Outcomes

Rheumatic and Immunologic Diseases

2006

Outcomes | 2006

Quality counts when referring patients to hospitals and physicians, so Cleveland Clinic has created a series of outcomes books similar to this one for its institutes and departments. Designed for a health care provider audience, the outcomes books contain a summary of our surgical and medical trends and approaches; data on patient volume and outcomes; and a review of new technologies and innovations. We hope you find these data valuable. To view all our outcomes books, visit Cleveland Clinic’s Quality Web site at clevelandclinic.org/quality/outcomes.

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Rheumatic and Immunologic Diseases | 

Table of Contents |
Chairman’s Letter Department Overview Center for Osteoporosis & Metabolic Bone Diseases Center for Vasculitis Care and Research Recent Awards and Appointments Selected Studies Quality & Outcome Measures Patient Experience Innovations New Knowledge Staff Listing Department Contacts | How to Refer Patients Locations Cleveland Clinic Overview Online Services Cleveland Clinic Contact Numbers 5 6 10 12 14 15 20 45 46 50 56 60 61 62 6 64

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Rheumatic and Immunologic Diseases | 5

Chairman’s Letter |

Cleveland Clinic’s Department of Rheumatic and Immunologic Diseases has a long-standing commitment to excellence in patient care and training physicians for future generations. The highest quality care depends on progress in clinical trials, outcomes research and understanding illness at genetic, molecular and cellular levels. Both clinical and basic research hold promises of discovering new treatment strategies and cures for our patients. The department has grown to include individuals with expertise in all areas of clinical rheumatology. Recruitment has emphasized selection of faculty with complementary skills in clinical, educational and research arenas. We have had the good fortune of growing in an environment that is rich in opportunities for collaboration in areas related to our own work in immunology, metabolic bone disease, orthopaedics, cardiovascular medicine and surgery, pathology and imaging. We have benefited from research partnerships with valued colleagues around the world. Opportunities for discovery are unprecedented and are likely to bear fruit, in large part because of team efforts that ignore intellectual and geographic boundaries. In the following pages, you will meet with members of our department and specialty teams, and consider how we at the Clinic can best serve you and your patients. Gary S. Hoffman, M.D., M.S. Chairman, Department of Rheumatic and Immunologic Diseases

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Department Overview |
A high volume of patients allowed the department to accomplish its primary goal to provide care for the sick. It also allowed us to meet our complementary goals in research and education.

Main Campus New Patient Visits
1,500

1,000

#
500

0

2002

2003

2004

2005

2006

Total new patient visits for Main Campus and Family Health Centers for 2006 was 1,797.

Main Campus Total Vists
25,000 20,000 15,000

#

10,000 5,000 0 2002 2003 2004 2005 2006

Total visits for Main Campus and Family Health Centers for 2006 was 41,94.

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Top Primary Diagnoses The breadth of skills within the Department of Rheumatic and Immunologic Diseases attracts patients who have a wide range of illnesses, both common and rare.
2002 Osteoporosis Rheumatoid Arthritis Fibromyalgia Systemic Lupus Erythematosus Bursitis Wegener’s Osteoarthritis Gout Psoriatic Arthritis Arteritis NOS / Vasculitis Scleroderma Juvenile Rheumatoid Arthritis Giant Cell Arteritis Ankylosing Spondylitis Polymyositis Dermatomyositis Takayasu’s Disease Hypersensitivity Angiitis Cerebral Arteritis Bechet’s Disease Polyarteritis Nodosa Reiter’s Syndrome Pseudogout Henoch Schoenlein Purpura 504 1,06 1,402 446 256 242 247 155 212 145 14 242 81 60 80 90 5 4 48 24 48 19 6 11 2003 566 1,215 1,19 402 265 25 188 17 161 185 117 195 8 49 78 81 58  49 25 0 11 19 11 2004 709 1,280 1,229 472 288 264 216 185 178 179 168 216 128 58 77 88 81  8 5 22 26 11 7 2005 1,077 1,251 1,241 48 204 29 7 22 175 179 21 214 108 64 85 92 81 42 7 9 6 22 24 10 2006 1,569 1,565 1,54 562 518 65 45  25 250 241 218 110 10 101 96 78 4 9  27 26 16 12

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Grant support from non-commercial sponsors continues to grow. This has been most successful in the areas of vasculitis, metabolic bone disease and outcomes research.

Active Research Grants
14
Federal and Foundation Grants Commercial

#

7

0

2002

2003

2004

2005

2006

Rheumatic and Immunologic Diseases | 9

Total Publications
100

#

50

0

2002

2003

2004

2005

2006

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Center for Osteoporosis and Metabolic Bone Diseases
Chad Deal, M.D.

The Center for Osteoporosis and Metabolic Bone Diseases is a multidisciplinary clinic staffed by rheumatologists, endocrinologists and radiologists. In addition, the Center has strong ties with the Departments of Biomedical Engineering, Orthopaedic Surgery and the Orthopaedic Research Center where molecular mechanisms of bone formation, skeletal repair and bone growth are active areas of basic and clinical research using cell-based therapies. Steady growth in faculty and patient numbers occurred in the Center for Osteoporosis and Metabolic Bone Disease.

Main Campus Osteoporosis
3,000
Unique Patient Total Patient Visits

2,000

#
1,000

0

2002

2003

2004

2005

2006

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Main Campus and Regional Medical Practice Osteoporosis
12,000
Unique Patient Total Patient Visits

8,000

#
4,000

0

2006

Below is a graph demonstrating growth in Bone Densitometry since the opening of the Center for Osteoporosis and Metabolic Bone Diseases.
Bone Densitometry
20,000

#

10,000

0

2002

2003

2004

2005

2006

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Center for Vasculitis Care and Research
Carol Langford, M.D.

Unique Vasculitis Patients The Center for Vasculitis Care and Research is a major area of service, research and educational commitment.
New Patient Vasculitis Volume*
1,000 750

#

500 250 0

2002

2003

2004

2005

2006

Outpatient Vasculitis Cases*
4,000 3,000

# 2,000
1,000 0

2002

2003

2004

2005

2006

* Main campus only. Data does not include Family Health Centers.

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Some of the most commonly encountered vasculitis diagnoses are presented in the table:

Unique Forms of Vasculitis Wegener’s Arteritis NOS / Vasculitis Giant Cell Arteritis Takayasu’s Disease Hypersensitivity Angiitis Cerebral Arteritis Bechet’s Disease Polyarteritis Nodosa Henoch Schonlein Purpura Total Vasculitis Cases 2002 242 145 81 5 4 48 24 48 11 686 2003 25 185 8 58  49 25 0 11 727 2004 264 179 128 81  8 5 22 7 787 2005 29 179 108 81 42 7 9 22 10 847 2006 65 250 110 78 4 9  27 12 957

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Recent awards and appointments: Highlights of 2006
Dr. Abby Abelson Three-year Clinical Scholar Educator Award from the American College of Rheumatology Dr. Leonard Calabrese Board of Directors of the Research and Education Foundation for the American College of Rheumatology | Deputy Editor Arthritis Care and Research | American College of Rheumatology Delegate to the Decade of the Bone and Joint World Health Organization. Dr. Chad Deal, Chair, Advisory Group on US Rheumatology Workforce | Investigator-initiated trial of zolendronic acid therapy following Forteo for osteoporosis (Novartis). The trial is designed to evaluate the effectiveness of an intravenous bisphosphonate, zolendronic acid, after patients finish a course of the anabolic agent for osteoporosis, Forteo. Dr. Gary Hoffman Reappointment to the FDA Advisory Panel for arthritis drugs Appointment as Editor of Current Opinion in Rheumatology Sam and Maria Miller Award for Excellence in Clinical Research Dr. Elaine Husni Two-year Clinical Investigator Award from the American College of Rheumatology Research and Education fund. This award supports investigation of atherosclerosis in rheumatoid arthritis. Executive committee member of the PRECISION trial, worldwide multicenter trial of over 20,000 patients to assess the cardiovascular risk profile of three commonly used nonsteroidal anti-inflammatory medications (celecoxib, ibuprofen and naproxen) in patients with osteoarthritis and rheumatoid arthritis. Dr. Carol Langford Pilot project grant, Rare Diseases Clinical Research Network (RDCRN), National Institutes of Health | Mechanistic studies of T cell regulation in Wegener’s granulomatosis | Coeditors: Fauci AS and Langford CA. Harrison’s Rheumatology. New York: McGraw Hill; 2006. Dr. Brian Mandell Editor ACP Medical Knowledge Self Assessment Program 14. Rheumatology book. 2006. Chairman of the American College of Rheumatology National Meeting Planning Committee | American College of Physicians annual meeting planning committee (member) | Editor of the Merck Manual (Rheumatology and Immunology sections)

