseal (primary care, internist, neurologist, Surgical Treatment plates. With gigantism, the child will show endocrinologist or neurosurgeon) for Acromegaly can be treated by a disproportionate vertical height changes, further evaluation before any non-emergent number of different methods including which do not occur frequently in the dental treatment is rendered. Medical surgery, radiation and medical therapy. adult with acromegaly. Management of evaluation will include the glucose challenge With recent surgical advances, more than the pediatric patient is similar to that of as discussed above and other studies as 90 percent of pituitary tumors are treated acromegaly in adults with normalization indicated. MRI studies and other specialized with a minimally invasive approach via of GH and IGF-1 levels but without examinations will be obtained before the transsphenoidal approach. CT-guided radiation secondary to the potential long- defi nitive treatment. It is not uncommon surgery and intraoperative MRI have term effects of the therapy on a child.5 to see enlargement and irregularity of the facilitated localization of pituitary tumors sella turcica on a CT scan as a result of to ensure complete resection and decreased Patient Examination the tumor growth as seen in FIGURE 3. surgical complications. Microadenomas, A patient with acromegaly will present For the patient who has been tumors with diameters < 1cm, have with myriad signs and symptoms that treated or controlled, when orthodontic remission rates of 80 percent with are related to increased stimulation of or orthognathic surgical treatment is normalization of GH and IGF-1 levels after

578 SEPTEMBER 2016 CDA JOURNAL, VOL 44, Nº9

side effects including nausea, constipation, headaches and dizziness, compliance is poor for these dopamine drugs.

Dental Management Dental providers are key in helping to make the initial diagnosis of acromegaly in the untreated patient. General dentists and specialists can recognize the clinical and radiographic signs, including an enlarged sella FIGURE 2A. Note long lower face height FIGURE 2B. Note prognathic mandible, or protruding forehead and newly occurring and prominent chin. (Courtesy of Sandy prominent chin and frontal bossing. (Courtesy prognathism. Patients may also present Ratner, DDS.) of Sandy Ratner, DDS.) with complaints of increased interdental spacing. Once appropriately diagnosed and the underlying cause of acromegaly is treated, dental professionals can facilitate oral rehabilitation. While frequently the quantity of bone is increased secondary to the disease, the quality of bone is unchanged from patients without acromegaly. Increased interdental spacing can be treated with veneers, crowns or orthodontics. Class III skeletal growth with a prognathic mandible can be managed with orthodontics and/or orthognathic surgery.12 FIGURE 3. Sagittal CT scan showing enlarged and Sleep apnea is a common comorbidity in irregular sella turcica. FIGURE 4. Lateral cephalometric fi lm showing acromegaly secondary to thickening of the frontal bossing and mandibular hyperplasia. airway walls, but will resolve in some patients following normalization of the GH levels. surgical resection, though the remission Medical Treatment However, the patient with acromegaly and rates drop to 30 percent for macroadenomas Treatment guidelines for acromegaly sleep apnea presents special problems, as with tumor diameter more than 1 cm. Side recommend surgical resection of retropositioning the mandible to treat the effects of surgery include local hemorrhage, pituitary adenomas as the primary prognathism is inconsistent with the principles cerebrospinal fl uid leak, diabetes insipidus, treatment.10 In cases when initial surgery of obstructive sleep apnea management, infection and pituitary hormone defi ciency.8 is contraindicated or disease persists, necessitating alteration in conventional medications have been developed. treatment planning.13,14 While it may seem Radiation Control of GH and IGF-1 is the goal for counterintuitive to be concerned about In larger tumors or those invading vital pharmacologic treatment of acromegaly. airway in patients with acromegaly, studies adjacent structures, adjunctive radiotherapy Blocking GH secretion with somatostatin have shown diminished dimensions at the is recommended. Conventional external- receptor analogs including octreotide nasal, uvular and mandibular pharyngeal beam radiation has been used with a and lanreotide are fi rst-line medical levels as well as at the narrowest point of maximum dose of 40-50 Gy spread into therapies.11 Bromocriptine, a dopamine the pharyngeal airway space compared to multiple weekly doses. Recent advances agonist, has been used in the past to healthy controls.15 In patients with partial have allowed a more localized radiation treat acromegaly with only a 10 percent or complete edentulism, rehabilitation of beam with stereotactic precision, which normalization of IGF-1 levels but has the dentition in a Class III relationship has delivers more localized irradiation with been replaced with cabergoline, a newer, been reported when orthognathic surgery is less toxicity to surrounding tissue.9 longer-acting dopamine agonist.5 With contraindicated or undesired by patients.16

SEPTEMBER 2016 579 acromegaly

CDA JOURNAL, VOL 44, Nº9

Management of Acromegaly

GH-secreting adenoma

likely Assess likelihood of unlikely Somatostatin surgical cure analogue

Debulking required for Surgery CNS pressure eff ects

controlled elevated controlled Measure GH/IGF-1 Measure GH/IGF-1

Somatostatin analogue Monitor Monitor controlled Measure GH/IGF-1

Increase dose/frequency of somatostatin analogue, add uncontrolled GH receptor antagonist or add dopamine agonist

■ GH receptor antagonist controlled uncontrolled ■ Radiation therapy Monitor Measure GH/IGF-1 ■ Reoperation

Source: Kasper DL, Fauci S, Hauser SL, Longo DL, Jameson L, Loscalzo J. Harrison’s Principles of Internal Medicine, 19th ed. www. accessmedicine.com Copyright © McGraw-Hill Education. All rights reserved.

FIGURE 5. Algorithm for management of acromegaly (Adapted from Melmed S, et al: J Clin Endocrinol Metab 94:1509–1517, 2009. Reprinted with permission from McGraw-Hill Education.)

Conclusion spacing, the quality and physiology of remission. J Clin Endocrinol Metab 2003; (88):3567–72. 9. Wilson CB. Surgical management of pituitary tumors. J Acromegaly is not a dental disease the bone is not altered and allows for Clin Endocrinol Metab 1997; 82:2381–85. but has multiple dental manifestations. routine dental and surgical care. ■ 10. Buchfelder M1, Schlaff er S. Surgical treatment of The insidious nature of the disease pituitary tumours. Best Pract Res Clin Endocrinol Metab REFERENCES 2009; 23(5):677–92. process could mean that the dentist 1. Holdaway IM, Rajasoorya C. Epidemiology of 11. Melmed S. New therapeutic agents for acromegaly. Nat might be the practitioner who sees a acromegaly. Pituitary 1999; 2(1):29–41. Rev Endocrinol 2016; 12(2):90–8. patient on a regular basis and takes 2. Mammis A, Eloy JA, Kiu JK. Early description of 12. Yagi T, Kawakami M, Takada, K. Surgical orthodontic acromegaly and gigantism and their historical evolution as correction of acromegaly with mandibular prognathism. note of the changes to facilitate early clinical entities. Neurosurg Focus 2010; 29(4): 1–6. Angle Orthod 2004;74:125–131. diagnosis. Unchecked acromegaly can 3. Scacchi M1, Cavagnini F. Acromegaly. Pituitary 2006; 13. Smith CB, Waite PD. Surgical management of obstructive lead to death, which emphasizes the 9(4):297–30d. sleep apnea in acromegaly with mandibular prognathism 4. Melmed S, et al. Guidelines for acromegaly management: and macroglossia: A treatment dilemma. J Oral Maxillofac need for early diagnosis and treatment. An update. J Clin Endocrinol Metab 2009; 94:1509–1517. Surg 2012; 70:207–210. Patients with acromegaly who 5. American Association of Clinical Endocrinologists. 14. Watson NF, Vitiello MV. Management of obstructive have been treated are a relatively rare Medical guidelines for clinical practice for the diagnosis sleep apnea in acromegaly. Sleep Med 2007; 8: 539–40. and treatment of acromegaly — 2011 update. Endocr Pract 15. Tuncer BB, Bavbek NC, et al. Craniofacial and occurrence in any practice. However, the 2011; 17(Suppl 4):1–44. pharyngeal airway morphology in patients with acromegaly. dental management of this patient cohort, 6. Dostolaova S, Sonka, K, Smahel Z, et al. Cephalometric Acta Odontol Scand 2014 73(6); 433–40. with very few exceptions, allows them to assessment of cranial abnormalities in patients with 16. McKenna G, Hayes M, Burke FM. Prosthodontic acromegaly. J Craniomaxillofac Surg 2003; 31:80–87. rehabilitation of a patient with acromegaly. Eur J Prosthodont be treated as normal patients. While the 7. Chang, HP, Tseng, YC, Chou TM. An enlarged sella turcica Restor Dent 2014; 22(3):98–100. amount of bone in the jaws is excessive, on cephalometric radiograph. Dentomaxillofac Radiol 2005; generally resulting in a prognathic 34:308–12. THE CORRESPONDING AUTHOR, Alan L. Felsenfeld, DDS, can be 8. De P, Rees DA, Davis N, et al. Transsphenoidal surgery for reached at [email protected]. mandible or increased interdental acromegaly in Wales: Results based on stringent criteria of

