AUTUMN CME: DERMATOSES of HIV/AIDS
Published by the DCMS Foundation Marking 161 Years of Local Organized Medicine
Volu me 65, N O 3
In partnership with the Medical Societies of Duval, Clay, Nassau, Putnam and St. Johns Counties
AUTUM N 2 014
DCMS online . org
Northeast Florida Medicine Vol. 65, No. 3 2014 3
VOLUME 65, NUMBER 3 Dermatology Autumn 2014
EDITOR IN CHIEF Raed Assar, MD (Chair)
MANAGING EDITOR Laura Townsend ASSOCIATE EDITORS Sunil Joshi, MD (Vice Chair) Kim Barbel-Johnson, MD Mark Fleisher, MD
Ruple Galani, MD James Joyce, MD Daniel Kantor, MD Joseph Sabato, Jr., MD James St. George, MD
EXECUTIVE DIRECTOR Bryan Campbell DCMS FOUNDATION BOARD OF DIRECTORS President: Todd Sack, MD President-elect: Guy Benrubi, MD Secretary: Allen Seals, MD Treasurer: Malcom Foster, MD At Large Seat 1: Ruple Galani, MD At Large Seat 2: Eli Lerner, MD
2013 DCMS FOUNDATION DONORS Todd Sack, MD James Borland, MD Karen Ostergren, MD Marianne McEuen, MD J. Eugene Glenn, MD George Mayer, MD Jefferson Edwards, MD James St. George, MD R. Jay Cummings, MD Janet Betchkal, MD Jack Giddings, MD Cesar Gorospe, MD J. Timothy Walsh, MD H. Wade Barnes, MD David Boyd, MD Joe Ebbinghouse, MD Troy Guthrie, MD James Townsend, MD Kenneth Horn, MD N. H. Tucker, MD Chalermchai Punya, MD Allen Marks, MD
Dermatoses of HIV/AIDS
By Rachel R. Marks, BA, Christina B. Brennan, MD The advent of the human immunodeficiency virus (HIV) epidemic in the 1980s brought with it a wave of fear, stigma and misunderstanding. More than 30 years have passed since the disease first appeared in the United States (US) and our understanding of its pathogenesis, transmission, diagnosis, prevention and treatment has advanced tremendously. Still, given the far-reaching effects of HIV, we have room to grow as healthcare providers for those so afflicted. Early diagnosis of HIV is vital to improving prognosis and quality of life. Since HIV first emerged in the US, associated opportunistic skin and mucous membrane diseases have served as essential clues to an underlying diagnosis. The objective of this article is to increase awareness of the cutaneous manifestations of HIV, and thereby increase the likelihood of early identification.
From the Editor’s Desk
From the President’s Desk
From the Executive Vice President’s Desk
37 Patient Page 48 New Members
Features Dermatology in Northeast Florida Jonathan Kantor, MD, MSCE, MA Guest Editor
Brief Overview of Skin Cancer By Brent Goedjen, MD and Juan-Carlos Martinez, MD
Understanding When to Recommend Mohs Micrographic Surgery: A Review of Appropriate Use Criteria (AUC)
By Scott D. Warren, MD, Fellow ACMS, AAD
Dysplastic Nevi and Melanoma 25 Precursors: Practical Approaches to Evaluation, Follow-Up and Management By Jonathan Kantor, MD, MSCE, MA
Psoriasis: A Review and Update 29 on Extracutaneous Manifestations By Juan A. Rosario-Collazo, MD, FAAD; Lara Ashley East Laneve, PA-C, MPAS; Erin E. Harris, PA-C, MPAS
Aesthetic Dermatology By Michael Bernhardt, MD
Please note: Editorial and contents of this magazine reflect the records of the Duval County Medical Society (DCMS). The DCMS has done their best to provide useful and accurate information, but please take into account that some information does change. E&M Consulting, Inc., publishers and the DCMS take no responsibility for the accuracy of the information printed, inadvertent omissions, printing errors, nor do they endorse products and services. We take no responsibility regarding representations or warranties concerning the content of advertisements of products/services for a particular use, including all information, graphics, copyrighted materials, and assertions included in the advertisements. The reader is advised to independently check all information before basing decisions on such information.
DCMS online . org
Northeast Florida Medicine Vol. 65, No. 3 2014 5
From the Editor’s Desk
Celebrating Medicine Generally speaking, it seems that people often tend to take for granted the medical achievements seen over the years which have contributed to improving their lives. Even physicians may, at times, underappreciate the real value their profession provides to the wellbeing of their communities and humanity in general. We try to leave this world a better place, but we rarely stop to celebrate our individual and combined contributions. This editorial will highlight some of the great medical accomplishments during the past 200 years. Physicians in North Florida have not changed their tradition of caring for their patients, but the science and practice of medicine have significantly changed for the better. Communicable diseases have had devastating effects on the course of human history. Vaccinations have virtually Raed Assar, MD, MBA eliminated many of these Editor-in-Chief threats. Diseases, such as Northeast Florida Medicine smallpox, that could potentially annihilate entire populations are no longer a foreseeable factor. Although in areas of conflict and poverty around the world there have been recently reported cases of polio, the infection has almost been globally eradicated thanks to coordinated efforts by the international medical community. Anesthesia and antiseptic advancements have allowed surgery to become a viable option from a safety and pain management perspective. Without such care, people previously perished from conditions that could have been easily treated with surgery. Public health initiatives such as clean water and improved sanitation have contributed greatly to reducing infant mortality. Many deadly threats such as cholera, malaria and other parasitic infections have been eliminated in many societies by discoveries in the fields of medicine and microbiology. It is difficult to believe that antibiotics were first discovered less than 100 years ago and to imagine the practice of medicine without such treatments. Since the 1980s, antiviral
medications have tremendously changed the outcomes of diseases such as HIV and hepatitis. Improvements in heart surgery and management of cardiac conditions also contributed greatly to prolonging life and productivity. The development of randomized clinical research and evidence based medicine has played an important role in improving the effectiveness of medical interventions for a variety of diseases including cancer. The field of psychiatry also progressed with the better understanding of the role of medical management and greater societal acceptance of mental health conditions. For example, depression diagnosis and management improved allowing patients to return to productive lives. Advancements in imaging have helped patients through early detection, prevention and diagnosis of conditions, which have saved enormous numbers of lives. Advancements in childbirth also have prevented countless tragic deaths of women and babies. Organ transplantation, which started in 1954, has advanced to include multi-organ transplants, greatly impacting the lives of many who had no other treatment options. Although progress and advancements are needed in many areas, the overwhelming evidence of the good our profession has brought to people’s lives should be a source of great pride. It is hard to imagine what the next 200 years is going to bring for medicine and our profession. If the previous 200 years provide an indication, then it is likely that our profession will continue to improve our lives and those of future generations. Given the great contributions of our profession, every new day is a reason to celebrate. Special invitation: Please get involved and participate in our journal via the following ways:
– Send Letters to the Editor about medical issues affecting our society. Please send these to firstname.lastname@example.org – Submit articles for Clinical Images in Medicine at www.clinicalimagesinmedicine.blogspot.com – Volunteer as Peer Reviewers of medical articles for the journal or the Times-Union. Please email email@example.com to get involved. We welcome your input and contributions. v
Dr. Assar is Aetna’s Medical Director for North Florida. Articles or opinions provided by Dr. Assar do not necessarily reflect the views of Aetna. 6 Vol. 65, No. 3 2014 Northeast Florida Medicine
DCMS online . org
From the Presidentâ€™s Desk
A Strong Case for a Robust Public Health Program The recent national attention to the newly identified Middle Eastern Respiratory Syndrome (MERS) is a reminder of the importance of an effective national surveillance and information dissemination system. The Centers for Disease Control and Prevention (CDC) does an exceptional job for both surveillance and communication. Even with outstanding work by the CDC, effective protection of Americans will in large part depend on the preparedness of local communities to meet the enormous challenges of infectious epidemics. Although State Departments of Health have to play a key role, local physicians and public health departments will be Mobeen H. Rathore, MD 2014 DCMS President the first line of defense against any potential infectious epidemic. As was clear from the MERS cases in Indiana and Florida, the healthcare providers were aware of the potential risk of MERS and had a high index of suspicion. Because of this local health departments were able to respond to these two cases in a timely manner that helped keep the public safe and informed. Duval County had its first case of Chikungunya infection this year. Your County Medical Society and Duval County Health Department were ahead of this story and effectively communicated with the public and healthcare providers. This funny sounding disease is not new, but is new to many healthcare providers in the United States (US). This disease was under surveillance by the healthcare authorities for a few years since it was first seen in the Caribbean in late 2013. United States healthcare authorities were concerned about Chikungunya becoming more common and having autochthnous cases in the US. This assumption is with good reason since many parts of the US, including Florida, have the mosquito vector (Aedes) that can spread Chikungunya virus from person-to-person. A similar scenario has already been seen with Dengue fever. There have been at least 22 autochthnous cases reported in Florida in 2013. You can learn more about these diseases and get up-to-date reports on the DCMS website at www.dcmsonline.org
DCMS online . org
Unfortunately, it is easy for the Chikungunya virus to make its way to the US with people entering and leaving the country every day. Florida is especially susceptible since it is a main stopping point when traveling to the Caribbean and other tropical locations. So far almost 60 percent of Chikungunya cases reported are in Florida. I report all of this to you as evidence that we need a robust public health program in Florida, which requires millions of dollars of investment in surveillance, coordination and communication with healthcare providers, institutions and the public. Infections such as MERS and Chikungunya are not alone. There are many others, such as the Zika virus infection which has not been reported in the news, which are a threat to Florida and the United States as a whole. Public health resources are needed to train and educate first responders, primary care physicians and Emergency Department personnel how to recognize these new diseases. Additionally, the local public health departments must be prepared to deal with any of these infections when they rear their head. The dedicated staff in public health departments needs resources, skills and leadership to be effective. Public health programs must attract our best and brightest. The CDC offers an example where entry is competitive and highly sought out. We must create an atmosphere where our local health departments are in a similar situation. There are some things that can only be done by government and public health is one of those. Our public health infrastructure has weakened over the years from the mixture of financial cuts and increased demand for their time and resources to provide tangential services. The hope is that with effective implementation of an improved Affordable Care Act, health departments can get back to the real business of public health. The medical profession must support and advocate for more funds for public health otherwise it is quite possible that citizens of Florida, our patients and you and I may very well suffer the consequences. Let us also not forget that like SARS, MERS is affecting healthcare providers and it is certain that future diseases that we have not even imagined can do the same. v
Northeast Florida Medicine Vol. 65, No. 3 2014 7
From the Executive Vice President
What’s Medical about Marijuana? Do you love political ads? If you do, I would suspect that you are probably in the minority, but love them or loathe them, there’s no escaping the political signs of the season. This year, amidst the flurry of ads for State and Federal offices, another campaign is near the front of the pack in spending money to get your vote. The issue is Amendment 2: The Florida Right to Medical Marijuana Initiative. This initiative, backed by powerful Tampa-based attorney John Morgan, would legalize the cultivation, purchase, possession and use of marijuana to treat unspecified medical condition is recommended by a physician. Proponents say that there is no evidence of harm and that it still requires physician approval. Opponents say there will be a pot-store on every Bryan Campbell corner. Many physicians DCMS Executive Vice President say “just leave us out of it.”
Politics of Pot It’s not a coincidence that the Amendment 2 campaign is happening in 2014. This year is a gubernatorial election year, and not a Presidential election year. Statistical review of voter turnout over the past several non-Presidential election years shows significantly lower turnout amongst Democratic voters. As I mentioned, the prime driver behind the Amendment 2 campaign is John Morgan, a personal injury attorney from the firm Morgan and Morgan. Republican Independent Democratic Gubernatorial candidate Charlie Crist is also an attorney for Morgan and Morgan. Proponents of both issues believe that the Amendment 2 issue may drive more Democrats to the polls this November in hopes of bolstering Crist’s chances. This is a primary reason why the Florida Medical Association has endorsed Rick Scott for a second term as Governor of Florida. Gov. Scott has been a supporter of physicians in several key issues, including the issue of compassionate use of medical marijuana.
8 Vol. 65, No. 3 2014 Northeast Florida Medicine
Wait… What? Gov. Scott signed into law this year called the “Compassionate Medical Cannabis Act of 2014.” This measure, which was supported by the FMA, allows physicians to prescribe a low-THC, non-euphoric marijuana extract known as “Charlotte’s Web.” This extract is not smoked. Rather, it is delivered in oil form under the tongue. Charlotte’s Web has been demonstrated to reduce seizures in children. The law will allow physician to prescribe the extract for patients suffering from cancer or “a physical medical condition that chronically produces symptoms of seizures… or severe and persistent muscle spasms.” The law was written and introduced by a pair of local State Senators: Sen. Aaron Bean from Jacksonville and Sen. Rob Bradley from Clay County. Sen. Bradley said “The reason I sponsored this law is simple and straight forward- a parent who seeks to use ‘Charlotte’s Web’ to treat his or her child suffering from intractable epilepsy or cancer is not criminal, and any law that states otherwise defies common sense.”
If There’s a Law, Do We Need an Amendment? This is a matter for much debate. The law, which will go into effect on January 1, 2015, does have restrictions. It does not legalize the smoking of marijuana. Additionally, the approval is limited to the non-euphoric strain, so the people who may be hoping to use legal medical marijuana for recreational purposes are out of luck. Also, it does require a prescription from a physician, following the exhaustion of other methods. The Amendment would simply require a physician “recommendation.” For compassionate care, the current law is a good place to start. It covers cancer and seizures, and does it in a way that does not open a dispensary on every corner. In fact, Surgeon General John Armstrong, MD, has issued proposed rules for the production and distribution of medical marijuana, and the rules are strict. The state will be limited to five dispensaries. More than 300 companies applied to receive the license to produce the medical marijuana strain. Because of the limited number of licenses, the winners will be selected by lottery.
DCMS online . org
From the Executive Vice President
What Happens if the Amendment Passes? If Amendment 2 passes by the 60% margin required, expect a bustle of activity as people try to capitalize on the same “green rush” that has hit Washington and Colorado. The Florida Legislature will be called upon to determine the rules and implementations for the Amendment. It is likely that, at least in the beginning, the rules set forth by Surgeon General Armstrong will govern the production and distribution of medical marijuana in any form. However, rest assured that those administrative rules will be challenged early and often.
Conclusion There is no question that this is a time of great change. Some believe that this is the dawn of a new era of compassionate care. Others believe that we are crossing a threshold which cannot be uncrossed. No matter the fate of the Amendment 2, YOU, as a physician in the state of Florida have been put at the center of the storm. The County Medical Society will be working closely with its members, other County Medical Societies, and the FMA to bring you the resources you need to safely and compassionately provide care for your patients.
Now it’s Your Turn We asked members to talk about the medical marijuana issue and received a number of wonderful responses. I think that marijuana should be decriminalized altogether. It is a natural product that has mild sedating and tranquilizing properties and I believe that it is less harmful than alcohol. Of course, one should exercise usual precautions, such as no use at or before work or driving. It can be abused. I have seen patients who used so much that their life became a complete waste. In my experience this is fairly rare and a much less severe problem than alcoholism.
DCMS online . org
I would like to see more studies related to Colorado and Washington’s experience, but perhaps these will be available by November. It appears that there has been no increase in violent crime, maybe a slight decrease, and no increase in auto accidents thus far. I certainly don’t think we should be incarcerating people for possession. It is a waste of public funds. Law enforcement should concentrate on crimes with victims.
Retired Physician Medical Marijuana will just stimulate Marijuana Doc in the Boxes just like the pain clinics w Rxs going to all kinds of people in a cash-cow business. I myself will never give a marijuana Rx but at the same time I believe Marijuana should be legalized for everyone. This Medical Marijuana classification is a farce!!!
Michael Gilligan, MD, FACS My stance is from a practical perspective. Marijuana will be consumed whether or not it is regulated, as it has been consumed for a long time. Without judging ethical or moral considerations, it is nearly as popular as alcohol or nicotine products. It should be regulated and taxed. Obviously, similar laws to driving under the influence of alcohol should be applied, but other than that, whatever folks do without driving or being publicly intoxicated, should be their own business. Florida can learn from the experiences in Colorado and Washington State, what works and what doesn’t.
Anonymous I actually agree with the concept of recreational MJ. Keep doctors out of the middle between the person who wants MJ and the supplier. It also keeps the Fed and the DEA out of our hair. To not do this makes the doctor the gatekeeper. This did not work for prohibition, and does not work for MJ. At the very least, tax it for the state and the county and the community as a new source of revenue. v
Northeast Florida Medicine Vol. 65, No. 3 2014 9
Residents’ Corner: Naval Hospital Jacksonville
Naval Hospital Jacksonville’s Family Medicine Residency By Lt. Stephen McMullan, MD
Naval Hospital Jacksonville family medicine chief resident
Naval Hospital (NH) Jacksonville—its hospital and five branch health clinics across Florida and Georgia—cares for service members (active and retired) and their families. NH Jacksonville offers broad spectrum services, including primary and specialty care, inpatient, surgical, maternity (at the First Coast’s first Baby Friendly certified hospital), pharmacy, laboratory, radiology, dental, wellness, nutrition, aviation and dive medicine, and pre- and post-deployment health. NH Jacksonville’s Family Medicine Residency Program—the Navy’s oldest and one of the most awarded—is a central part of Family Medicine’s four Medical Home Port teams at the hospital. This year, all 14 of the command’s primary care clinics earned Patient Centered Medical Home 2011 Recognition (Level III) from the National Committee for Quality Assurance. Currently, the program is welcoming the next generation of family medicine physicians to Navy Medicine. Joining this summer are 13 new interns (an increase of one slot) along with two new PGY-2 residents returning from the fleet. It’s also time to say “fair winds and following seas” to the graduating class, which had a 100 percent pass rate on the American Board of Family Medicine certification exam. The program welcomes four new faculty members this summer and sadly says “goodbye” to a few others (who have contributed greatly to the curriculum) who are moving on to new duty stations. The program’s research excellence has been recognized on the national level. It earned the 2014 Outstanding Achievement in Scholarly Activity Award from the Uniformed Services Academy of Family Physicians. The program also earned the 2013 Excellence in Teaching Award and 2011 Family Medicine Clinical Site of the Year Award from the Uniformed Services University of the Health Sciences. NH Jacksonville’s program is fully accredited by the Accreditation Council for Graduate Medical Education.
JACKSONVILLE, Fla. (June 5, 2014) – Nine Family Medicine physicians, who recently graduated from medical school, prepare to begin their first year of Naval Hospital Jacksonville’s three-year, award-winning Family Medicine Residency Program. Front row (left to right): Lt. Brittany Wiles, Lt. Sajeewane Seales and Lt. Paul Seales. Second row (left to right): Lt. Andrew Moore, Lt. Brandon Hill and Lt. Christopher Weber. Back row (left to right): Lt. Jason Pesqueira, Lt. Daniel Kuckel and Lt. Timothy Algiers. (U.S. Navy photo by Jacob Sippel, Naval Hospital Jacksonville Public Affairs/Released)
DCMS online . org
To showcase the residents’ work, the program held its annual Research Symposium in June, in collaboration with St. Vincent’s HealthCare’s Family Medicine Residency Program. The program continues to train residents to provide highly skilled, patient-centered care—both here at home and on, above and below the sea. Rotations at UF Health provide additional experience in adult and neonatal intensive care, emergency/ trauma, and newborn care; while training at Wolfson Children’s Hospital provides higher-acuity experience in pediatric inpatient and emergency care. Residents enjoy working with their counterparts from St. Vincent’s HealthCare, UF Health and Mayo Clinic on these rotations. Upon completion of the first year, some interns choose to go directly to the fleet to serve as general medical officers, flight surgeons or undersea medical officers. Many stay to complete the residency in three years. The program seeks to provide leadership in family medicine training and military medicine, and strives for consistent excellence in quality care, academics and research. It’s an honor to reside in Duval County and provide top quality care to the men and women in uniform and their families—and to work alongside medical colleagues in the community. NH Jacksonville’s priority since its founding in 1941 is to heal the nation’s heroes and their families. The command is comprised of the Navy’s third largest hospital and five branch health clinics across Florida and Georgia. Of its patient population—about 163,000 active and retired sailors, soldiers, Marines, airmen, guardsmen and their families—70,000 are enrolled with a primary care manager and Medical Home Port team at one of its facilities. To find out more, visit the command website at www.med.navy.mil/sites/NavalHospitalJax. v
JACKSONVILLE, Fla. (June 12, 2014) – Lt. Anna Oberhofer, a Naval Hospital (NH) Jacksonville Family Medicine resident physician, discusses a research project on display at the Annual Scholarly Activity Symposium at NH Jacksonville. The symposium is an opportunity for the graduating, third-year Family Medicine residents to showcase their scholarly pursuits, which advance the science of medicine. Each Family Medicine resident conducts research—from case studies to large-scale research studies. (U.S. Navy photo by Jacob Sippel, Naval Hospital Jacksonville Public Affairs/released)
Northeast Florida Medicine Vol. 65, No. 3 2014 11
Dermatology in Northeast Florida It has been my distinct pleasure to serve as Guest Editor for the Dermatology issue of Northeast Florida Medicine. Skin complaints remain one of the top reasons patients seek medical care, and I appreciate the opportunity to share a variety of articles and insights from some of our local clinicians. In this issue of Northeast Florida Medicine, Drs. Brent Goedjen and Juan-Carlos Martinez provide an excellent general review of skin cancer diagnosis and Jonathan Kantor, MD, MSCE, MA management in the United States. They highlight some of the most common forms of skin cancer, and briefly address some of the less commonâ€”but still potentially deadlyâ€”skin cancers, such as Merkel cell carcinoma.