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Selected Studies and Why They Are Important
Stone JH, Holbrook JT, Marriott MA, Tibbs AK, Sejismundo LP, Min Y-I, Specks U, Merkel PA, Spiera R, Davis JC, St. Clair EW, McCune WJ, Ytterberg SR, Allen NB, Hoffman GS. Solid malignancies among patients in the Wegener’s granulomatosis etanercept trial. Arthritis Rheum 2006; 54:1608-1618. This study demonstrated the concurrent use of etanercept and cyclophosphamide is associated with an increased risk of solid tumors in patients with Wegener’s granulomatosis. The combined use of these agents should be avoided. Villa-Forte A, Clark TM, Mascha E, Karafa MT, Gomes M, Carey JJ, Arrigain S, Roberson G, Hoffman GS. Wegener granulomatosis: Customized treatment using cyclophosphamide and methotrexate. A 12-year single-practice experience. Arthritis Rheum 54 (S): 1178. 2006. This study demonstrated minimizing cyclophosphamide use or, when possible, avoiding it in patients with mild disease is associated with excellent outcomes and survivals in patients with Wegener’s granulomatosis. Finkielman JD, Merkel PA, Schroeder D, Hoffman GS, Spiera R, St. Clair EW, Specks U for the WGET Research Group. Antineutrophil cytoplasmic antibodies against proteinase  do not predict disease relapses in Wegener’s granulomatosis. Arthritis Rheum 2006; 54: s85-86. This study demonstrated that changes in ANCA titers correlate poorly with disease activity and risk of relapse in Wegener’s granulomatosis and should not be used as a guide to therapy. Koening CL, Langford CA, Kirchner HL, Hoffman GS. Renal graft survival in Wegener’s granulomatosis (WG): Comparison to systemic lupus erythematosus (SLE) from a national database. Arthritis Rheum 2006; 54:s486. This study demonstrated that patients with Wegener’s granulomatosis who require renal transplantation have excellent outcomes and only rarely have recurrent disease within the graft. Molloy ES, Langford CA, Clark TM, Gota CE, Calabrese LH, Hoffman GS. Durable remission in patients with refractory Takayasu’s arteritis treated with infliximab and etanercept. Arthritis Rheum 2006; 54:s487. This study addressed the difficulty in achieving lasting remissions for patients with Takayasu’s arteritis. The experimental use of infliximab led to unprecedented improvement in most patients who had previously been treatment-resistant.

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Lee MS, Smith SD, Galor A, Hoffman GS. Antiplatelet and anticoagulant therapy in patients with giant cell arteritis. Arthritis Rheum 2006;54:06-09. This study demonstrated the use of low-dose aspirin could reduce cerebral ischemic events in giant cell arteritis by a factor of , without producing serious side effects. Hoffman GS, Cid MC, Rendt KE, Merkel PA, Weyand CM, Stone JH, Salvarani C, Xu W, Visvanathan S, Rahman MU for the Infliximab-GCA study group. Prednisone and infliximab for giant cell arteritis: a randomized, double-blind, placebo-controlled, multicenter study of efficacy and safety. Ann Intern Med May 2007; 146(a):621-0. This study was the first-ever randomized double-blind trial of a biologic agent in GCA. It demonstrated the use of infliximab in GCA did not add value to usual therapy with corticosteroids. Molloy E, Calabrese LH. Tumor-like mass lesions: an under-recognized presentation of primary angiitis of the central nervous system. Arthritis & Rheum 2006; 54(9):S486. This series highlights the potential for CNS vasculitis to present as mass lesions and indicates when this presentation should be considered. Bharadwaj SS, Hajj-Ali RA, Hammel JP, Calabrese LH. Evolution of the syndrome of benign angiopathy of the central nervous system (BACNS): retrospective review of 48 patients. Arthritis & Rheum 2006; 54(9):S485. This study represents an important review of the clinical features, diagnoses and treatments of BACNS. Hajj-Ali RA, Yee A, Calabrese LH. Central nervous system vasculitis secondary to sarcoidosis. Arthritis & Rheum 2006; 54(9):S492. This report describes the clinical features seen when sarcoidosis manifests as a CNS vasculitis. Deal C, Barr W, Harrington T, Hooker R, Hogan P, Bouchery E, Birnbaum N for the ACR Workforce Subcommittee COTW. US Rheumatologist Supply and Demand: 2005-2006 Workforce Study. Arthritis Rheum 2007; 56():722-729. This study developed a model to predict rheumatology supply and demand through 2025. Solomon DH, Chibnik LB, Losina E, Huang J, Fossel AH, Husni ME, Katz JN. Development of a preliminary index that predicts adverse events after total knee replacement. Arthritis Rheum 2006;54:156-42. This paper examined patient and hospital level factors that may be important to predict poor outcomes following total knee replacement surgery.

Rheumatic and Immunologic Diseases | 17

Harrington T, Deal C. Successes and failures in improving osteoporosis care after fragility fracture: results of a multi-site clinical improvement project. Arthritis Rheum (Arthritis Care & Research). 2006;55:724-728. Demonstration of a practice improvement project to address the critical issue of evaluation and treatment after hip fracture. Calabrese LH, Zein N, Vassilopoulos D. Hepatitis B (HBV) reactivation with immunosuppressive therapy in rheumatic diseases. Ann Rheum Dis 2006; 65:98989. This review represents an important dialogue in the rheumatology profession for examining and exploring the problem and proposing guidelines for avoiding serious and/or fatal cases of HBV reactivation. Oliveira S, Ravelli A, Pistorio A, Castell E, Malattia C, Prieur AM, Saad-Magalhaes C, Murray KJ, Sang-Cheol B, Joos R, Foeldvari I, Duarte C, Wulffraat N, Lahdenne P, Dolezalova P, de Inocencio J, Pratsidou-Gertsi P, Hofer M, Nikishina I, Ozgogan H, Hashkes P, Martini A, Ruperto N for the Pediatric Rheumatology International Trials Organization (PRINTO). Health related quality of life of patients with juvenile idiopathic arthritis: The PRINTO multinational quality of life cohort study. Arthritis Rheum. In press. This very large international study included 6,667 subjects (,52 with juvenile idiopathic arthritis (JIA) and ,15 controls) showed a significant impairment of healthrelated quality of life among JIA patients, especially in the physical domains in all types of JIA except persistent oligoarthritis. Uziel Y, Butbul-Aviel Y, Barash J, Padeh S, Mukamel M, Gorodnitski N, Brik R, Hashkes PJ. Recurrent transient synovitis of the hip in childhood: the long-term outcome among 9 patients. J Rheumatol 2006;:810-811. This is the first paper to study the long-term outcome of this very common form of episodic arthritis in children. Husni, ME, Bershadsky B, Worley S, Barsoum W, Muschler G. Clinical variation in health status and outcome following primary hip and knee arthroplasty. American Academy of Orthopedic Surgeons. 7rd Annual Meeting Proceedings Chicago, IL. 2006; 7:128. This study examines preoperative clinical factors that may be important to predict outcomes following total knee and hip arthroplasty.

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Muschler GF, Husni ME, Lograsso M, Barsoum W, Thornton J, Worley S, Bershadsky B. Early outcome assessment comparison of unilateral and bilateral primary total knee arthroplasty. American Association of Orthopedic Society. 2006. American Academy of Orthopedic Surgeons. 7rd Annual Meeting Proceedings. Chicago, IL. 2006; 7:12. This study examines early outcomes of unilateral versus bilateral total knee arthroplasty in a large academic setting. Muschler GF, Rossi S, Lograsso M, Husni E, Gerz D, Emmerich C, Thornton J, Worley S. A practical quality reporting system for hip and knee arthroplasty procedures. American Association of Orthopedic Society. 2006. American Academy of Orthopedic Surgeons. 7rd Annual Meeting Proceedings. Chicago, IL. 2006; 7:287. This study assesses the use of an innovative patient self report system following total knee and hip arthroplasty. Qureshi AA, Cohen D, Mody E, Husni ME. Development and evaluation of PASE: A self-administered psoriatic arthritis screening and evaluation tool. J Am Acad Dermatol. 2007. In press. Given emerging therapies for psoriatic arthritis, this abstract demonstrates an innovative, patient self-report tool to help screen and evaluate for psoriatic arthritis. Mody, E Qureshi AA, Husni, ME. Diagnosis of arthritis in psoriasis patients presenting with joint pain to a dermatology-rheumatology clinic. Br J of Dermatol. 2007. In press This study highlights the importance of proper diagnosis of musculoskeletal complaints in patients with psoriasis and psoriatic arthritis. In patients with psoriasis, not all joint pain is consistent with psoriatic arthritis. Whyte M, Mumm S, Deal C. Adult Hypophosphatasia Treated with Teriparatide. J Clini Endocrinol Metab 2007; 92:120-1208. This is the first study to document effective treatment for hypophosphatasia.

Rheumatic and Immunologic Diseases | 19

Carey JJ, Delaney MF, Richmond B, Cromer BA, Love TE, Lewis S, Thomas CA, Miller PD, Licata AA. Equivalence of technology generated T-scores and Z-scores in young adult bone densitometry. J Bone Miner Res 2006; 21: S51. This study showed that DXA-generated T-scores and Z-scores in young adults may differ significantly and substantially. Schulte ME, Licata AA, Carey JJ, Delaney MF. Inappropriate PTH response to severe vitamin D deficiency in patients with chronic liver disease. J Bone Miner Res 2006; 21: S45. This study showed people with liver disease and vitamin D deficiency have lower than expected corresponding PTH levels. Carey JJ, Delaney MF, Cromer BA, Love TE, Lewis S, Thomas CA, Miller PD, Licata AA, Richmond B. Diagnostic agreement between DXA generated T-scores and Zscores in young adults. International Bone Densitometry Workshop, Kyoto, Japan. November 2006. Oral presentation. This study shows use of DXA-generated Z-scores instead of T-scores in young adults results in significant diagnostic discordance using either 1994 W.H.O. or 2005 I.S.C.D. criteria. Richmond B, Delaney MF, Cromer BA, Love TE, Lewis S, Thomas CA, Miller PD, Licata AA, Carey JJ. The impact of body weight on DXA generated Z-scores in young adults. International Bone Densitometry Workshop, Kyoto, Japan. November 2005. Oral presentation. This study shows adjustment for body weight accounts for a large part of the differences seen between DXA-generated Z-scores and T-scores and that this adjustment is inappropriate. Sikon AL, Thacker HL, Carey JJ, Deal C, Licata AA. Secondary Osteoporosis: Are We Recognizing It? J Women’s Health. 2006; 15:1174-8. This study demonstrates secondary causes of low bone mass should be screened as they are very common in people with low Z-scores.