580 SEPTEMBER 2016 Specialists in the Sale and Appraisal of Dental Practices Serving California Dentists since 1966 Practices How much is your practice worth?? Wanted Selling or Buying, Call PPS today! VisitVisit PPPSPS aatt CCDADA BBoothooth ##14141414 NORTHERN CALIFORNIA SOUTHERN CALIFORNIA (415) 899-8580 – (800) 422-2818 (714) 832-0230 – (888) 440-5957 Raymond and Edna Irving Thomas Fitterer and Dean George [email protected] [email protected] www.PPSsellsDDS.com www.PPSDental.com California DRE License 1422122 California DRE License 346937 6110 CONCORDCORD WWellell ccaredared fforor ppractice.ractice. 20201515 ccollectedollected ANTELOPE VALLEY Has grossed $1.8 Million. Fantastic location. $260,000 in 2015. 3-ops. 580 patients. Great curb appeal. Little 60,000 autos pass by per day. 8 ops. Partnership for $250,000 or buy all. done in marketing. Great merger opportunity for nearby practice. ARCADIA Facility only. 3-ops equipped. $65,000 or $95,000 with Ortho. 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Beautiful office. UCR Fees! Extremely NORCO – CORONA Will do $1.5 Million. 8-ops. Exquisite. Full attractive selling features available to retain the goodwill. Price $1.2 Million. NORWALK Fantastic high identity location. 5 ops. Full Price 6103 SAN FRANCISCO’S UNION SQUARE Opportunity to $250,000. SOLD acquire highly regarded practice with condo. Beautiful 5-ops, ORAL SURGERY PRACTICE – LOS ANGELES Established 40 years. digital and paperless. 6th op available. 2015 collected $658,000. ORANGE Beautiful 10 operatory office ready for merger. 6100 SANTA CLARA Phenomenal launching pad for next Owner. PASADENA Established 60 years. 7-ops. Always $1+ Million. Full Fantastic location, 5-op facility. Management not taking advantage Price $600,000. of what is possible even though 2015 collected $758,000 with REDLANDS Shopping center. Grosses $350,000. Full Price $250,000. Profits of $323,000. Perfectly positioned to be a $1 Million+ year RIVERSIDE Facility only. 4 ops. Full Price $50,000. performer immediately! Needs young DDS. SOUTH ORANGE COUNTY BEACH CITY Grosses $650,000. 4 ops. Beautiful! 6098 WEST PETALUMA Petaluma has become THE business PERIO PRACTICE - PRESTIGIOUS BEACH CITY Established center of the North Bay! Business parks are growing and young 40 years. professionals are being drawn to this great family community per TORRANCE Established 12 years. 5 star building. 3-ops. Grossing the unique amenities of this historic river city. Collected $468,000 $250,000. Full Price $195,000. with Profits of $199,000. 3-days of Hygiene with 4th day starting TUSTIN Dental building. Full Price $1.5 Million. September. VENTURA - OXNARD 5-ops. Grossing $850,000. High identity. Full Price $685,000. 6089 MOUNT SHASTA Small town living renowned for outdoor YUCCA VALLEY 8/10th of an acre. Great highway visibility. Full lifestyle. Best air and water! Escape Rat Race and corporate Price $250,000. intrusion. 3-day week collected $881,000. Available Profits totaled Seeking Senior Dentists wishing to have more time to enjoy life, be free $485,000. Digital radiography including Pano. Full price of management & overhead to join a Dental Cooperative. Call Tom $350,000. Fitterer at 714-832-0230 or cell 714-345-9659. 6070 VISALIA This practice is well positioned for its next **FOUNDERS OF PRACTICE SALES** caretaker. Strong Hygiene Department, beautiful facility, well 120+ years of combined expertise and experience! equipped. Digital throughout.SOLD Collected $727,000 on part-time 3,000+ Sales - - 10,000+ Appraisals schedule in 2015. Extend hours and be busier. Best location! **CONFIDENTIAL** PPS Representatives do not give our business name when returning your calls. *>4280:8E8<68<@4::8<60<30>>?08@8<634?02A824@5=?=C4? D40?@

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           ... %)+-# ,% , (& )7=<4  +  RM Matters CDA JOURNAL, VOL 44, Nº9

Hiring Done Right: License Verifi cation and Background Checks TDIC Risk Management Staff

s a dentist, you’ve made certain This case could have been avoided promises. You’ve promised to if the dentist had simply verifi ed the serve patients with compassion Practice owners are employee’s license. The process is quick and and integrity. You’ve promised encouraged to keep easy, and in most states, can be done online. to keep patients safe when In fact, practice owners are encouraged to Athey seek treatment within your walls. But copies of employee keep copies of employee licenses on fi le and what steps have you taken to ensure you licenses on fi le and to to check their validity at least once a year. are able to deliver on those promises? check their validity at “The practice owner is responsible For practice owners, hiring competent, for ensuring all licensed staff have qualifi ed and properly licensed staff is a least once a year. current licenses and permits,” said Taiba key responsibility. However, sometimes Solaiman, TDIC risk management the requirements as an employer are analyst. “We recommend designating murky, and tasks associated with hiring can get pushed to the back burner. The Dentists Insurance Company, TDIC, reports several cases in which practice owners failed to conduct the proper background checks prior to bringing a new employee onboard. This not only puts patients in danger, it also lays the groundwork for potential negligent You are not a sales goal. hiring and employment-related claims. In one case, a dentist discovered his dental assistant had been practicing without a license for several years. Though she had previously been licensed, her license was revoked due to nonpayment of taxes. It was only when the offi ce manager happened to be checking CPR certifi cations that the deception was exposed. When confronted, the assistant You are a dentist deserving of an insurance company relentless said the license was at home, but she in its pursuit to keep you protected. At least that’s how we see fi nally admitted the truth when a it at The Dentists Insurance Company, TDIC. Take our Risk representative from the dental board Management program. Be it seminars, online resources or our called her directly at the offi ce. Needless Advice Line, we’re in your corner every day. With TDIC, to say, the employee was immediately terminated. The doctor acknowledged you are not a sales goal or a statistic. You are a dentist. his obligation to report this issue to the dental board, and informed the board of the situation. Although self-reported, ® Protecting dentists. It’s all we do. the case still resulted in the requirement that the dentist retake his state’s 800.733.0633 | tdicinsurance.com | CA Insurance Lic. #0652783 jurisprudence exam. While not considered a corrective action, it is public record.