Cosmetic dermatology remains an area of interest for many patients, as our population ages and demand for aesthetic interventions continues to rise. Dr. Michael Bernhardt addresses some common cosmetic treatments and their indications in a review of neurotoxins and fillers in dermatology. Finally, while many clinicians are familiar with CME articles touching on HIV management, this issue of Northeast Florida Medicine brings a CME article on HIV-related dermatoses. Though HAART has fortunately changed the face of HIV, and the skin complications seen with AIDS are no longer as prevalent in the US as they were two decades ago, Ms. Rachel Marks and Dr. Christina Brennan discuss HIV dermatoses and provide an overview of HIV management for the clinician. I hope you enjoy this issue of Northeast Florida Medicine! v
For patients with high-risk non-melanoma skin cancers, or with lesions in cosmetically sensitive areas, the Mohs technique may be appropriate. Dr. Scott Warren provides a general review of indications for Mohs surgery, a timely addition as last year the American Academy of Dermatology, American College of Mohs Surgery, and American Society for Mohs Surgery published a joint statement regarding indications for this increasingly utilized technique. While non-melanoma skin cancers are incredibly common in Florida, melanoma remains responsible for the vast majority of skin cancer deaths worldwide. Managing and following dysplastic nevi is a significant challenge for dermatologists and primary care physicians alike, and I have included a review of this important area. Psoriasis is one of the most common dermatologic problems in the United States, with approximately three percent of US adults affected. Data over the past decade have suggested that psoriasis morbidity is not limited to the skin, and this disease is associated with a broad array of connective tissue and cardiac complications. In this issue, Dr. Juan Rosario-Collazo, Ms. Laura Ashley East Laneve and Ms. Erin E. Harris discuss the epidemiology of psoriasis and some of the therapeutic options available for this sometimes frustrating and debilitating condition.
12 Vol. 65, No. 3 2014 Northeast Florida Medicine
DCMS online . org
Brief Overview of Skin Cancer By Brent Goedjen, MD and Juan-Carlos Martinez, MD
Abstract: Collectively, skin cancer represents the most common malignancy in humans. Patients are often initially diagnosed and sometimes treated by primary care physicians. This article discusses the most common skin cancers: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. Additionally, this article will discuss a particularly aggressive tumor called Merkel cell carcinoma (MCC). We provide a brief overview regarding epidemiology and risk factors as well as diagnostic and management considerations.
Introduction Skin cancers are the most common human malignancy, and their incidence continues to increase.1-3 A majority of the population may see their primary care provider (PCP) for the majority of their health issues including skin issues.4 As such, PCPs can diagnose these cancers early in their development and play an integral role in reducing the morbidity and mortality of this growing public health concern. Unfortunately, dermatologic training is inconsistent across medical schools and residency programs.5 This lack of formalized training highlights the importance of self-education with regards to skin cancer diagnosis and management, especially for practitioners in Florida, where harmful sun exposure can be more prevalent than other states.
Classification and Epidemiology of Skin Cancer Skin cancer is most broadly divided into melanoma and non-melanoma types. Non-melanoma skin cancer (NMSC) is a term generally used to refer to basal cell carcinoma
Address correspondence to: Mayo Clinic Jacksonville 4500 San Pablo Rd S, Jacksonville, FL 32224 Goedjen.Brent@mayo.edu; Martinez.JuanCarlos@mayo.edu
DCMS online . org
(BCC) and squamous cell carcinoma (SCC). These are grouped together because of their common derivation from the keratinocyte, as well as their similar clinical behavior if diagnosed early in their development. The exact burden of NMSC is uncertain because of inconsistent reporting to cancer registries. The annual incidence of NMSC in the US is 2.5 to 4.3 million with a four to one BCC to SCC ratio.6,7 Annual deaths from skin cancers excluding melanoma are approximately 3,170.2 NMSC incidence increases dramatically with age and becomes increasingly male predominant after age 80.2 Direct annual costs related to treatment of NMSC are estimated at approximately $1.5 billion.8 Melanoma is derived from melanocytes, and has relatively high rates of metastasis and death.9 Melanoma represents about five percent of skin cancers, but is responsible for more than 75 percent of skin cancer deaths. New cases of melanoma in the United States (US) were 76,690 in 2013 resulting in 9,480 deaths. The incidence is estimated to be increasing at a rate of 3.1 percent annually.10 Excluding NMSC, melanoma is the fifth most common cancer in men and the seventh most common in women. In addition, it is the leading cause of cancer death in women 25 to 30 years of age.2,9 Direct costs related to melanoma treatment in the US is approximately $2.36 billion annually.11 Merkel cell carcinoma (MCC) is a much less common, but very aggressive cutaneous malignancy. Recent developments in the diagnosis and pathogenesis of this entity have led to an increased awareness of its existence among physicians. The annual incidence of 950 to 1,300 continues to rise.12 This increase in incidence has been attributed in part to larger numbers of elderly and immuno-compromised individuals.12,13 Even if diagnosed in the earliest stages of disease, five-year survival is only 79 percent, and drops precipitously if disease is more advanced at presentation.13
Northeast Florida Medicine Vol. 65, No. 3 2014 13
Risk Factors for Development of Skin Cancer
cinoma Syndrome (Gorlin’s Syndrome). Gorlin’s syndrome is the most common of congenital diseases characterized by development of multiple BCCs.22
Mutations in p53, a tumor suppressor gene, are seen in SCC and its precursors: actinic keratosis (AK) and squamous cell carcinoma in situ (SCCIS).23 There are several genetic conditions, characterized by defective DNA repair mechanisms that are associated with rampant SCC development. Xeroderma Pigmentosum (XP), the prototype of these disorders, often leads to death from metastatic SCC in childhood.24
Protection from the external environment, including the harmful effects of ultraviolet (UV) radiation, is one of the primary functions of the skin.14 UV radiation is a risk factor in the development of all types of skin cancer. SCC development is correlated with chronic cumulative sun exposure, while BCC development is associated with intermittent and childhood sun exposure.15 Factors that correlate with melanoma risk include: • intermittent sunburns in childhood • numerous melanocytic nevi • proximity to the equator. In addition, tanning bed use prior to age 35 results in a 75 percent increased risk of melanoma.16,17 Recognition of this risk led the World Health Organization (WHO) to classify tanning beds as group I carcinogens (the same group as cigarettes) in 2009.16 UV exposure is the greatest modifiable risk factor for all types of skin cancer, and sunscreen use has been shown to reduce the risk of melanoma.17 Appealing to the vanity of younger patients by citing the aging effect of UV light may be more effective than warning about skin cancer risk alone.18
Genetic Factors Familial characteristics associated with melanoma and NMSC include: • family history of melanoma • lightly pigmented skin • inability to tan, • red hair (MC1R gene).19 Independent risk factors for melanoma development include: large numbers of acquired nevi, atypical nevi, numerous solar lentigines, and history of previous melanoma. These features are reflective of both genetics and environmental exposure.19-21 Two thirds of BCC tumors demonstrate a mutation in the Patched gene (PTCH), which encodes a tumor suppressor. This gene is constitutively defective in Nevoid Basal Cell Car-
14 Vol. 65, No. 3 2014 Northeast Florida Medicine
Mutations in the gene CDKN2A (cyclin-dependent kinase inhibitor 2A) can be seen in familial melanoma syndromes. Commercial testing is available and can be considered after genetic counseling for individuals who meet a specific set of criteria.25 Mutations in the proto-oncogene, BRAF, occur in 45 percent of melanomas. It is the target of promising new melanoma drugs such as vemurafenib and dabrafenib.26,27
Viral Infectious Factors Human papillomavirus (HPV) is associated with anogenital and head and neck SCC, particularly in the setting of HIV and immunosuppression. Its ability to act as a co-carcinogen of cutaneous malignancies in the general population, however, is questionable.28,29 Current research is evaluating the utility of HPV vaccination for SCC prophylaxis in high risk populations.30,31 Merkel Cell Polyomavirus is present in up to 80 percent of MCC tumor samples. However, it is also present in a significant portion of healthy individuals.32 It is believed this virus may induce cellular transformation leading to MCC development. This effect may be magnified in the setting of immunosuppression (i.e. leukemia, organ transplant), and could explain the increased incidence in these populations.33
Immunosuppression Immunosuppression-associated skin cancer is most frequent in the setting of solid organ transplant (SOT) and chronic lymphocytic leukemia (CLL).34 These patients have a 40 to 250 times greater risk of SCC and five to ten times increase of BCC. The magnitude of risk correlates with cumulative sun exposure and age at transplantation. Other important factors are the degree, duration and mechanism of immunosuppression.35 The skin cancers in SOT patients and CLL patients tend to have a more aggressive course.36 DCMS online . org
Dermatology Figure 1 Basal Cell Carcinoma One cohort study showed up to 27 percent of heart transplant patients and five percent of renal transplant patients succumbed to skin cancer.37 Patients with a history of NMSC prior to transplantation are 49 times more likely to develop additional NMSCs after transplantation, and nearly 100 percent will get an additional NMSC within five years of the primary NMSC diagnosis.38 Reducing dosage or transitioning to m-TOR inhibitors (e.g. Sirolimus), rather than calcineurin inhibitors (e.g. Tacrolimus), may be protective.38 Primary care providers can play a role in coordinating these interventions with the transplant team.
A. Infiltrating BCC B. Nodular BCC C. Superficial BCC D. List of high risk tumor features with respective treatment options
Diagnosis and Management of Skin Cancer Basal Cell Carcinoma Clinical Diagnosis: BCC can often be diagnosed on just clinical grounds. It often appears as a smooth, pearly papule or nodule with a rolled edge and superimposed ‘arborizing’ telangiectatic vessels. Observing a waxy quality to the skin during gentle tension on physical exam can be helpful for indeterminate lesions. A history of ulceration or friability leading to spontaneous bleeding with only minimal trauma may also be helpful clues to the diagnosis. In contrast, the superficial subtype may have the appearance of a persistent scaling red plaque.
BCC, is a very superficial disease process, typically with lower potential for local destruction, and can be treated successfully with less invasive techniques such as ED&C. In addition, 5-Fluorouracil and Imiquimod are FDA approved for topical treatment of superficial BCC. Newer unproven therapies include photodynamic therapy (PDT) and laser.
Biopsy Technique and Histologic Subtypes: A shave biopsy is often the preferred diagnostic technique given its simplicity for the patient and practitioner. In contrast to other malignancies, tumor depth is relatively unimportant in determining treatment or prognosis. The most common histologic variants are superficial, nodular, micronodular, morpheaform and metatypical.37 Treatment Considerations: BCC very rarely metastasizes, but can cause significant morbidity if neglected.39 The treatment choice is guided by risk stratification of individual tumors (histologic subtype, location, size, etc.) as shown in Figure 1. Because some histologic subtypes (morpheaform/infiltrative/micronodular/metatypical) are more likely to be missed on routine pathologic examination, Mohs surgery is often used for these tumors. Primary excision or electrodesiccation and curettage (ED&C) is often sufficient for the smaller or more well-defined subtypes, such as nodular BCC. Superficial
DCMS online . org
Squamous Cell Carcinoma Clinical Diagnosis: SCC can be more clinically ambiguous than BCC. It can present as an indurated, tender, scaly papule or plaque, sometimes with focal erosion and crust. It most frequently develops within areas of extensive sun damage. Actinic keratoses, referred to as ‘pre-cancers,’ can be precursors to SCC with estimated rates of conversion at 0.076 to 0.53 percent per lesion per year.40 The prototypical lesion is a small erythematous papule with white to yellow adherent scale. SCC in situ (Bowen’s Disease) may develop de novo or from a pre-existing AK, and is characterized histologically by atypia involving the entire thickness of the epidermis. It can present as an erythematous scaling plaque sometimes confused with psoriasis or dermatitis.
Northeast Florida Medicine Vol. 65, No. 3 2014 15
Figure 2 Squamous Cell Carcinoma A. Moderately differentiated SCC B. Well differentiated SCC C. Squamous cell carcinoma in situ D. List of high risk tumor features and respective treatment options
priate use criteria (AUC) for Mohs surgery are covered in the Understanding When to Recommend Mohs Micrographic Surgery article in this journal. SCC is the most common cancer with the ability to metastasize (approximately 3.7 to five percent). Therefore, a careful lymph node examination should be performed.42,43 SCC with multiple high risk features can be considerably more aggressive with metastatic rates approaching 10 to 25 percent. SCC arising within injured or chronically inflamed skin can see metastatic rates approaching 40 percent.42 The American Joint Committee on Cancer (AJCC) recently revised their SCC grading system with these features in mind to improve prognostic discrimination.44 Sentinel lymph node biopsies (SLNBs), imaging, or adjuvant therapies are considered in particularly high risk situations.
Melanoma Clinical Diagnosis:
Biopsy Technique and Histologic Subtypes: The depth of an SCC tumor can have prognostic and therapeutic implications. Care should be given to obtain the full thickness of the tumor using a shave or punch biopsy technique.
aThe ABCDE criteria [Asymmetry, Border (notched), Color (multiple, uneven), Diameter (>6mm), Elevation] can aid in the identification of suspicious lesions, and can be easily taught to patients. A history of changing nevi, symptomatic nevi, or new nevi (if older than 30 years of age) should also be looked upon with suspicion. A mole that stands out
SCC is subclassified by the degree of histologic differentiation (well to poor) and the number of high risk features (Figure 2). A keratoacanthoma is a very well-differentiated subtype that often follows a benign course. Treatment Considerations: For individual AKs, local destruction with liquid nitrogen (cryotherapy) is the simplest intervention. Field therapy allows for treatment of many lesions existing in an area of extensive actinic damage with less risk of the postinflammatory hypopigmentation inherent in cryotherapy. Options include topical 5-fluorouracil, imiquimod, ingenol mebutate or PDT. In addition, up to 25 percent of lesions may regress spontaneously highlighting the importance of regular sun protection as part of the treatment regimen.41 The exact treatment modality for SCC is guided by the characteristics of the individual tumor (Figure 2). Mohs surgery and primary excision are the most frequently used procedures for invasive SCC. The recently published appro-
16 Vol. 65, No. 3 2014 Northeast Florida Medicine
Figure 3 Melanoma A. Nodular melanoma B. Superficial spreading melanoma C. Melanoma in situ D. Lentigo maligna melanoma E. Amelanotic melanoma DCMS online . org
against a patientâ€™s normal, or signature nevi, should also be closely evaluated. This is sometimes referred to as the â€˜ugly duckling sign.â€™ Dermoscopy in the hands of an experienced user is a helpful tool for indeterminant lesions. Pediatric melanoma is rare and can present differently than in adults. This difference prompted the creation of a modified ABCD criteria for pediatric patients: (Amelanotic, Bleeding, Bump, Color uniformity, De novo, any Diameter).45 Biopsy Technique and Histologic Subtypes: The major subtypes of melanoma include superficial spreading, nodular, lentigo maligna, acral lentiginous, desmoplastic and amelanotic (Figure 3). Acral lentiginous melanoma is the most common type in darkly pigmented individuals.37 Patient survival is inversely proportional to depth of invasion. Therefore, it is critical that the entire tumor depth be evaluated upon initial diagnosis. Complete removal of the primary melanoma with initial diagnosis is ideal. This can be accomplished by a variety of techniques based on size and estimated depth. Saucerization, punch excision (with trephine) or excisional biopsies are common techniques. Management of patients with melanoma is largely dependent upon initial staging of the patient. The most important staging criteria are depth of the primary tumor and sentinel lymph node status. Fortunately, the vast majority of melanomas are less than one mm in depth, and do not require more treatment than excision at the primary site. Diagnosis of melanoma should prompt referral to a specialist for consultation and treatment. Overall prognosis varies according to stage, with the most superficial tumors having a 10 year survival rate of 95 percent. Prognosis decreases precipitously with increasing depth and is only 40 to 60 percent once nodal disease is present.46
Merkel Cell Carcinoma Clinical Diagnosis: MCC most commonly presents on the sun-exposed areas as a rapidly growing, dome-shaped, purplish-red nodule (Figure 4). It is often confused with an inflamed cyst or other benign lesion. As such, a high index of suspicion is critical to early diagnosis. Treatment Considerations: MCC is a rare and aggressive neoplasm. Initial biopsy of the lesion is usually required to make the diagnosis. Treatment at the primary site is wide surgical excision with consideration of adjuvant radiotherapy. Because of its high propensity for nodal metastases, sentinel lymph node biopsy is an important aspect of initial staging. Treatment of nodal basins depends on sentinel lymph node status.47 Diagnosis of Merkel cell carcinoma should prompt referral to a specialist for consultation and treatment.
Screening and Follow Up Follow up by a dermatologist after diagnosis of melanoma or high risk NMSC is generally increased to three to six months for the first two to three years and then annually thereafter.9 There are no consensus guidelines for regular skin cancer screenings in the general population, but new data have emerged proving its value. Some cancer organizations already suggest annual screenings.48 If the US Preventive Task Force were to make a concrete recommendation in the future, it may profoundly increase the number of patients seeking evaluation. This would increase the role of the PCP and stress the importance of continued self-education on these topics.
Summary Skin cancer comprises a diverse group of malignancies. They are most broadly classified as squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma. The behavior of individual tumors within these groups can vary significantly based on certain features. Understanding these features is crucial in selecting the appropriate treatment approach. The incidence of all types of skin cancer is increasing which has shifted more responsibility to the primary care provider for recognition and management. v
Figure 4 Merkel Cell Carcinoma DCMS online . org
Northeast Florida Medicine Vol. 65, No. 3 2014 17
References: 1. Cakir BO, Adamson P, Cingi C. Epidemiology and economic burden of nonmelanoma skin cancer. Facial Plast Surg Clin North Am. Nov 2012;20(4):419-422. 2. Society AC. Cancer Facts & Figures 2013. Atlanta: American Cancer Society; 2013. 3. Rogers HW, Weinstock MA, Harris AR, et al. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol. Mar 2010;146(3):283-287. 4. Verhoeven EW, Kraaimaat FW, van Weel C, et al. Skin diseases in family medicine: prevalence and health care use. Ann Fam Med. Jul-Aug 2008;6(4):349-354. 5. Hansra NK, O’Sullivan P, Chen CL, Berger TG. Medical school dermatology curriculum: are we adequately preparing primary care physicians? J Am Acad Dermatol. Jul 2009;61(1):23-29 e21. 6. Bickers DR, Lim HW, Margolis D, et al. The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. J Am Acad Dermatol. Sep 2006;55(3):490-500. 7. Perera E, Sinclair R. An estimation of the prevalence of nonmelanoma skin cancer in the U.S. F1000Res. 2013;2:107. 8. Society AC. Skin Cancer: Basal and Squamous Cell. 2012. 9. Trotter SC, Sroa N, Winkelmann RR, Olencki T, Bechtel M. A Global Review of Melanoma Follow-up Guidelines. J Clin Aesthet Dermatol. Sep 2013;6(9):18-26. 10. Linos E, Swetter SM, Cockburn MG, Colditz GA, Clarke CA. Increasing burden of melanoma in the United States. J Invest Dermatol. Jul 2009;129(7):1666-1674. 11. Health NCIatNIo. “The cost of cancer”. 2013; http:// www.cancer.gov/aboutnci/servingpeople/understanding-burden/costofcancer. Accessed 3/14/14. 12. Duprat JP, Landman G, Salvajoli JV, Brechtbuhl ER. A review of the epidemiology and treatment of Merkel cell carcinoma. Clinics (Sao Paulo). 2011;66(10):1817-1823. 13. Agelli M, Clegg LX. Epidemiology of primary Merkel cell carcinoma in the United States. J Am Acad Dermatol. Nov 2003;49(5):832-841. 14. Proksch E, Brandner JM, Jensen JM. The skin: an indispensable barrier. Exp Dermatol. Dec 2008;17(12):10631072.
