Rheumatology Connections

Rheumatology

Connections

An Update for Physicians | Summer 2011

Atherosclerosis and Wegener’s Granulomatosis 3|Meeting CME Needs of Rheumatology Community 4|Examining Autoimmunity 6|Who Should Be Treated for Low Bone Mass? 8

Dear Colleague,

It is my honor to serve as Chair of the Cleveland Clinic Department of Rheumatic and Immunologic Diseases. As you can see from the articles in this issue of Rheumatology Connections, the 30 talented rheumatologists in our Department are engaged in innovative activities in patient care, education and research. I am delighted to share this issue of Connections with you to give you a window into some of our exciting projects.

We have had several recent CME activities including recent meetings on Vasculitis:

• Vasculitis Summit: “New Directions in Small Vessel Vasculitis” – On May 4, 2011, this summit had almost 300 participants from 26 states and many countries. The Activity Directors Drs. Carol Langford, Gary Hoffman and Leonard Calabrese presented an ambitious and impressive program by both Cleveland Clinic staff as well as national and international faculty that demonstrated the interdisciplinary collaboration that is essential in care and research in vasculitis.

• Vasculitis Patients’ Symposium – On Tuesday, May 3, Dr. Langford and other members of the vasculitis staff presented a symposium for individuals with vasculitis, which was attended by more than 275 patients with a variety of vasculitis conditions. They were enthusiastic about the opportunity to obtain information on their rare diseases from multiple thought leaders in the field. • Biologics Therapies Summit IV – Our summit from May 5-7, 2011 was attended by more than

450 people! Dr. Calabrese has organized the Biologics summits over the last 10 years, and the excellent presentations by faculty from Cleveland Clinic and national and international physician scientists have earned this course a reputation as one of the best.

In addition to the CME courses, the vasculitis fellowship here has trained specialists who have provided much-needed care and research throughout the world.

In this issue, Dr. Gary Hoffman’s article on autoimmunity and the issues of immune regulation and target organ specificity offers a fascinating view on this intriguing topic. In another section, Dr. Hajj-Ali shares information on her translational work on the relationship of microparticles to premature atherosclerosis in patients with Wegener’s. We also highlight research in multiple areas in addition to vasculitis, including Dr. Elaine Husni’s work on psoriatic arthritis as well as Dr. Chad Deal’s leadership in osteoporosis.

We all hope that you enjoy this issue of Rheumatology Connections and welcome your questions and comments.

Sincerely,

Abby Abelson, MD

Chair, Rheumatic and Immunologic Diseases 216.444.3876 | [email protected]

From the Chair of Rheumatic and Immunologic Diseases

The Department of Rheumatic and Immunologic Diseases hosted three successful vasculitis CMEs in May.

Advancements in treatment have lead to better survival in patients with Wegener’s granulomatosis (WG); however, premature atherosclerosis has emerged as a significant morbid-ity that occurs independent of the traditional cardiovascular risk factors. The link between WG and atherosclerosis is not well characterized but the association raises the possibility that persistently active vasculitis, or nonspecific inflammation, play a role in early atherosclerosis.

In concordance with our mission at the Vasculitis Care and Research Center, which is to ensure the best possible care for patients with vasculitis and to discover the causes of these diseases, I have partnered with Roy Silverstein, MD, Chairman of Cell Biology Department within the Cleveland Clinic Lerner Research Institute to study the relationship between inflam-matory disease in WG with the development of atherosclerosis to better understand the pathogenesis of atherosclerosis in WG. The study assessed different parameters in relationship to atherosclerosis as measured by carotid-intima media thickness. These parameters included the traditional atherosclerotic risk factors, disease duration and number of relapses, platelet aggre-gation and microparticles (MP).

MP are membrane fragments that bud off from normal cells, including leukocytes, platelets and vascular endothelial cells, during either activation or apoptosis. There is substantial evidence suggesting that MP are potential prognostic markers for thrombosis and atherosclerotic vascular disease. These characteristics made these markers ideal to be considered the interface between inflammation and atherosclerosis. A total of 45 patients with WG were included. The results of this study indicated that the total number of patients with disease relapse, age at onset of the disease and diastolic pressure were independent risk factors for atherosclerosis in WG. Moreover, the data revealed that MP counts and platelet aggregation are increased during disease relapse in WG. These results open a new paradigm in the evaluation of atherosclerosis in WG. The findings indicate that the frequency of disease relapse in WG is an independent risk factor for atherosclerosis. In addition, the level of MP and platelet aggregation during each relapse indicates that MP generated during relapse may sensitize platelets to activation and contribute to the development of atherosclerosis in WG.