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Quality & Outcomes Measures |
Arthritis Clinical Research
Elaine Husni, M.D., M.P.H.

Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen (PRECISION) Systemic rheumatic diseases affect approximately 20 million Americans, over 5% of the population. In connective tissue diseases, such as rheumatoid arthritis and systemic lupus erythematosus (SLE), there is a marked increase in cardiovascular (CV) complications compared with patients without a systemic rheumatic disease. In addition to CV risk, common treatments used for these diseases, non-steroidal antiinflammatory drugs (NSAIDs) especially cyclooxygenase (COX)-2 inhibitors, may also increase a patient’s CV risk. What is the study purpose? This clinical trial will evaluate the overall benefit and risk of celecoxib, a Cox 2 inhibitor, compared to two commonly prescribed traditional (non-selective) nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of arthritis pain. The trial definitively addresses the relative safety of celecoxib compared with ibuprofen and naproxen. While rofecoxib was found to significantly increase CV events, the evidence is less clear with celecoxib. Observational studies reported less CV risk with celecoxib compared with rofecoxib, but similar risks compared with naproxen or ibuprofen. This trial is funded by Pfizer, but will be conducted at Cleveland Clinic under the leadership of Dr. Steven E. Nissen; Dr. Elaine Husni will be the principal investigator. What is the study design? Approximately 20,000 patients with osteoarthritis (OA) or rheumatoid arthritis (RA) on a chronic analgesic regimen for >6 months, with existing CV disease or at high risk for disease, will be randomized to celecoxib, ibuprofen or naproxen in this doubleblind, triple-dummy, multicenter, multinational study utilizing a -arm parallel group design. All patients will receive esomeprazole for gastro protection. Aspirin will be administered for cardiovascular prophylaxis when clinically indicated.

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Who qualifies for this study? Adult patients with a clinical diagnosis of OA or RA for at least 6 months and who have required a chronic analgesic regimen for at least 6 months and patients with established or who are at high risk for CV disease qualify for this study.

Every 6 months

Celecoxib 100-200 mg twice daily Established or at high risk for CVD Ibuprofen 600-800 mg three times daily

Diagnosis of symptomatic osteoarthritis or rheumatoid arthritis

Screen

Naproxen 375-500 mg twice daily

-3wks Visit 1

Rand 2

M1 3

M2 4

M3 5

M4 6

M8 7

M12 8

M24 9

M30 10

M36 11

M42 12

M48 13

Minimum follow-up

What is the primary endpoint for this study? The primary composite endpoint is the first occurrence of cardiovascular death, non-fatal MI or non-fatal stroke. This is an event-driven trial. Patients will be followed a minimum of 18 months until 762 events have occurred. The PRECISION trial is the first study to enroll patients with existing CV disease (or high risk of disease) undergoing treatment with a COX-2 inhibitor compared with nonselective non-steroidal anti-inflammatory agents. This large scale study will define the CV safety profile of celecoxib versus ibuprofen and naproxen and, thereby, help determine the optimal strategy for pain control in this at-risk population.

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Development and Evaluation of PASE: A Self-administered Psoriatic Arthritis Screening and Evaluation Tool M. Elaine Husni, M.D., M.P.H. and Abrar Qureshi, M.D., M.P.H. Psoriatic arthritis may be an under-recognized disorder. Nearly one of three patients with psoriasis alone may develop psoriatic arthritis and, often, these patients are solely followed by dermatology providers. Complications associated with psoriatic arthritis can be prevented with early diagnosis and referral to a specialist. Our objective was to evaluate the reliability and validity of the PASE questionnaire to detect inflammatory arthritis in patients with psoriasis. What is being studied? We developed a self-administered instrument (the Psoriatic Arthritis Screening and Evaluation questionnaire – PASE) that allows dermatologists to screen psoriasis patients for signs and symptoms of inflammatory arthritis. A multidisciplinary team of experts was involved in the design of the questionnaire. PASE was developed using standardized methodology for the development of both functional and health-related instruments geared toward musculoskeletal diseases. This study provided the means to evaluate the reliability and validity of PASE for detecting an inflammatory arthritis. How was this studied? Patients with psoriasis-like skin complaints who presented to a combined dermatology/rheumatology clinic at an academic medical center were studied from October 2005 to September 2006 and stratified according to the clinical diagnosis made by a Board-certified dermatologist and rheumatologist. All patients completed a PASE questionnaire of 15 five-choice questions divided into two subscales: symptoms and function. Diagnosis of psoriasis or psoriatic arthritis was based on clinical evaluation, history and physical, and radiographs, if necessary, by a Board-certified rheumatologist and dermatologist. The goal of the analyses was to evaluate the ability of the PASE total, function and symptom scores, to distinguish psoriatic arthritis from non-psoriatic arthritis patients.

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What were the study results? A total of 108 psoriasis patients completed PASE questionnaires. Thirty-seven patients were excluded due to missing data or inadequate responses. Of 71 participants, 18 were diagnosed with psoriatic arthritis and 5 with psoriasis alone. The PASE questionnaire distinguished psoriatic arthritis from psoriasis with specificity of 74% and sensitivity of 8%. The Wilcoxon rank sum test was used to test for differences between these groups. Receiver Operator Curves (ROC) was used to choose the best cut-point for each score by optimizing sensitivity and specificity in predicting psoriatic arthritis. In addition, 95% exact binomial confidence intervals were calculated. Both the subscale scales scores were significantly different between the psoriatic arthritis and non-psoriatic arthritis groups. Cronbach’s alpha coefficient had good internal consistency (raw 0.97 and standardized 0.98). What does this mean in clinical practice? In patients with psoriasis, the PASE questionnaire is a reliable and valid tool to help screen patients for psoriatic arthritis. There is a need to identify patients with psoriatic arthritis so that earlier referral to a rheumatologist can be made, timely therapy can be initiated and long-term disability avoided.

Total PASE Score
8 7 6 5 # 4 3 2 1 0 Psoriasis Psoriatic Arthritis

Scatter plot of total PASE scores for participants with psoriasis and psoriatic arthritis. The horizontal line represents a score of 47 which, in this study, best differentiates the psoriatic arthritis (PsA) group from the non-PsA group.

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Self Assessed Health Status and Outcome Following Primary Hip and Knee Arthroplasty Elaine Husni, M.D. M.P.H., Wael Barsoum, M.D., George F. Muschler, M.D., and Boris Bershadsky, Ph.D. Total joint arthroplasty is generally considered an effective procedure, but the current literature does not support specific recommendations about which patients are most likely to benefit from this surgery. Previous studies focused on baseline functional status, preoperative pain levels and prosthesis survival. Less attention was been placed on patient reported outcomes which may have the potential of being modifiable prior to surgery. What is being studied? The study is to determine if patient self-assessment of health (including mental health and psychosocial variables) and presence of comorbidities are associated with outcome for patients undergoing primary total hip and knee replacement surgery. How did we study this? A prospective arthroplasty registry that provided demographics, co-morbidities and SF-6 data before and one-year after surgery was studied. Between December 2000 and March 2004, 85 patients underwent primary total knee arthroplasty (TKA) and 1,008 underwent primary total hip arthroplasty (THA). A total of 16 joint arthroplasty surgeons performed the procedures. Data were gathered on preoperative and postoperative information provided by 489 patients (22 TKA and 257 THA). The relationship between functional outcomes 1-year postoperatively with patient characteristics, including mental health, associated comorbidities and patient demographics, was assessed.

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What were the results? Preoperative SF 6 scores (physical component score (PCS), mental component score (MCS), age, and number of co-morbid conditions) were significant predictors of the magnitude of improvement in PCS one year following surgery. Greater improvement of PCS was associated with better MCS, younger age, less co-morbid conditions while higher body mass index (BMI) was associated with worse PCS. In addition, greater BMI was associated with lower preoperative PCS. Preoperative SF 6 scores (PCS and MCS) were significant predictors of the magnitude of improvement in their MCS score at one year following surgery. How does this improve patient care? Our results suggest an association between preoperative mental health and BMI with outcome measured by improvement in PCS in patients undergoing hip and knee arthroplasty. This suggests a role of preoperative intervention targeting patients with higher BMI and worse mental component scores in order to improve outcomes. Reasons that may explain the association of poor mental health preoperatively and worse functional status include reduced activity levels, lack of motivation to overcome functional impairments and inability to adopt healthier lifestyles. This supports current literature findings for the importance of targeting this patient population with increased education and emotional support prior to total knee and hip replacement surgery. Risk factors and associated interventions to improve outcomes of patients undergoing total knee and hip arthroplasty.
Potential interventions Maintain healthy pre op weight Preoperative counseling More frequent post op counseling Risk factors for poor outcome High BMI Low mental score

SF-36

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Patients Undergoing Total Hip (THA) Versus Total Knee Arthroplasty (TKA): Does One Procedure Have a Better Outcome? Elaine Husni, M.D. M.P.H., Wael Barsoum, M.D., George F. Muschler, M.D., and Boris Bershadsky, Ph.D. Orthopedic outcomes for total knee arthroplasty and total hip arthroplasty are well described in the orthopedic literature. Little published data, however, compares the health outcomes of each procedure. Conflicting reviews exist on which type of arthroplasty procedure, hip or knee, provides greater overall improvement. Current literature suggests patients who undergo total hip replacements improve more than patients who undergo total knee replacements. What is being studied? To address gaps in the literature, a large sample of patients who underwent TKA and THA was studied. One-year postoperative outcomes were analyzed using the most comprehensive model. We propose that measuring SF-6 preoperatively and one-year postoperatively may be a practical resource to identify characteristics of the cohort that may lead to better outcomes. How did we study this? The primary objective of this study was to prospectively compare THA versus total TKA with respect to improvement in general health-related quality-of-life (HRQoL) outcomes. What were the results? The improvement in postoperative PCS for hip and knee replacement is highly dependent on comprehensive review of baseline characteristics of the patient cohort. In examining THA and TKA, improvement in PCS is associated with lower age, lower BMI and lower number of comorbidities. Better MCS at baseline is significantly associated with better improvement in the physical component.