18 Vol. 65, No. 3 2014 Northeast Florida Medicine
15. Rosso S, Zanetti R, Martinez C, et al. The multicentre south European study ‘Helios’. II: Different sun exposure patterns in the aetiology of basal cell and squamous cell carcinomas of the skin. Br J Cancer. Jun 1996;73(11):1447-1454. 16. Mogensen M, Jemec GB. The potential carcinogenic risk of tanning beds: clinical guidelines and patient safety advice. Cancer Manag Res. 2010;2:277-282. 17. Green AC, Williams GM, Logan V, Strutton GM. Reduced melanoma after regular sunscreen use: randomized trial follow-up. J Clin Oncol. Jan 20 2011;29(3):257-263. 18. Mahler HI, Kulik JA, Gibbons FX, Gerrard M, Harrell J. Effects of appearance-based interventions on sun protection intentions and self-reported behaviors. Health Psychol. Mar 2003;22(2):199-209. 19. Nikolaou VA, Sypsa V, Stefanaki I, et al. Risk associations of melanoma in a Southern European population: results of a case/control study. Cancer Causes Control. Sep 2008;19(7):671-679. 20. Clark WH, Jr., Reimer RR, Greene M, Ainsworth AM, Mastrangelo MJ. Origin of familial malignant melanomas from heritable melanocytic lesions. ‘The B-K mole syndrome’. Arch Dermatol. May 1978;114(5):732-738. 21. Reimer RR, Clark WH, Jr., Greene MH, Ainsworth AM, Fraumeni JF, Jr. Precursor lesions in familial melanoma. A new genetic preneoplastic syndrome. Jama. Feb 20 1978;239(8):744-746. 22. Hutchin ME, Kariapper MS, Grachtchouk M, et al. Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle. Genes Dev. Jan 15 2005;19(2):214-223. 23. Brash DE, Rudolph JA, Simon JA, et al. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci U S A. Nov 15 1991;88(22):10124-10128. 24. Mareddy S, Reddy J, Babu S, Balan P. Xeroderma Pigmentosum. ScientificWorldJournal. Dec 29 2013;2013:534752. 25. Leachman SA, Carucci J, Kohlmann W, et al. Selection criteria for genetic assessment of patients with familial melanoma. J Am Acad Dermatol. Oct 2009;61(4):677 e671-614.
DCMS online . org
26. Greaves WO, Verma S, Patel KP, et al. Frequency and spectrum of BRAF mutations in a retrospective, single-institution study of 1112 cases of melanoma. J Mol Diagn. Mar 2013;15(2):220-226.
38. Tessari G, Girolomoni G. Nonmelanoma skin cancer in solid organ transplant recipients: update on epidemiology, risk factors, and management. Dermatol Surg. Oct 2012;38(10):1622-1630.
27. Estrozi B, Machado J, Rodriguez R, Bacchi CE. Clinicopathologic findings and BRAF mutation in cutaneous melanoma in young adults. Appl Immunohistochem Mol Morphol. Jan 2014;22(1):57-64.
39. McCusker M, Basset-Seguin N, Dummer R, et al. Metastatic basal cell carcinoma: Prognosis dependent on anatomic site and spread of disease. Eur J Cancer. Jan 9 2014.
28. Dimon MT, Wood HM, Rabbitts PH, Liao W, Cho RJ, Arron ST. No Evidence for Integrated Viral DNA in the Genome Sequence of Cutaneous Squamous Cell Carcinoma. J Invest Dermatol. Jan 30 2014.
40. Werner RN, Sammain A, Erdmann R, Hartmann V, Stockfleth E, Nast A. The natural history of actinic keratosis: a systematic review. Br J Dermatol. Sep 2013;169(3):502-518.
29. Nindl I, Gottschling M, Stockfleth E. Human papillomaviruses and non-melanoma skin cancer: basic virology and clinical manifestations. Dis Markers. 2007;23(4):247-259.
41. Marks R, Foley P, Goodman G, Hage BH, Selwood TS. Spontaneous remission of solar keratoses: the case for conservative management. Br J Dermatol. Dec 1986;115(6):649-655.
30. Diniz MO, Cariri FA, Aps LR, Ferreira LC. Enhanced therapeutic effects conferred by an experimental DNA vaccine targeting human papillomavirus-induced tumors. Hum Gene Ther. Oct 2013;24(10):861-870.
42. Alam M, Ratner D. Cutaneous squamous-cell carcinoma. The New England journal of medicine. Mar 29 2001;344(13):975-983.
31. Haedicke J, Iftner T. Human papillomaviruses and cancer. Radiother Oncol. Sep 2013;108(3):397-402. 32. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. Feb 22 2008;319(5866):1096-1100. 33. Amber K, McLeod MP, Nouri K. The Merkel cell polyomavirus and its involvement in Merkel cell carcinoma. Dermatol Surg. Feb 2013;39(2):232-238. 34. Brewer JD, Habermann TM, Shanafelt TD. Lymphoma-associated skin cancer: incidence, natural history, and clinical management. Int J Dermatol. Mar 2014;53(3):267-274. 35. Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med. Apr 24 2003;348(17):1681-1691. 36. Adamson R, Obispo E, Dychter S, et al. High incidence and clinical course of aggressive skin cancer in heart transplant patients: a single-center study. Transplant Proc. Jun 1998;30(4):1124-1126. 37. Bolognia JL. Dermatology. Vol 2. 3rd ed. St. Louis: Elsevier Saunders; 2012.
DCMS online . org
43. Schmults CD, Karia PS, Carter JB, Han J, Qureshi AA. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. JAMA Dermatol. May 2013;149(5):541-547. 44. Jambusaria-Pahlajani A, Kanetsky PA, Karia PS, et al. Evaluation of AJCC tumor staging for cutaneous squamous cell carcinoma and a proposed alternative tumor staging system. JAMA Dermatol. Apr 2013;149(4):402-410. 45. Cordoro KM, Gupta D, Frieden IJ, McCalmont T, Kashani-Sabet M. Pediatric melanoma: results of a large cohort study and proposal for modified ABCD detection criteria for children. J Am Acad Dermatol. Jun 2013;68(6):913-925. 46. Network NCC. NCCN Guidelines, Melanoma Version 3.2014. http://www.nccn.org/professionals/physician_ gls/pdf/melanoma.pdf. 47. Network NCC. NCCN Guidelines Version 1.2014, Merkel Cell Carcinoma. 2014; http://www.nccn.org/ professionals/physician_gls/pdf/mcc.pdf. 48. Fernandez CA, McClure LA, Leblanc WG, et al. Comparison of Florida skin cancer screening rates with those in different US regions. South Med J. Oct 2012;105(10):524-529.
Northeast Florida Medicine Vol. 65, No. 3 2014 19
Understanding When to Recommend Mohs Micrographic Surgery: A Review of Appropriate Use Criteria (AUC) By Scott D. Warren, MD, Fellow ACMS, AAD Abstract: Mohs micrograpic surgery gained popularity among dermatologists in the 1970’s when the fresh frozen tissue technique was developed. This allowed the Mohs trained dermatologist to remove skin cancer in a staged method, in an outpatient setting. Tracing the tumors in a staged fashion led to cure rates in the high 90th percentile. Not all skin cancers need this highly specialized treatment and can be treated with more traditional procedures. The AAD developed the Appropriate Use Criteria (AUC) for Mohs micrographic Surgery, in collaboration with the ACMS, ASDSA, and ASMS. The AUC are used as a guide for determining when Mohs micrographic surgery should be utilized instead of another removal method.
Clinicians who treat skin cancer need a clear understanding of when Mohs surgery is the best and most appropriate treatment. There are “gray” areas; however, this review will concentrate on the most commonly treated tumors. Skin Cancer is the most common form of cancer consisting of approximately one third of all cancers, with approximately three million Basal Cell Carcinomas (BCC), 700,000 Squamous cell Carcinomas and 77,000 Melanomas diagnosed in the United States (US) in 2013. One to two percent of Squamous Cell Carcinoma patients will die from the disease.1 Rarely will BCC lead to death, with a metastatic rate of .0028 to 0.55 percent. (2) Metastatic BCC has a five year survival rate of 10 percent.2 About one out of two patients diagnosed with BCC will develop another skin cancer within five years.3 The incidence of BCC is increasing by 10 percent per year worldwide. The lifetime risk in white populations in North America is 30 percent, and 50 percent of people in the US will develop skin cancer if they live to be 65 years of age or older.2 All skin types get skin cancer, but light skin individuals are more likely to develop skin cancer than dark skin individuals because the most common skin cancers are associated with ultraviolet radiation. Close to 80 percent of lifetime UV exposure occurs by 60 years of age, and about 25 percent by 18 years of age.1
Address Correspondence: Scott D. Warren, MD 6890 Belfort Oaks Place Jacksonville, FL 32216 www.firstcoastmohs.com
DCMS online . org
MMS is a combined surgical and pathological procedure designed by Dr. Frederick Mohs in 1936 to remove cancer. (Today, the physician is both the surgeon and pathologist during Mohs Surgery.) This has led to higher cure rates due to real time in-vivo fixation techniques that ensure 100 percent of a lesion’s margins are removed. In the past, time delay was an issue with in-vivo fixation. The fresh tissue technique, initially tried by F. Mohs in 1953 around the eyes, was presented by Stegman and Tromovitch at the annual Chemosurgery Conference in December, 1970. Perry Robins, M.D. and Rex Amonette, M.D. presented fresh tissue cases at the annual meeting of the American Academy of Ophthalmology and Otolaryngology (AAOO) in October, 1970. Dr. Amonette is still practicing in Memphis, TN, using this technique, now referred to as Mohs Micrographic Surgery.4 This fresh tissue technique results in the excised tissue being examined after frozen sections of the entire peripheral and deep margins are microtomed, placed on slides, and stained. The surgeon then examines the slides, and removes additional tissue if cancer remains in the peripheral and/or deep margins. The excised tissue is mapped which provides the Mohs surgeon a reference for the removal of additional tissue. Each stage examines all margins, only where tumor remains, until it is clear. MMS cure rates vary between 95 and 99 percent for primary BCC and SCC tumors, and 94 percent for recurrent BCC/SCC. Also, there is a 95 to 98 percent five year cure for melanoma-in-situ with experienced Mohs surgeons.5 The Centers for Medicare and Medicaid Services (CMS) is currently revising local coverage determinations (LCD’s) for Mohs Micrographic Surgery (MMS). The determinations are used to ensure the medical necessity of all services and payment. Appropriate Use Criteria (AUC) recommendations by the American Association of Dermatologists (AAD), American College of Mohs Surgery, American Society for Dermatologic Surgery Association and the American Society for Mohs Surgery were used as an initial starting point by CMS’ contractor to determine if MMS is necessary in treating a specific lesion in a specific location. The AAD, et al analyzed 270 scenarios for MMS and rated the appropriateness (developed by the RAND Corp.) by a rating panel. The findings were simultaneously published in the Journal of the American Academy of Dermatology and Dermatologic Surgery (October 2012, Volume 38, Number
Northeast Florida Medicine Vol. 65, No. 3 2014 21
Dermatology Figure 1
10). Although this report can be a helpful guide, CMS has not yet published those criteria.
CMS is currently investigating indications for MMS. The AUC and CMS have very similar indications in area H central face, eyelids, periorbital, eyebrows, nose, lips, chin, ear, periauricular, temple, genitalia, hands, feet, ankles, nipples/areola)7 and area M (cheeks, forehead, scalp, neck, jawline). They differ in trunk and extremities (area L) recommendations. (Figures 1 and 2)
CMS is currently defining and considering providers of Mohs surgery limited to physicians (ie. MD/DO) as follows: - Enrolled in Medicare and a licensed physician who has completed residency training in Dermatology or general/subspecialty surgery after 2013, and completed a Mohs fellowship (ACMS or ACGME) of one to two years. Five hundred Mohs cases must be completed during their fellowship with 125 of the cases being done by the fellow as the primary surgeon.6 - If training was completed before 2014, then residency trained Dermatology or general/subspecialty surgery do not need to complete a Mohs fellowship (ACMS or ACGME) of one to two years, or have completed 500 Mohs cases (125 as primary surgeon) during fellowship. The Medicare/licensed physician must have training and expertise acquired in residency or fellowship with a nationally recognized organization or accredited post-graduate training course covering MMS. Hours trained or cases performed not specified as of 2014.6 • MMS surgeon must be surgeon and pathologist, and often must function as the reconstructive surgeon. • Physician must provide services in the appropriate setting for the patient’s surgery and related pathological evaluation.6
22 Vol. 65, No. 3 2014 Northeast Florida Medicine
Area H is gray (Fig. 1). Area M is light gray (Fig.1) or circled (Fig. 2). Area L is not circled (Fig. 2). Invasive Melanoma is typically not treated with MMS. Gray or H region- most all skin cancers meet AUC for MMS except AK with focal Squamous Cell Carcinoma In-situ (SCI) and Bowenoid Papulosis. Angiosarcoma and Desmoplastic Trichoepithelioma are uncertain. Light gray or M region – all recurrent or primary BCC, SCC, SCI, MIS • no primary superficial BCC < 0.5cm and • no primary or recurrent AK with focal SCI Trunk and extremities or L region – all aggressive BCC > 0.6cm • all nodular BCC > 2 cm or immunocompromised (IC) > 1 cm. • all aggressive SCC, all recurrent SCC • all non-aggressive SCC and SCI > 2cm • all recurrent MIS • no superficial BCC • no AK with focal SCI
DCMS online . org
* All the information on AUC is summarized from Connolly, et al. JDS 38.10: October 2012
Discussion CMS is currently revising local coverage determinations for MMS (2014). They will have indications and limitations of coverage and/or medical necessity. MMS will be limited to physicians who have residency training in Dermatology or general/subspecialty surgery with expertise training of Mohs surgery by fellowship (one to two years) or other prior to 2014. In 2014 or after, the same residency training is required, but fellowship training of one to two years in a Mohs fellowship while completing 500 cases with 125 cases as lead physician will be needed to qualify. Preoperative indications must be given on why Mohs surgery is the best option for surgery. Accepted diagnoses and the diagrams from AUC are being considered by the CMS. Actinic Keratoses with focal Squamous Cell Carcinoma In-situ SCI is
not appropriate for MMS in any location. All BCC, SCC and SCI can be treated in the “H” or mask region, except focal SCI in AK. All BCC, except superficial BCC < 0.5cm, and all SCC and SCI, except verrucous SCC and focal SCI in AK, can be treated in the “M” areas. In the “L” area, it is easier to remember what can’t be treated. You would not treat superficial BCC, and most other BCC under 2 cm, verrucous SCC, non-aggressive SCC, KA < 1cm, or SCI < 2cm. There are multiple other skin cancers that fit AUC in all areas, as well. The Mohs surgeon must consider all criteria determined by CMS to evaluate medical necessity. v
References 1. Skin Cancer Foundation.org [Internet]. New York: The Skin Cancer Foundation [EIN: 13-2948778] is a 501(c)(3) non-profit organization. Last Updated: June 4, 2014. Available from http://www.skincancer.org/ skin-cancer-information/skin-cancer-facts 2. National Center for Biotechnology Information, U.S. National Library of Medicine [Internet]. Bethesda, MD. Case Rep Dermatol Med. 2012; 2012: 157187. Published online Dec 6, 2012. doi: 10.1155/2012/157187. Available at http://www.ncbi. nlm.nih.gov/pmc/articles/PMC3523573/ 3. College Of American Pathologists [Internet]. Available at http://www.cap.org/apps/microsites/MyBiopsy/ basal_cell.html 4. Skin Cancer Foundation.org [Internet]. New York: The Skin Cancer Foundation [EIN: 13-2948778] is a 501(c) (3) non-profit organization. Available at http://www. skincancer.org/skin-cancer-information/mohs-surgery/ evolution-of-mohs 5. Wikipedia: The Free Encyclopedia [Internet] Wikimedia Foundation, Inc., last modified on 14 July 2014 Available at http://en.wikipedia.org/wiki/Mohs_surgery 6. First Coast Service Options Inc.[Internet] Last Modified: 7/7/2014 Location: FL Available at http://medicare. fcso.com/index.asp 7. Connolly et al. Journal Dermatologic Surgery 38:10: October 2012
Pictures 1. Images provided with permission by Modernizing Medicine, Inc. and Modernizing Medicine, Inc. reserves all rights with respect to the images.
DCMS online . org
Northeast Florida Medicine Vol. 65, No. 3 2014 23
Dysplastic Nevi and Melanoma Precursors: Practical Approaches to Evaluation, Follow-Up and Management By Jonathan Kantor, MD, MSCE, MA
Introduction One of the greatest challenges for dermatologists and primary care physicians alike is the management of complex pigmented lesions. Subtlety of diagnosis, slow evolution over time, and presentation in a broad array of demographic groups all add to the difficulty in appropriately assessing and managing these complex lesions. Most importantly, inadequate management or imprecise evaluation may result in tragic consequences, as melanoma represents the fifth most common cancer overall in the United States (US), and is responsible for the majority of cancer deaths amongst women 25 to 30 years of age.1 Moreover, the precipitous drop in 10-year survival—patients with lesions less than one mm thick have a survival rate of 88 percent, while those with melanomas four mm or greater in thickness with ulceration have a survival rate of 32 percent—means that early detection is critical and has the potential to save lives.2 Despite the known value of early diagnosis and therapeutic intervention, recommendations regarding screening for melanoma in the US remain ambiguous. The United States Preventative Services Task Forces (USPSTF), charged with developing recommendations for cancer screening in the US, still does not recommend regular full skin examinations for all patients.3 Despite a growing body of evidence, most notably recent data from the Schleswig-Holstein Province of Germany, suggesting that regular skin cancer screenings may be associated with as much as a 50 percent reduction in mortality rate from melanoma.4,5
Clarifying the Terminology Ever since Wallace Clark described what are now known as dysplastic nevi in 1978, there has been a gradual evolution in terminology used to describe these atypical moles.6,7 Today, the terms “dysplastic nevus,” “atypical nevus,” and “Clark’s nevus” are often used synonymously, though significant regional variation remains the norm.8-11
Address correspondence: Jonathan Kantor, MD Florida Center for Dermatology, PA 105 Southpark Boulevard, Suite A103 St. Augustine, FL 32086 (904) 342-7765 DCMS online . org
This subject has also been the topic of two separate National Institute of Health (NIH) Consensus Conferences; it has been suggested to refer to a “nevus with architectural disorder,” though this approach has not been broadly adopted.12,13 Clinically, nevi may be conceived of as presenting on a spectrum, with banal nevi (dermal, junctional or compound) on the far end of the benign spectrum with potential gradual evolution to malignant melanoma. This may, however, be an oversimplification since the vast majority of dysplastic nevi do nothing more than evolve into potentially more severely dysplastic nevi.10,14 Indeed, approximately 50 percent of melanomas arise de novo, and of the remaining half that arise from precursor lesions, not all begin as dysplastic nevi. Histologically diagnosed dysplastic nevi are usually accompanied by a severity grade as well as margin status. This aids the clinician in deciding on the need for, and nature of, potential further treatment.15,16 On a pragmatic level, most biopsy-proven mildly dysplastic nevi, regardless of margin status, can be followed clinically.17 For mild to moderately dysplastic nevi, if the histologic margins are clear, clinical follow-up is generally appropriate. For mild to moderately dysplastic nevi with margin involvement, a simple shave removal may be quickly and efficiently performed with minimal morbidity. Moderately dysplastic nevi biopsied with clear margins can be followed clinically, while those with marginal involvement may be excised with tight margins. All of these recommendations, however, may be modified depending on clinical circumstance. For example, an active runner with a moderately dysplastic nevus on the leg could be treated with a shave removal rather than an excision in order to avoid the need to cease activity during the healing period. Moderate to severely dysplastic nevi and frank severely dysplastic nevi should be treated slightly more aggressively. While most dysplastic nevi will never evolve into melanoma, severely dysplastic nevi may have a greater risk of malignant transformation, and therefore more involved intervention is warranted.18,19 A full-thickness excision with margins of three mm or more should probably be taken around these histologically advanced dysplastic nevi, even if clear margins are evident on a superficial shave biopsy.
Northeast Florida Medicine Vol. 65, No. 3 2014 25
Dysplastic Nevi and Melanoma Whether dysplastic nevi represent a step on the spectrum from benign nevi to melanoma or simply a risk factor for melanoma development remains an area of some controversy.20-25 Rationales for treating dysplastic nevi are varied. First, as noted above, there is the possibility that a dysplastic nevus will evolve into melanoma over time.26-28 Severely dysplastic nevi, however, should be treated aggressively because of their increased potential to evolve into melanoma. Second, histopathological diagnosis of dysplastic nevi is not a precise science. There is some discordance in grading these lesions.29-31 This results from both inter-observer variability in grading, as well as the risk that partial sampling of pigmented lesions may not reveal the full extent of the atypia. Indeed, one study found that 29 percent of melanomas in situ were reclassified as invasive melanoma after a full thickness excision was performed.32 Finally, the presence of dysplastic nevi represents an independent risk factor for the development of melanoma.33-35 Floridly expressed dysplastic nevi are of particular concern since it is more challenging to follow the individual atypical moles for progression, and because those with larger numbers of dysplastic nevi have a higher likelihood of developing melanoma over time.