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CDA JOURNAL, VOL 44, Nº9

a staff member to secure copies of all after treatment by an unlicensed employee, In California, for example, the Dental current licenses. Many dentists display there is a rebuttable presumption of Board conducts periodic crackdowns current licenses in their offi ces, which fault,” Bernadette Bantly, an attorney on unlicensed dental practitioners. eliminates any questions about license with Bradley, Curley, Asiano, Barrabee, “The board has recently indicated that status and gives patients confi dence in the Abel & Kowalski in Larkspur, Calif., it is concerned about both unlicensed professionalism of the dental team. For said. “That means that for even routine employees and licensed employees working staff whose job is dependent on a license, complications, the burden will be on beyond the scope of their licenses,” Bantly the individual should not be scheduled to the dentist, and employee, to prove said. “We can expect more enforcement work until an active license is provided.” that the unlicensed employee was in this area. So there are potential adverse Should it be discovered that an not the cause of the problem.” administrative consequences as well.” employee is practicing without a license, Curbing the unlicensed practice Dentists are subject to vicarious there are serious repercussions for both of dentistry is a priority for many liability, meaning they are responsible the unlicensed employee and the practice state dental boards. In addition to for the actions of their employees during owner. Not only is it a violation of law in civil and criminal penalties, allowing the course of employment. Keeping most states, it puts patients in harm’s way. an employee to practice without a copies of active licenses on fi le, properly “If a patient suffers injury during or license can destroy a dentist’s career. vetting potential staff members and ensuring employees work within their scope of practice are a few simple steps that can help keep patients safe and prevent potential negligent hiring and employment-related claims. TDIC also reports numerous calls about conducting employee background checks. Practice owners who intend to check references are encouraged to include a waiver for the applicant to sign authorizing the investigation of all submitted information. It is also essential to become familiar with what can and cannot be asked during these checks. CDA has a “Sample Reference Check Form” available at cda.org/resources. In one case, a dentist had hired a fi nancial coordinator. During her 90- day introductory period, the employee informed the dentist that she was pregnant. Also during this time, the dentist delivered the employee’s performance review, in which he identifi ed needed areas of improvement. Shortly thereafter, several concerns arose regarding the fi nancial coordinator’s handling of insurance benefi ts. At that point, the dentist called her former employer, who divulged confi dential details of the employee’s job performance. Based on this information, the dentist fi red the employee.

584 SEPTEMBER 2016 QUESTIONS MOST OFTEN ASKED BY SELLERS:

1. Can I get all cash for the sale of my practice?

2. If I decide to assist the Buyer with financing, how can I be guaranteed payment of the balance of the sales price?

3. Can I sell my practice and continue to work on a part time basis?

4. How can I most successfully transfer my patients to the new dentist?

5. What if I have some reservation about a prospective Buyer of my practice?

6. How can I be certain my Broker will demonstrate absolute discretion in handling the transaction in all aspects, including dealing with personnel and patients?

7. What are the tax and legal ramifications when a dental practice is sold? QUESTIONS MOST OFTEN ASKED BY BUYERS:

1. Can I afford to buy a dental practice?

Can I afford not to buy a dental practice? LEE SKARIN 2. INC. & ASSOCIATES

3. What are ALL of the benefits of owning a practice?

4. What kinds of assets will help me qualify for financing the purchase of a practice?

5. Is it possible to purchase a practice without a personal cash investment?

6. What kinds of things should a Buyer consider when evaluating a practice?

7. What are the tax consequences for the Buyer when purchasing a practice? 2IÀFHV Lee Skarin & Associates have been successfully assisting Sellers and Buyers of Dental Practices for nearly 30 years in providing the answers to these and other 805.777.7707 questions that have been of concern to Dentists. 818.991.6552 Call at anytime for a no obligation response to any or all of your questions Visit our website for current listings: www.LeeSkarinandAssociates.com 800.752.7461 CA DRE #00863149 SEPT. 2016 RM MATTERS

CDA JOURNAL, VOL 44, Nº9

A few months later, the employee fi led a claim alleging pregnancy disability discrimination and wrongful termination. The case resulted in the employee’s favor, with the dentist at the losing end of a signifi cant settlement. In this case, the dentist could have Paul Maimone avoided the situation had he called Broker/Owner It is a Great Time to Sell! Inventory & the employee’s former employer prior

Rates are Still Low & Buyer Demand is to making a hiring decision. In fact,

High! Call for a Free in Office Valuation! TDIC recommends that practice owners require applicants to provide ARCADIA – (4) op comput G.P. Located in a well known Prof. Bldg. on a main thoroughfare. their previous employers’ contact Cash/Ins/PPO pt base. Annual Gross Collect $300K+ on a (3) day week. REDUCED GROVER BEACH - (3) op Turnkey Office w included charts (not guaranteed). (2) ops eqt’d w information to research and assess newer eqt. 3rd plmbed. Digital Pano & x-ray. Dentrix. In a strip ctr. LL incentives. SOLD the accuracy of their work history. HUNTINGTON BEACH - (5) op plumbed space for lease. Some eqt available. TI’s too. NEW MONTEBELLO - (4) op comput G.P. (2) ops eqt’d. Located in a busy shop. ctr. w exposure & “The application, résumé and notes visibility. Annual Gross Collect. $200K on a p.t. schedule. Cash/Ins/PPO. Seller retiring. from the interview should contain OXNARD #9 - (3) op comput G.P. & a Prof Office Condo for sale. Located on a main much of the same information as thoroughfare. (3) ops eqt’d. Annual Gross Collect $200K+ p.t. Cash/Ins/PPO/HMO $4.5K/mos Cap Cks. Digital x-rays. Low overhead. Buy & Combine or open a satellite. NEW the applicant’s work history, so it is PORT HUENEME – (3) op comput. G.P. located in a large strip ctr. with exposure, visibility, & important to check these resources signage. 2.5 - 3.5 year old eqt. Mostly associate run. Gross Collect $200K p.t. w no adv. NEW SANTA BARBARA COUNTY – (3) op comput G.P. & a 1,900 sq ft Bldg. that houses the for consistent representations practice & a residential unit that can be rented or lived in. “Fee for Service.” No PPO, HMO or of education, experience and Denti-Cal. 2015 Gross Collections ~ $275K on a relaxed 3½ day week. Seller refers all O.S., Perio, Ortho, Endo & implant placement. Seller retiring but will assist w transition. references,” Solaiman said. So. EAST KERN COUNTY - (5) op comput. G.P. located in a free stand bldg. w exposure/ Bantly said in addition to verifying visibility & signage. VERY LIMITED COMPETITION. 2015 Collect $600K. Cash/Ins/PPO. licenses, practice owners should call Digital x-rays & CT Scan. (6) sensors, Bldg. also available. Seller retiring. SAN FERNANDO VALLEY #9 - (8) op comput. G.P. w modern eqt. In a prof. bldg. on a main previous employers going back at least thoroughfare. Cash/Ins/PPO/HMO. Cap Ck approx $7K/mos. 2015 Collect $1.4M+ PENDING fi ve to 10 years. However, it is important SAN FERNANDO VALLEY #10 - Located in an exclusive area of the Valley. (5) op comput G.P. w high end buildout. Digital x-ray and CT Scan, Laser, Dentrix s/w & (5) year old eqt. Gross to limit questions to the basics in Collect $1M+/yr. Cash/Ins/PPO pts. Reasonable overhead, high Net! NEW order to protect the confi dentiality of SAN GABRIEL VALLEY - (4) op comput G.P. w newer P&C Chairs/Eqt, All the toys & personnel records. These questions whistles. Paperless, Schick digital x-rays, Solaris Steril Ctr, Soprocare Intra Oral Camera, Velscope Cancer Screen, The Wand, Air , Electric Hand Pieces, Laser, etc. FFS, 2015 could include the following: Gross Collect. $881K+ on a 3½ day week. (4) days of Hygiene. Seller retiring. PENDING What was the employee’s job title and SANTA ANA - absentee owned (6) op fully eqt’d G.P. First floor street front location on a main thoroughfare. Exposure/visibility/signage. Cash/Ins/PPO. No HMO & No Denti-Cal. Pano eqt’d dates of employment? & Comput. Annual Gross Collect. $400K- $500K on a (3) to (4) day week. BACK ON MARKET Why did the employee leave your THOUSAND OAKS (4) ops/(2) eqt’d comput. Turnkey Office w included charts. Chart included but not guaranteed. Sirona Eqt. Located in a condo in a Prof. Bldg. PENDING employment? WESTLAKE VILLAGE - Turnkey Office. (4) ops/(3) eqt’d. Located in a smaller prof. bldg. Would you rehire the employee? Very reasonable Lease terms. Newer build out & some newer eqt. Comput. & digital. NEW Bantly said more detailed background UPCOMING PRACTICES: Bakersfield, Beverly Hills, Central Coast, Covina, Downey, Duarte, Goleta, Oxnard, Pomona, San Gabriel, Palm Desert, Van Nuys, Visalia & West L.A.. checks, which often include criminal D&M SERVICES: records, credit checks and drug testing, Q Practice Sales and Appraisals Q Practice Search & Matching Services must comply with state and federal Q Practice and Equipment Financing Q Locate and Negotiate Dental Lease Space laws, so it is important to check with Q Expert Witness Court Testimony Q Medical/Dental Bldg. Sales & Leasing an attorney before proceeding. ■ Q Pre - Death and Disability Planning Q Pre - Sale Planning P.O. Box #6681, WOODLAND HILLS, CA. 91365 Toll Free 866.425.1877 Outside So. CA or 818.591.1401 www.dmpractice.com TDIC’s Risk Management Advice Line Serving CA Since 1994 CA BRE Broker License # 01172430 at 800.733.0634 is staffed with trained analysts who can answer hiring and other CA Representative for the National Association of Practice Brokers (NAPB) questions related to dental practice.