We are further assessing the role of MP and their interaction with the platelet through the scavenger receptor CD36 in the pathogenesis of atherosclerosis in WG.

The results of this study have shed light on the pathogenesis of atherosclerosis in WG and could serve as a model to further explore the role of inflammation in atherosclerosis in both inflammatory and noninflammatory conditions.

Dr. Rula Hajj-Ali is a staff physician in the Vasculitis Care and Research Center, Department of Rheumatic and Immunologic Disease, who has a special interest in systemic vasculitides and central nervous system vasculitis. She can be reached at 216.444.9643 or [email protected].

Atherosclerosis and Wegener’s Granulomatosis

In 2005, The R.J. Fasenmyer Center for Clinical Immunol-ogy was created and providing education in the field of Clinical Immunology was made a core mission. I led the development of a strategic plan centered around the rapidly changing field of biologic therapeutics because it was recognized that many clinicians, including rheumatologists, had critical needs in understanding the immunologic under-pinnings of the long pipeline of biologic therapeutics ahead. They also required new and innovative ways of keeping abreast of advances in efficacy and toxicity.

Having served in various capacities on the CME Commit-tee of the American College of Rheumatology, including as its Chair, I was well aware of the challenges and changing environment in the CME world. Working with the CME department at Cleveland Clinic, one of the oldest institu-tions of its kind in the country and led by William Carey, MD, a multiple-platform approach was drafted centering heavily on the use of the internet. Over the past decade, Cleveland Clinic’s site for web-based education ( ccfcme. org ) has won many national awards and currently plays host to approximately 300,000 visitor sessions per month seeking medical education. It has developed into one of the largest and most diverse academic medical websites in the country. Since the launch of the Fasenmyer Educational initiative, the rheumatology site is now the largest single source of online programming.

The Center’s philosophy is based on the principle that there is no single learning style capable of meeting the needs of the rheumatology community. Furthermore, it operates based on the belief that – even for an individual learner – multiple learning styles are essential and influenced by time and cost factors, educational desires and needs (i.e. for changing practice standards, providing basic scientific data, recertification) and level of competency in the given subject area. Also critical to the success of any programming is that it be of the highest quality, well balanced and free of commercial bias.

With these goals, the cornerstone of the live programs put on by the Center is the Biologics Summit (I-IV held every other year since 2005). These programs, which are designed for advanced practitioners and researchers prescribing or investigating biologic therapies, have become a tradition with a growing number of attendees. Initially a small gathering with barely 100 attendees, the meeting must now close its registration at 365, the current venue’s maximum capacity. Fortunately, my initial philosophy of not holding any live event that will not be repurposed has allowed the Biologics Summits to broadcast globally to tens of thousands of additional participants over the past six years, all without cost to those attending online. Figure 1 shows the live and on line attendance for Biologics III (the last meeting with complete data). Figure 2 shows the overall total participation in Fasenmyer-sponsored online CME at ccfcme.org.

Dr. Calabrese heads the RJ Fasenmyer Center for Clini-cal Immunology and is the Vice Chairman of the Depart-ment of Rheumatic and Immunologic Diseases at Cleve-land Clinic. He also serves as a Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, the R.J. Fasenmyer Chair of Clinical Immunology, and the Theodore F. Classen D.O. Chair of Osteopathic Research and Education. He can be reached at [email protected] or 216.444.5258.

Meeting the Global CME Needs of the

Rheumatology Community

By Leonard H. Calabrese, DO

“ Having served in various

capacities on the CME

Committee of the American

College of Rheumatology,

including as its Chair,

I was well aware of

the challenges and

changing environment

in the CME world.

* as of 02/17/2011

Education Participants

Biologics III Live CME Event 355

Biologics III Online CME Series 23,689* Figure 1

Have Rheum in Your Schedule?