Evaluation and Follow-up Clinical evaluation remains the cornerstone of management, while the ABCD criteria are often taught to patients.36,37 As many early melanomas are quite small, and since subtle early changes may not fall within the predefined criteria, clinicians should be especially on the lookout for any change whatsoever in preexisting nevi. The presence of erythema should always be interpreted as a warning sign, as many subtle melanomas arising in preexisting nevi may be heralded by inflammation in an otherwise normal-appearing mole. In addition to serial clinical exams, several other options are available to the clinician. It is critical, however, that full skin exams be offered to all patients, or at least those presenting to dermatologists, as a study published in 2009 demonstrated that more than half of all melanomas arise in areas that would not be seen on a cursory exam alone.38 Patients should ideally be performing self-exams on a regular basis. It may be useful to review ABCD criteria with patients, and also stress the importance of looking for change in existing nevi or the development of new moles. Any clinical change in a patient’s nevi, particularly those of an adult patient with dysplastic nevi, merits evaluation by the clinician.
26 Vol. 65, No. 3 2014 Northeast Florida Medicine
While the vast majority of clinically dysplastic nevi may be followed with serial examinations, some nevi should be biopsied based on their degree of clinical atypia or a history of marked change or evolution. Some authors have addressed the rate of biopsies, and particularly the ratio of the number of biopsies performed for each melanoma detected, or number needed to treat (NNT), as a marker for quality.39,40 Precisely because the downside of delayed detection is so high, however, and because of the tragic consequences of delayed melanoma detection, it is probably inappropriate to consider the NNT when considering the appropriate lesions to biopsy to detect melanoma.41 Rather, just as a healthy proportion of negative appendectomies is a sign of good clinical practice, so too biopsies of dysplastic nevi that have not reached criteria for the diagnosis of melanoma is probably reasonable. Moreover, these numbers do not account for the precursor or indeterminate lesions, such as early evolving melanoma in situ, severely dysplastic nevi, or melanocytic tumors of uncertain malignant potential. A final caveat on the NNT is that much of this data comes from Australia. While Australians certainly have a broad experience with melanoma management, their management of atypical pigmented lesions is different from most US clinicians. They often excise their putative dysplastic nevi in toto resulting in an increased perceived risk to the benefit of biopsy when considering the risk: benefit ratio, as a full-thickness excision has far greater consequences to both the healthcare system (in time and cost) and to the patient (in risk of morbidity and size of scar) than a simple shave biopsy. Since shave biopsies, as long as they are sufficiently deep, are appropriate for most pigmented lesions, it is preferable to biopsy a few extra lesions than tragically miss a melanoma.42,43 Photography is another adjunct to the clinical examination that has been gaining in popularity during the past decades.44,45 Options run the gamut from patients taking their own photographs to in-house photographers in pigmented lesion clinics and entire companies dedicated to cutaneous photography. The chief benefit of skin photography is the ability to follow lesional evolution over time. Since melanoma may arise de novo or from a preexisting melanocytic neoplasm, this allows the clinician and patient to either appreciate that a possibly new or evolving pigmented lesion is truly new or evolving, or—more frequently—to reassure both clinician and patient that a putatively changing lesion has been present for years and is unchanged. It is, critical to recall that serially photographing an evolving melanoma does not treat it. Dermatoscopy has become an increasingly common tool in the clinician’s armamentarium over the past two decades, and studies have suggested a possible benefit in the specificity of biopsies. Newer technologies, including confocal microscopy, confocal optical coherence tomography and MelaFind are currently being studied more aggressively. None of these approaches, however, can take the place of biopsy. Any techniques beyond the clinical DCMS online . org
examination, but short of biopsy, have only limited utility and should not be relied upon in the face of strong clinical suspicion. Given these challenges, patients presenting with multiple dysplastic nevi should be closely evaluated and followed, especially if additional risk factors for melanoma are present. While there is no firm consensus on the appropriate frequency of examinations, all patients with dysplastic nevi should perform self-exams on a monthly basis. Those with dysplastic nevi on the mild to moderate spectrum should be followed every six to 12 months. Those with moderate to severely dysplastic nevi should be seen every six months or more frequently, based on level of concern, presence of large numbers of dysplastic nevi, family history of melanoma, and other clinical and pragmatic considerations.
Conclusions The evaluation and management of dysplastic nevi remains a considerable clinical challenge. Terminological ambiguity, regional variation in management, and the clinical challenge of identifying those lesions at risk of evolution all contribute to the difficulties associated with dysplastic nevus evaluation and therapy. Clinically, any changing pigmented lesion in an adult likely merits biopsy or referral. Those occurring in the context of a personal or family history of melanoma, or associated with marked color or diameter change, or the presence of underlying erythema merit particular concern. Educating patients on the importance of self-examinations, the utility of self-photography, as well as the simple act of offering a full skin examination to patients may help mitigate the dramatic increase in melanoma seen over the past four decades. v
References 1. Elston D. Practical advice regarding problematic pigmented lesions. Journal of the American Academy of Dermatology. Jul 2012;67(1):148-155. 2. Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Aug 15 2001;19(16):3635-3648. 3. Campos-Outcalt D. USPSTF: What’s recommended, what’s not. The Journal of family practice. May 2014;63(5):265-269. 4. Eisemann N, Waldmann A, Katalinic A. [Incidence of melanoma and changes in stage-specific incidence after implementation of skin cancer screening in Schleswig-Holstein]. Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz. Jan 2014;57(1):77-83. 5. Breitbart EW, Waldmann A, Nolte S, et al. Systematic skin cancer screening in Northern Germany. Journal of the American Academy of Dermatology. Feb 2012;66(2):201-211.
DCMS online . org
6. Elder DE, Goldman LI, Goldman SC, Greene MH, Clark WH, Jr. Dysplastic nevus syndrome: a phenotypic association of sporadic cutaneous melanoma. Cancer. Oct 15 1980;46(8):1787-1794. 7. Elder DE, Green MH, Guerry Dt, Kraemer KH, Clark WH, Jr. The dysplastic nevus syndrome: our definition. The American Journal of dermatopathology. Oct 1982;4(5):455-460. 8. Ackerman AB, Milde P. Naming acquired melanocytic nevi. Common and dysplastic, normal and atypical, or Unna, Miescher, Spitz, and Clark? The American Journal of dermatopathology. Oct 1992;14(5):447-453. 9. Ackerman AB. “Dysplastic nevus” syndrome: does a survey make it real? Journal of the American Academy of Dermatology. Mar 2003;48(3):461-463. 10. Ackerman AB, Mihara I. Dysplasia, dysplastic melanocytes, dysplastic nevi, the dysplastic nevus syndrome, and the relation between dysplastic nevi and malignant melanomas. Human pathology. Jan 1985;16(1):87-91. 11. Clark WH, Jr., Ackerman AB. An exchange of views regarding the dysplastic nevus controversy. Seminars in dermatology. Dec 1989;8(4):229-250. 12. Precursors to malignant melanoma. National Institutes of Health consensus development conference summary. 1984;4(9):6 p. 13. NIH Consensus conference. Diagnosis and treatment of early melanoma. JAMA : the journal of the American Medical Association. Sep 9 1992;268(10):1314-1319. 14. Ackerman AB, Elder DE. An exchange of ideas about dysplastic nevi and malignant melanomas. The American Journal of dermatopathology. 1985;7 Suppl:99-105. 15. Bronsnick T, Kazi N, Yasmine Kirkorian A, Rao BK. Outcomes of Biopsies and Excisions of Dysplastic Acral Nevi: A Study of 187 Lesions. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]. Jan 23 2014. 16. Comfere NI, Chakraborty R, Peters MS. Margin comments in dermatopathology reports on dysplastic nevi influence re-excision rates. Journal of the American Academy of Dermatology. Nov 2013;69(5):687-692. 17. Elston D, McNiff J, Maize J, Sr. Histologically dysplastic nevi that extend to a specimen border. Journal of the American Academy of Dermatology. Apr 2013;68(4):682-683. 18. Abello-Poblete MV, Correa-Selm LM, Giambrone D, Victor F, Rao BK. Histologic outcomes of excised moderate and severe dysplastic nevi. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]. Jan 2014;40(1):40-45. 19. Shors AR, Kim S, White E, et al. Dysplastic naevi with moderate to severe histological dysplasia: a risk factor for melanoma. The British journal of dermatology. Nov 2006;155(5):988-993.
Northeast Florida Medicine Vol. 65, No. 3 2014 27
20. Barnhill RL, Cerroni L, Cook M, et al. State of the art, nomenclature, and points of consensus and controversy concerning benign melanocytic lesions: outcome of an international workshop. Advances in anatomic pathology. Mar 2010;17(2):73-90.
34. Duffy K, Grossman D. The dysplastic nevus: from historical perspective to management in the modern era: part I. Historical, histologic, and clinical aspects. Journal of the American Academy of Dermatology. Jul 2012;67(1):1 e1-16; quiz 17-18.
21. Elder DE. Dysplastic naevi: an update. Histopathology. Jan 2010;56(1):112-120.
35. Tucker MA. Melanoma epidemiology. Hematology/oncology clinics of North America. Jun 2009;23(3):383-395, vii.
22. Shapiro M, Chren MM, Levy RM, et al. Variability in nomenclature used for nevi with architectural disorder and cytologic atypia (microscopically dysplastic nevi) by dermatologists and dermatopathologists. Journal of cutaneous pathology. Sep 2004;31(8):523-530.
36. Katalinic A, Kunze U, Schafer T. Epidemiology of cutaneous melanoma and non-melanoma skin cancer in Schleswig-Holstein, Germany: incidence, clinical subtypes, tumour stages and localization (epidemiology of skin cancer). The British journal of dermatology. Dec 2003;149(6):1200-1206.
23. Tucker MA, Halpern A, Holly EA, et al. Clinically recognized dysplastic nevi. A central risk factor for cutaneous melanoma. JAMA : the journal of the American Medical Association. May 14 1997;277(18):1439-1444.
37. Aldridge RB, Zanotto M, Ballerini L, Fisher RB, Rees JL. Novice identification of melanoma: not quite as straightforward as the ABCDs. Acta dermato-venereologica. Mar 2011;91(2):125-130.
24. Seykora J, Elder D. Dysplastic nevi and other risk markers for melanoma. Seminars in oncology. Dec 1996;23(6):682-687. 25. Skender-Kalnenas TM, English DR, Heenan PJ. Benign melanocytic lesions: risk markers or precursors of cutaneous melanoma? Journal of the American Academy of Dermatology. Dec 1995;33(6):1000-1007. 26. Halpern AC, Guerry Dt, Elder DE, Trock B, Synnestvedt M, Humphreys T. Natural history of dysplastic nevi. Journal of the American Academy of Dermatology. Jul 1993;29(1):51-57. 27. Elder DE, Clark WH, Jr., Elenitsas R, Guerry Dt, Halpern AC. The early and intermediate precursor lesions of tumor progression in the melanocytic system: common acquired nevi and atypical (dysplastic) nevi. Seminars in diagnostic pathology. Feb 1993;10(1):18-35. 28. Halpern AC, Guerry Dt, Elder DE, et al. Dysplastic nevi as risk markers of sporadic (nonfamilial) melanoma. A case-control study. Archives of dermatology. Jul 1991;127(7):995-999. 29. Meyer LJ, Piepkorn M, Goldgar DE, et al. Interobserver concordance in discriminating clinical atypia of melanocytic nevi, and correlations with histologic atypia. Journal of the American Academy of Dermatology. Apr 1996;34(4):618-625. 30. Duncan LM, Berwick M, Bruijn JA, Byers HR, Mihm MC, Barnhill RL. Histopathologic recognition and grading of dysplastic melanocytic nevi: an interobserver agreement study. The Journal of investigative dermatology. Mar 1993;100(3):318S-321S. 31. Clemente C, Cochran AJ, Elder DE, et al. Histopathologic diagnosis of dysplastic nevi: concordance among pathologists convened by the World Health Organization Melanoma Programme. Human pathology. Apr 1991;22(4):313-319. 32. Megahed M, Schon M, Selimovic D, Schon MP. Reliability of diagnosis of melanoma in situ. Lancet. Jun 1 2002;359(9321):1921-1922.
38. Kantor J, Kantor DE. Routine dermatologist-performed fullbody skin examination and early melanoma detection. Archives of dermatology. Aug 2009;145(8):873-876. 39. Hansen C, Wilkinson D, Hansen M, Argenziano G. How good are skin cancer clinics at melanoma detection? Number needed to treat variability across a national clinic group in Australia. Journal of the American Academy of Dermatology. Oct 2009;61(4):599-604. 40. Baade PD, Youl PH, Janda M, Whiteman DC, Del Mar CB, Aitken JF. Factors associated with the number of lesions excised for each skin cancer: a study of primary care physicians in Queensland, Australia. Archives of dermatology. Nov 2008;144(11):1468-1476. 41. Esdaile B, Mahmud I, Palmer A, Bowling J. Diagnosing melanoma: how do we assess how good we are? Clinical and experimental dermatology. Mar 2014;39(2):129-134. 42. Ng JC, Swain S, Dowling JP, Wolfe R, Simpson P, Kelly JW. The impact of partial biopsy on histopathologic diagnosis of cutaneous melanoma: experience of an Australian tertiary referral service. Archives of dermatology. Mar 2010;146(3):234-239. 43. Moore P, Hundley J, Hundley J, et al. Does shave biopsy accurately predict the final breslow depth of primary cutaneous melanoma? The American surgeon. May 2009;75(5):369-373; discussion 374. 44. Risser J, Pressley Z, Veledar E, Washington C, Chen SC. The impact of total body photography on biopsy rate in patients from a pigmented lesion clinic. Journal of the American Academy of Dermatology. Sep 2007;57(3):428-434. 45. Menon K, Dusza SW, Marghoob AA, Halpern AC, Nehal KS. Classification and prevalence of pigmented lesions in patients with total-body photographs at high risk of developing melanoma. Journal of cutaneous medicine and surgery. Mar-Apr 2006;10(2):85-91.
33. Goldstein AM, Tucker MA. Dysplastic nevi and melanoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. Apr 2013;22(4):528-532. 28 Vol. 65, No. 3 2014 Northeast Florida Medicine
DCMS online . org
Psoriasis: A Review and Update on Extracutaneous Manifestations By Juan A. Rosario-Collazo, MD, FAAD; Lara Ashley East Laneve, PA-C, MPAS; Erin E. Harris, PA-C, MPAS Abstract: Psoriasis is a chronic, recurrent inflammatory skin
disorder that is present in one to three percent of the population.1 In the United States, there are approximately three to five million people that have been diagnosed with psoriasis.2 Men and women are equally affected, and there are two peaks of onset: one between the ages of 20 and 30 and the other between the ages of 50 and 60.
Primary care physicians will initially treat 58 percent of the estimated 150,000 new cases of psoriasis diagnosed each year, however, dermatologists still manage 80 percent of the psoriasis cases.3 Psoriasis is a genetic autoimmune disease of dysregulated inflammation that results in thick, white-silvery or red plaques of the skin. The physical characteristics of psoriasis can negatively affect ones quality of life. The mechanism of inheritance is not completely understood, however, environmental factors are known to play an important role. The following risk factors can increase the chance of developing psoriasis: • • • • • • •
family history infections such as streptococcal physical trauma stress cold weather smoking alcohol consumption
Certain medications have also been identified as a trigger such as lithium, beta-blockers, antimalarial drugs, iodides and systemic glucocorticoids. Of the patients diagnosed with psoriasis, about 30 percent will develop psoriatic arthritis at some point in the disease.1 Other co-morbidities include cardiovascular disease, diabetes, depression, and other auto-immune diseases such as Crohn’s disease. Due to the systemic co-morbidities of psoriasis and negative impact on ones quality of life, it is important that this disease is diagnosed during the early stages by the primary care physician to ensure proper treatment.
Clinical Findings Psoriasis can be characterized into the following categories: • • • • •
chronic plaque psoriasis guttate psoriasis inverse psoriasis pustular psoriasis erythrodermic psoriasis
The diagnosis of psoriasis is typically made by clinical presentation, however, if the diagnosis is uncertain, a biopsy can be performed or consultation by a dermatologist can be ordered. Chronic plaque psoriasis is the most common form of psoriasis accounting for 80 to 90 percent of cases.3 The classic lesion is a sharply demarcated thick erythematous plaque with a silvery-white scale. Smaller plaques may coalesce into larger lesions. Plaques can be painful and pruritic. When the scales are removed there will be some bleeding (Auspitz Sign). The lesions are characteristically symmetrically located on the scalp, ears, elbows, knees and nails. Psoriasis can also form at any site of physical trauma (Koebner phenomenon). Patients with plaque psoriasis experience nail changes such as thickening, pitting, discoloration, and loosening of the nail from the nail bed. Plaques may also be localized to the palms of the hands and soles of the feet in palmo-plantar psoriasis.3 Guttate psoriasis is the second most common form of psoriasis.1 Guttate psoriasis is characterized by numerous small, oval, scaly lesions located on the trunk and extremities. The onset may be preceded by a streptococcal infection or upper respiratory infection. Inverse psoriasis appears in skin folds such as axillae, intergluteal cleft, genitals, groin, submammary folds and other skin folds. These lesions present as smooth, red patches without scale. Pustular psoriasis may be localized to the palms and soles, however, may cover the entire body. Numerous pustules will form on an erythematous base. These pustules are sterile. Patients with generalized pustular psoriasis need to be hospitalized due to the risk of fever, fluid imbalances and infections.
Address correspondence: Juan A. Rosario-Collazo, MD First Coast Dermatology 4479 Baymeadows Road Jacksonville, FL 32217 DCMS online . org
Northeast Florida Medicine Vol. 65, No. 3 2014 29
Erythrodermic psoriasis is a rare type of psoriasis that occurs in one to two percent of patients diagnosed with psoriasis.3 It mainly affects people that have unstable plaque psoriasis. The skin appears fiery red with extensive fine scale over about 90 percent of body surface area. Patients will be in extreme pain and have severe itching. Hospitalization is usually required because it can cause protein and fluid loss, decrease in temperature, and life threatening illnesses. Psoriatic arthritis affects approximately one third of patients with psoriasis.3 It is a chronic arthropathy that mainly affects the proximal and distal interphalangeal joints of the hands and feet. The lower back, wrists, ankles and knees may also be affected. Early diagnosis is extremely important, as delayed diagnosis will result in loss of function for the patient. The presence of skin lesions is not necessarily an indication of the severity of psoriatic arthritis.
Topical and Systemic Treatments for Psoriasis • Topical corticosteroids and vitamin D derivatives are appropriate for patients with localized disease and who are not candidates for systemic or biologic therapy. Caution should be used with corticosteroids due to atrophy of the skin. To prevent atrophy, application of the corticosteroid can shift from twice daily applications to weekend only applications. Patients can then apply the vitamin D cream during the weekdays. • Light therapy such as narrow band UVB (ultraviolet light B) has proven beneficial. This can take several weeks at two to three times per week.4 PUVA (psolaren + ultraviolet light A treatment), UVA (ultraviolet light A) therapy + oral psoralen, is also effective. The risk for nonmelanoma skin cancer in Caucasians increases. Oral psoralen is also contraindicated in pregnancy.4 • Methotrexate, an oral immunosuppressant, has proven effective for generalized psoriasis, however, it has a propensity for hepatoxicity. Not only does methotrexate affect the liver, but also it is teratogenic. Methotrexate should not be used in patients with renal dysfunction, hepatitis, cirrhosis, leukemia or thrombocytopenia.4 Blood work, including a complete blood count and comprehensive metabolic panel, should be done regularly.4 • Cyclosporine, another immunosuppressant, may be considered for generalized psoriasis. An advantage to cyclosporine is that it works rapidly, however, it should only be used for three to four months due to the potential of renal impairment and cutaneous malignancies.4 Cyclo-
30 Vol. 65, No. 3 2014 Northeast Florida Medicine
sporine is also ideal for erythrodermic psoriasis due to its rapid effect.5 Regular blood work to test renal function and complete blood counts should be done. • Acitretin (Soriatane), another systemic medication, is useful for palmar and plantar psoriasis.5 The biggest side effect is teratogenicity. Women who take acitretin should not get pregnant for three years after stopping the medication or significant birth defects can occur.5 Hyperlipidemia, dry skin and lips, and high liver enzymes can occur.4 Monthly blood work should include a complete blood count, comprehensive metabolic panel, total cholesterol and triglycerides, and a pregnancy test for females of childbearing potential.