Rheumatic and Immunologic Diseases | 27

How does this improve patient care? It is critically important to include health-related quality-of-life variables (sociodemographic data, body mass index, comorbidities and social/emotional status) to help isolate characteristics associated with improved outcomes for each procedure. The comparisons between THA and TKA can better allow patients and surgeons to understand the relative risks and benefits of the procedures when similar criteria are used. Risk adjustment should be included as a mandatory component for orthopedic observational studies. The non adjusted comparison of observations studies has potential for selection bias. Future research should be aimed at developing a minimal core set of risk adjustors needed to demonstrate baseline equivalency of comparing two groups. This will help clinicians make more informed decisions regarding which types of patients will benefit most from which particular joint replacement surgery. Interpretation of DXA Generated T-scores and Z-scores
Carey JJ, Delaney MF, Love TE, Cromer BA, Richmond BJ, Miller PD, Manilla-McIntosh M, Thomas CL, Lewis SA, Licata AA. The Cleveland Clinic, Case Western Reserve University and The Colorado Center for Bone Research.

Background Bone density (DXA) measures bone density in grams per centimeter2 (g/cm2). Using this measurement, DXA software calculates a T-score and Z-score. Clinical guidelines for the management of osteoporosis incorporate T-scores rather than actual bone density in g/cm2. T-scores are not used in premenopausal women or men under age 50 where only Z-scores are reported. For these patients, low bone mass for age is diagnosed at a Z-score <-2.0 and a workup for secondary osteoporosis is usually recommended. Both T-scores and Z-scores are dependent on several factors: bone density measurement, skeletal site, subject demographics, DXA manufacturer and DXA software used. Alterations in any of these factors could lead to changes in the T-score or Z-score value.

28 | Rheumatic and Immunologic Diseases 2006

Conceptually, T-scores and Z-scores should be identical or very similar in young adults. At the Center for Osteoporosis and Metabolic Bone Disease, however, surprisingly large differences in some young individuals have been noticed. We undertook a comprehensive study of this phenomenon in order to better understand the magnitude of these differences and their implications for clinical practice and osteoporosis guidelines. Methods A retrospective cohort was used to evaluate the equivalence of DXA generated T-scores and Z-scores in young adults scanned on either Hologic or Lunar machines. Multiple analyses were performed to describe and compare differences between measures. Results Young adult Z-scores and T-scores differed substantially and significantly in men and women for both technologies. These differences resulted in significant diagnostic discordance if Z-scores were substituted for T-scores, using either 1994 World Health Organization or 2005 International Society for Clinical densitometry diagnostic criteria. The folded empirical cumulative distribution plot of the differences between the T-score and Z-score at the total hip site for one technology is shown.
50 40 30

%
20 10 0

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

1.5

hip z-score - hip t-score

Conclusions and Significance Large differences may be seen between T-scores and Z-scores in young adults. Substitution of Z-scores for T-scores may result in significant ascertainment bias. DXA-generated Z-scores should be interpreted with caution in clinical practice. Standardization of Z-score definition and method of calculation is needed to avoid mistakes in both diagnoses and evaluation recommendations.

Rheumatic and Immunologic Diseases | 29

Transplant Evaluation: Center for Osteoporosis and Metabolic Bone Disease Miriam Delaney, M.D., Chad Deal, M.D., Abby Abelson, M.D., Angelo Licata, M.D., Ph.D., John Carey, M.D. Cleveland Clinic has one of the largest organ transplant programs in the United States. In 2006, there were 594 transplants performed. These patients are at risk for osteoporosis because of underlying disease (liver disease with vitamin D deficiency or alcohol use) or lung disease (steroid treatment of chronic obstructive pulmonary disease (COPD), low body weight and malabsorption with cystic fibrosis), or bone marrow transplant (graft versus host disease and steroid use). All transplant recipients receive steroids at the time of transplant and, often, for long periods of time after surgery. Fracture rate in this population is significant. In 2004, the Center for Metabolic Bone Disease established a transplant evaluation program in coordination with the transplant center. The purpose was to evaluate clinically and obtain a bone density and treat patients at the time of transplant evaluation or soon after transplantation. The percent of liver transplant patients having a bone center evaluation increased from 22% in 2004 to 4% in 2005 to 69.2% in 2006. A similar program is ongoing for cardiac and lung transplant patients.
Liver Transplant Patients with Osteoporosis Clinic Evaluations

80 60 % 40 20 0

2004

2005

2006 

0 | Rheumatic and Immunologic Diseases 2006

R.J. Fasenmyer Center for Clinical Immunology
Leonard Calabrese, D.O.

Toward Better Diagnosis and Treatment of Vasculitis of the Central Nervous System (CNS) Central nervous system vasculitis is one of the rarest and most challenging forms of vascular inflammatory diseases. For nearly 20 years we have been interested in and working in this area, attempting to clarify subsets of patients with more benign outcomes who may be candidates for less aggressive therapies. While reversible vasoconstriction has long been appreciated in the wake of subarachnoid hemorrhage, it was only suspected as playing a role in CNS inflammatory diseases in the early 1990s. A disorder labeled Benign Angiopathy of the Central Nervous System (BACNS) was first described by our group in 199 and believed to be, but not proven, a form of reversible cerebral vasoconstriction. These patients were mostly labeled as true CNS vasculitis based upon angiographic appearance, but they appeared to have a far more benign course. Over the past decade, more of these patients have been evaluated and subjected to repeated neurovascular imaging within a few weeks to months, demonstrating remarkable and rapid reversal of vascular abnormalities. These patients are now designated as having Reversible Cerebral Vasoconstrictive Syndromes (RCVS). These can occur idiopathically or can be seen in a variety of clinical settings: 1) after head trauma of neurovascular surgical procedure 2) in the postpartum period and ) associated with an increasing number of drugs including sympathomimetics such as ephedrine, cocaine and others. Diagnostic features of the syndrome are noted in the following table.

Rheumatic and Immunologic Diseases | 1

Characteristics Mean Age Male age Female age Females Race Caucasian African American Others Associated Triggers Postpartum state Sympathomimmetic amines Social marijuana Smoking history PMHx Migraine Clinical Signs/Symptoms Headache (HA) Classic thunderclap HA Thunderclap like Migraine HA Coitus HA Exercise HA Valsalva HA Recurrent Headaches Neurological s/s Focal Diffuse Both Seizures Transient ischemic attack Isolated visual symptoms without stroke (blurry, diplopia, transient loss, floaters, etc.) Sought medical care on day of Symptom onset

Number of Cases Total n=48 4.8 years+ 11.6 years 4.1 + 5.0 years 44.9 + 11.6 years 4/48 7/48 5/48 6/48 2/48 4/48 7/48 20/48 11/48 4/48 18/48 14/48 6/48 7/48 4/48 8/48 20/48 7/48 /48 /48 1/48 2/48 /48 10/48

Percentage

89.6 77.1 10.4 12.5 4.1 8. 14.6 41.7 22.9 89.6 7.5 29.1 12.5 14.5 8. 16.6 41.6 14.6 6.2 6.2 2.0 4.2 6. 20.8

18/48 

7.5 

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Summary of Critical Elements for Diagnosis of RCVS 1. Transfemoral angiography or indirect (CT or MR) angiography documenting segmental cerebral artery vasoconstriction. 2. No evidence for aneurysmal subarachnoid hemorrhage. . Normal or near-normal cerebrospinal fluid analysis (proteins of <60 mg%, white blood cells < 10 per mm, normal glucose). 4. Severe, acute headache, with or without additional neurologic signs or symptoms. 5. The diagnosis cannot be confirmed until reversibility of the angiographic abnormalities is documented with 12 weeks after onset, or if death occurs before the follow-up studies are completed. Autopsy rules out conditions such as vasculitis, intracranial atherosclerosis and aneurysmal subarachnoid hemorrhage, which can also manifest with headache and stroke. In 2006, the largest series of such patients was presented at the American College of Rheumatology meeting in Washington, DC. A summary of these patients is presented in the table. Of note is the fact that angiographic follow-up was available in 8 patients, showing reversibility in 97%.

Rheumatic and Immunologic Diseases | 

Optimal treatment for this disorder has not yet been established, as opposed to patients with true vasculitis of the central nervous system who require prolonged therapy with glucocorticoids and cytotoxic drugs. RCVS patients can often be treated with observation or calcium channel blockers alone.