Try one of the following rheumatology educational programs:

In addition to the Biologics Summits, the Center has created Rheumatology Highlights Reports, a series of 15 different topics delivered by recognized global leaders in the field, summarizing recent data and international meetings. All presentations last 15 minutes or less; the program is now in its third year and is updated twice annually. These programs are designed for those looking for a streamlined and efficient summary of a given topic (i.e. vasculitis, advances in basic science, SLE, TNF inhibitor, crystal disease, metabolic bone disease, etc.). The RHR programs have reached an audience of nearly 23,000 and have garnered outstanding reviews with extreme-ly high levels of learner satisfaction (see Figure 3). While each activity in this series is certified for 15 minutes, the average user stays three times longer, investigating the supplemental educational material within this series. The motto of “Give us 15 minutes and we will give you the world of rheumatology” is embodied by this program.

Figure 2

Total Participants 2005 – 2010

Rheumatology Highlights Report:

This series provides 15-minute reports by clinical experts on key scientific presentations and/or abstracts at international and national rheumatology meetings. Participants can choose from multiple activities: live meetings, webcasts, podcasts, slide sets, and related abstracts. A new enhancement to this series is RheumBuzz, an online blog with our leading experts. Check it out at http://rheumbuzz.clevelandclinicmeded.com.

Rheumatology Highlights Report

Live & Advances in B Cell Biology:

This unique program was offered in both Fort Lauderdale, Fla., and Scottsdale, Ariz., this year in conjunction with the Florida Society of Rheumatology and the Phoenix Rheumatology Association. Didn’t get a chance to attend? Check out the webcast and audio files at ccfcme.org/15minutes and ccfcme.org/abcb.

Advances in B Cell Biology:

This series of live meetings and webcasts reviews and analyzes cutting-edge data regarding B cells and B cell–directed therapies. Expert faculty will bridge the gap between the current immunobio-logic data and the day-to-day workings of clinical practice.

The R.J. Fasenmyer Center for Clinical Immunology offers more than 100 free online CME activities. For more, visit us online at

www.ccfcme.org/RheumCME. 200,000 180,000 160,000 140,000 120,000 100,000 80,000 60,000 40,000 20,000 0 2005 2006 2007 2008 2009 2010 170,000 97,522 47,275 16,086 13,575 875

Traditional thoughts regarding the pathogenesis of diseases, such as rheumatoid arthritis, systemic lupus erythematosus, myositis, vasculitis and similar conditions has favored a primary role for acquired abnormalities of immune function. There are reasons to question this assumption and consider that abnormalities in the affected tissue might be early factors in disease. Data from studies of single-organ autoim-mune disease, associations of infection with autoimmunity, protein modifica-tions that occur with aging, and lessons learned from embryonic development of the vascular system all support the notion that changes in the targeted tissue may be at least as important as abnormalities in the immune response in certain autoimmune diseases (Figure).

Autoimmune diseases of single organs

(e.g., thyroid, pancreas, adrenal gland, brain, skin, kidneys etc.) involve immune responses to unique organ antigens/ proteins (e.g., thyroglobulin, thyroid peroxidase, TSH cell surface receptor, pancreatic islet cell proteins, acetylcho-line receptor at neuromuscular junctions, etc). In some instances,

disease susceptibility may be enhanced by modifications of the target organ or native proteins as the result of spontaneous mutations or organ injury, such as that associated with infection or radiation.

Cancer and autoimmunity: In the seemingly unrelated area of oncol-ogy, tumor-specific neoantigens are recognized and elicit unique immune responses. In this setting, experimental strategies that enhance the immune response have led to therapeutic benefits. Tumor-associated antigens have been used to expand populations of immune reactive cells (cytotoxic T cells), which can then be deployed as therapeutic agents. While enhancement of autoimmune responses may not be a sound strategy, this example illustrates how aberration in cell development may produce neoantigens that lead to unique immune responses. It would not appear far fetched to consider whether mutations, other than associated with malignancies, also can produce changes in cellular antigens that may be the first step in generating certain autoimmune diseases.

Relevance to vasculitis: These compari-sons of single organ autoimmunity and cancer are most compelling in regard to single-organ vasculitides (SOV), a group of diseases that may affect many

differ-ent unique organs and for which surgi-cal resection is often curative. We have questioned whether these most simple forms of vasculitis might provide a key to better understanding of the pathogenesis of systemic vasculitides.