586 SEPTEMBER 2016

“Matching the Right Dentist CARROLL to the Right Practice” &COMPANY

CComplete Evaluation of Dental Practices & All Aspects of Buying and Selling Transactions

4103 SAN FRANCISCO GP 4096 MENDOCINO COUNTY GP Vibrant downtown location in historic high-rise bldg. Retiring doctor Seller offering well est. 48 year practice. Located in outdoorsman's offering 30+ years of goodwill. 4.5 days of hygiene, 1,500+ active paradise. Just 2 hours North of SF surrounded by redwood forest, patients, 20-25 new patients/mo. Gorgeous, spacious facility in vineyards and mountains. 950 sq. ft. office in single level building w/ 4 approx. 2,500 sq. ft. 2015 GR $796K. 2014 GR $768K. Average fully equipped ops. 2014 GR $565. Asking $300K. adjusted net income $274K+ Asking $599K. 4099 MT VIEW DENTAL FACILITY 4085 SANTA ROSA GP & BUILDING Dental facility offered in a desirable location in the heart of silicon valley Practice and R/E are offered for sale in a well-established medical/ between Mountain View, Los Altos and Sunnyvale. Minutes from dental complex conveniently located near Memorial Hospital. 3 fully downtown Mountain View/Castro Street and downtown Los Altos. equipped ops in 1,200 sq. ft. Approx 750 active patients. Average Great patient population including Google, Apple, and many local Gross Receipts of $264K with adj. net of approx. $116K. Seller willing startups. Family friendly neighborhood with close proximity to many to help for a smooth transition. Price reduced to $125K for the wonderful schools. Excellent for a starter office to build a patient base practice and $245K for the real estate. or grow your existing patient base here. Approx 1,164 sq feet with 5 plumbed ops. Front desk, reception area, sterilization area, darkroom, 4108 HUMBOLDT COUNTY GP restroom and storage. Asking price for facility only $105K. Well-established, high performing general practice boasts 6 fully equipped ops. in 2,900 sq. ft. free standing office w/Digital X- ray, 2 4093 SAN JOAQUIN VALLEY ORTHO platinum Dexis sensors, & Cerec Omnicam & MCXL units. Loyal & Established over 35 years with a solid reputation, near several referral stable pt. base in charming community, w/ a small town feel. Perfect sources in seller owned building. 2,500 sq. ft. office with 7 chair open for a dentist who wants to escape the grind and live along the bay in professional center on a well-travelled street with many retailers. coastline. Avg. GR $1.4M+, 2016 on schedule for $1.5M+. Seller Avg. Gross Receipts $763K. Seller retiring and willing to help for willing to help for smooth transition. Asking $1,041K. smooth transition. Asking $561K. The building is available to purchase as well for $608K. 4091 HOLLISTER GP & PEDIATRIC Country living at it’s best ~ small town feel with affordable housing, in 4065 LAKE COUNTY GP quaint bedroom community to Silicon Valley. Fully equipped 1,600 sq. Seller retiring from general practice located in a slower paced, relaxed ft. office with 2 enclosed adult ops and 3 open pedo ops, near Hazel community. Plenty of hunting and fishing and out door activities for the Hawkins Hospital. Turn-key practice, great opportunity for a pediatric enthusiast. Approx. 1,600 square foot office with 4 fully-equipped dentist. Approx. 565 active patients. 2015 GR $219K. Seller is operatories. Over 2,000 active patients, average $697K+ in Gross relocating but will help for a smooth transition. Asking price $125K. Receipts with an overhead of just 56%, and 4 doctor days per week. Asking $463K. 4114 CONCORD GP Well-established practice offering 30+ yrs of goodwill. Concord is on 4105 STANISLAUS COUNTY GP the verge of redevelopment of the old Naval Weapons Base later this Get away to a less demanding commuter friendly town. Seller retiring year, which will cover 2,300 acres and include 12,000 housing units. from practice est. over 30 years ago with loyal patient base in The project will include Residential/Commercial/Recreational and Open charming community with historic small town feel. 3 fully-equipped Space. This practice opportunity is strategically located for growth ops. in 1,200 sq. ft. office. Approx. 1,400 active pts. w/4 doctor days/ potential due the slotted re-development. Office has 3 fully equipped week. 5 year avg. GR $647K+ w/approx. 50% overhead. Seller willing ops in 836 sq. Average GR $360K+ on 2 doctor days. Asking $224K. to help for smooth transition. Asking $375K. 4114 WALNUT CREEK GP 4120 SF GP Walnut Creek practice in gorgeous facility with recent leasehold Well est. downtown family practice grossing over $1M with an avg. improvements plus new and upgraded equipment. Practice has 30+ overhead of 61%. 5 fully equipped ops., in remodeled office. Retiring years of goodwill. Looking for a mature, experienced practitioner for a seller works 3.5 Dr. days/week. Seasoned, dedicated staff & loyal loyal and mature patient base. Located in commercial center with patient base. Terrific opportunity for experienced & confident dentist. several amenities and marketing opportunities. Doctor works 2 days Asking $806K. per week. Owner available for a smooth transition. Asking $432K.