This is a cerebral angiography of a 40 y/o female who presented with  weeks of severe headaches and an episode of transient paresis of her left arm. An MRI was normal and CSF studies were normal. Her angiogram revealed multiple areas of stenosis and dilatation in multiple vessels (left) which resolved one month after treatment with prednisone 60 mg/day and verapamil 240 mg/day (right). RCVS was diagnosed. The outcome was favorable in the majority with persistent morbidity related to whether or not the patient experienced stroke at presentation. Outcome Total recovery Recovery with residual neurological deficits Death Relapse Not known/lost to follow-up 2/48 16/48 0/48 /48 6/48

In 2007, working with colleagues at the Massachusetts General Hospital and the Mayo Clinic, a definitive review of this disorder was published in the Annals of Internal Medicine which, for the first time, integrates the clinical features and pathophysiologic concepts into a single review for a broad medical audience.
Hajj-Ali R, Furlan A, Abou-Chebel A, Calabrese LH: Benign angiopathy of the central nervous system (BACNS): Cohort of 16 patients with clinical course and long-term follow-up. Arthritis Care and Research 2002;47:662-669. Calabrese LH, Gragg LH, Furlan AJ: Benign angiography: A distinct subset of angiographically defined primary angiitis of the central nervous system. J Rheumatology 199;20:2046-2050. Calabrese LH, Dodick DW, Schwendt T, Singhal A: Narrative review: reversible cerebral vasoconstrictive syndromes. Ann Int Med 2007;146:4-44. 

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Center for Vasculitis Care and Research
Carol Langford, M.D.

Renal Graft Survival in Wegener’s Granulomatosis (WG): Comparison to Systemic Lupus Erythematosus (SLE) from a National Database Curry L. Koening, Carol A. Langford, H.L. Kirchner, Gary S. Hoffman Nearly three-fourths of Wegener’s granulomatosis (WG) patients will develop glomerulonephritis at some time during their disease course. Despite treatment with immunosuppressive drugs, up to 20% of patients develop end-stage renal disease (ESRD). For patients with ESRD, kidney transplantation is an important medical advance. Although case reports and small cohort studies report excellent graft survival rates in WG, it is not known how these results compare to patients who undergo renal transplant for more common rheumatic conditions. This led us to compare renal graft survival rates in patients transplanted for WG to patients transplanted for systemic lupus erythematosus (SLE). The study used data from the Organ Procurement and Transplantation Network’s (OPTN) national transplant database. Renal graft survival rates were compared among patients who received a first episode renal transplantation for either WG or SLE between October 1987 and February 2006. A total of 982 patients received renal transplantation for WG and 6,574 patients for SLE.
100 75

% 50 Survival
25 0
WG SLE Log-Rank P < 0.0001

0

200

400 600 Weeks to Failure

800

1,000

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Wegener’s Granulomatosis Rate (95% CI) Survival Rate 6 month 1 year 5 year 95.6% (94.1-96.7) 95.2% (9.6-96.4) 90.0% (87.9-91.7)

Systemic Lupus Erythematosus Rate (95% CI)

92.7% (92.1-9.) 90.7% (90.0-91.4) 79.7% (78.7-80.7)

Kaplan Meier analysis of the two groups showed patients transplanted for WG had better graft survival rates at 6 months, 1 year, and 5 years compared to patients transplanted for SLE. After adjusting for various confounding factors, patients transplanted for SLE had a 71% (P<0.0001 95% CI 4%- 104%) increased risk of renal graft failure compared to patients with WG. Furthermore, the number of patients reported to have recurrent disease as a cause for their graft failure was small in both WG and SLE patients (4.% and 4.8% respectively). This is the largest study to compare renal graft survival rates in patients transplanted for WG to those transplanted for SLE. Results show patients transplanted for WG had better graft survival rates than those transplanted for SLE. How graft survival rates in WG patients compare to those transplanted for more common, non-rheumatic causes of renal failure will be determined in the future from this database. 

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Substitution of Methotrexate for Cyclophosphamide in Wegener’s Granulomatosis A 12-year Single-practice Experience Alexandra Villa-Forte, Tiffany M. Clark, Marcelo Gomes, John Carey, Edward Mascha, Matthew T. Karafa, Susana Arrigain, Gerald Roberson and Gary S. Hoffman Objective The objective of the study is to assess outcomes of therapy in newly-diagnosed Wegener’s granulomatosis (WG) using methotrexate (MTX) for mild-to-moderate disease or short-term treatment with cyclophosphamide followed by MTX for severe disease. Methods Retrospective review: Patients with WG were included if their initial plan of therapy and subsequent care were directly supervised by the Cleveland Clinic Center for Vasculitis Care and Research. Severe disease (i.e. immediately life-threatening or involving critical organs) was initially treated with cyclophosphamide and glucocorticoids. Mild-to-moderate disease was initially treated with MTX and glucocorticoids if serum creatinine was less than 2mg/dl. Following initial improvement of severe disease, treatment was changed to MTX if serum creatinine was originally less than 2mg/dl or had diminished to less than 2mg/dl. Disease activity was determined at each visit and later converted to a Birmingham Vasculitis Activity Score, modified for Wegener’s granulomatosis (BVAS/WG). Laboratory monitoring of disease and treatment toxicity was initially weekly and never less often than monthly. Results Eighty-two (2%) of 25 patients referred to the Center for Vasculitis Care and Research with WG met eligibility criteria. Ineligible patients did not have new onset disease or were not able to be followed principally in our center. Seventy percent of patients (57/82) initially had severe disease and received a short course of cyclophosphamide for remission-induction. In over half of these patients, illness was judged to be severe because of pulmonary hemorrhage, rapidly progressive glomerulonephritis, including need for dialysis, or neurologic abnormalities.

Rheumatic and Immunologic Diseases | 7

All patients improved; remission was achieved in 50% (41/82) of patients within 6 months and 72% (59/82) within 12 months. Sustained remission (BVAS/WG = 0, for at least 6 consecutive months) was ultimately achieved in 77% (6/82) of patients. Among patients with sustained remissions, the mean duration of remission prior to relapse was 20.5 months (SD ± 21.2).
100 75

Time to Remission

% 50
25
BVAS/WG of zero

0

0

1 Years (follow-up)

3

3

Seventy-five patients (91%) achieved remissions of any duration [mean duration ± SD = 11.2 ± 16.8 months]. Among the 75 (91%) patients who achieved remission of any duration, 45% relapsed within 1 year and 66% relapsed within 2 years after remission. Eighty-two percent of relapsed patients achieved subsequent remissions after additional treatment. About three-fourths of relapses were mild and promptly responded to treatment. Seventeen percent of patients developed serious infections. Cyclophosphamideassociated cystitis or bladder cancer did not occur in any patients. At least one form of permanent morbidity from WG alone was noted in 74% of patients. Three patients (.7%) died over a median follow-up period of 4.5 years. No deaths were due to active disease. Although treatment was primarily directed toward achieving clinical improvement and not calculated to achieve marked lymphopenia, patients in whom treatment produced lymphocyte counts of less than < 500/mm, sustained over a median time of 4 (quartiles, 1-8.5) months, were .8 times more likely to achieve a sustained remission (> 6 months; p = 0.015). Conversely, following remission, an absolute lymphocyte count of >1000/mm was associated with a hazard ratio for relapse of .0, although the latter difference was not statistically significant. 

8 | Rheumatic and Immunologic Diseases 2006

Conclusions In patients with Wegener’s granulomatosis, a strategy that limits or avoids cyclophosphamide therapy has produced excellent results as judged by frequency of remissions, survival and avoidance of long-term cyclophosphamide toxicity. Relapses, however, were common and incremental permanent morbidity occurred in most patients. While not a goal of therapy, when treatment produced marked lymphopenia, prolonged remissions were more likely. Evolution of the Syndrome of Benign Angiopathy of the Central Nervous System (BACNS) Retrospective review of 48 patients Swati S. Bharadwaj, Rula A. Hajj-Ali, Jeffrey P. Hammel, Leonard H. Calabrese Purpose The entity of BACNS was first proposed in 199 as a subset of Primary Angiitis of Central Nervous System (PACNS), defined by acute headache and/or stroke, benign cerebrospinal fluid, high probability cerebral angiogram and a favorable clinical outcome without intense immunosuppression. In 2002, we described a series of 16 patients with BACNS with rapid reversal of angiographic changes suggesting the underlying mechanism was reversible vasoconstriction rather than true vasculitis. Recognizing this entity is clinically important to spare patients from aggressive studies such as a brain biopsy and the toxicities of unnecessary immunosuppression. The clinical description of BACNS was extended with a larger cohort of 48 patients in an attempt to refine our diagnostic and treatment strategies. Methods A retrospective chart review was conducted on BACNS patients. Diagnosis was based on prior descriptions (Hajj-Ali Arth Rheum 2002; 47:662-669). Information was collected on demographics, triggers, strokes, headaches, visual symptoms, seizures, laboratory markers, spinal taps, brain biopsies, initial and follow-up neuroimaging, treatments, outcomes and dates. Information was entered into an Oracle Database and a descriptive analysis conducted.

Rheumatic and Immunologic Diseases | 9

Results Forty-eight patients were included in the study. Mean age was 4.8 years; 90% were females. Associated factors were marijuana use in 14.6% and sympathomimetic amine use in 8.%. Past history of migraine was seen in 22.9%. Headache was most common and present in 89.6%, stroke in 14.6%, isolated visual symptoms in 20.8% and seizure in 4.2%. Of the 8.% of patients who had spinal taps, 82.5% had normal WBCs and 85% had normal CSF proteins (7.5% were not reliable due to trauma/bleed, 7.5% had mild elevations). Brain biopsy was performed in 22.9% and found normal in all except one patient with a concomitant glioma. Initial MRI was normal in 17.1%. Subsequent MRIs revealed abnormalities in 81.4% (44.2% ischemia, 18.6% cerebral hemorrhage, 14% subarachnoid hemorrhage). Stroke was bilateral or multiple in 5%. All patients had high probability neurovascular imaging abnormalities consistent with vasculitis. Follow-up neurovascular imaging performed in 79.2% demonstrated reversibility of the vascular abnormality in all except one recent patient with a premature MRA. Median time to reversibility was 92 days. Treatment was non-standardized with brief course glucocorticoids used most frequently; more recently, patients were encountered receiving calcium channel blockers. Total clinical recovery occurred in 47.9%; recovery with residual deficits occurred in .%; relapses occurred in %. Conclusions BACNS is a common mimic of PACNS and appears to represent a syndrome of reversible cerebral vasoconstriction and not true cerebral vasculitis. Initial neuroimaging can be negative in many patients. Outcome morbidity appears to be limited to stroke. Studies to define validated diagnostic criteria and optimal therapy are needed.