The notion of a primary modification(s) in the target tissue initiating autoim-munity would not detract from the well-known effects of genetic susceptibil-ity or gender on the expression of some autoimmune diseases.

The concepts presented here merely emphasize how endogenous and environmental factors may generate stimuli that may produce disease in a single organ. For this model to be relevant to multisystem autoimmune diseases would require expansion of the immune response to other organs, though mechanisms, such as molecular mimicry or, in the case of an infectious trigger, selective binding to common or similar ligands in multiple organs in which neoantigens or modified antigens are generated.

What would be the utility of discover-ing an incitdiscover-ing Ag(s) in autoimmune disease?

1. It could provide an approach to more effective therapeutic interventions through peptide tolerance-induc-tion or specific immunological or biochemical blockade of target. 2. Recognition of one target in a focal

form of vasculitis may shed light on the origin of multisystem autoim-mune vascular disease. Binding of reactive species to highly homologous Ag in other organs may provide

Autoimmunity: A Lesion of Immune

Regulation, the Affected Organ or Both?

*tools to study hypotheses

Conceptual mosaic for organ targeting

Pathogenic factors in immune-mediated diseases may be endog-enous and/or exogendog-enous. Whether disease results may be related, in part, to general or tissue-specific host susceptibility factors. Deter-minants of organ targeting may reside within the target itself and include unique native or acquired characteristics (e.g., ligands for pathogens, age-related changes, post-infectious changes) that influ-ence the adhesion, retention, and penetration of a pathogen (organ-ism or molecule). In the healthy host, pathogenic factors would be cleared, the immune response would be appropriately down-regulated, and normal structure and function would be restored. Genetic Factors

Mosaic of

Illness

Genomics and proteomics*

Pathogen/products

• Cleared • Retained • Cleared but

tissue altered Genomic and Proteomics*

Variation in immune response

From Hoffman GS. Arthritis Rheum. 2003. 48: 2406-14.

insights into disease patterns. 3. In regards to autoimmune aortitis,

demonstration of similarities and differences among three forms of aortitis (e.g. focal and multifocal in youth vs. the elderly) may provide insight into whether these disease phenotypes differ because of the Ag targeted vs. distinctions in immune response profiles.

This approach to pathogenesis of vascu-litis is the basis for ongoing research studies at Cleveland Clinic.

References:

1. Hernandez-Rodriguez J, Molloy ES, Hoffman GS. Single organ vasculitis. Curr Opin Rheumatol. 2008; 20: 40-46

2. Hernández-Rodríguez J, Tan CD, Molloy ES, et al. Vasculitis involving the breast. A clinical and histologi-cal analysis of 34 patients. Medicine (Baltimore). 2008; 87:61-9. 3. Absi TS, Sundt TM 3rd, Tung WS,

et al. Altered patterns of gene expres-sion distinguishing ascending aortic aneurysms from abdominal aortic aneurysms: complementary DNA expression profiling in the molecular characterization of aortic disease. J Thorac Cardiovasc Surg. 2003; 126:344-57.

4. Weck K, Dal Canto AJ, Gould JD, et al. Murine gamma-herpesvirus 68 causes severe large-vessel arteritis in mice lacking interferon-gamma

responsiveness: a new model for virus-induced vascular disease. Nat Med. 1997; 3:1346-53.

5. Dal Canto AJ, Swanson PE, O’Guin AK, et al. IFN-gamma action in the media of great elastic arteries, a novel immunoprivileged site. J Clin Invest. 2001; 107 :15-22.

6. Pryshchep O, Ma-Krupa W, Younge BR, Goronzy JJ, Weyand CM Vessel-Specific Toll-Like Receptor Profiles in Human Medium and Large Arteries. Circ 2008; 118: 1276-84.

7. Hoffman GS. Disease patterns in vasculitis – still a mystery. Bull NYU Hosp Joint Dis. 2008; 66: 224-7.

Dr. Hoffman is the Harold C. Schott Professor of Medicine, Department of Rheumatic and Immunologic Diseases, Center for Vasculitis Care and Research, Cleveland Clinic Lerner College of Medicine. He can be reached at [email protected] or 216.445.6996.