4121 NAPA GP Carroll & Company Gorgeous, state-of-the-art office available in beautiful wine 2055 Woodside Road, Ste 160 country! Incredible location with super high visibility on the corner Redwood City, CA 94061 of two major cross streets near Queen of the Valley Hospital. 7 P (650) 362-7004 ops in 3,250 sq. ft. facility. Seller retiring but would like to transition F (650) 362-7007 with buyer after the sale. 2,100+ active patients, 9 days of [email protected] hygiene, 15-20 new patients/mo. 2015 GR $1.56M, 2014 GR www.carrollandco.info $1.62M. Average Adjusted net income of $513K. Asking BRE #00777682 $1,151K. Mike Carroll Pamela Carroll-Gardiner

www.carrollandco.info [email protected] P (650) 362-7004 F (650) 362-7007 Regulatory Compliance CDA JOURNAL, VOL 44, Nº9

HIPAA Privacy Tips and Reminders CDA Practice Support Staff

Here are tips and reminders for information. Acquiescing to the request And, must you obtain it each time a maintaining the privacy of your patients’ helps the second practice, but the dental parent makes an inquiry even if the parent information. practice with the information should is fi nancially responsible for treatment not forward it without fi rst obtaining the rendered? The simplest and safest solution Patients’ cameras patient’s authorization. If the information is to obtain the patient’s authorization Capturing an image of a child’s is provided without authorization, the to disclose information to his parents for fi rst dental visit is important to many action takes away the patient’s right a set period or until an event, such as families, and a dental practice’s privacy to restrict disclosure of information dropping off the parents’ insurance, takes policies need not prohibit the recording to a dental benefi t or health plan. place. The CDA Practice Support website of this milestone. Your privacy policy (cda.org/practicesupport) has a resource can state that use of a camera on site Disclosures to parents of adult patients you can use, “Consent Form for Use or by patients, visitors and practice staff When the minor patient you have Disclosure of Patient Health Information.” requires permission from the appropriate treated all these years becomes an A dental practice can share with a individual (privacy offi cer or dentist). adult, must you obtain that patient’s payer and without patient authorization The policy also can state that staff must authorization to continue to share his the minimum information necessary to be check that no patient information, or her information with the parents? paid. In other words, the date, description documents, images or other patients can be seen in the background of a photo. Train your staff on the policy. Inform patients and visitors of the policy by posting or distributing a notice. HIPAA- When Looking To Invest In Professional covered entities are not expected to prevent all unauthorized disclosures Dental Space Dental Professionals Choose but they are expected to make every effort in their attempt to do so.

Employees’ cameras A dental practice’s policy on Linda Brown employees’ personal cameras can vary. A practice can strictly prohibit employees’ 30 Years of Experience Serving use of cameras on site, or it can limit use to the Dental Community Proven off-site work functions or to work-specifi c purposes. Prohibit staff from taking photos Record of Performance or video with patients on an employee’s camera. If a patient wants a photo, it • Dental Office Leasing and Sales should be taken with the patient’s device. For your next move, • Investment Properties Sharing patient payment information contact: LINDA BROWN • Owner/User Properties with specialist practice Federal and state privacy laws allow a • Locations Throughout health care provider to share patient health Direct: (818) 466-0221 Southern California information, without patient authorization, Office: (818) 593-3800 with another health care provider for the Email: [email protected] purpose of care coordination. A dental Web: www.TOLD.com practice may get a request from another Cal BRE: 01465757 practice to provide treatment information and the patient’s fi nancial and insurance

SEPTEMBER 2016 589 SEPT. 2016 REGULATORY COMPLIANCE

CDA JOURNAL, VOL 44, Nº9

and fee for treatment. A covered entity, authorization of all parties to audio ■ Appointment reminders, using his or her professional judgment in record. If considering audio recording in postcards and voicemail consideration of the patient’s benefi t, may only the practice staff side of a phone messages, that do not include the disclose information to family members conversation, remember that the purpose of the appointment. or others known to be involved in the recording may need to be managed as ■ Sign-in sheet at the front desk care of the patient in limited situations protected health information if the that does not ask the visitor to without the patient’s authorization. It is staff repeats/confi rms the information state the purpose of the visit. expected, under HIPAA, that a patient be the caller is providing. If you want to ■ Calling out the patient’s name in provided with an opportunity to object to assess your staff’s phone skills, there the reception area without stating the presence of another individual during are other methods that can be used the purpose of the appointment. ■ the patient’s treatment or the patient’s other than recording telephone calls. discussion with a health care provider. Regulatory Compliance appears monthly Incidental disclosures and features resources about laws that Recording telephone calls Incidental disclosures of patient impact dental practices. Visit cda.org/ Stay on the right side of the law information are allowed under HIPAA as practicesupport for more than 600 practice and do not follow customer service long as a covered entity keeps the disclosure support resources, including practice consultant recommendations to record to the minimum necessary information. management, employment practices, dental telephone calls. State law requires Examples of incidental disclosures are: benefi ts plans and regulatory compliance.

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590 SEPTEMBER 2016 DENTAL PRACTICE BROKERAGE Making your transition a reality.

Dr. Lee Dr. Thomas Dr. Dennis Dr. Russell Jim Kerri Mario Jaci Steve Thinh Maddox Wagner Hoover Okihara Engel McCullough Molina Hardison Caudill Tran LIC #01801165 LIC #01418359 LIC #0123804 LIC #01886221 LIC #01898522 LIC #01382259 LIC #01423762 LIC #01927713 LIC #00411157 LIC #01863784 (949) 675-5578 (916) 812-3255 (209) 605-9039 (619) 694-7077 (925) 330-2207 (949) 566-3056 (949) 675-5578 (949) 675-5578 (951) 314-5542 (949) 675-5578 25 Years in Business 40 Years in Business 36 Years in Business 33 Years in Business 42 Years in Business 35 Years in Business 35 Years in Business 26 Years in Business 25 Years in Business 11 Years in Business