40 | Rheumatic and Immunologic Diseases 2006

Takayasu’s Arteritis: Guarded Outcomes in an American Cohort Kathleen Maksimowicz-McKinnon, Tiffany M. Clark, Gary S. Hoffman Purpose 1) To describe clinical, laboratory, and radiographic manifestations of Takayasu’s arteritis (TAK) in an American cohort. 2) To evaluate response to interventions, remission and relapse rates and disease progression. ) Compare observations to cohorts from the United States, Japan, India, Italy and Mexico. Methods Seventy-five patients were retrospectively studied using a uniform database that included clinical, laboratory and imaging data. Vascular imaging studies were performed at least yearly to monitor disease progression. Results Ninety-two percent of patients were Caucasian; 89% female. Median age at onset was 26 years; median duration of follow-up was  years. Common manifestations included loss or asymmetry of pulse (57%), limb blood pressure discrepancy (5%) and bruits (5%). Eleven percent of patients were asymptomatic prior to disease diagnosis. Angiographic studies demonstrated aortic abnormalities in 79% of patients. Subclavian (65%) and carotid (4%) arteries were also frequently affected. Ninety-three percent of longitudinally followed patients attained disease remission of any duration, but only 28% attained a sustained remission of at least 6 months duration while receiving less than 10 mg/day of prednisone. Both angioplasty and vascular surgery procedures were initially successful, but recurrent stenosis occurred in 78% of angioplasty and 6% of bypass/reconstruction procedures. Vascular claudication limited routine daily activities in 60%. Cerebral ischemic disease occurred in 17%. Complete occupational disability occurred in 2% which correlated with number of relapses. There were two disease-related deaths. Disease manifestations in our cohort are similar to the NIH, Italian, Japanese and Mexican cohorts in female predominance and disease manifestations, but differed from the Indian cohort in that the latter group had a higher frequency of males, abdominal aortic involvement and hypertension.

Rheumatic and Immunologic Diseases | 41

Cohort Comparisons: Demographics And Diagnostic Evaluations
Cohort CCF NIH () Italy (6) India (7) Japan (8) (Ueda) Japan (9) (Nakao) Japan (10) (Ishikawa) Mexico (11) (Lupi-Herrera) 107 NR NR 84 100 21 14 120 0 * 0 9 NR** 12 1 84 NR NR 86 64 NR 7 52 24 NR 81 90** NR 12 *** Patient (#) 5 60 104 106 Mean Age at onset 26 25 * 40 27 Caucasian (%) 92 75 99 NR Female Vascular (%) imaging (%) 89 97 88 61 100 100 100 90** PTA/surgical Mortality (%) intervention (%) 48 50 50 1   NR 11

NR = not reported. *Only median age reported. **Diagnosis and disease features were assessed at least once in the entire cohort by vascular imaging, at the time of surgery, or at autopsy. ***Based on reported number of patients that underwent autopsy.

Manifestations at disease onset in the American, Italian, and Indian cohorts.*
Aortic arch Thoracic aorta Abdominal aorta Left carotid Right carotid Left subclavian Right subclavian Celiac * Superior mesenteric * * Left renal Right renal Left iliac Right iliac
* * * *

CC NIH Italy Japan India Mexico

0

25

50 % Affected

75

100

*Instances in which data were not provided for a cohort are indicated by absence of a comparison bar.

42 | Rheumatic and Immunologic Diseases 2006

Vascular Interventions and Outcomes in the Longitudinal Cohort* Aneurysm/dilatation Site Aortic root Descending aorta Axillary Stenosis Site Abdominal aorta Carotid Axillary Subclavian Coronary Mesenteric Renal Iliofemoral Bypass (#) NA 7  5 12 2 5 1 Bypass/reconstruction (#) 7 1 1 Patent (%) NA 71 0 80 50 100 60 100 *** Angioplasty (#) 1 2 2 4 1 NA 8 2 Patent (%)** 86 100 100 Patent (%) 100 0 100 0 100 NA 0 100 ***

* 21 of 0 patients in longitudinal cohort required revascularization procedures. **Sustained over the period of observation, without further intervention required. ***1 patient with iliofemoral bypass and one with iliofemoral angioplasty had partial restenosis at follow-up imaging.

Conclusions Takayasu’s arteritis in the United States is characterized by chronic, relapsing disease in the majority of patients. Although most patients are able to attain remission with the use of glucocorticosteroid therapy, attaining sustained steroid-free remission is uncommon. The majority of disease relapses in our cohort occurred while patients were on immunosuppressive therapy. Seventy percent of patients required revascularization procedures. In contrast to prior studies from Indian cohorts, sustained vascular patency following angioplasty was infrequent. Sustained vascular patency at  years was superior for arterial bypass/reconstruction (68%) compared with angioplasty (25%). Although mortality rates were low, chronic morbidity and disability were frequent in this young population. The frequency of disease relapse and the need for revascularization highlight the inadequacy of current therapy for Takayasu’s arteritis.

Rheumatic and Immunologic Diseases | 4

Durable Remission in Patients with Refractory Takayasu’s Arteritis Treated with Infliximab or Etanercept Eamonn S. Molloy, Carol A. Langford, Tiffany M. Clark, Carmen E. Gota, Leonard H. Calabrese, Gary S. Hoffman While up to 20% of Takayasu’s arteritis (TAK) patients have a monophasic illness, most have a relapsing/remitting course, typically requiring prolonged treatment with glucocorticoids and additional immunosuppressive agents, such as methotrexate, azathioprine and, in severe cases, cyclophosphamide. More than one-third of patients are unable to achieve adequate disease control on these therapies. As tumor necrosis factor alpha (TNFa) is critical for granuloma homeostasis and granulomatous inflammation is the pathologic hallmark of TAK, TNFa is an attractive therapeutic target in TAK; anti-TNF therapy has been employed in TAK patients with encouraging results. We sought to assess the efficacy of anti-TNF therapy in patients with TAK refractory to other therapies. Twenty-eight TAK patients were identified as having received anti-TNF therapy;  patients were excluded because of insufficient followup data. No patient was in remission at the time of initiation of anti-TNF therapy; 1 had not achieved remission at any time since initial diagnosis. Twenty-five patients were treated with anti-TNF therapy for up to 6.5 years. Twenty patients were treated with infliximab (INF) with a mean follow-up of 27 months (range 2-76). Nine patients were treated with etanercept (ETA) with a mean follow-up of  months (range 4-78). Four patients received both agents (all initially treated with ETA, later switched to INF). No patients were treated with adalimumab. Of 25 patients, 22 were female; mean age was 5 years (range 15-6). Patients’ ethnicities were Caucasian, 20, Asian,, Hispanic,1, and one unknown. Median disease duration was 108 months (range 1-6). All patients were previously treated with prednisone and a mean of 2 additional immunosuppressive agents (range 0-6) including 22 methotrexate, 10 cyclophosphamide, and 12 with a variety of other agents.

44 | Rheumatic and Immunologic Diseases 2006

Major Outcomes in Refractory TAK Patients Treated with anti-TNF Therapy. Anti-TNF Agent Patients treated Complete remission* Partial remission** Discontinuation within 6 months Treatment failure - Adverse event - Other Infliximab 20 12 5  1 1 1 Etanercept 9 4 2   -

*Complete remission defined as resolution of symptoms, lack of new changes on vascular imaging and discontinuation of glucocortocoids for at least 6 months. **Partial remission defined as resolution/improvement in symptoms, lack of new changes on vascular imaging and tapering of glucocortocoids to <10mg/day of prednisone or equivalent, for at least 6 months.

Overall, prednisone was discontinued in 15/25 patients (60%) and tapered below 10 mg/day in a further 7/25 (28%). Median prednisone dose before and after anti-TNF therapy was 19 mg (range 5-90) and 0 mg (range 0-0). Nine out of 18 patients were able to taper or discontinue additional immunosuppressive agents used concurrently with the anti-TNF agent. Six patients had definite new changes noted on MR imaging ( INF,  ETA); 5 patients entered remission on higher dose anti-TNF therapy. Three patients who stopped ETA had disease flares within a median of 2 months (range 1-2); 6/7 patients that stopped INF had disease flare at a median interval of 6 months (range 2-12); 1 patient recommenced INF treatment and achieved sustained remission. Conclusions In this group of TAK patients refractory to other immunosuppressive therapies, anti-TNF therapy led to complete or partial remission in 79% of patients. AntiTNF therapy allowed prednisone to be discontinued or tapered in 60% and 28%, respectively. Of those patients taking concurrent immunosuppressive drugs other than prednisone, anti-TNF therapy allowed reduction of the dose of these agents in 50%. These findings provide further support for the rationale for randomized controlled trials of anti-TNF therapy in TAK.

Rheumatic and Immunologic Diseases | 45

Patient Experience |
We ask our patients about their experiences and satisfaction with the services provided by our staff. Although our patients are already indicating we provide excellent care, we are committed to continuous improvement.