How to Best Identify Patients who will Benefit

from Osteoporosis Treatment

By Chad Deal, MD

The new guidelines replace the 2003 NOF guidelines, which recommended treatment in all women with a T-score less than -2.0 and between -1.5 to -2.0 if one of four risk factors were present (low body weight, current smoking, family history of osteoporosis, and previous fracture). Note that age and important risk factor for fracture were not a part of the 2003 guidelines. As a result, many young women with T-score of -1.5 and a risk factor were recommended for treatment even though their absolute fracture risk was low. Since the major-ity of fractures in a population occur in patients with osteopenia, it is critical to identify those patients who will benefit from intervention. The new guidelines are an attempt to determine who in this category has a fracture risk high enough to warrant treatment in a cost-effective manner. The 2008 guidelines change the algorithm from treatment recom-mendation based on T-score to one based on absolute fracture risk. The guide-lines are really a hybrid of T-score and absolute risk, patients with a T-score less

than or equal to -2.5 are recommended for treatment while patients with T-score between -1.0 and -2.5 are treated based on absolute fracture risk.

A physician may rightly ask, “What about the concept of prevention, treating to prevent a patient from becoming high risk?” There are no trial data that show treating patients at low risk of fracture with antiresorptive therapy is beneficial. Furthermore, treatment at this stage would expose these patients to drug side effects without benefit. However, there will be patients in whom prevention is reasonable even though their absolute fracture risk is not at recommended treatment thresholds: examples might be the newly post-menopausal woman who has had a repeat bone density test demonstrating a high rate of bone loss, a women on an aromatase inhibitor for breast cancer who has a high rate of bone loss on serial bone density testing or the

male undergoing androgen deprivation therapy with a high rate of bone loss. The FRAX® uses femoral neck bone mineral density (BMD), and clinical risk factors (CRFs) that have been shown to contribute to fracture risk independent of bone density. CRFs include a previ-ous fragility fracture, parental history of hip fracture, glucocorticoid use, current smoking, alcohol intake greater than three units/day, and rheumatoid arthritis. Two other CRFs are impor-tant when BMD is not measured: BMI and secondary causes for osteoporosis (insulin-dependent diabetes mellitus (IDDM), malabsorption, malnutrition, chronic liver disease, menopause before age 45, untreated hyperthyroidism, and osteogenesis imperfecta). BMD, country of origin, race (for U.S. patients) height, weight and CRFs are entered (using the WHO website shef.ac.uk/FRAX/ or an application on a hand-held device) and a 10-year absolute fracture risk for the hip and for major osteoporotic fracture is calculated. Treatment recommendations, hip fracture risk of more than 3 percent and/or major osteoporotic fracture risk of more than 20 percent, are based on a health economic analysis and take into account what the particular healthcare system is willing to pay to prevent a fracture. Cost-effective treatment in the U.S. is based on an expenditure of $60,000 per quality-adjusted life year (similar to what we spend on blood pressure medication to prevent stroke and statins to prevent a coronary event). The model assumption are based on a treatment period of five years, an off time for treatment effect of five years, fracture reduction of 35 percent, adherence of 100 percent, and a yearly medication cost of $600. A change in

Who should be treated for low bone mass? In the United

States, the simple answer is to apply the 2008 National

Osteoporosis Foundation guidelines. They recommend

treatment in patients with a hip or spine T-score less than or

equal to -2.5, a hip or spine fracture, and applying the World

Health Organization’s fracture risk assessment, or FRAX®

tool for patients with low bone mass (osteopenia, T-score

-1.0 to -2.5). In the U.S., treatment is recommended if the

10-year risk for hip fracture is greater than 3 percent, and/

or major osteoporotic fracture (hip, clinical spine, humerus,

wrist) is greater than 20 percent.

any of these assumptions would result in a change in the treatment threshold. It is obvious that some of these assumptions may vary in your patient. Medication costs in the U.S. may be lower or higher; adherence is unlikely to be 100 percent; off time for medications other than bisphosphonates are shorter; fracture reduction in the spine is greater than 35 percent but may be less than 35 percent for non-vertebral fractures.