Biologic Therapy in Psoriasis Psoriasis is considered to be a chronic T-cell mediated autoimmune disease, and because of this more recent research has focused on drugs targeting tumor necrosis factor alpha (TNF-), as well as therapies that directly target cytokine signaling or T-cell function. Biologic therapies, such as etanercept (Enbrel), adalimumab (Humira), and ustekinumab (Stelara), have been FDA approved in the treatment of moderate to severe psoriasis. These have proven beneficial, especially since systemic agents have such severe side effects.5 • Etanercept (Enbrel) is a TNF- inhibitor and has a dosing regimen of 50 mg subcutaneously twice weekly for three months, and then 50 mg once weekly thereafter. Research has demonstrated an improvement of PASI-75 (Psoriasis Area Severity Index) in 49 percent of patients by week 12. Some patients do demonstrate a loss of response after the 12 week period, probably due to decreasing the dosage from twice to once weekly.4 • Adalimumab (Humira) is another TNF- inhibitor and is dosed at 80 mg subcutaneously once on week one, 40 mg once on week two, then 40 mg every other week thereafter.5 Studies have shown 80 percent of patients achieve PASI-75 (Psoriasis Area Severity Index) -75 by week 12.4 • Ustekinumab (Stelara) has a different pathway than etanercept or adalimumab. It is a monoclonal anibody directed at the p40 subunit common to IL-12 and IL-23.5 Unlike the TNF- inhibitors, dosing is weight based. It is dosed at 45 mg subcutaneously for patients who weigh less than 220 pounds (100 kg) and 90 mg for patients weighing more than 220 pounds (100 kg).5 Ustekinumab often provides a good response to patients who are overweight in contrast to etanercept. Because etanercept’s dosing decreases after week 12, patients who are overweight can have a flare of psoriasis.5
DCMS online . org
When considering a biologic, a thorough history and physical exam must be performed. Baseline laboratory tests are essential in order to rule out any underlying pathology. These include a complete blood count, hepatitis panel, complete metabolic panel with liver function tests, and tuberculosis (TB) test.4 Biologic therapy is contraindicated in patients with active infections such as hepatitis B or TB.4 Patients should be periodically evaluated for any symptoms of new infection or malignancy. Yearly TB tests should be done, as well as periodic complete blood counts and liver function tests. There is no set guideline for how often a patient should have bloodwork.5 Because the biologics target the immune system, patients are at risk for increased viral, bacterial and fungal infections. Biologics are contraindicated in patients with peripheral or central demyelinating disorders like multiple sclerosis.4 Caution should be used in patients who have a history of congestive heart failure as clinical studies have provided mixed results as to whether biologics increase or decrease morbidity and mortality in these patients.4 Patients on biologics are also at an increased risk of lymphoma, melanoma and nonmelanoma skin cancers. Lastly, patients should avoid live vaccines including varicella, mumps, measles, rubella, oral typhoid, yellow fever, intranasal influenza and herpes zoster once biologic therapy has begun.4
Extracutaneous Manifestations of Psoriasis Psoriatic Arthritis
The most common extracutaneous manifestation of psoriasis is psoriatic arthritis (PsA).7 Depending on studies, its prevalence ranges from four percent to 42 percent. PsA typically manifests several years after cutaneous lesions develop. On the other hand, psoriatic arthritis changes may precede skin lesions, thus the clinician must have a high-level of suspicion. PsA is differentiated from rheumatoid arthritis (RA) with the help of serology (Rheumatoid Factor) and its clinical manifestations. RA is generally symmetric, affecting the metacarpophalangeal and proximal joints, whereas PsA is an asymmetrical oligoarthritis.8 It is estimated that 20 percent of patients with PsA will suffer from the debilitating and destructive disease.8 The gold-standard in the management of PsA is methotrexate and/or anti-TNF alpha agents, but more controlled studies are needed to further evaluate their long-term benefits and effects.
Psoriasis and the Metabolic Syndrome
Metabolic syndrome affects approximately 15 percent to 25 percent of the general population. It is thought to arise from insulin resistance and abnormal adipocyte function.9 Individual components of the metabolic syndrome are obesity, hypertension, diabetes and dyslipidemia. The specific DCMS online . org
criteria for the metabolic syndrome is beyond the scope of this article but can be obtained from a variety of sources such as the International Diabetes Foundation, the World Health Organization, the European Group for the Study of Insulin Resistance, and the updated National Cholesterol Education Program Adult Treatment Panel III10. Armstrong, Harskamp and Armstrong meta-analysis11 of 41,853 psoriasis patients from 1.4 million participants revealed two-fold odds of metabolic syndrome in psoriatic patients compared to matched controls. The estimated prevalence of metabolic syndrome among patients with psoriasis ranges from 14 percent to 40 percent. Furthermore, there also appears to be a dose-response relationship between the severity of psoriasis and prevalence of metabolic syndrome.11
Psoriasis and Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease in Western countries, and is considered the hepatic manifestation of the metabolic syndrome.12 The prevalence of NAFLD ranges from 15 to 34 percent, but can be as high as 74 percent in obese patients. The condition is mostly asymptomatic, but is the most common cause of abnormal liver enzymes in Caucasians. Liver damage from NAFLD ranges from mild steatosis to nonalcoholic steatohepatitis, advanced fibrosis and liver cirrhosis. NAFLD might become the leading cause of liver transplantation by 2020.13 Recent studies suggest that psoriatic patients are 1.5 to three times more likely to have NAFLD compared to controls.14,15 These studies also demonstrated that psoriasis was independently associated with NAFLD, increasing the likelihood of having NAFLD by 70 percent. In turn, patients with psoriasis are also more likely to experience methotrexate-induced liver damage compared to healthy control subjects and patients with rheumatoid arthritis.14,15 The high rate of NAFLD in psoriasis patients has significant implications because NAFLD has been implicated as an independent predictor of cardiovascular disease.15
Psoriasis and Diabetes Mellitus
Chronic inflammation caused by psoriasis can promote insulin resistance, disordered metabolism and hypertension.16 The Lee, Lin and Lai study16 demonstrated an increased risk of insulin resistance and type II diabetes mellitus in patients with severe psoriasis. Systemic treatment for psoriasis, such as methotrexate and cyclosporine may indirectly promote diabetes. Additionally, antihypertensive therapy commonly used in diabetics such as thiazide diuretics and beta-blockers, may have a dose-related negative effect on psoriatic patients.
Psoriasis and Cardiovascular Risk
Risk factors for cardiovascular disease (CVD), such as age, hypertension, obesity, smoking and genetics are often found in psoriatic patients.17 The progression of atherosclerosis has been associated with chronic systemic inflammation.18 The Prodanovich et al study19 found a higher rate of ischemic heart Northeast Florida Medicine Vol. 65, No. 3 2014 31
disease, cerebrovascular disease and peripheral vascular disease in patients with psoriasis. Similar findings have not been observed in patients with atopic dermatitis or other dermatosis. Data suggests that psoriasis may serve as an independent risk factor for development of diabetes and other components of the metabolic syndrome, and indirectly for CVD.20 There are studies showing decreased risk of CVD on psoriatic patients treated with methotrexate, or anti-TNF alpha agents, but more prospective studies are needed to further evaluate this positive response, as well as the long term effects of these therapies.
Psoriasis and hyperuricemia
There is growing epidemiologic evidence suggesting the association of elevated levels of serum uric acid (SUA) and the metabolic syndrome with resultant increased risk of cardiovascular disease, morbidity and mortality,21,22 Gisondi et al23 demonstrated a three-fold higher prevalence of asymptomatic hyperuricemia in psoriatic patients compared to matched controls (19 percent vs. 7 percent). Although the hyperuricemia in patients with psoriasis could be related to coexisting metabolic disorders, their study suggested that psoriasis itself may directly contribute to elevated SUA.
Psoriasis and Infectious Diseases
Psoriatic patients may have an increased risk of infections due to intrinsic immunologic disturbances associated with the disease.24 Other contributing factors may include systemic therapies such as methotrexate, cyclosporine and biologic therapy. In Wakkee et al study,24 patients with psoriasis had a one and a half times higher rate for serious infections, but an association with systemic therapy was not observed.
Psoriasis and ocular manifestations
Psoriasis can be associated with a variety of eye complications. Unfortunately, both physicians and their patients may not readily identify these diverse, yet vague symptoms. Blepharitis is the most prevalent ocular abnormality is psoriatic patients. Chronic blepharitis may result in ectropion, trichiasis, madarosis, loss of lid tissue, and vision impairment.25,26 Anterior uveitis, a potentially serious complication, has been reported in seven to 20 percent of patients with psoriasis.27
Psoriasis and Inflammatory Bowel Disease
Ulcerative colitis and Crohn’s disease are common chronic inflammatory diseases of the gastrointestinal system. A higher rate of psoriasis has been observed in patients with inflammatory bowel disease, particularly those with Crohn’s disease.28 The risk of developing Crohn’s disease in psoriatic patients appears to be seven times higher compared to healthy individuals.29
Psoriasis and malignancy
The chronic inflammatory state of psoriasis has been postulated as a predisposing factor for lymphoproliferative cancers. The risk is greatest for patients with severe psoriasis and likely receiving systemic agents, and minimal for those with mild disease when compared with controls.30 Non-melanoma 32 Vol. 65, No. 3 2014 Northeast Florida Medicine
skin cancers have been observed at higher rates compared to controls, but likely due to effects from systemic therapies and/or phototherapy.
Psoriasis and Neuropsychiatric disorders
Psoriasis patients are commonly afflicted with depression, with approximately 15 percent of patients reporting the disease.31 Depression appears to be worse in patients with higher body surface involvement. A higher rate of suicidal ideation has also been noted.32 Other conditions such as anxiety, bipolar disorder and delirium have been observed at higher rates compared to the control group.33 Higher Parkinsonism rates have also been seen in patients with psoriasis, with a hazard ratio of 1.7 compared to controls in a five-year follow up period.34 This study was Asian population-based and cannot be generalized to Western populations. Control studies are needed to determine if the neuropsychiatric disorders would improve with systemic (biologic) therapies offered to those patients with more severe disease.
Conclusion Psoriasis is more than “skin deep.” Rather than a simple disorder of keratinocyte hyperproliferation and differentiation, it is a chronic immune-mediated inflammatory disease with a prevalence of one to three percent in the United States. Psoriatic patients present with higher prevalence of metabolic syndrome, cardiovascular risk, and other extra-cutaneous disorders. These include ocular, rheumatologic, infectious, gastrointestinal, neuropsychiatric diseases and malignancies. Psoriasis has a significant negative impact on quality of life which results in increased healthcare costs and loss of productivity. The clinician needs to carefully evaluate psoriatic patients, especially those with moderate-to-severe disease. Patients with psoriasis should be assessed not only in the context of a having a cutaneous disorder, but also having a systemic disease. The provider must be cognizant of all extracutaneous manifestations and associated comorbidities seen in psoriasis. Physician education and technological advancements will continue to help psoriatic patients live full and prosperous lives. v
References 1. LoSicco K, Camisa C, Grandinetti L. Psoriasis. Cleveland: Cleveland Clinic, 2013. 2. Menter A, Gottlieb S, Feldman S, et al. Guidelines of care for the Management of Psoriasis and Psoriatic Arthritis. J Am Acad Dermatology 2008; 58:826-850. 3. Pardasani A, Feldman S, et al. Treatment of Psoriasis: An Algorithm Based Approach for Primary Care Physicians. Am Fam Physician 2000 Feb 1; 63(3):725-733.
DCMS online . org
4. Menter A, Gottlieb A, Feldman S., et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis of biologics. J Am Acad Dermatology. 2008 May; 58: 826-50. 5. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: Case-based presentations and evidence-based conclusions. J Am Acad Dermatology. 2011 July; 65: 137-74. 6. Prussick R, Prussick L. Biologic therapies for psoriasis in 2013: Do we use them enough? Practical Dermatology. 2013 Feb; 10(2): 32-34. 7. Onumah N, Kircik LH. Psoriasis and its comorbidities. J Drugs Dermatology. 2012; 11(5 Suppl): s 5 -10. 8. Gladman DD, Antoni C, Mease P , Clegg DO, Nash P. Psoriatic arthritis: Epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005; 64 Suppl 2: ii 14 -7. 9. Olufadi R, Byrne CD. Clinical and laboratory diagnosis of the metabolic syndrome. J Clin Pathol 2008; 61:697-706. 10. Grundy SM, CLeeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/ National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112:2735-52. 11. Armstrong AW, Harskamp CT, Armstrong EJ, Psoriasis and metabolic syndrome: A Systematic review and meta- analysis of observational studies. J Am Acad Dermatology. 2013; 68(4):654-662. 12. Hamaguchi M, Kojima T, Takeda N, Nakagawa T, Taniguchi H, Fujii K, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med 2005; 143:722-8. 13. Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med 2011; 43:617-49. 14. Taylor WJ, Korendowych E, Nash P, Helliwell PS, Choy E, Krueger GG, et al. Drug use and toxicity in psoriatic disease: focus on methotrexate. J Rheumatol 2008; 35:1454-7. 15. Van der Voort, et al. Psoriasis is independently associated with non-alcoholic fatty liver disease in patients 55 years old or older: Results from a population-based study. J Am Acad Dermatology. 2014; 70(3): 517-524.
19. Prodanovich S, Kirsner RS, Kravetz JD, Ma F, Martinez L, Federman DG. Association of psoriasis with coronary artery, cerebrovascular, and peripheral vascular diseases and mortality. Arch Dermatol. 2009; 145(6): 700-703. 20. Shapiro et al. Psoriasis and cardiovascular risk factors: a case control study on inpatients comparing psoriasis to dermatitis. J Am Acad Dermatology. 2012; 66(2):252-258. 21. Feig DI, kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med 2008; 359-1811-21. 22. Zoppini G, Targher G, Bonora E. The role of serum uric acid in cardiovascular disease in type 2 diabetic and non-diabetic subjects: a narrative review. J Endocrinol Invest 2011; 34:881-6. 23. Gisondi et al. Hyperuricemia in patients with chronic plaque psoriasis. J Am Acad Dermatology. 2014; 70(1): 127-130. 24. Wakkee et al. Increased risk of infectious disease requiring hospitalization among patients with psoriasis: a population-based cohort. J Am Acad Dermatology. 2011; 65(6): 1135-1144. 25. Catsarou-Catsari A, Katsambas A, Theodoropoulos P, Stratigos J. Opthalmological manifestations in patients with psoriasis. Acta Derm Venereol 1984:64:557-9 26. Huynh N, Cervantes-Castaneda RA, Bhat P, Gallagher MJ, Foster CS. Biologic response modifier therapy for psoriatic ocular inflammatory disease. Ocul immunol Inflamm 2008; 16:89-93. 27. Durrani K, Foster CS. Psoriatic uveitis: A distinct clinical entity? Am J Opthalmol. 2005:139(1):106-111 28. Bernstein CN, Wajda A, Blanchard JF. The clustering of other chronic inflammatory diseases in inflammatory bowel disease: A population based study. Gastroenterology. 2005;129(3) 827-836. 29. Lee Fl, Bellarys SV, Francis C. Increased occurrence of psoriasis in patients with Crohn’s disease and their relatives. Am J Gastroenterol. 1990;85(8):962-963 30. Margolis D, Bilker W, Hennessy S, Vittorio C, Santanna J. Strom BL. The risk of malignancy associated with psoriasis. Arch Dermatol. 2001; 137(6):778-783. 31. Kimball AB, Jacobson C, Weiss S, Vreeland MG, Wu Y. The psychosocial burden of psoriasis. Am J Clin Dermatol. 2005:6(6):383-392. 32. Picardi A, Mazzotti E, Pasquini P. Prevalence and correlates of suicidal ideation among patients with skin desease. J Am Acad Dermatol. 2006; 54(3)420-426. Epub 2006 Jan 18.
16. Lee MS, Lin RY, Lai MS. Increased risk of diabetes mellitus in relation to the severity of psoriasis, concomitant medication, and comorbidity: a nationwide population – based cohort study. J Am Acad Dermatology. 2014; 70(4): 691-698.
33. Han C, Loftland JH, Zhao N, Schenkel B. Increased prevalence of psychiatric disorders and health care associated cost among patients with moderate-to-severe psoriasis. J Drugs Dermatol. 2011, 10(8):843-850.
17. Xiao J, Chen LH, Tu YT, Deng XH, Tao J. Prevalence of myocardial infarction in patients with psoriasis in central China. J Eur Acad Dermatol Venereol 2009; 23:1311-5.
34. Sheu et al. Psoriasis is associated with an increased risk of Parkinsonism: A population-based 5 – year follow up study. J Am Acad Dermatology. 2013; 68(6):992-999.
18. Dreiher J, Weitzman D, Davidovici B, Shapiro J, Cohen AD. Psoriasis and dyslipidemia: a population-based study. Acta Derm Venereol 2008; 88:561-5. DCMS online . org
Northeast Florida Medicine Vol. 65, No. 3 2014 33
Aesthetic Dermatology By Michael Bernhardt, MD
Beauty has always been, and will continue to be a major component of the human psyche. There are several historical figures that are often referenced for their appearance. Helen of Troy reportedly had the face that launched one thousand ships. The Mona Lisa had an enduring, captivating vision, and continues to inspire people today. Also, Marilyn Monroe, Raquel Welsh and Bridgette Bardot were considered legends because of their beauty.
Kerner3 reported the first oral ingestion of botulinum and the first noted medical illness related to botulinum between 1817 and 1822. Van Emergen identified and named the responsible bacterial agent in 1897 Burgen and Brooks discovered the presynaptic activity of the botulinum toxin, noting the effect of blocking presynaptic release of acetylcholine from motor nerve terminals Schantz then developed the purification and crystallization of the toxin.4
The book “Survival of the Prettiest,”1 discusses an almost subliminal transference to people who have a higher aesthetic appeal. “Prettier” people seem to be perceived in a more favorable light regardless of parameters being evaluated. Interestingly, even those who seem to have a fairer complexion than others, still maintain a personal level of dissatisfaction in their appearance. Our current culture favors a youthful vigorous symmetrical appearance, and patients usually try to mirror what society favors when it comes to appearance. So, what are the available options to redress these beauty issues? While surgical procedures are effective, surgery is not for everyone. There are issues such as cost, length of recovery, and concerns over potential outcomes. Less invasive techniques offer an alternative to those patients whose conditions are not severe enough; they lack motivation, or do not have the means to have more aggressive surgical procedures performed.
Initially studied for use in treating strabismus and blepharospasm, patients who received these treatments developed effacement and smoothing of concurrent dynamic facial lines. The US Food and Drug Administration (FDA) approved botulinum toxin (as BOTOX cosmetic) for use in treating glabellar lines in 2002.5
Selective neurotoxin use revolutionized the field of less invasive rhytid control. The use of modern fillers has also revolutionized the concept of treatment of age-related atrophy and tissue displacement in a less invasive manner. The two most common alternatives to surgical intervention include (1) the use of selective neurotoxins to paralyze specific muscle groups leading to the effacement of dynamic rhytids, and (2) the use of soft tissue fillers to augment areas that have age related atrophy and tissue migration. According to Monheit2 botulinum toxin (BOTOX) administration is the most common cosmetic procedure performed in the United States, with 11 million injections performed since 2001.
Address correspondence to: Michael Bernhardt, MD Academic Dermatology Consultants 1514 Nira Street Jacksonville, FL 32207
34 Vol. 65, No. 3 2014 Northeast Florida Medicine
Basic science Botulinum toxin is a 150 kd protein consisting of a heavy and light chains. In some preparations, this central core is surrounded by several additional proteins called neurotoxin associated proteins (NAP). When injected into the muscle target tissue the neurotoxin is internalized into the neuronal cytoplasm where the light chain is then released. Upon release, the light chain binds to and inactivates the Synaptosomal-associated protein (SNAP) 25. SNAP 25 is part of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) protein complex which is responsible for vesicle formation. Release of vesicle contents, in this case being acetyl choline (ACH), from the motor neuron end plate is responsible for maintaining synaptic transmission. By blocking SNAP 25, there is no release of ACH across the synaptic junction, paralyzing the muscular target and inactivating the muscle. Studies show onset of effect in one to two days, peak onset at 30 days, and a tapering diminution of effect by 120 days.6 There is an increased effect on the subsequent second and third treatments. Varied opinions exist about the dosage and concentration to be used in given areas by a given injector with varied dilutions noted.6
DCMS online . org
What areas are treated multiple times is dependent on the experience of the injector and the comfort of the patient. Botox is FDA approved for only glabellar lines. However, off label uses for the forehead and lateral canthal folds (crowâ€™s feet) is also very common. In addition, lower facial area treatments are becoming more common including treatment of platysmal bands.7 Botulinum toxin has recently received FDA approval for migraine headaches, and there is ongoing research into the use of this agent for certain chronic pain syndromes including postherpetic neuralgia.
Soft Tissue Augmentation The concept of using fillers for cosmetic reasons has changed in the last several decades. Initially, in the 1980s when collagen was available, fillers were used to correct individual wrinkles and lines.8 Because of localized allergic reactions, patients needed to be prescreened with a 0.1cc subcutaneous challenge prior to use. Non bovine sources of collagen were developed as an alternative. Hyaluronic acid became an alternative to collagen. However, Restylane was FDA approved in 2003 and replaced the use of hyaluronic acid. The Juvederm family of fillers was approved by the FDA in September 2006. Additional fillers such as poly L lactic acid and Calcium hydroxyl lappetite became available in the early 2000s. The concept has now shifted to evaluate the overall face, look for areas of tissue atrophy and volume depletion, and correct accordingly. As beauty is in the eyes of the beholders, the choice of filler type to use is an individual decision based on the comfort of the injector with the product, the location to be injected, and the needs and concerns of the patient. The bulk of this discussion will be in regards to the Hyaluronic acid fillers. Hyaluron is an anionic hydrophilic non-sulfated gluycosaminoglyc that is found in human connective tissue.9 The chemical structure of hyaluron is uniform and lacks a protein component. This minimizes the risk of immunogenic potential when injected into humans. Hyaluron stabilizes intercellular structures, and forms part of the fluid matrix in which collagen and elastic fibers become embedded. The half-life of natural hyaluron is one to two days, with metabolism in the liver converting it to carbon dioxide and water. Hyaluron can absorb up to 1,000 times its molecular weight in water.10 This humectant action makes hyaluronic acid a reasonable choice for tissue volume enhancement.