Outpatient Overall Rating of Care 2006
100 80 60

100 80 60 40 20
Excellent Very Good Good Fair Poor

%

40 20 0

0

46 | Rheumatic and Immunologic Diseases 2006

Innovations |
The Future of the Rheumatology Workforce in the United States 2005-2025. Authors: Chad Deal, M.D., Chair, Subcommittee on Workforce, Roderick Hooker, Ph.D., P.A., Timothy Harrington, M.D., Neal Birnbaum, M.D., Paul Hogan, Ellen Bouchery, Marisa Klein-Gitelman, Walter Barr, M.D. The American College of Rheumatology (ACR) retained the Lewin Group to conduct a workforce study in 2005-2006. The purpose was to develop and apply a model that allows prediction of current and future supply and demand for rheumatology services in the United States. A supply model was developed using the age and sex distribution of current physicians, retirement and mortality rates, the number of fellowship slots and fill rates, and practice patterns of rheumatologists. A survey instrument was designed and sent to 1,68 U.S. rheumatologists to obtain more detailed information, including work effort, productivity, measures of excess demand, and retirement plans. A computerbased Markov projection model was created to project supply and permit sensitivity analyses of factors affecting the future workforce. Supply and demand was assumed to be equal in 2005, although there is likely to be current excess demand for adult and pediatric services. (The computer model can be adjusted to reflect different scenarios.) The number of adult rheumatologists in 2005 was 4,946. Male and female rheumatologists are equally distributed up to age 44, though above age 44, males are more predominate. By 2025, the percent of women in the adult rheumatology workforce is projected to increase from 0.2% to 4.6% and in the pediatric workforce, from 51.5% to 62.7%. The mean number of patient visits is ,758 for male and 2,800 for female rheumatologists. The productivity of rheumatologists under age 40 was lower than older rheumatologists. If the supply and demand in 2025 were assumed to be equal, the demand for rheumatologists is projected to exceed supply by 2,576 adult (supply=4,64, demand=7,219) and  pediatric (supply=254, demand=287) rheumatologists. (Current data suggest the pediatric rheumatology workforce is experiencing a substantial excess of demand versus supply.) Primary factors in the excess demand include: an aging population (which will increase the number of people with rheumatic disorders), growth in the real per capita income and flat rheumatology supply due to fixed numbers entering the workforce and retiring.

Rheumatic and Immunologic Diseases | 47

Unknown affects that could influence these projections include technology advances, practice redesign, changes in insurance reimbursement and shifting lifestyles. Based on assessment of supply and demand under current scenarios, the demand for rheumatologists is expected to exceed supply in the coming decades. Strategies for the profession to adapt to this changing healthcare landscape include: increasing the number of fellows (an additional 188 slots would be required), utilizing physician assistants and nurse practitioners in greater numbers and improving practice efficiency. The R.J. Fasenmyer Center for Clinical Immunology is dedicated to patient care, education and research in clinical immunology with an emphasis on autoimmunity and chronic viral illness. As part of our goal to support education, the construction of a state-of-the art meeting center within the Department of Rheumatic and Immunologic Diseases will occur in 2008. This center will expand the educational mission of the Fasenmyer Center and the Department of Rheumatic and Immunologic Diseases to students, residents and physicians. A comprehensive immunology curriculum has been developed with ongoing lectures in immunology and autoimmunity. Julie C. Huang, Stanley L. Hazen, Gary Hoffman, Elaine Husni. Abstract Impact of a Best Practice Clinical Alert on Preventive Cardiology Referral for Patients with Systemic Rheumatic Disease Julie C. Huang, Stanley L. Hazen, Gary Hoffman, Elaine Husni. There is known increased risk of cardiovascular morbidity and mortality in patients with systemic rheumatic diseases. Despite significant cardiovascular risk, there is low utilization of preventive cardiology services at our institution. Purpose To assess the impact of a best practice clinical alert on referral patterns of patients with systemic rheumatic diseases from the Cleveland Clinic Department of Rheumatic and Immunologic Diseases to the Section of Preventive Cardiology.

48 | Rheumatic and Immunologic Diseases 2006

Methods An automatic clinician alert system was implemented via the electronic medical record in June 2006. Any patient with a diagnosis of systemic rheumatic disease seen in the Cleveland Clinic Department of Rheumatic and Immunologic Diseases triggered a “pop-up” alert recommending referral to Preventive Cardiology for cardiovascular risk assessment. The Section of Preventive Cardiology PreCIS® database was then queried using SAS data retrieval for a monthly report of patients referred from Rheumatology or for a diagnosis of systemic rheumatic disease. The referral pattern was compared to that prior to implementation of the best practice clinical alert to assess its impact on referrals to Preventive Cardiology. Results In the three months following implementation of the best practice clinical alert system, the monthly average referral rate increased by 1,495%. The majority of patients required some form of cardiac risk intervention, including initiation of statin therapy for dyslipidemia, electrocardiogram, and/or non invasive cardiac testing for suspicion of coronary artery disease. Conclusion Use of a best practice clinician alert system is a highly effective means of increasing referral of patients with systemic rheumatic diseases to preventive cardiology. Addressing cardiovascular risk in this high risk patient population is critical. Further research will be needed to determine whether adoption of best practice clinical alerts results in reduced cardiovascular burden in this group of patients.

Education
Abby Abelson, M.D., Education Program Director of the Department of Rheumatic and Immunologic Diseases, was awarded the Clinical Scholar Educator Grant of the American College of Rheumatology Research and Education Foundation for July 20072010. Decisions about career choices are often made during medical school and early in resident training. Medical school curricula include rheumatology sections in the first two years. Clinical rheumatology faculty teach medical students and residents during clinical

Rheumatic and Immunologic Diseases | 49

rotations. We feel a well-designed Web-based curriculum that would be available to all rheumatology faculty could improve students’, residents’ and fellows’ understanding of the field of rheumatology and provide more informed decisions on career choices. Dr. Abelson’s grant provides support to develop an interactive Web-based, case-based rheumatology curriculum that will facilitate the teaching of the clinical and basic science of rheumatic disease to medical students, residents and rheumatology fellows. The format will be case-based, problem-based learning (PBL) curriculum and will increase medical students’ and residents’ knowledge of the rapidly evolving field of rheumatic diseases. Cleveland Clinic College of Medicine at Case Western University has established expertise in Web- and case-based medical education that will be utilized for curriculum development. The diversity of the disease mechanisms, illnesses, prognoses and large numbers of new effective therapies will be addressed in this curriculum. The flexible Web-based format will allow the curriculum to be utilized in a variety of settings, from individual self-directed learning to small conference or larger group seminar settings, therefore maximizing the opportunities for medical educators to expose students and residents to the depth and breadth of rheumatology.

Best Practices: Steroid Alert in Epic
Steroids are frequently used to treat many diseases across all medical specialties. Current American College of Rheumatology guidelines recommend a bone density in patients on more than 5 mg of prednisone for more than three months. In addition, treatment with a bisphosphonate is recommended in patients at initiation of steroid therapy and in patients with ongoing steroids at T-score < -1.0. To improve compliance with ACR guidelines, a best practice alert system was initiated in the Department of Rheumatic and Immunologic Diseases and for all rheumatologists in the Cleveland Clinic system. Epicare evaluates the patient’s medical record for steroid use of more than three months, whether a bone density has been done in the last 12 months and an alert screen is generated with a smart form that allows the clinician to order a bone density test if indicated.

50 | Rheumatic and Immunologic Diseases 2006

New Knowledge |
Selected Publication Highlights
Calabrese LH. Primary Angiitis of the Central Nervous System. In Rheumatology. 4th ed. Hochberg M, Silman A, Smolen J, Weinblatt M, Weisman MH, eds. St. Louis, Mo.: Mosby; 2006. Vassilopoulos D, Calabrese LH. Rheumatic aspects of human immunodeficiency virus infection and other immunodeficiency states. In Rheumatology. 4th ed. Hochberg M, Silman A, Smolen J, Weinblatt M, Weisman MH, eds St. Louis, Mo.: Mosby; 2006. Fauci AS, Langford CA, eds. Harrison’s Rheumatology. New York: McGraw Hill; 2006. Hoffman GS, Langford CA, Calabrese LH. In Vasculitis Hospital Medicine 2nd ed. Wachter RM, Goldman L, Hollander H, eds. Philadelphia, Pa: Lippincott, Williams and Wilkins; 2005: 1121-. Stone JH, Hoffman GS. In Rheumatology 4th ed. Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, eds. Wegener’s granulomatosis. St. Louis, Mo.: Mosby; 2007. In press. Chapter in book Villa-Forte A, Santos A, Hoffman GS. In Head and Neck Manifestations of Systemic Diseases. Harris J, Weisman M, eds. Vasculitis and Otolaryngology; New York, Marcel Dekker; 2007. Hajj-Ali R, Mandell BF. Rajagopalan, Mukherjee, eds. Approach to and Management of Inflammatory Vascular Disease in Manual of Vascular Diseases. Philadelphia, Pa: Lipincott, Williams and Wilkins; 2005.

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Mandell BF, Johnson B. The patient with arthritis or systemic autoimmune disease. In Just the Facts in Perioperative Medicine, Cohn, Smetana, Weed, eds. New York.: McGraw Hill; 2006. Mandell BF. Differential diagnosis of arthritis. American College of Physicians Medical Knowledge Self Assessment Project. 14. Rheumatology. 2006. Mandell BF. Septic Arthritis. American College of Physicians Medical Knowledge Self Assessment Project. 14. Rheumatology. 2006. Mandell BF. Crystal Disease. American College of Physicians Medical Knowledge Self Assessment Project. 14. Rheumatology. 2006. Mandell BF. Perioperative management of the patient with rheumatologic disease. In: Medical Consultation of the Surgical Patient. Merli, Weitz eds Philadelphia, Pa: Lipincott Press; In press 2007. Mandell BF. Dale D, ed. Systemic Vasculitis. ACP Scientific American Medicine. 2006. Deal C, Abelson A, Carey J. Management of Osteoporosis. In: Rheumatology. 4th ed. Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, eds. St Louis, MO: Mosby; In press 2007.