Like all tools, FRAX has to be wielded with skill to achieve the best results. FRAX is a platform to help clinical decision making and is not an all-in-one tool to enable appropriate treatment decisions in all cases. FRAX should not be used in the clinic without an appre-ciation of its limitations as well as its strengths. FRAX omits CRFs that may be important, such as falls, because they are not felt to be altered by medication. Medications such as aromatase

inhibi-tors that may accelerate bone loss are not part of the model. In some cases, CRFs that might help clinical decision making (such as bone turnover markers) were not collected in the FRAX cohorts. FRAX assumes CRF are dichotomous (yes/no) when in the real world there is likely to be a “dose” effect for many of the CRFs, such as glucocorticoid dose, alcohol intake and smoking. The gradient of risk for a CRF is derived from the FRAX cohort and represents an average across a large population, but may not accurately represent your patient’s risk.

FRAX uses femoral neck bone density and is thus “hip-centric,” with lumbar spine not being part of the model. Many of the FRAX cohorts did not measure spine density and many spine densities have artifacts from degenerative changes that make interpretation impossible. Thus, FRAX will underestimate patients with lower spine than hip bone mass.

Family history of osteoporosis is defined only as parental history of hip fracture. This may under-estimate the importance of family history when a patient is sure that a relative had a history of verte-bral fractures. FRAX also will underestimate fracture risk in patients with rapid bone loss, a significant

independent risk factor for fracture, and a situation in which the physician may want to treat regardless of the absolute fracture risk. Lastly, absolute fracture risk is presented as a 10-year fracture risk in percentage with no confidence intervals. For instance, a patient with a 10-year risk of major osteoporotic fracture of 19 percent may have a risk of 17 percent or 21 percent, a fact that is not presented as part of the model. Even with all these FRAX “caveats,” the new tool represents a significant advance in our effort to evaluate and treat patients with low bone mass. In several cohorts that have been studied, fewer women in their 50s and 60s are treated using the new guideline while more women in their 70s and 80s are treated. This is a reasonable result based on absolute fracture risk and should result in more cost-effective treatment. 1. Dawson-Hughes B, Looker AC,

Toste-son NA, et al. The potential impact of the new National Osteoporosis Fouindation guidance on treatment patterns. Osteoporos Int 2010;21:41-52

2. Silverman S. Selecting patients for osteoporosis therapy. J Bone Miner Res 2009; 24:765-767

3. Andrews NA. When to treat bone fragility, 2010: FRAX and beyond. IBMS Bone Key 2010; 7: 141-146 4. Watts, NB, Ettinger B, LeBoff M.

FRAX Facts. J Bone Miner Res 2009;24:975-979.

Dr. Deal is Head of the Center for Osteoporosis and Metabolic Bone Diseases. Physicians may contact him at 216.444.6575 or at [email protected]. Capture in Powerpoint file

Predicting cardiovascular disease in patients

with psoriasis and psoriatic arthritis

By M. Elaine Husni, MD, MPH

People with psoriatic diseases such as psoriasis and psoriatic arthritis have a higher risk for developing heart disease compared to the general population. It is difficult to identify which of these patients are at the greatest cardiovascular risk and warrant the most aggressive therapeutic strategies. The goal of this latest research at Cleveland Clinic is to explore methods to detect the risk of heart disease earlier in patients with psoriatic diseases. Initially, these patients were thought to be at an increased cardiovascular (CV) risk due to more traditional lifestyle risk factors, such as physical inactivity, smoking, and obesity, but this is not the case. Further study looked at modifiable risk factors, such as dyslipidemia, hypertension, insulin resistance and inflammatory disease-related treatment (such as NSAIDs and steroids). However, studies have been variable in our population. Newer risk factors are emerging, including chronic inflammatory burden, metabolic syndrome, and novel cardiac biomarkers such as dysfunctional HDL, myeloperoxidase and paroxanase. Cardiac biomarkers have emerged as a cornerstone of modern cardiovas-cular medicine in the general population to help predict worse CV outcomes. The implementation of such CV biomarkers in patients with psoriatic diseases have been limited. Since the elevation in inflammatory markers are very high in these inflammatory diseases, reflecting skin and joint inflammatory burden, the more specific CV biomarkers may potentially provide a better indication of CV risk in these patients.