PRACTICE SALES • PARTNERSHIPS • MERGERS • VALUATIONS/APPRAISALS • ASSOCIATESHIPS • CONTINUING EDUCATION

NORTHERN CALIFORNIA PINOLE:2S(QGRRI¿FHZ'LJLWDO;UD\ BEVERLY HILLS: Perio practice. Beautifully PALM SPRINGS: New Listing! 2SV 0LFURVFRSHVDQG3%6(QGRLQDSSUR[VT designed, 4 Ops, Desirable prof. bldg. Dentrix, years of goodwill. Good location, Doctor wants BENICIA: Practice & Building. 1,545 sq. ft., ft. 2014 GR $672K. #CA284 \HDUVRI*RRGZLOO*5RI. WRUHPDLQDQGZRUNSDUWWLPHLISRVVLEOH 4 ops, Open-Dental software, digital X-ray & *5.&$ Pan, Laser. 2014 GR $550K. #CA298 ROSEVILLE:(TXLSSHG2SVDGG¶O BEVERLY HILLS:2SV(DJOH6RIW'LJLWDO SOXPEHGVTIWZ'LJLWDO;UD\/DVHU &(5(&/RQJWHUPVWDIIQHZHUHTXLSPHQW PASADENA AREA: 3UDFWLFH %XLOGLQJ BENICIA: VTIWRI¿FHRSV*5 'HQWUL[VRIWZDUH*5.&$ 2015 GR 1.2M+, #CA210 2SV'HQWUL['H[LV&(5(&HVWDEOLVKHGIRU .GD\ZHHN6LVWHUSUDFWLFH&$VDOH 50+ yrs. #CA282 FRPELQHGRUVHSDUDWH&$ SACRAMENTO: New Listing!2SVZ BURBANK: New Listing! *HQHUDO3URVWK 6FKLFNGLJLWDO[UD\3DQR/DVHUDQG(DJOHVRIW Implant practice. 15 years of goodwill,retail S. ORANGE COUNTY: Pedo Practice with 4 CITRUS HEIGHTS: Prosthodontic practice & VRIWZDUH*50&$ FHQWHU2SVHTXLSSHG(DV\'HQWDO'LJLWDO 2SV\HDUQHZ(TXLSPHQW'LJLWDO3DQR VWDQGDORQHEXLOGLQJIRUVDOH2SV*5RI 2015 GR $291K, $118K Adj. Net. *5.ZLWKURRPWRJURZ&$ &$ SACRAMENTO:VTIWRI¿FHZ(TXLS &$ 2SVDGG¶O3OXPEHG'HQWDO0DWHVRIWZDUH SANTA BARBARA: 4 Ops, est. for 40+ years. EL DORADO COUNTY: VTIWZ2SV *5&$ CARSON:2SV3DSHUOHVV(DJOH6RIW'LJLWDO GD\V+\JLHQHZHHNORQJWHUPVWDII))6*5 LQWUDRUDOFDPHUDGLJLWDO[UD\3UDFWLFH:RUNV SACRAMENTO: VTIW(TXLSSHG 3DQR$OO(TXLS \UVROG*5. of $827K. #CA291 VRIWZDUH*5.&$ VWDWLRQVLQED\DGG¶O3OXPEHG*5 #CA280 SANTA MARIA: 2SVLQVTIWVXLWH GREATER EL DORADO HILLS: $590K. #CA269 CENTRAL ORANGE COUNTY: 2SV New Listing! ))6332GD\ZRUNZHHNZGD\RIK\JLHQH VTIWRI¿FH2SV'LJLWDO SAN FRANCISCO: New Listing! )LQDQFLDO Paperless, digital, busy retail center. 2015 GR of *5.&$ 3DQ'LJLWDO6HQVRUV(DJOHVRIWVRIWZDUH 'LVWULFWRI¿FH2SV5RRPIRUWKVT .ZLWK.$GM1HW&$ *5.&$ VICTORVILLE: 2SV3OXPEHG ft. 2015 GR $1.2 mil, Adjusted Net $480,000. COASTAL ORANGE COUNTY: &$ 6T)W(VW\UV6RIW'HQW*5 GREATER REDDING: New Listing! 2,600 2SV(TXLSSHG'HQWUL['H[LV3URIEOGJ $277K. #CA149 Price Reduced! VTIWRI¿FHZ2SVLQWUDRUDOFDPHUDGLJLWDO SAN FRANCISCO: Periodontal Practice & Z\HDUVRIJRRGZLOO*5RI. x-ray, Pano, Dentrix software. 2015 GR of &RQGR8QLWVTIWZ2S*5 $GM1HWRI.&$ WHITTIER: 2SV(TXLSSHG'HQWUL[ 0&$ .Z.$GM1HW&$ 'H[LV(VWIRU\UVRQ0DLQ6WUHHW*5 FULLERTON: New Listing! 6 Ops, 4 SAN JOSE: $195K. #CA276 GREATER REDDING: VTIWZ2SV *5.RQòGD\ZHHN (TXLSSHG\HDUVRI*RRGZLOO'HQWUL['LJLWDO (TXLSSHGRSVDGG¶O3OXPEHG6T Intra-Oral, Digital, Pano, Laser, CAD-CAM, Paperless. Great location. 2015 GR of $410K. SAN DIEGO Dentrix. 2014 GR $1M. #CA260 )W(='HQWDO'H[LV¿OPEDVHG3DQRUDPLF &$ &$ CHULA VISTA: (VW\UV2SVò GREATER ROSEVILLE/AUBURN: SAN RAFAEL: New Listing! General & GREATER LOS ANGELES: Perio Practice. 5 GD\VRI+\JLHQH'HQWUL[.*5LQ New Listing! 3UDFWLFH %OGJVTIWZ ,PSODQWVTIWRI¿FH2SV*5 2SV

BAY AREA BAY AREA CONTINUED NORTHERN CALIFORNIA CONTINUED CENTRAL VALLEY

Largest AC-335 SAN FRANCISCO: Great Practice! 2100sf, BN-586 BRENTWOOD: Unlimited growth poten- EG-556 SACRAMENTO: IC-468 SAN JOAQUIN VALLEY 8ops in desirable location of SF. Call for Details al! Carry on the stellar reputaon of the Prac- $389k $425k $475k ce! 2,800 sf w/ 8 ops. $1.4M EG-589 SACRAMENTO: IC-572 MODESTO: Broker in AC-566 SAN FRANCISCO: Spectacular views of CC-552 SAN RAFAEL: 3ops in 800sf. Practice & $475k $160k Washington Square. 3ops +2 add’l plumbed in Lease Concession: $225,000 / Charts Only: EN-534 ROSEVILLE Facility: IN-506 TURLOCK: 1400sf office $225k $175,000 + an add’l amt for EQ $45k $425k Northern AC-585 SAN FRANCISCO: Near Union Sq., 3ops, CC-567 ST. HELENA: Live and Practice in beautiful EG-560 CARMICHAEL: IN-577 W. STANISLAUS CO: 566sf. All reasonable offers will be considered. Wine Country, 5ops in 1842sf, single-story bldg. $130k $250k $270k for the Practice / $160k for the Goodwill Price Reduced $790k EN-573 SACRAMENTO: JC-541 FRESNO Facility California AG-564 SAN FRANCISCO: Over 25 yrs goodwill. CG-583 SEBASTOPOL: Practice & Real Estate. Sell- $93.1k Call for Details! Large 5,600+ sf w/ 9 ops near Land’s End er Willing to consider all reasonable offer. Health EG-579 ROCKLIN Perio/Gen JG-491 FRESNO: $2.225M Forces Sale PR $175/RE $750k $325k REDUCED! $395k AG-576 SAN FRANCISCO: Part time practice w/ DC-476 DUBLIN: Shared Facility. Great for Special- EN-588 SACRAMENTO: JN-551 COALINGA AREA: Amazing Growth Potential. Perfect for 1-3 DDS 4 ist - Endo, Pedo or Ortho. 1100 sf w/ 2 ops+1 $315k REDUCED! $395k! Extensive Buyer ops 1.400 sf $550k add’l $125k EN-603 ELK GROVE JN-593 FRESNO: AN-514 SAN FRANCISCO Facility: Located in the DC-604 LIVERMORE Facility: Turn Key Facility in $318k $375k Database & bustling financial district! 1,007 sf w/4 ops. Re- fast growing city, 3ops +3 add’l plumbed in FC-415 FT. BRAGG: duced to $125k! 2380sf modern office, $110k $425k SPECIALTY PRACTICES Unsurpassed AN-565 SAN FRANCISCO: This remarkable oppor- DN-497 PLEASANTON Facility: Great Location! FC-489 CLEARLAKE: tunity could be your “dream come true”! 2,067 sf 870 sf w/ 3 ops + 1 add’l. Owner Financing $470k / 50% interest in RE Also Available AC-601 SAN FRANCISCO Perio: w/ 6 ops. $1.05M w/10% Down! Reduced! $95k FN-527 TRINITY COUNTY: “Pride Instute” $800k Exposure allows AN-592 SAN FRANCISCO: Imagine accessibility, DG-519 SANTA CLARA Facility: Move In Ready! designed! $250k BC-544 ALAMEDA COUNTY Pedo: visibility & free parking in San Francisco! 1,000sf 2240 sf w 6 fully equipped ops $225k GC-472 ORLAND: $225k us to offer you w/ 2 ops + 1 add’l $100k DG-530 SAN JOSE: Highly respected quality prac- $160k BG-517 NORTH EAST BAY Endo: BC-361 OAKLAND: Established for over 23+ years! ce! 2015 collecons $1M+ Priced at $899k GG-386 REDDING: $500k 2,200 sf w/ 7 ops. Seller is retiring. $330k DG-581 SAN JOSE: Must See to Appreciate! Gor- ONLY $260k CC-346 SO MARIN CO Perio: No reasonable