DCMS online . org
The problem with the compoundâ€™s short half-life has been overcome by crosslinking. Different products have different proprietary cross linking techniques enhancing the duration of the product. Some filler may last six to 12 months or longer depending on the filler and the location injected. In addition to its humectant qualities, hyaluronic acid fillers are malleable, have good flow dynamics for ease of injection, and are reversible. Hyaluronidase is an enzyme that can degrade hyaluronic acid if necessary.11 Many of the compounds now are provided premixed with 0.3 cc of xylocaine, so patients need to be tested for xylocaine allergies prior to use. The areas to be filled vary depending on the skill and comfort of the injector. Correction of the nasolabial folds is FDA approved on label indication for all NAHSA fillers.12 Other treatable areas include the lips, melolabial folds, jowls and cheeks. A newer hyaluron acid is now available for placement along the zygoma allowing for elevation of the nasal alar crease without having to inject into this area. The injector should be well versed in the anatomy of the areas to be injected so as to avoid potential areas of concern. There have been cases reported of embolization from injections with significant consequences.13 An allergy to bee venom is important to note since hyaluronidase is one of the biologically active components in bee venom.14 Some preparations of hylaurinidase are bovine-derived, so a history of allergies to bovine collagen is important to obtain. Allergies to thimerasol would be important to note also, as some preparations of hyaluronidase contain thimerasol. Hyaluronidase can spread infection, and should be treated with systemic antibiotics if necessary.15 Hyalurinidase can enhance adverse effects of other co-administered drugs, so it should not be used in conjunction with furosemide, epinephrine, benzodiazpines, heparin and/ or phenytoin. Hyaluronidase may be less effective when used with salicylates, cortisone estrogens, adrenocortoctropic hormone and antihistamines.16
Conclusion We live in a culture where people now have the choice of invasive or less invasive techniques to achieve their personal appearance goals. With fillers and selective neurotoxins, enhancement can be achieved with a minimum of down time and cost. This technology allows everyone to feel they are most beautiful. v
Northeast Florida Medicine Vol. 65, No. 3 2014 35
References 1. Survival of the Prettiest: the Science of Beauty Etcoff, Nancy; Random House publishers; 1999 2. Monheit G Botulinum Toxin; IN Procedures in Cosmetic Dermatology Botulinum Toxin; Series editor Jeffery Dover; edited by Carruthers and Carruthers, pp 26 3. Brin, Blitzer, Botulinum toxin; IN Procedures in Cosmetic Dermatology Botulinum Toxin; Series editor Jeffery Dover; edited by Carruthers and Carruthers, pp 6 4. Brin, Blitzer, Botulinum toxin; IN Procedures in Cosmetic Dermatology Botulinum Toxin; Series editor Jeffery Dover; edited by Carruthers and Carruthers, pp 7 5. Brin, Blitzer, Botulinum toxin; IN Procedures in Cosmetic Dermatology Botulinum Toxin; Series editor Jeffery Dover; edited by Carruthers and Carruthers, pp 9 6. Gallagher, carruther; IN Procedures in Cosmetic Dermatology pp 22 7. Levy IN Procedures in Cosmetic Dermatology; Botulinum Toxin Series editor Jeffery Dover Pp 129 8. Procedures in Cosmetic Dermatology; Series editor Jeffrey Dover; Associate editor Murad Alam Soft Tissue Augmentation Edited by Jean Carruthers and Alastair Carruthers pp 4 9. Procedures in Cosmetic Dermatology; Series editor Jeffrey Dover; Associate editor Murad Alam; Soft Tissue Augmentation; Edited by Jean Carruthers and Alastair pp 10
36 Vol. 65, No. 3 2014 Northeast Florida Medicine
10. Procedures in Cosmetic Dermatology; Series editor Jeffrey Dover; Associate editor Murad Alam; Soft Tissue Augmentation; Edited by Jean Carruthers and Alastair pp 11 11. Procedures in Cosmetic Dermatology; Series editor Jeffrey Dover; Associate editor Murad Alam; Soft Tissue Augmentation; Edited by Jean Carruthers and Alastair pp 201 12. Procedures in Cosmetic Dermatology; Series editor Jeffrey Dover; Associate editor Murad Alam; Soft Tissue Augmentation; Edited by Jean Carruthers and Alastair pp 13 13. Procedures in Cosmetic Dermatology; Series editor Jeffrey Dover; Associate editor Murad Alam; Soft Tissue Augmentation; Edited by Jean Carruthers and Alastair pp 200 14. Procedures in Cosmetic Dermatology; Series editor Jeffrey Dover; Associate editor Murad Alam; Soft Tissue Augmentation; Edited by Jean Carruthers and Alastair pp 203 15. Procedures in Cosmetic Dermatology; Series editor Jeffrey Dover; Associate editor Murad Alam; Soft Tissue Augmentation; Edited by Jean Carruthers and Alastair pp 203 16. Procedures in Cosmetic Dermatology; Series editor Jeffrey Dover; Associate editor Murad Alam; Soft Tissue Augmentation; Edited by Jean Carruthers and Alastair pp 204
DCMS online . org
DCMS online . org Reprinted with permission from the American Academy of Dermatology 2014. All rights reserved.
Northeast Florida Medicine Vol. 65, No. 3 2014 37
Reprinted with permission from the American Academy of Dermatology 2014. All rights reserved.
Dermatoses of HIV/AIDS Background:
The Duval County Medical Society (DCMS) is proud to provide its members with free continuing medical education (CME) opportunities in subject areas mandated and suggested by the State of Florida Board of Medicine to obtain and retain medical licensure. The DCMS would like to thank the St. Vincent’s Healthcare Committee on CME for reviewing and accrediting this activity in compliance with the Accreditation Council on Continuing Medical Education (ACCME). This issue of Northeast Florida Medicine includes an article, “Dermatoses of HIV/AIDS” authored by Christina Brennan, MD and Rachel Marks, which has been approved for 1 AMA PRA Category 1 credits.TM For a full description of CME requirements for Florida physicians, please visit www.dcmsonline.org.
Cr. Brennan works at Towne Centre for Dermatology in St. Augustine, FL. Rachel Marks is a third year medical student at the Medical College of Georgia.
1. Identification of common mucocutaneous manifestations of HIV/AIDS 2. Recognition of risk factors for HIV/AIDS and encouragement of early testing for at-risk individuals 3. Understanding of Florida HIV/AIDS legislation Date of release: August 1, 2014
Date Credit Expires: August 1, 2016
Estimated Completion Time: 1 hour
How to Earn this CME Credit:
1. Read the “Dermatoses of HIV/AIDS” article, complete posttest following the article and email your test to Patti Ruscito at firstname.lastname@example.org or mail it to 1301 Riverplace Blvd. Suite 1638 Jacksonville, FL 32207. 2. Go to www.dcmsonline.org to read the article and take the CME test online. 3. All non-members must submit payment for their CME before their test can be graded.
CME Credit Eligibility:
A minimum passing grade of 70% must be achieved. Only one re-take opportunity will be granted. A certificate of credit/ completion will be emailed within four to six weeks of submission. If you have any questions, please contact Patti Ruscito at 904.355.6561 or email@example.com.
Dr. Brennan reports no significant relations to disclose, financial or otherwise with any commercial supporter or product manufacturer associated with this activity.
Disclosure of Conflicts of Interest:
St. Vincent’s Healthcare (SVHC) requires speakers, faculty, CME Committee and other individuals who are in a position to control the content of this educations activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly evaluated by SVHC for fair balance, scientific objectivity of studies mentioned in the presentation and educational materials used as basis for content, and appropriateness of patient care recommendations.
Joint Sponsorship Accreditation Statement This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of St. Vincent’s Healthcare and the Duval County Medical Society. St. Vincent’s Healthcare designates this educational activity for a maximum of 2 AMA PRA Category 1 credits. TM Physicians should only claim credit commensurate with the extent of their participation in the activity.
DCMS online . org
Northeast Florida Medicine Vol. 65, No. 3 2014 39
Dermatoses of HIV/AIDS By Rachel R. Marks, BA, Christina B. Brennan, MD
Abstract: The advent of the human immunodeficiency virus (HIV)
epidemic in the 1980s brought with it a wave of fear, stigma and misunderstanding. More than 30 years have passed since the disease first appeared in the United States (US) and our understanding of its pathogenesis, transmission, diagnosis, prevention and treatment has advanced tremendously. Still, given the far-reaching effects of HIV, we have room to grow as healthcare providers for those so afflicted. Early diagnosis of HIV is vital to improving prognosis and quality of life. Since HIV first emerged in the US, associated opportunistic skin and mucous membrane diseases have served as essential clues to an underlying diagnosis. The objective of this article is to increase awareness of the cutaneous manifestations of HIV, and thereby increase the likelihood of early identification.
The History and Social Impact of HIV HIV has been identified in humans as early as 1959 in the Democratic Republic of the Congo.1 It was not recognized in the US until 1981, when Dr. Michael S. Gottlieb discussed in The Center for Disease Control and Prevention’s (CDC) Morbidity and Mortality Weekly Report five cases of Pneumocystis carinii pneumonia (PCP) in previously healthy homosexual men from the Los Angeles area.2 This publication elicited a barrage of reports of PCP and other opportunistic diseases.2 It became apparent that a disease capable of destroying the immune system had emerged. The following year, the CDC came to refer to this disease as “AIDS,” (acquired immunodeficiency syndrome) and within the year, the responsible virus was detected in the tissues of infected patients and propagated in tissue culture.1,2 The identification of the virus allowed for the development of immunological testing and approval for zidovudine (AZT), the first drug available to treat AIDS. Also, numerous other therapies aimed at preventing and treating associated opportunistic infections were developed.3 Within a decade of its discovery, AIDS had become the leading cause of death for both genders between 25 and 44 years of age in the US.2 In 1995, hope arrived in the form of the first protease inhibitor, and by 1997 “hit early, hit hard”
Address Correspondence: Christina B. Brennan, MD 1750 Tree Boulevard, Suite #10 St. Augustine, FL 32086 904-824-4005 firstname.lastname@example.org
40 Vol. 65, No. 3 2014 Northeast Florida Medicine
became the motto for treating HIV with highly active antiretroviral therapy (HAART).2 Unfortunately, the widespread use of protease inhibitors brought about multidrug-resistant strains of HIV, and a fear of significant adverse drug reactions.3 Development of new HIV drug regimens, testing modalities, and public health campaigns have continued since the early 1990s, helping ebb the rising tide of new infections worldwide.
Preventive Measures Early identification and treatment are the cornerstones of prevention. Recently, much attention has come to the idea of post-exposure prophylaxis (PrEP). In 2010, the National Institutes of Health (NIH) demonstrated through the iPrEX study that a daily dose of certain HIV drugs reduces the rate of transmission among HIV-negative men who have sex with men (MSM) by up to 44 percent.2 The 2013 Bangkok Tenofovir Study showed that daily oral PrEP with tenofovir could reduce the risk of HIV transmission in IV drug users by 49 percent.5 Male circumcision has also been identified as a prophylactic measure.6 Since HIV is commonly transmitted through sexual intercourse, taking a detailed sexual history is essential in the prevention of HIV transmission. A detailed sexual history should include: numbers of sexual partners, types of sexual behaviors, prior history of STIs, condom use, and a review of systems pertinent to STIs and HIV infections.7 In addition to utilizing barrier protection for all forms of sexual intercourse, patients should be advised to clean blood or bodily fluid-contaminated surfaces and needles with 10 percent bleach solution.8 Clean needles are even available for IV drug users in certain areas of the country to help curb the risk of spreading blood-borne infections. Other high-risk behaviors include: use of testosterone injections by young athletes, body piercing, tattooing and snorting cocaine using a shared “straw.”9 Additionally, healthcare workers have a 0.3 percent risk of acquiring HIV after percutaneous exposure, and the risk increases with a larger volume of blood transferred, the use of a hollow bore needle, and a higher titer of HIV in the source patient’s blood.10 To this end, universal precautions should be taken in the execution of procedures in which there could be an exposure of bodily fluids. In the case of accidental exposure, postexposure prophylaxis with zidovudine has been shown to be protective.10
DCMS online . org
While the incidence of HIV in the US has stabilized in recent years, the infection rate of approximately 50,000 per year remains concerning.6 Recognizing that certain groups are at higher risk allows for a higher sense of clinical suspicion and a more carefully tailored medical history. MSM make up 4 percent of the total US population, yet account for 63 percent of all new infections in this country. In comparison, heterosexuals account for 25 percent of new HIV infections, and IV drug users account for eight percent.6 Certain racial and ethnic groups are also at higher risk. The greater prevalence of HIV within certain communities, the tendency to engage in sexual intercourse with persons of the same race, and the stigmatization of HIV testing are major reasons for this occurrence.6 African Americans face the most severe burden of HIV, accounting for 44 percent of all new HIV infections, followed by American Indians and Native Alaskans. Meanwhile, Asians have one of the lowest rates of HIV infection.6 Regardless of risk factors, screening should be offered to all persons 13 to 64 years of age on an “opt out” basis.8 Screening should also take place in patients • initiating treatment for tuberculosis; • seeking treatment at an STD clinic; • living in a high-risk setting, such as a correctional facility; • or having been the victim of sexual assault.8 Also, screening is an important part of prenatal care, particularly in the third trimester, and should be offered to laboring women of unknown serostatus.8
Florida Legislation on HIV Testing In the state of Florida, HIV testing requires informed oral or written consent of all test subjects, including minors, and that all positive preliminary tests be followed up with confirmatory testing.11 Exceptions to this rule include: • medical emergencies in which the patient is unable to consent; • accidental exposure while emergency medical services are being rendered; • cases in which informed consent is considered “detrimental to the health of the patient”; • cases involving a prostitute, an inmate anticipating release, or a cadaver; • criminal offenses involving the transmission of bodily fluids; • organ or tissue donation; • research; • and abandonment of an infant.11
and partner notification is not required.11,12 For healthcare workers, HIV testing is voluntary, but encouraged, and patients may be notified of a healthcare provider’s positive serostatus on a case-by-case basis.12 HIV-positive healthcare providers are restricted to procedures that are not considered “exposure-prone.”12
Cutaneous Clues Just as identifying risk factors can help raise clinical suspicion of HIV, recognizing the early signs and symptoms can help uncover an underlying HIV diagnosis. Many patients may present with an unusual skin finding. Dermatologic disease is prevalent in HIV infection not only because of impaired cellular immunity, but also because of viral attack on the skin’s antigen-presenting cells, the Langerhans cells.4,13 Characteristic skin and mucous membrane conditions manifest throughout the course of the disease, and many appear early. Additionally, many dermatologic conditions of HIV correlate with a patient’s CD4 counts, giving an approximation of a patient’s degree of immunosuppression.14 (Table 1)
Acute Retroviral Syndrome One of the first signs of HIV infection is an erythematous, morbiliform exanthema sparing the palms and soles.4 This characteristic rash is indicative of acute retroviral syndrome (ARS), which occurs in 50 to 90 percent of patients within days or weeks of exposure and may be accompanied by fever, fatigue, rash, lymphadenopathy, myalgia and diarrhea.9,15 It is during this time that the virus disseminates widely and infectivity is the highest.4,16 Unfortunately, due to ARS’ resemblance to infectious mononucleosis, influenza, severe streptococcal pharyngitis, viral hepatitis, toxoplasmosis and secondary syphilis, a diagnosis is missed in as many as 75 percent of patients.9 Since serologic tests at the time of this eruption of symptoms are frequently negative or indeterminate, a viral load should be obtained.16 Untreated, the signs and symptoms of ARS will spontaneously disappear, and the patient will enter a prolonged latent phase, during which HIV RNA levels will be low to undetectable and viral blood culture will be negative.9 Symptomatic HIV disease may not appear for five to 10 years.9 By recognizing ARS, HAART can be initiated early, leading to a possible recovery of CD4+ counts, lower plasma concentration of viral RNA, delay of disease progression, and long term benefit for the patient.9,16
Following testing, the physician must make “all reasonable efforts” to notify the patient, and counseling must be offered.11,12 Results of all HIV tests are considered “super-confidential,”
DCMS online . org
Northeast Florida Medicine Vol. 65, No. 3 2014 41
Table 1: Correlation of HIV-Associated Dermatoses with CD4+ T Cell Counts3,7,15-17 CD4+ T Cell Count > 500/uL
500/uL > CD4+ T Cell Count > 250/uL
Acute retroviral syndrome
Recurrent or persistent dermatophyte infections
Herpes zoster infection (nondisseminated)
Hyperkeratotic scabies (Norwegian scabies)
CD4+ T Cell Count < 200/uL
Oral hairy leukoplakia
Cutaneous military tuberculosis
Herpes zoster infection (disseminated)
M. avium skin infection
Varicella zoster infection
Herpes simplex virus Idiopathic pruritis Invasive fungal infections Kaposi’s sarcoma Molluscum contagiosum (extensive; giant mollusca with CD4+ T cell count < 50/uL) Papular pruritic eruption Herpes zoster infection (large, non-healing ulcers) Eosinophilic folliculitis
Viral Infections Exaggerated presentations of common viral infections occur frequently in concert with HIV infection. Ebstein Barr Virus (EBV) characteristically appears in the form of oral hairy leukoplakia (OHL) relatively early in the course of HIV.4,17 The lesions appear as shaggy, white, keratotic plaques with hair-like projections along the sides of the tongue.4 It is important to differentiate oral hairy leukoplakia from pre-malignant lesions of the lateral tongue, such as erythroplakia, as OHL has no malignant potential and requires no treatment unless symptomatic.4 Kaposi’s sarcoma, associated with human herpes virus 8 (HHV 8), is another virally-induced condition that can occur relatively early in the course of HIV. Overall, it is the most common tumor and fourth most common dermatologic manifestation of HIV.17 Skin lesions can have a variety of appearances ranging from small, violaceous papules to large plaques to ulcerated nodules.18 Lesions are often seen in skin lines, along sites of local trauma on the upper body, on the face, and on nasal and oral mucosae.4 Kaposi’s sarcoma has been observed to regress with initiation of HAART, though it can also be locally obliterated using cryotherapy, topical alitretinoin gel, superficial radioliposomally encapsulated doxorubicin, daunorubicin or paclitaxel.4 Varicella-zoster virus (VZV) is seen in patients with a CD4+ count of 400 cells/mm3 or below, or with initiation of HAART once the CD4+ count rises to approximately 250 cells/mm3.4,17 Whereas VZV generally appears in a single dermatome in immunocompetent individuals, in patients with HIV it manifests as multidermatomal, ul-
42 Vol. 65, No. 3 2014 Northeast Florida Medicine
cerative, chronic, verrucous lesions that may in some cases become widely disseminated with systemic involvement and bacterial superinfection.4 Like VZV, herpes simplex virus can appear with CD4+ counts as high as 400 cells/mm3, but the severity and incidence of HSV increases as CD4+ counts decline.7,17 Atypical morphologies may also be seen, including hyperkeratotic, verrucous papules and nodules.14 Once the CD4+ count reaches 50 cells/mm3 or below, the lesions become large, non-healing mucutaneous ulcers, particularly perirectally, but lesions may also occur beyond the genital region.4 Since resistance to acyclovir is common, antivirals such as foscarnet or cidofovir must be used.4 Human papilloma virus (HPV) is especially common in HIV-positive individuals. In fact, since the introduction of HAART, the incidence of HPV infections has risen in this population.14 Lesions can involve the face, limbs and genitalia, and may form large plaques.4 The increased risk of developing cervical and anal intraepithelial neoplasia (AIN) that progresses more rapidly to high-grade pre-malignant lesions is a significant concern in this situation.19 In fact, AIN is seen in up to 75 percent of HIV-infected MSM.19 Although anogenital warts are caused by usually benign or low-risk HPV types, the majority of anogenital warts in HIV-positive patients represent co-infection by low and high-risk HPV types.14 Management is targeted toward detection of high-grade dysplasia before progression to squamous cell carcinoma, using techniques such as application of acetic acid, which can highlight subclinical dysplastic lesions.14 HPV infections can be treated in a number of ways:
DCMS online . org
• immunomodulators, such as imiquimod; • cytotoxic or destructive therapies, such as podophyllotoxin, trichloroacetic acid, cryotherapy, electrodessication or CO2 laser; • or surgical excision.4 In spite of the many treatment options, HPV relapse rate remain high.4 Molluscum contagiosum, caused by poxvirus, commonly involves the face, neck, trunk and inter-triginous areas in HIV-positive patients, and the severity of this presentation is heavily dependent on immune function.13,17 Extensive disease can be seen once the CD4+ decreases to 250 cells/mm3, and giant mollusca (up to 15 mm in diameter) can be seen with CD4+ counts lower than 50 cells/mm3.13 While molluscum contagiosum may regress spontaneously with antiretroviral therapy, imiquimod and topical cidofovir can help improve immunological competence and paclitaxel can be used in resistant disease.4,13
Cutaneous Cytomegalovirus (CMV) manifestations include maculopapular rashes, urticarial eruptions, verrucous or purpuric papules and vesicles, hyperpigmented and indurated plaques, and ulcers that are frequently localized within the perianal and perigenital areas.20,21 Ganciclovir, valganciclovir, foscarnet and cidofovir have all been approved as treatments.21
Fungal Infections Of the many systemic fungal infections seen in HIV-positive patients, some have distinctive cutaneous manifestations characteristic of increasing immune compromise. Candidiasis is among the most frequently seen HIV-associated conditions. Vaginal candidiasis can be an early sign in female patients.4 Oropharyngeal candidiasis is seen in approximately 90 percent of HIV-positive patients and can have four different clinical presentations: pseudomembranous, hyperplastic, erythematous or atrophic, or angular chelitis.14 Symptomatic disease can be treated with oral fluconazole or other conventional antifungals, though caution should be taken in patients with a CD4+ count lower than 50 cells/ mm3 due to an increased risk of resistance.18 Disseminated candidiasis is potentially fatal.20 Dermatophyte infections have a range of morphologies, including pustules, crusted papules, papulonodules, verrucous plaques and mucocutaneous ulcerations.22 Inter-digital tinea pedis with involvement of the dorsal foot and Majocchi’s granuloma, a deep folliculitis in which there is rupture of the follicle wall, are two presentations relatively unique to HIV that often indicate more severe and resistant disease.23 The most common dermatophyte
DCMS online . org
species seen in this population overall are Trichophyton rubrum and Trichophyton mentagrophytes.14 T. rubrum is typically more severe and causes distal, lateral and proximal subungual onychomycosis.14
Seborrheic dermatitis, which is thought to be an inflammatory response to Malassezia furfur, a normal inhabitant of the skin, occurs in up to 85 percent of HIV-infected individuals.20 Just as in immuno-competent individuals, it appears as erythema with a yellowish, greasy scale on the face, scalp, central chest, and inguinal creases. Facial plaques may appear with more severe disease.4 It can be treated with low-potency topical steroids and topical antifungals.14 Eosinophilic folliculitis, one of the most common and characteristic pruritic dermatoses associated with HIV infection, represents an exaggerated Th2 predominant immune reaction to M. furfur or other organisms normally present within the hair follicle.4 The inflamed hair follicles appear as excoriated papules on the face and upper trunk and, although often resistant to drug therapy, can be treated with topical corticosteroids, tacrolimus or permetherin, UVB phototherapy, systemic antibiotics, itraconazole, dapsone, or oral retinoids such as isotretinoin.4 With advanced HIV infection, certain fungal infections, including Cryptococcus neoformans, Histoplasma capsulatum, Coccidiodes immitis, Aspergillus, and Penicillium marneffi, can disseminate and spread to the skin either by local invasion or with reactivation of a latent pulmonary infection.14 The most common of these are Cryptococcus neoformans and Histoplasma capsulatum infections4 both of which cause translucent, dome-shaped papules with central umbilification, generally on the face.24 These disseminated fungal infections are treated primarily with IV amphotericin B, though other antifungals, such as itraconazole, fluconazole, voriconazole, posaconazole and caspofungin are sometimes used.4 Although mycobacterial infections are common in HIV disease, cutaneous forms are relatively rare. Cutaneous tuberculosis can have a variety of manifestations, including scrofuloderma, lichen scrofulosorum, disseminated milliary tuberculosis, gummatous tuberculosis and tuberculous abscesses.14 Infections with M. kansaii, M. haemophilum and M. fortuitum typically cause erythematous papules and nodules, ulcers, verrucous plaques and deep nodules.4 Skin infections caused by M. avium, which manifests in the form of papules, nodules and abscesses, typically do not appear until the CD4+ count is less than 50 cells/mm3.4
Bacterial Infections In addition to bacterial infections common in the general population, certain conditions are more unique to patients
Northeast Florida Medicine Vol. 65, No. 3 2014 43
with HIV. Bacillary angiomatosis, caused by Bartonella henselae and Bartonella quintana, appears with reddish-purple “vascular appearing” papules or nodules, or ulcers of varying size and shape.4 This infection can be treated with macrolides or tetracyclines.20
Syphilis, caused by Treponema pallidum, can appear in the classic papulosquamous form, as well as in HIV-specific presentations: • a noduloulcerative form, • papular eruptions mimicking molluscum contagiosum, • palmoplantar keratoderma, • and lues maligna, an aggressive, widespread eruption of papulopustular or necrotic lesions associated with secondary syphilis.4,18 Scabies is the most common ectoparasitic skin infection in patients with HIV. It may appear classically, with burrows on the hands, wrists, ankles, and interdigital areas, and may also affect the face, ears and scalp.4 Norwegian or hyperkeratotic scabies infection is characterized by generalized, keratotic, crusted, occasionally pruritic plaques.4 This type is extremely infectious due to an extraordinarily high mite load, and
can become secondarily infected leading to potentially fatal bacteremia and septicemia.4 It can be treated with topical permetherin and salicylic acid to aid in penetration, or oral ivermectin for resistant cases.4
Non-infectious Skin Conditions Certain non-infectious dermatologic conditions are also seen more frequently and with greater severity in the HIV-positive population. Non-melanoma skin cancers (NMSC) are, for instance, three to five times more common in HIV-infected patients, and of these, squamous cell carcinoma is far more aggressive with a greater likelihood of metastasis.20 Cutaneous lymphomas tend to occur after the onset of AIDS, appearing as pink to violaceous papules and nodules, occasionally with ulcerations.20 Non-Hodgkin B-cell lymphomas, often associated with EBV infection, are more common. Cutaneous T-cell lymphomas, particularly the mycosis fungiodes variant, as well as T-cell lymphoproliferative disorders can also be seen.4
Table 2: Highly Active Antiretroviral Therapy by Class26
U.S. Brand names are listed parenthetically under generic names.