The National Psoriasis Foundation has funded Dr. Husni to explore how CV biomarkers can help determine the prognosis, risk assessment and management of patients with psoriasis and psoriatic arthritis who may be at greatest risk for adverse cardiovascular outcomes. The grant is co-funded by the Arthritis National Research Foundation. Dr. Husni is currently collecting a biorepository of clinical assessments, self-report patient question-naires, and blood and urine samples from patients with psoriatic diseases. A subset of these patients also will undergo cardio-vascular outcome studies. These findings will help determine the best methods to evaluate cardiovascular risk based on risk factor profiles of individual patients and assist physicians to make decisions concerning cardiovascular disease prevention. Dr. Husni hopes to identify key CV biomarkers that may allow for early detection of these risks in patients with psoriasis and psoriatic arthritis.

What is the connection between skin/joint

inflammation and atherosclerosis?

The paradigm of atherosclerosis has shifted from a lipid storage disease to a vascular disease resulting from inflammation. It is now postulated that inflammation may play a role in every step

of atherosclerosis progression from a) the early initiation phase known as intimal endothelial dysfunc-tion, to b) progression via smooth muscle cell proliferation and finally the c) fibrous plaque and plaque rupture leading to myocardial infarction. In fact, up to 80 to 85 percent of myocardial infarction can occur in vessels of less than 30 percent stenosis. Thus, the potential hypotheses for this are complex and numer-ous. Leading theories include atherogenic lipid profile, oxidative stress, endothelial dysfunction, infection and inflammatory burden. The aware-ness of the role that inflammation plays in atherosclerosis has provided a mechanistic framework whereby therapeutic strategies to halt or decrease the inflammatory burden may be helpful to those patients at high risk for coronary artery disease.

Dr. Husni is the Vice Chair of the Arthritis and Musculoskeletal Center. She is the recipient of the National Psoriasis Founda-tion and Arthritis NaFounda-tional Research FoundaFounda-tion award for her work on novel cardiovascular biomarkers in patients with psoriatic diseases. She can be reached at [email protected] or 216.445.1853.

Physician education is an essential part of the mission of the Center for Vasculitis Care and Research. One facet of this education has been a one- to two-year vasculitis fellowship. One-year fellowships are directed towards those who want an in-depth clinical experience that will allow them to bring vasculitis expertise to their institution. The two-year vasculitis fellowship is for physicians seeking an investigational career and includes the expectation of a Masters degree or compa-rable post-graduate training. During the fellowship, physicians receive intensive exposure to the care of patients with vasculitis from the nine faculty members of the Vasculitis Center and multispecialty colleagues within Cleveland Clinic. Support for vasculitis fellowships has come from the National Institutes of Health through the Vasculitis Clinical Research Consortium (VCRC), the RJ Fasenmyer Foundation, the Vasculitis Founda-tion, the fellows’ sponsoring institutions, and philanthropic support to the Center for Vasculitis Care and Research. The best evidence of the success of this program has been the accomplishments of its recent graduates who have all gone on to make meaningful contributions to the field of vasculitis:

Alexandra Villa-Forte, MD, MPH received her vasculitis training from 2003 to 2004, during which time she completed a Masters of Public Health degree from Northeastern Ohio University. During her fellowship, she was the recipient of the first research grant given by the Vasculitis Foundation. In 2004, she returned to Brazil where she founded a vasculitis center at Universidade do Estado do Rio de Janeiro. In 2007, she returned to Cleveland Clinic to become a faculty member at the Center for Vasculitis Care and Research.

Curry Koening, MD, MS received his vasculitis training from 2005 to 2007, during which time he completed a Masters of Science from Case Western Reserve University. Dr. Koening received a grant from the VCRC to support his fellowship. In 2007, he joined the University of Utah where he is an

Assis-tant Professor of Medicine and he began a vasculitis center. Dr. Koening has been the recipient of a Veterans Administration career development award and a K12 grant from the National Center for Research Resources.

Eamonn Molloy, MD, MS received his vasculitis training from 2006 to 2008, during which time he received a Masters of Science from Case Western Reserve University. Dr. Molloy was the recipient of educational grants from the Vasculitis Foundation and RJ Fasenmyer Founda-tion. From 2008 to 2010, he was a member of the faculty at Cleveland Clinic. In 2010, Dr. Molloy joined the faculty of St Vincent’s University Hospital in Dublin, Ireland, where he is beginning a vasculitis center.