BC-520 HAYWARD Facility: Located in Down- geous Pracce, stable paent base & loyal staff GG-453 CHICO: $325k offer will be refused! Reduced $150k town, 1500 sf, 4 equipped ops, X-Rays in 3 ops. $570k GG-454 PARADISE: CG-424 NAPA Prostho: Call for Details $65k DG-582 SAN JOSE: Collecons over $900k! $525k BC-432 PITTSBURG: Own this family-oriented 3000 sf w/8 ops. Top of the Line! $675k GG-574 SIERRA FOOTHILLS: $690k Practice! 1,640 sf w/ 6 ops. Seller is Retiring DN-542 FREMONT Facility: Spacious & beauful- $875k DC-459 SF PENINSULA Perio: $350k ly equipped State-of-the-Art! 3,400 sf w/ 5 ops + GN-244 OROVILLE: $600k BC-549 LAMORINDA AREA Facility: Excellent 4 add’l. $295k Only $315k EG-579 ROCKLIN Perio/Gen Location! Highly Visible, 900sf w/ 3ops +1 DN-557 SALINAS: 3,000 sf w/ 7 ops and collecng GN-399 REDDING: $325k plumbed add’l. Reduced $75k over $2.225M. Priced at only $1.4M $150k FN-536 LAKE COUNTY Pedo: BC-563 BERKELEY: Excellent, Well-established, GN-507 CHICO: before Now Only: $225k! Family-oriented Practice, 4ops in 1382sf 10pts/ NORTHERN CALIFORNIA Practice $535k IC-543 CENTRAL VALLEY Ortho: day, 35npts/mo $450k GN-546 CHICO AREA: $180k BG-570 SAN LEANDRO: 30+ yrs goodwill w/focus EC-525 SACRAMENTO: Great Location& Visibility! JC-540 FRESNO Sleep Apnea on C&B. 2100 sf w 5 ops. Room for 6th op. Over 1,500 sf w/ 3ops, 10-15 new pts/mo $220k $350K Call for Details! $908k in 2015 $625k EC-531 GREATER SACRAMENTO: Pracce and HC-461 SONORA: BN-504 RICHMOND: Established Practice and Real Estate for Sale! 1,750sf w/ 4ops + 1 add’l, Practice $700k & RE Also Available! Real Estate! 1,450 sf w/ 2 ops + 2 add’l $100k / 8npts/mo $800k HN-213 ALTURAS: RE $700k EN-464 ROCKLIN Facility: Don’t miss out on this $115k remarkable opportunity! 2,150 sf w/ 4 ops. HN-280 NO EAST CA: REDUCED! Now Only: $100k ONLY $60k

800.641.4179 [email protected] Timothy Giroux, DDS Jon B. Noble, MBA Mona Chang, DDS John M. Cahill, MBA Edmond P. Cahill, JD

BAY AREA BAY AREA CONTINUED NORTHERN CALIFORNIA CONTINUED CENTRAL VALLEY

Largest AC-335 SAN FRANCISCO: BN-586 BRENTWOOD: EG-556 SACRAMENTO: Near CSUS Campus. Long-term 2nd generation IC-468 SAN JOAQUIN VALLEY: High-End Restore Pracce! 6 ops in office. 935 sf w/ 4 ops $389k 2500+ sf office. $425k $475k $1.4M EG-589 SACRAMENTO: Perfect Downtown Locaon near Capitol. 2,300 sf IC-572 MODESTO: In desirable Dental/Medical Professional building of Broker in AC-566 SAN FRANCISCO: CC-552 SAN RAFAEL: Practice & w/ 6 ops $475k town, 3ops in 1300sf office. $160k Lease Concession: $225,000 / Charts Only: EN-534 ROSEVILLE Facility: Locaon, Locaon, Locaon! Turn-key…just IN-506 TURLOCK: Practice in the heart of the Central Valley! 2,000 sf $225k $175,000 + an add’l amt for EQ needs you! 2,000 sf w/4 ops. $45k w/ 5ops + 1 add’l. $425k Northern AC-585 SAN FRANCISCO: CC-567 ST. HELENA: EG-560 CARMICHAEL: Focusing on the philosophy of treang paents IN-577 W. STANISLAUS CO: Offering that “Main Street” feel and quality as family! 1,200 sf w/ 3 ops + 1 add’l. $130k of life. 1,800 sf w/ 4ops + 1 add’l. $250k $270k for the Practice / $160k for the Goodwill Price Reduced $790k EN-573 SACRAMENTO: The goal and focus of this pracce is to provide JC-541 FRESNO Facility: 1,210 square feet and consists of 2 fully California AG-564 SAN FRANCISCO: CG-583 SEBASTOPOL: excellent service! 1,075 sf w/ 2 ops. $93.1k equipped ops and plumbed for add’l op Call for Details! EG-579 ROCKLIN Perio/Gen: Aracve, well-appointed pracce in the JG-491 FRESNO: Well-established. 40-50 new Pt/mo. 1,452 sf w/ 4 $2.225M PR $175/RE $750k presgious Whitney Oaks area. 1,600 sf w/3 op + 1 add’l. $325k fully equipped ops. REDUCED! $395k AG-576 SAN FRANCISCO: DC-476 DUBLIN: EN-588 SACRAMENTO: well-established pracce awaits your talent and JN-551 COALINGA AREA: Serving this community of working families! skill! 1,500 sf w/ 4ops. $315k Paperless Pracce. 1,200 sf w/ 3 ops. REDUCED! $395k! Extensive Buyer $550k $125k EN-603 ELK GROVE: Absolutely one of California’s most desirable JN-593 FRESNO: Change smiles in this quality family-oriented pracce! AN-514 SAN FRANCISCO Facility: DC-604 LIVERMORE Facility: communies to both live and work. 1,300 sf w/ 3 ops. $318k 2,430 sf w/ 6ops. $375k Database & Re- FC-415 FT. BRAGG: Excellent Practice! Dr. avgs 18+ pts/day & 20+ npts/ duced to $125k! $110k mo, 1,800 sf w/ 5 ops + 1 hyg. Op $425k SPECIALTY PRACTICES Unsurpassed AN-565 SAN FRANCISCO: DN-497 PLEASANTON Facility: FC-489 CLEARLAKE: Located on “4-Corners” of Hwy 53, 4ops in shared Owner Financing 3600sf facility. $470k / 50% interest in RE Also Available AC-601 SAN FRANCISCO Perio: High quality practice, 30npts/mo, 3ops $1.05M w/10% Down! Reduced! $95k FN-527 TRINITY COUNTY: Be the only dentist in town! “Pride Instute” in shared 1963sf office, Seller workback for smooth transition $800k Exposure allows AN-592 SAN FRANCISCO: DG-519 SANTA CLARA Facility: designed! 2350sf w/ 5 ops +1 add’l. $250k BC-544 ALAMEDA COUNTY Pedo: 1,056sf w/ 4 chairs in growing, revi- $225k GC-472 ORLAND: Live & Practice in charming small town community. talized community, Seller Retiring $225k us to offer you $100k DG-530 SAN JOSE: 1,000 sf w/ 2ops. Seller Retiring. $160k BG-517 NORTH EAST BAY Endo: 2,750 sf w/ 8 ops! Strong Practice! BC-361 OAKLAND: Priced at $899k GG-386 REDDING: Amazing Practice. Lease or Buy Real Estate! 2,860 sf $500k $330k DG-581 SAN JOSE: w/ 4 ops. Plumbed for 2 add’l! ONLY $260k CC-346 SO MARIN CO Perio: Beautiful 1,142 sf w/ 3 ops. No reasonable