Nucleoside/ Nucleotide Reverse Transcriptase Inhibitors
NonNucleoside Reverse Transcriptase Inhibitors
Zidovudine/lamivudine (Combivir) Zidovudine/lamivudine/abacavir (Trizivir)
Saquinavir (Invirase, Fortovase) Tirapranavir (Aptivus)
44 Vol. 65, No. 3 2014 Northeast Florida Medicine
DCMS online . org
Pruritus is a common, chronic complaint in advanced HIV infection. Pruritic papular eruption (PPE) of AIDS is a symmetrically distributed, non-follicular, papular rash with eosinophilic folliculitis that generally involves the extremities to a greater degree than the trunk or face.4,14 PPE is only moderately responsive to antihistamines and topical steroids. In general, it is extremely difficult to treat.14 Pruritus may be secondary to other skin conditions, such as xerosis, fungal infections, seborrheic dermatitis, eczema, prurigo nodularis, lichen simplex chronicus, psoriasis or scabies, as well systemic disorders, such as hepatobiliary or renal disease.4 Psoriasis can become especially severe, and even erythrodermic.4 Since reactive arthritis can often be associated with this explosive form of psoriasis, it is wise to test any patient with recent onset of reactive arthritis for HIV infection.20
Management Although many cutaneous manifestations of HIV have targeted therapies, the ideal treatment for these conditions is prevention with HAART. While there is some fear of adverse drug reactions and the emergence of multidrug resistant strains with HAART, the general consensus is that the benefits of early intervention outweigh the disadvantages. By maintaining maximal immune function, cutaneous and other systemic diseases are less likely to appear. HAART has changed HIV from a potentially fatal infection to a chronic, manageable condition.16 Currently, more than 30 drugs or drug combinations exist that target five different stages of the viral life cycle to reduce replication of the virus and destruction of CD4+ T cells.16 (Table 2) For both acute and established HIV infection, a combination of three drugs from at least two drug classes can increase the effectiveness of treatment, and prevent or delay the occurrence of multidrug resistant HIV mutations. Interruptions or non-compliance in treatment, however, can result in poorer prognoses with an increased risk of non-HIV-associated end-organ failure and cancer.8 Virologic success, defined as the reduction of the viral load to undetectable levels (<20 copies/mm3), is possible within 12 to 24 weeks of initiation of HAART in patients that have not received previous treatment.8 HAART can, however, have some dramatic effects on the skin. Restitution of the immune system can result in an inflammatory reaction in some patients, generally within the first three months of initiation of treatment.4,27 Certain latent infections, such as VZV, can become reactivated resulting in a sudden onset of symptoms. This immune reconstitution syndrome (IRS) may be confused with disease progression; thus, it is important to be able to distinguish IRS and recognize that the problem is generally self-limited.27
DCMS online . org
HIV/ART-associated lipodystrophy, or abnormal fat redistribution, is a common and often distressing side effect of long-term antiretroviral treatment. Physicians should be aware that ritonavir, a cytochrome P450 inhibitor, can cause drug to drug interactions,4 and patients should be tested for HLA B5701 to prevent hypersensitive reactions.16 Great caution should also be exercised with the use of the NNRTIs, efavirenz and nevirapine, and the protease inhibitors, amprenavir, fosamprenavir, and darunavir. These drugs pose an increased risk of Stevens Johnsons Syndrome.16 Although HAART is no cure for HIV, its introduction sheds light on the remarkable progress made in HIV management during the last three decades. HIV is no longer a death sentence for those who can be identified early and treated appropriately. In consideration of the multitude of cutaneous conditions associated with HIV disease, an understanding of dermatology serves as a cornerstone of diagnosis and symptomatic treatment. We can furthermore identify specific skin conditions and gain a clinical estimation of the immune status of our patients with HIV. Given the profound impact of HIV in our community, it also remains paramount that, in addition to treating patients with the appropriate medical therapies, we remain aware of the legislation guides testing protocols and dictates patient confidentiality. Ultimately, by recognizing and understanding the signs and symptoms of HIV infection, including those that affect the skin and mucous membranes, we can better help our patients enjoy an improved quality of life and increased longevity. v
References 1. Holland, Kimberly. The history of HIV. Healthline [Internet]. [reviewed 2013 Feb 12; cited 2014 Apr 5]. Available from: http://www.healthline.com/health-slideshow/history-hiv 2. AIDS. gov: HIV/AIDS Basics [Internet]. Washington, DC: U.S. Department of Health and Human Services; c2011. A timeline of AIDS; 2011 [cited 2014 Mar 25]. Available from: http://aids.gov/hiv-aids-basics/hivaids-101/aids-timeline/ 3. FDA.gov: Timeline/history [Internet]. Silver Spring, MD: U.S. Food and Drug Administration; [modified 2012 Mar 28; cited 2014 Apr 6]; Available from http://www.fda. gov/ForConsumers/ByAudience/ForPatientAdvocates/ HIVandAIDSActivities/ucm117935.htm 4. Bolognia JL, Jorizzo JL, Schaffer JV. Dermatology. 3rd ed., Elsevier Limited; c2012. Chapter 78, Cutaneous manifestations of HIV infection; p. 1285-1302.
Northeast Florida Medicine Vol. 65, No. 3 2014 45
5. Choopanya K. et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet 2013;381:2083-90 6. CDC: HIV/AIDS [Internet]. Atlanta: Center for Disease Control and Prevention; [modified 2014 Mar 28; cited 2014 Apr 5]; Available from: http://www.cdc.gov/hiv/ default.html 7. Bagdades EK, Pillay D, Squire SB, et. al. Relationship between herpes simplex virus ulceration and CD4+ cell counts in patients with HIV infection. AIDS. 1992;6:1317-20. 8. Feinberg J. Management of newly diagnosed HIV infection. Ann Intern Med. 2011; 155(7): ITC4-1. doi: 10.7326/0003-4819-155-201110040-01004 9. Perlmutter BL, Glaser JB, Oyugi SO. How to recognize and treat acute HIV syndrome. Am Fam Physician 1999; 60(2): 535-42. 10. Cardo DM, Culver DH, Ciesielski CA, et. al. A case control study of HIV seroconversion in health care workers after percutaneous exposure. New Engl J of Med. 1997; 337(21): 1485-90. 11. Florida Department of Health. Floridaâ€™s omnibus act: a brief legal guide for healthcare professionals. Available from: http://www.floridahealth.gov/diseases-and-conditions/aids/operations_managment/_documents/ Omnibus-booklet-update-2013.pdf. Updated Aug 2013. Accessed 10 Apr 2014. 12. The Center for HIV Law and Policy: Florida [Internet]. New York, NY. [cited 2014 Apr 25]. Available from: http://www.hivlawandpolicy.org/states/florida 13. Filo-Rogulska M, Pindycka-Plasczynska M, Januszewski K, Jarzab J. Disseminated atypical molluscum contagiosum as a presenting symptoms of HIV infection. Postep Derm Alergol 2013; 30(1): 56-58. doi: 10. 5114 14. Tschachler, E. The dermatologist and the HIV/AIDS pandemic. Clinics in Dermatology 2014; 32: 286-9. 15. de Vries HJC. Skin as an indicator for sexually transmitted infections. Clinics in Dermatology 2014; 32, 196-208.
17. Jung AC, Paauw DS. Diagnosing HIV-related disease using CD4 count as a guide. J Gen Intern Med. 1998; 13(2): 131-36. 18. Ray MC, Gately LE III. Dermatologic manifestations of HIV infection and AIDS. Infect Dis Clin North Am. 1994;8:583-605. 19. Kreuter A, Potthoff A, Brockmeyer HN, et al. German Competence Network HIV/AIDS. Anal carcinoma in human immunodeficiency syndrome in the United States. Cancer. 2010;116:5507-16. 20. Porras B, Costner M, Friedman-Klen AE, Cockerell CJ. Update on cutaneous manifestations of HIV infections, Med Clin Normth Am. 1998;13:513-16. 21. Schoenfeld J, Cannon S, Cam K, Keller M. Cutaneous co-infected cytomegalovirus and herpes simplex virus perigenital ulcers in human immunodeficiency virus patients. J Clin Aesthet Dermatol. 2013; 6(1): 41-43. 22. Cohen PR, Grossman ME. Recognizing skin lesions of systemic fungal infections in patients with AIDS. Am Fam Physician. 1994; 49: 1677-34. 23. Myskowski PL, Ahkami R. Dermatologic complications of HIV infection. Med Clin North Am. 1996;80:1415-35. 24. Durden FM, Elewski B. Cutaneous involvement with Cryptococcus neoformans in AIDS. J Amer Acad Dermatol. 1994; 30:844-8. 25. FDA.gov: Antiretroviral drugs used in the treatment of HIV infection [Internet]. Silver Spring, MD: U.S. Food and Drug Administration; [modified 2013 Aug 20; cited 2014 Apr 6]; Available from http://www.fda. gov/ForConsumers/byAudience/ForPatientAdvocates/ HIVandAIDSActivities/ucm118915.htm 26. San Francisco AIDS Foundation: Approved antiretroviral drugs [Internet]. San Francisco, CA: San Francisco AIDS Foundation; [modified 2014; cited 2014 May 5]; Available from http://www.sfaf.org/hiv-info/hot-topics/ beta/2011-beta-winterspring-haart-chart.pdf 27. Cheonis N. Immune reconstitution syndrome. Bulletin of Experimental Treatments for AIDS: a Publication of the San Francisco AIDS Foundation 2005; 17(2): 12-15.
16. Uihlein L, Saavedra AP, Johnson R. Chapter 198. Cutaneous Manifestations of Human Immunodeficiency Virus Disease. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K. eds. Fitzpatrickâ€™s Dermatology in General Medicine, 8e. New York, NY: McGraw-Hill; 2012.http://accessmedicine.mhmedical. com/content.aspx?bookid=392&Sectionid=41138927. Accessed April 13, 2014.
46 Vol. 65, No. 3 2014 Northeast Florida Medicine
DCMS online . org
CME Post Test
CME Questions & Answers (circle one answer)/Free to DCMS Members/$50.00 charge non-members* (Return by August 1, 2016 by mail: 1301 Riverplace Blvd. Suite 1638, Jacksonville, FL 32207 or online: www.dcmsonline.org.)