José Hernández-Rodriguez, MD, received his vasculitis training from 2006 to 2008, during which time his research focused on the investigation of single organ vasculitis. In 2008, he returned to Barcelona, Spain, where he is a member of the Vascular Inflammation Research Group and an investigator within the Vasculitis Research Unit at the August Pi i Sunyer Biomedical Research Institute at the University of Barcelona. Since his departure, he has continued his work in single organ vasculitis and giant cell arteritis.

Atul Khasnis, MD, is our current vasculitis fellow who will be complet-ing his traincomplet-ing in July 2011. He is in the process of completing a Masters of Science through Case Western Reserve University. Dr. Khasnis was awarded grants from the VCRC and RJ Fasenmy-er Foundation to support his fellowship.

Dr. Langford is the Director of the Center for Vasculitis Care and Research. She can be contact-ed at 216.445.6056 or [email protected].

Training the Next Generation:

Vasculitis Fellowships through the Center

for Vasculitis Care and Research

Services for Physicians

Physician Directory

View all Cleveland Clinic staff online at clevelandclinic.org/staff.

Referring Physician Center

For help with service-related issues, information about our clinical specialists and more, contact us at [email protected], 216.448.0900 or 888.637.0568.

Critical Care Transport Worldwide

Cleveland Clinic’s critical care transport team serves critically ill and highly complex patients across the globe. The transport fleet comprises mobile ICU vehicles, helicopters and fixed-wing aircraft. The transport teams are staffed by physicians, critical care nurse practitioners, critical care nurses, paramedics and ancillary staff, and are customized to meet the needs of the patient. Critical care transport is available for children and adults.

To arrange a transfer for STEMI (ST elevated myocardial infarction), acute stroke, ICH (intracerebral hemorrhage), SAH (subarachnoid hemorrhage) or aortic syndromes, call 877.279. CODE (2633).

For all other critical care transfers, call 216.444.8302 or 800.553.5056.

Track Your Patient’s Care Online

Whether you are referring from near or far, DrConnect offers secure access to your patient’s treatment progress at Cleveland Clinic. To establish a DrConnect account, visit clevelandclinic.org/ drconnect or email [email protected].

Online Medical Second Opinions

Request a secure online medical second opinion from Cleveland Clinic specialists. Visit clevelandclinic.org/myconsult for more information.

Outcomes Data Available

The latest Outcomes book from the Cleveland Clinic Orthopaedic & Rheumatologic Institute is available. Our Outcomes books contain clinical outcomes data and information on volumes, innovations, research and publications. To view Outcomes books for many Cleveland Clinic institutes, visit clevelandclinic.org/ quality.

Stay connected to Cleveland Clinic

Rheumatology Connections, published by Cleveland Clinic’s Department of Rheumatic and Immunologic Diseases, provides information about state-of-the-art diagnostic and management techniques as well as current research for physicians. Please direct any correspondence to: Abby Abelson, MD

Chair, Rheumatic and Immunologic Diseases Cleveland Clinic/A50

9500 Euclid Avenue Cleveland, Ohio 44195 Phone: 216.444.3876 Email: [email protected]

Managing Editor: Ann Milanowski Art Director: Irwin Krieger

Photography: Willie McAllister, Ken Baher

To view our online staff directory for the Department of Rheumatic and Immunologic Diseases, please visit clevelandclinic.org/rheum. For a hard copy of the Staff Directory, please contact Marketing Manager Beth Lukco at 216.448.1036 or [email protected]. Rheumatology Connections is written for physicians and should be relied upon for medical education purposes only. It does not provide a complete overview of the topics covered, and should not replace the independent judgment of a physician about the appropriateness or risks of a procedure for a given patient.

© The Cleveland Clinic Foundation 2011 11-RHE-005 General Referrals to Cleveland Clinic

24/7 hospital transfers or physician consults 800.553.5056 Referrals to Department of Rheumatic and Immunologic Diseases

216.445.0096 or 800.223.2273, ext. 50096 Arthritis and Musculoskeletal Center Referrals/ Appointments

216.445.0096 or 800.223.2273, ext. 50096

On the Web at clevelandclinic.org/rheum and clevelandclinic. org/ortho

The Cleveland Clinic Foundation 9500 Euclid Avenue / AC311 Cleveland, Ohio 44195