BC-520 HAYWARD Facility: GG-453 CHICO: 5,000 sf w/ 7 ops Perfect for 1 or more dentists! $325k offer will be refused! Reduced $150k $570k GG-454 PARADISE: ~2,550 sf w/ 9 ops. 40 yrs goodwill! Amazing Oppor- CG-424 NAPA Prostho: Office has Digital X-ray & NEW 3D Imaging $65k DG-582 SAN JOSE: tunity! $525k Unit! Ready for Experienced, high-end Prosthodontist! On track to col- BC-432 PITTSBURG: $675k GG-574 SIERRA FOOTHILLS: Popular Professional Plaza. Spacious 3,000 lect just under $1m $690k DN-542 FREMONT Facility: sf w/ 7 ops $875k DC-459 SF PENINSULA Perio: 50% Partnership Buy In! Call for Details! $350k GN-244 OROVILLE: Must See! Gorgeous, Spacious. 2,500 sf w/5 ops! $600k BC-549 LAMORINDA AREA Facility: $295k Collections over $450k in 2013. Only $315k EG-579 ROCKLIN Perio/Gen: Aracve, well-appointed pracce in the DN-557 SALINAS: GN-399 REDDING: Loyal patient base and relaxed workweek schedule. presgious Whitney Oaks area. 1,600 sf w/3 op + 1 add’l. $325k Reduced $75k Priced at only $1.4M 1,440 sf w/3 ops. $150k FN-536 LAKE COUNTY Pedo: Focusing on Prevent dental problems BC-563 BERKELEY: GN-507 CHICO: It just doesn’t get any better than this! 3,500 sf w/ before they begin! 1,750 sf w/ 3ops. Now Only: $225k! NORTHERN CALIFORNIA 7ops. Practice $535k IC-543 CENTRAL VALLEY Ortho: 1,650 sf w/ 5 chair bays & plumbed for $450k GN-546 CHICO AREA: Catering to fearful paents, this office is well- 2 add’l, Strong Refs & Satisfied Pts Base $180k BG-570 SAN LEANDRO: EC-525 SACRAMENTO known for offering quality denstry with sedaon. 2,600sf w/ 4 ops. JC-540 FRESNO Sleep Apnea: Movated Seller rering! Step right in $220k $350K and make yours! Call for Details! $625k EC-531 GREATER SACRAMENTO: Pracce and HC-461 SONORA: In the beautiful Sierra Foothills, 4ops, 1350sf, free- BN-504 RICHMOND: Real Estate for Sale! standing bldg.. Practice $700k & RE Also Available! $100k / $800k HN-213 ALTURAS: This well managed pracce connues to have con- RE $700k EN-464 ROCKLIN Facility: sistent revenues! 2,200 sf w/ 3 ops + 1 add’l. $115k HN-280 NO EAST CA: Only Practice in Town 900 sf w/ 2 ops REDUCED! Now Only: $100k ONLY $60k

“ASK THE BROKER” CAN NOW BE FOUND AT WWW.WESTERNPRACTICESALES.COM Tech Trends CDA JOURNAL, VOL 44, Nº9

A look into the latest dental and general technology on the market

SmartQuit (Free, 2Morrow Inc.) CDA app (Free, CDA) Patient awareness continues to be a strong motivator in the journey to Having recently celebrated its third anniversary, the CDA app curb tobacco addiction. SmartQuit is a mobile app that is part of a continues to deliver helpful information for CDA members, including clinical program proven eff ective in helping smokers quit compared to regularly updated news, practice support information and resources, other approaches. The most important component of SmartQuit is the Ask an Expert Q&A and CDA Presents program information for completion of the user profi le. This information is used to customize a convention attendees. With CDA Presents The Art and Science specifi c “quit plan.” Users enter personal details that include how many of Dentistry set for Sept. 8 to 10, attendees can now download cigarettes smoked per day, cost per pack, time it takes to smoke a event information into the CDA app (available at cda.org/apps) cigarette and commitment level for quitting. Additional information such and begin planning their convention experience. Serving as an as triggers, concerns and things that matter are also required for the quit interactive version of the printed on-site program, app users can plan. Afterward, users enter motivators that include what they can do with access (and search) such information as speakers, schedules, the time saved per day and money saved per month by not smoking. exhibitors, information for new dentists and hotel and parking info. When the profi le is completed, users enter a desired quit date in addition The convention information will continue to update up to and during to medications and/or members of their support team to share their plan the convention, with real-time updates for any schedule changes, with. The process of entering this information is time consuming and can ability to download course handouts, access a real-time social be a detractor. However, when users do complete the profi le, a beautiful, media feed from the convention and more. To download the CDA personalized dashboard of their progress, motivators and goals is the Presents program information, simply click on the “CDA Events” result. Users unlock a series of eight daily exercises that can be done to orange bar on the bottom of the app homescreen and click the fi ght urges. Users can record and keep track of urges directly from the “Find” button to download the “San Francisco 2016” event data app. When combined with exercises, awareness and motivators, this app into the app. seeks to fi ght any urge to smoke and take the focus off the habit. Users — Blaine Wasylkiw, CDA director of online services can take advantage of the full program via an in-app purchase ($49.99), which includes more customizations, tips and tools for six months. — Hubert Chan, DDS Eff ect of Social Media in Curbing Opioid Abuse Studied Average Person Touches His Phone A new research projects aims to help slow down opioid abuse through social media, according to sciencemag.com. The Harnessing 2,617 Times a Day Online Peer Education (HOPE) intervention project is led by It is pretty well known by now that people have a diffi cult time putting researchers at the University of California Institute for Prediction their phones down, but a new study reveals just how addicted we Technology. The project received funding from the National Institutes are to our smartphones. The study, conducted by dscout, found that of Health for a 12-week pilot project at the Ronald Regan UCLA people touch their phones a whopping 2,617 times a day. For the Medical Center that will analyze how social media messaging study, 94 smartphone users out of a pool of more than 100,000 infl uences approximately 60 patients with a history of drug and people were sampled across fi ve days for 24 hours. A “touch” was abuse who are dealing with chronic pain and going through considered a tap, type, swipe and click. The study revealed that the long-term opioid therapy. The researchers will create a private heaviest users averaged 5,427 touches per day. This all translates Facebook group for the participants where they can communicate into 2.42 hours for average users and 3.75 hours for heavy users. with each other and receive tips and success examples. The Facebook got the “most touches” and Google had the most sessions. participants’ use of opioids will be monitored during the study. — Blake Ellington, Tech Trends editor — Blake Ellington, Tech Trends editor

594 SEPTEMBER 2016 What will you discover?

Accept your invitation to CDA Presents and see.

• Motivation from industry-leading speakers • C.E. at new courses and hands-on workshops • Gear from hundreds of exhibitors at special pricing • After-hours attractions, camaraderie and fun

Adventure, innovation, community and inspiration await you. Learn more at cdapresents.com.

The Art Anaheim, CA San Francisco, CA and Science May 4– 6, 2017 August 24– 26, 2017 of Dentistry WHAT IS

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