1. Which of the following has been identified as an antenatal measure to reduce HIV transmission? a. Prophylactic administration of HAART to mothers of unknown serostatus b. Prophylactic administration of tenofovir to mothers of unknown serostatus c. Circumcision of male babies d. Prophylactic use of tenofovir in pregnant IV drug users
2. Which of the following medications should be used in the event of an unintended occupational exposure to bodily fluids? a. Tenofovir b. Zidovudine c. Stavudine d. Tenofovir/emetricitabine
3. Which of the following circumstances does not require consent for HIV screening in the state of Florida? a. A minor who has admitted to illicit drug use b. A minor who has admitted to unprotected sexual intercourse c. A minor who has presented for sexual assault d. A minor who is also being screened for tuberculosis
4. Oral hairy leukoplakia is caused by which of the following viruses? a. Ebstein Barr virus b. HHV-6 c. HHV-8 d. HPV 5. Kaposi’s sarcoma is caused by which of the following viruses? a. Ebstein Barr virus b. HHV-6 c. HHV-8 d. HPV
8. Seborrheic dermatitis can be treated with: a. High-potency topical steroids b. Oral anti-fungals c. Low-potency topical steroids and topical anti-fungals d. Watchful waiting
9. All of the following can present as dome-shaped papules with central umbilification EXCEPT: a. Cryptococcus neoformans b. Molluscum contagiosum c. Histoplasma capsulatum d. Trichophyton rubrum
6. Which of the following conditions is frequently associated with immune reconstitution syndrome? a. HSV infection (disseminated) b. VZV c. Molluscum contagiosum d. Psoriasis
10. Testing for HLA B5701 is wise before initiation of which of the following HIV medications? a. Efavirenz b. Ritonavir c. Fosamprenavir d. Nevirapine
7. Cutaneous HPV infections can be treated with all of the following therapies EXCEPT: a. Imiquimod b. Podophyllotoxin c. Tretinoin d. Ablative laser
Evaluation questions & CME Credit Information (Please evaluate this article. Circle one number using this scale: 1= Strongly Agree to 5= Strongly Disagree) The articles met the stated objectives: 1 2 3 4 5 The articles were appropriate to my practice: 1 2 3 4 5 The topics were current and well presented: 1 2 3 4 5 Comments: Name (Print) Email Address/City/State/Zip Phone Fax
DCMS Member (circle)
*Non-Member Charge ($50.00) - See payment options below Credit card: Visa
Account # Expiration date Signature
DCMS online . org
Northeast Florida Medicine Vol. 65, No. 3 2014 47
New Members Jane Benson UF Health Pediatrics
Danisha Figueroa UF Health Infectious Disease
Francois Jo-Hoy UF Health Internal Medicine
Robert Palmer UF Health Orthopedic Sports Medicine
Kristine Tibavisky UF Health Obstetrics & Gynecology
Astrid Botty Van Den Bruele UF Health Other Specialty
Mark Flora UF Health Emergency Medicine
Thomas Kaiser UF Health Orthopedic Surgery
Kamalpreet Parmar UF Health Pathology
Omar Tolaymat UF Health Internal Medicine
Richard Scott Suny Downstate Medical Center Family Medicine
James Gable UF Health Other Specialty
Ozdemir Kanar UF Health Internal Medicine
Dhruv Patel UF Health Radiology
Stephanie Tootle UF Health Obstetrics & Gynecology
Maedeh Ganji UF Health Internal Medicine
Ikechi Konkwo UF Health Other Specialty
Nachiket Patel UF Health Cardiovascular Disease
Christopher Trautman Mayo Internal Medicine
Joseph Geffen UF Health Internal Medicine
Ryan Kunjal UF Health Internal Medicine
Rutvi Patel UF Health Emergency Medicine
Laura Travers UF Health Pediatrics
Mahlet Girma UF Health Psychiatry
Sara Largen UF Health Pediatrics
Alexandra Petraszko UF Health Oral & Maxillofacial Surgery
Janese Trimaldi UF Health Cytopathology
Naila Choudhary UF Health Cardiovascular Disease
Rene Daniel GomezEsquivel Mayo Clinic Gastroenterology
Michael Latzko UF Health Other Specialty
Nicholas Phillips UF Health Psychiatry
Sara Venezia UF Health Radiology
Michael Clegg UF Health Musculoskeletal Radiology
Sasha Gourgue UF Health Obstetrics & Gynecology
Deanne Leonard Mayo Clinic Nephrology
Wally Plante UF Health Internal Medicine
Alyson Vokes UF Health Obstetrics & Gynecology
Meredith Coulter UF Health Obstetrics & Gynecology
Sanjiv Gray UF Health Other Specialty
Leslie lester UF Health Internal Medicine
Monica Plazarte UF Health Endocrinology
Colin Vokes UF Health Other Specialty
Jessica Covington UF Health Obstetrics & Gynecology
Amit Gupta UF Health Cardiovascular Disease
Jeremiah Libby UF Health Radiology
Ramon Rodriguez Quijano UF Health Psychiatry
Alexander Volsky UF Health Other Specialty
Pedro Cox-Alomar UF Health Interventional Cardiology
Sheena Gupta UF Health Pediatrics
Danielle Lindgren UF Health Radiology
John Sarandria UF Health Pediatrics
Jared Walker UF Health Emergency Medicine
William Cullinane UF Health Internal Medicine
Eric Hall UF Health Radiology
Reem Louli UF Health Internal Medicine
Michael Seawell UF Health Interventional Cardiology
Joseph Dayan UF Health Anesthesiology
William Adam Hammond Mayo Clinic Hematology/Oncology
Matthew Lowery UF Health Emergency Medicine
Douglas Shapiro UF Health Pediatrics
Caronia Wallace UF Health Pediatric Emergency Medicine
Bhagirathbhai Dholaria Mayo Clinic Hematology/Oncology
Reham Hasan UF Health Pediatric Endocrinology
Alexandra Mannix UF Health Emergency Medicine
Rohit Sharma UF Health Pathology
Christopher Dudek UF Health Pediatrics
Rex Holliday Mayo Clinic Radiology
Andrew Martin UF Health Emergency Medicine
Andrea Sharp UF Health Hospice & Palliative Medicine
Firas Baidoun UF Health Internal Medicine
Anne Elliott UF Health Hospice & Palliative Medicine
Eric Iheme UF Health Emergency Medicine
Caryl Bailey UF Health Other Specialty
Hans Eriksson UF Health Emergency Medicine
Ryan Baker UF Health Pediatrics
Khadeeja Esmail UF Health Internal Medicine
James Barr UF Health Emergency Medicine
Abigail Estelle UF Health Oral & Maxillofacial Surgery
Urvashi Barua-Nath UF Health Pediatric Emergency Medicine
Mary-Ann Fares UF Health Neurology
Christopher Bender UF Health Emergency Medicine
Lee Ferguson UF Health Ophthalmology
New Active Members: Louis A. Akra Akra Professional Services Internal Medicine John Harris John B. Harris Plastic Surgery Plastic Surgery Derek Joseph Schemmel Drs. Mori, Bean & Brooks, PA Radiology Leigh Speicher Mayo Clinic Internal Medicine Turkessa J. Walker Nemours Childrens Clinic Allergy & Immunology Morris S. Dees, III Ponte Vedra Medical Center Internal Medicine Lee B. Epstein McIver Center for Urogynecology Gynecology Juan Carlos Fuentes Baptist Primary Care at WGV Family Medicine New Resident Members: Rabie Adam-Eldien UF Health Nephrology Emmanuel Agosto-Arroyo UF Health Pathology Dan Alexis UF Health Emergency Medicine Ezekiel Anderson UF Health Anesthesiology Douglas Baasch UF Health Oral & Maxillofacial Surgery Nathan Bach UF Health Emergency Medicine
Lindsay Cadorette UF Health Pediatrics Christina Cannon UF Health Emergency Medicine Ayham Chamseddin UF Health Endocrinology
Farzin Imani UF Health Radiology Rommy Issa UF Health Internal Medicine Adnan Javed UF Health Emergency Medicine Abbie Jensen UF Health Other Specialty Matthew Jenson UF Health Radiology
48 Vol. 65, No. 3 2014 Northeast Florida Medicine
Christopher Martin UF Health Emergency Medicine Amr Matoq UF Health Pediatrics Matthew Mcdiarmid UF Health Internal Medicine David Michel UF Health Orthopedic Surgery Omar Moore UF Health Internal Medicine Stacey Nedrud UF Health Oral & Maxillofacial Surgery
Aaron Wallender UF Health Pediatric Surgery Jessica Win UF Health Pediatrics Jeffrey Winder UF Health Internal Medicine
Amanda Jean Shreders Mayo Clinic Hematology/Oncology
Sidra Younus UF Health Nephrology
Zahid Siddiqui UF Health Cytopathology
Irving Zamora UF Health Other Specialty
Lauren Stemboroski UF Health Internal Medicine
Zimei Zhou UF Health Vitroretinal Ophthalmology
Kylie Swearingen UF Health Other Specialty
New Retired Members:
John Taliaferro UF Health Orthopedic Surgery
Arnold Lawrence Tanis Pediatric Associates, P.A. Pediatrics
Ankita Taneja UF Health Pediatrics
DCMS online . org
A Unique Case of Cardiac Arrest Following K2 Abuse Saif Ibrahim, MD, Farah Al-Saffar, MD, Thomas Wannenburg MD University of Florida College of Medicine
Abstract: Approximately 50 percent of deaths associated with car-
diovascular disease are sudden, and when using a time period of less than 24 hours since presentation sudden cardiac death (SCD) accounts for up to 450,000 deaths every year in the United States. 1 Coronary artery disease leading to ischemia and refractory ventricular arrhythmias accounts for the majority of these deaths. While recreational drug use, such as cocaine and marijuana, have been previously described in patients suffering sudden cardiac arrest, the use of novel drugs such as synthetic cannibus (K2) has not been previously described in this patient population. We describe a case of out of hospital cardiac arrest in a patient abuser of the street drug known as K2.
Introduction Designer drugs have been a long time problem due to difficulty detecting these products during routine laboratory analysis, and the synthetic cannabinoid K2 is not an exception. K2, also known as spice, is heavily marketed as incense and until recently was widely available at specialty shops and the internet. New federal legislation has classified it as a scheduled 1 controlled substance.2 Recent reports have noted a steady increase in abuse of this product due to its marijuana-like effects and the inherent difficulty detecting it on a routine urine drug screen. Address Correspondence: Department of Internal Medicine 653-1 W 8th Street Jacksonville, FL 32209
K2 is an herbal blend sold as an herbal marijuana alternative which contains multiple metabolites, many of which are unknown. The most frequent compound found in the herbal mixture is JWH-018 which was first described by John W. Huffman at Clemson University in his efforts to study synthetic analogs of tetrahydrocannabinol (THC).3, 4 The effect on the cardiovascular system of many of these metabolites is unknown, and few data is available on their pharmacological properties. A case series of pediatric patients who suffered a myocardial infarction after use of K2 has been recently reported. We report a case of an adult patient who suffered cardiac arrest after using K2.4
Observation A 56 year old man with a past medical history of hypertension, dyslipidemia, coronary artery disease and previous myocardial infarction with a four vessel bypass grafts 10 years prior to admission presented to a tertiary care hospital after he suffered an out-of-hospital cardiac arrest. The patient was witnessed to collapse by a coworker who activated the emergency medical response. Upon arrival of emergency medical service (EMS), the patient was found to be in ventricular fibrillation and cardiopulmonary resuscitation (CPR) was initiated. The patient was defibrillated twice and resuscitation was provided according to the advance cardiac life support (ACLS) protocol. He was administered epinephrine, atropine and lidocaine intravenously, and within an estimated 15 minutes the
Figure 1. ECG at the time of hospitalization shows sinus tachycardia and inferior myocardial infarction, age undetermined.
50 Vol. 65, No. 3 2014 Northeast Florida Medicine
DCMS online . org
patient had return of spontaneous circulation (ROSC). Upon arrival to the emergency room, the patient had a documented pulse, found to be in sinus tachycardia and remained comatose with a Glasgow coma scale (GCS) of three. An electrocardiogram (ECG) obtained at the time of admission is shown in figure 1.
The main challenge that arises as the phenomenon progresses is the difficulty of detecting these metabolites given the usual screening tests currently available. There is an increasing need for a feasible, adequate diagnostic test since the current objective measurement is the rate-limiting step for a more evidence-based management.
The patient’s family stated the patient complained of increasing dyspnea on exertion, but no other symptoms were reported. The family informed physicians the patient had been using increasing amounts of a street drug called K2 or spice. Laboratory analysis at the time of admission showed: elevated troponin T at 0.632, elevated CKMB (creatinine kinase myocardial band) at 70.2 with an index of 8.6 percent. Normal levels of potassium, magnesium and calcium were also noted. A routine urine drug screen at the time of admission was negative. He had normal alcohol and salicylate levels. A chest radiograph at the time of admission showed findings suggestive of pulmonary edema. An echocardiogram at the time of admission showed normal left ventricular size and wall thickness, septal asynchrony but no other segmental wall motion abnormality noted, with an estimated left ventricular ejection fraction (LVEF) of 50 percent.
Collaboration with our colleagues in the biochemical and toxicology fields is indispensable to optimize our novel synthetic Cannabinoids detection tools. This will be a cornerstone for future research that will be geared towards estimating the real incidence of cardiovascular events related to consumptions of these novel agents. This information will be valuable as these events are underestimated. It will also be interesting to examine other pathological entities associated with this type of behavior.
Induced therapeutic hypothermia was initiated for neurological protection in the setting of a witnessed ventricular fibrillation arrest with ROSC within 15 minutes. After the patient was successfully rewarmed he had evidence of normal neurological function. He underwent a diagnostic left heart catheterization which showed evidence of severe native coronary vessel artery disease, two saphenous bypass grafts (right coronary artery and first obtuse marginal branch), and a left internal mammary graft to the left anterior artery which appeared angiographically normal. A saphenous graft to the first diagonal branch had moderate disease not deemed significant without further interventions. There was evidence of inferior wall hypokinesis on a left ventriculogram. Before discharge, the patient had an automated implantable cardiac defibrillator (AICD) placed for secondary prevention. He admitted to be a long time user of marijuana, but recently had been using K2 instead because he could consume larger amounts as it was more affordable. He was discharged home in stable condition with meaningful neurological recovery and counseled to abstain from further use of recreational drugs including K2.
Discussion Novel synthetic Cannabinoids have recently been increasing in popularity; abusing these products has hence been a recent trend among adults as well as teenagers. The case described above reports sudden cardiac arrest in a middle aged male with several other cardiovascular risk factors.
DCMS online . org
Lastly, we report a case in an adult patient with multiple other cardiovascular risk factors (dyslipidemia, hypertension, and coronary heart disease). As most cases of cardiovascular events related to K2-family drug abuse have been reported in pediatrics, it will be vital to further examine their effects on adults and the way their physiological effects interact with other underlying, literature-documented risk factors for cardiovascular diseases. We believe, given the increase prevalence of this type of abuse, that this untapped topic is an interesting area for future research that is yet to be explored. v
Bibliography 1. Zipes, Douglas P., Arthur J. Moss, George Klein, Gabriel Gregoratos, Martin Fromer, Bernard Chaitman, Alfred E. Buxton, Martin Borggrefe, A. John Camm, and Robert J. Myerburg. “ACC/AHA/ESC 2006 Guidelines For Management Of Patients With Ventricular Arrhythmias And The Prevention Of Sudden Cardiac Death—Executive SummaryA Report Of The American College Of Cardiology/American Heart Association Task Force And The European Society Of Cardiology Committee For Practice Guidelines (Writing Committee To Develop Guidelines For Management Of Patients With Ventricular Arrhythmias And The Prevention Of Sudden Cardiac Death).” Journal of the American College of Cardiology 48.5 (2006): 385-484. Print. 2. “News from DEA, Domestic Field Divisions, Washington DC News Releases, 03/01/11.” News from DEA, Domestic Field Divisions, Washington DC News Releases, 03/01/11. N.p., n.d. Web. 10 Dec. 2013. <http://www.justice.gov/dea/pubs/pressrel/ pr030111.html>.”John W. Huffman.” Clemson University. N.p., n.d. Web. 10 Dec. 2013. <http://www.clemson.edu/ chemistry/people/huffman.html>. 3. Rosenbaum CD, Carreiro SP and Babu KM. (2012). Here today, gone tomorrow…and back again. A review of herbal marijuana alternatives (K2, Spice), synthetic cathitones (Bath salts), Kratom, Salvia divinorum, Methoxetamin and Piperazines. Journal of Medical Toxicology, 8, 15-32. 4. Mir, A., Obafemi, A., Young, A., percent Kane, C. (2011). Myocardial infarction associated with use of the synthetic cannabinoid K2. Pediatrics, 128(6), e1622-e1627. Northeast Florida Medicine Vol. 65, No. 3 2014 51
Hospitalist Patient Education Card and Effect on Patient Satisfaction Mary S. Hedges, MD1*; Lynsey A. Cassidy-Seim, MD1; Hope E. Greig, MSH2; Dawn M. Mussallem, DO1; Teresa Veneziale, MBA3; Nancy L. Dawson, MD1 Division of Hospital Internal Medicine, Mayo Clinic, Jacksonville, Florida, USA
Division of Clinical Operations, Mayo Clinic, Jacksonville, Florida, USA
Division of Quality Management Services, Mayo Clinic, Jacksonville, Florida, USA
Abstract: Objective: Patient satisfaction with hospitalist services is often low. An educational card with physician photographs was implemented to help patients understand the role of the hospitalist in their care. Methods: Patients were provided an educational card on admission to the hospitalist service. The card included a description of the hospitalist model of care and photographs of the institution’s hospitalists. Patients were surveyed by telephone at random after discharge. Results: Many aspects of patient satisfaction scores improved after the educational card was implemented. The most dramatic improvement was in the area of patient perception of overall teamwork among doctors, nurses and staff. Other notable improvements included the patient’s perception of their time with the doctor, the impact of their communication with the doctor and their overall quality of care. Conclusion: Patient satisfaction improved after introduction of an educational card, which included photographs of all of the Hospitalist team members. This is an inexpensive and practical intervention that may improve patient satisfaction scores, especially in hospitalized patients.
Introduction The rise of the hospitalist model of care over the past decade has transformed inpatient medicine. The care that is delivered by hospitalists has improved patient outcomes, cost-effectiveness and length of stay. Despite this improvement, patient satisfaction remains at risk because many patients prefer to be treated by their primary care physicians.1-4 As one of the fastest growing areas of medical practice in the United States, it is imperative to have strategies in place to improve patient satisfaction. Health care reform is driving patient-centered care, and hospital reimbursement is increasingly linked to patient satisfaction.5
Corresponding author at: Division of Hospital Internal Medicine – Mayo Clinic 4500 San Pablo Road Jacksonville, FL 32224 Ph: 904-953-6722 / Fax: 904-953-0655 email@example.com
52 Vol. 65, No. 3 2014 Northeast Florida Medicine
Physician performance ratings can be hampered by patients’ inability to correctly identify their inpatient physician. It has been reported that patients often have difficulty identifying their physicians.6,7 Placing the physician’s picture in a patient’s room may help them to better identify the physician, and possibly lead to improved patient satisfaction scores.8
DCMS online . org
We implemented an educational card for distribution to patients, which included photographs of all of the physician team members to help improve overall patient satisfaction scores for our Hospitalist Service. The card also included a brief description of the hospitalist model of care (Figure 1). We compared patient satisfaction scores before and after implementation of this card.
Methods This project was part of a quality improvement project to increase patient satisfaction. The project took place in a 214bed teaching hospital. Each hospitalist team was composed of one physician hospitalist and one nurse practitioner. Each hospitalist team admitted patients and adjusted to evenly distribute work among hospitalist teams (sentence does not make sense). At the time of the initial evaluation of each patient, the educational card was given to the patient or their family. To obtain patient satisfaction data, 500 discharged patients per quarter were contacted by our institution approximately two to three weeks after discharge. Data was compiled quarterly and transmitted to the various departments. Information specific to the hospitalist group was collected from that data pool. Patients were asked to complete a predefined 75-question telephone survey. Respondents were asked to rank their answers using a five-point scale: excellent, very good, good, fair or poor. This survey was administered by a representative from Professional Research Consultants, Inc. This company routinely measures patient satisfaction.
Table 1: Percentage of Excellent Scores April-June 2011 % Excellent (Total No.)
July-Sept 2011 % Excellent (Total No.)
Doctor being thorough with exam
Doctor spending time with patient during appointment and not seeming rushed
Doctor involving patient in decision-making process
Doctor understanding and caring
Doctor’s instructions/explanations of treatment/tests
Table 2: Available National Percentiles April-June 2011 National Percentile Ranking
July-Sept 2011 National Percentile Ranking
Doctor listening and understanding what is important to patient
Doctor involving patient in decision-making process
Doctor’s instructions/explanations of treatment/tests
Overall quality of doctor’s care
Overall teamwork between doctors, nurses, and staff
Overall quality of care
Results Baseline data from 2010 showed that 57 percent of patients (13 of 23) rated the hospitalist division as “excellent” for overall quality of care, which was in the 66th percentile nationally. Subsequently, the educational card with photographs was created. Improvement in the percentage of “excellent” scores was seen in all categories after the card was implemented in April 2011. As the satisfaction surveys were performed a few weeks after discharge, the effect of the card implementation would be expected during the third quarter of the year (July-September). Data received demonstrates notable improvement in patient satisfaction scores during this third quarter (Table 1). National percentile rankings were also reported when available (Table 2). The most dramatic improvement was in the area of patient perception of overall teamwork among doctors, nurses and staff. Other notable improvements included patient perception of the time that they spent with the physician, improvement in listening and understanding, and overall quality of care.
Table 3: Hospitalist Service Census by Month Month 2011
No. of Patients
Doctor listening and understanding what is important to patient
Overall quality of doctor’s care
Overall teamwork between doctors, nurses, and staff
Overall quality of care by doctor
DCMS online . org
Northeast Florida Medicine Vol. 65, No. 3 2014 53
Data showed that improvement in patient satisfaction was possible despite an increasing patient load on the hospitalist service. The hospitalist service census data by month are shown in Table 3. The only identifiable change during this time was the implementation of the educational card.
Discussion To our knowledge, this is the first study to evaluate whether combining physician photographs with patient education material regarding the hospitalist’s role in their care improves patient satisfaction scores. After implementing the educational card for our patients, we found a notable trend toward improved patient satisfaction based on our available survey results. The educational card was the only identifiable change during this time, and this improvement occurred despite increased patient load. Patient education about the provider role and photographs of their physicians may be more important than previously realized.
Conclusion Patient satisfaction is increasingly being used as part of the overall quality ranking of hospitals. Tools are needed to help hospitals and physicians achieve the goal of improved measurable patient satisfaction. Although our low overall survey numbers limited the ability to prove statistical significance, our data showed improvement in patient satisfaction with distribution of an educational card with physician photographs. The simplicity of this intervention makes it a practical and affordable tool for hospitalist groups to implement. v
References 1. Lindenauer PK, Chehabeddine R, Pekow P, et al. Quality of care for patients hospitalized with heart failure: assessing the impact of hospitalists. Arch Intern Med. 2002 Jun 10;162(11):1251-6. PubMed PMID: 12038943 2. Everett GD, Anton MP, Jackson BK, et al. Comparison of hospital costs and length of stay associated with general internists and hospitalist physicians at a community hospital. Am J Manag Care. 2004 Sep;10(9):626-30. PubMed PMID: 15515995 3. Coffman J, Rundall TG. The impact of hospitalists on the cost and quality of inpatient care in the United States: a research synthesis. Med Care Res Rev. 2005 Aug;62(4):379-406. PubMed PMID: 16049131 4. Meltzer DO, Shah MN, Morrison J, et al. Decreased length of stay, costs and mortality in a randomized trial of academic hospitalists [abstract]. J Gen Intern Med. 2001;16(1 Suppl):208-9. 5. Centers for Medicare & Medicaid Services. HCAHPS: hospital survey. March, 2013 http://www.hcahpsonline. org/files/HCAHPS%20V8.0%20Appendix%20A%20 -%20HCAHPS%20Mail%20Survey%20Materials%20 (English)%20March%202013.pdf. Hospital Care A. Accessed March 21, 2013 6. Arora V, Gangireddy S, Mehrotra A, et al. Ability of hospitalized patients to identify their in-hospital physicians. Arch Intern Med. 2009 Jan 26;169(2):199-201. PubMed PMID: 19171817 7. Maniaci MJ, Heckman MG, Dawson NL. Increasing a patient’s ability to identify his or her attending physician using a patient room display. Arch Intern Med. 2010 Jun 28;170(12):1084-5. PubMed PMID: 20585079 8. Francis JJ, Pankratz VS, Huddleston JM. Patient satisfaction associated with correct identification of physician’s photographs. Mayo Clin Proc. 2001 Jun;76(6):604-8. PubMed PMID: 11393499
54 Vol. 65, No. 3 2014 Northeast Florida Medicine
DCMS online . org
Duval County Medical Society Foundation 1301 Riverplace Blvd. Suite 1638 Jacksonville, FL 32207
Our Autumn 2014 issue on Dermatology is guest edited by DCMS member Dr. Jonathan Kantor. It offers one CME exam on Dermatoses of HIV/AIDS. C...
Published on Jan 5, 2015
Our Autumn 2014 issue on Dermatology is guest edited by DCMS member Dr. Jonathan Kantor. It offers one CME exam on Dermatoses of HIV/AIDS. C...