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ES Molloy, Hoffman GS. Pusey C, J Mason,eds.Large and medium vessel vasculitis – clinical features and treatment. In The Kidney in Systemic Autoimmune Diseases. Elsevier Saunders. In press. Gota C, Mandell BF. Fitzpatrick et al., eds Systemic Vasculitis. In: Textbook of Dermatology in General Medicine. New York: McGraw Hill. In press. Mandell BF, Hoffman GS. Rheumatic diseases and the cardiovascular system. In: Braunwald/Zipes/Libby, eds. Heart Disease: A Textbook of Cardiovascular Medicine. In press. Calabrese LH, Kirchner E, Shrestha R. Rheumatic Complications of human immunodeficiency virus (HIV) infection in the era of highly active antiretroviral therapy (HAART): emergence of a new syndrome of immune reconstitution and changing patterns of disease. Sem Arthritis Rheum 2005; 5:166-174. Calabrese LH, Zein N, Vassilopoulos D. Hepatitis B (HBV) reactivation with immunosuppressive therapy in rheumatic diseases. Ann Rheum Dis 2006 [Epub ahead of print]. Chatterjee S, Dombi GW, Severson RK, Mayes MD. Risk of malignancy in scleroderma: a population-based cohort study. Arthritis Rheum 2005;52:2415-2424. Hashkes PJ, Laxer RM. Medical treatment of juvenile idiopathic arthritis. JAMA 2005;294:1671-1685. Uziel Y, Butbul-Aviel Y, Barash J, Padeh S, Mukamel M, Gorodnitski N, Brik R, Hashkes PJ. Recurrent transient synovitis of the hip in childhood: the long-term outcome among 9 patients. J Rheumatol 2006;:810-811.

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Oliveira S, Ravelli A, Pistorio A, Castell E, Malattia C, Prieur AM, Saad-Magalhaes C, Murray KJ, Sang-Cheol B, Joos R, Foeldvari I, Duarte C, Wulffraat N, Lahdenne P, Dolezalova P, de Inocencio J, Pratsidou-Gertsi P, Hofer M, Nikishina I, Ozgogan H, Hashkes P, Martini A, Ruperto N for the Pediatric Rheumatology International Trials Organization (PRINTO). Health-related quality of life of patients with juvenile idiopathic arthritis: The PRINTO multinational quality of life cohort study. Arthritis Rheum 2007;57;5-4. Karlson, EW, Costenbader, KH, McAlindon TE. Massarotti EM, Fitzgerald LM, Jajoo R, Husni ME, Wright EA., Pankey H, and Fraser PA. High Sensitivity, specificity and predictive value of the connective tissue disease screening questionnaire (CSQ) among urban African-American women. Lupus 2005;14:82-86. Solomon DH, Chibnik LB, Losina E, Huang J, Fossel AH, Husni ME, Katz JN. Development of a preliminary index that predicts adverse events after total knee replacement. Arthritis Rheum 2006; May; 54 (5):156-42. Stone JH, Hoffman GS, Liota L et al. A serum proteomic approach to gauging the state of remission in Wegener’s granulomatosis. Arthritis Rheum 2005;52:902-910. The WGET Research Group. (PI: Stone JH, Co-PI- Hoffman GS). Etanercept plus standard therapy in patients with Wegener’s granulomatosis. N Engl J Med 2005; 52:51-61. Merkel PA, Lo GH, Holbrook JT, Tibbs AK, Allen NB, Davis JC, Hoffman GS, McCune J, St. Clair EW, Specks U, Spiera R, Petri M, Stone JH for The WGET Research Group. Incidence of venous thrombotic events among patients with Wegener’s granulomatosis. Ann Intern Med 2005;142:620-626.

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Seo P, Min YI, Holbrook JT, Hoffman GS, Merkel PA, Spiera R, Davis JC, Ytterberg SR, St Clair EW, McCune WJ, Specks U, Allen NB, Luqmani RA, Stone JH. Damage caused by Wegener’s granulomatosis and its treatment: prospective data from the Wegener’s Granulomatosis Etanercept Trial (WGET). Arthritis Rheum 2005;28;52:2168-2178. Hoffman GS, Cid MC, Rendt KE, Merkel PA, Weyand CM, Stone JH, Salvarani C, Xu W, Visvanathan S, Rahman MU for the Infliximab-GCA study group. Prednisone and infliximab for giant cell arteritis: a randomized, double-blind, placebo-controlled, multicenter study of efficacy and safety. Ann Intern Med 2007. 146(9):621-60. Stone JH, Holbrook JT, Marriott MA, Tibbs A, Sejismundo LP, Min Y-I, Specks U, Merkel PA, Spiera R, Davis JC, St. Clair EW, McCune J, Ytterberg SR, Allen NB, and Hoffman GS for the WGET Research Group. Solid malignancies in the Wegener’s Granulomatosis Etanercept Trial. Arthritis Rheum 2006; 54:1608-1618. Wung PK, Holbrook JT, Hoffman GS, Tibbs AK…. Stone JH for the WGET Research Group. Herpes Zoster in immunocompromised patients. Incidence, timing and risk factors. Am J Med 2005; 118: 1409-1416.

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Lee MS, Smith SD, Galor A, Hoffman GS. Antiplatelet and anticoagulant therapy in patients with giant cell arteritis. Arthritis Rheum 2006;54:06-09. Deal C, Omizo M, Schwartz,E, et al.Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: Results from a 6-month double-blind placebo-controlled trial. J Bone Miner Res 2005;20:1905-1911. Harrington T, Deal C. Successes and failures in improving osteoporosis care after fragility fracture: results of a multi-site clinical improvement project. Arthritis Rheum (Arthritis Care & Research) 2006;55:724-728. Deal C, Barr W, Harrington T, Hooker R, Hogan P, Bouchery E, Birnbaum N for the ACR Workforce Subcommittee COTW7. U.S. Rheumatologist Supply and Demand: 20052006 Workforce Study. Arthritis Rheum 2007;56:722-729. Calabrese LH, Dodick DW, Schwendt T, Singhal A. Narrative review: reversible cerebral vasoconstrictive syndromes. Ann Intern Med 2007;146:4-44.

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Staff Listing | Chairman
Gary S. Hoffman, M.D., M.S.
Chairman, Department of Rheumatic and Immunologic Diseases Appointed: 1992 Medical School: Virginia Commonwealth University Medical College, Richmond, Va. Specialty Training: Residency – Dartmouth Medical School and Mary Hitchcock Memorial Hospital, Hanover, N.H.; Fellowship – Dartmouth Medical School and Mary Hitchcock Memorial Hospital, Hanover, N.H.; National Institutes of Health, NIAID, Vasculitis Other Education: B.A. – State University of New York at Binghamton, Binghamton, N.Y.; M.S. – Howard University, Washington, D.C. Specialty Interests: Vasculitis

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Staff Listing |
Chairman Gary S. Hoffman, M.D., M.S. Quality Review Officer Chad Deal, M.D. Center for Osteoporosis and Metabolic Bone Diseases Chad Deal, M.D., Director Abby Abelson, M.D., Education Director John Carey, M.D., M.S. Elizabeth File, M.D. Angelo Licata, M.D., Ph.D., Clinical Trials Director General Rheumatology Matthew Bunyard, M.D., Director of Clinical Operations Abby Abelson, M.D., Education Program Director John Carey, M.D., M.S. Soumya Chatterjee, M.D., M.S. John Clough, M.D. Carmen Gota, M.D. Rula Hajj-Ali, M.D. Elaine Husni, M.D., M.P.H. Anna Koo, M.D. Brian Mandell, M.D., Ph.D. Daniel Mazanec, M.D., Head Center for the Spine Raymond Scheetz, M.D. William Wilke, M.D.

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Section of Clinical Immunology Leonard Calabrese, D.O., Section Head Elizabeth Kirchner, C.N.P. Section of Pediatric Rheumatology Philip Hashkes, M.D., MSc. Section Head Steven Spalding, M.D. Center for Vasculitis Care and Research Carol Langford, M.D., M.H.S., Director Leonard Calabrese, D.O. Carmen Gota, M.D. Rula Hajj-Ali, M.D. Gary Hoffman, M.D., M.S., Chairman Tiffany Clark, C.N.P. Center for Clinical Research Debora Bork, M.F.A., Administrator Sonya Crook, R.N. Louise Kincade, R.N. Katherine Tuthill, C.N.P.

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Regional Medical Practices Feyrouz Al-Ashkar, M.D. – Lorain Chad Deal, M.D. – Solon Rajul Desai, M.D. M.P.H. – Solon Howard Epstein, M.D. – Beachwood Elizabeth File, M.D. – Strongsville Janice Granieri, M.D., Ph.D. – Willoughby Stephen MacIntyre, M.D., Ph.D. – Westlake Judith Manzon, M.D. – Westlake Susan Mathai, M.D. – Westlake Alla Modell, M.D. – Independence Denise Smith Hauser, C.N.P. – Independence Rochelle Rosian, M.D. – Solon Jeffrey Wisnieski, M.D. – Willoughby

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Department Contacts | How to Refer Patients
For Hospital Transfers or Physician Consults 800.55.5056 24 hours a day, seven days a week Main Campus 9500 Euclid Avenue – Desk A50 Cleveland, Ohio 44105 Appointment Office: Financial Counselor: Research Office: Toll-Free Number: 216.444.562 216.444.665 216.445.85 800.22.227

www.clevelandclinic.org/arthritis

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Locations
Lake Erie Willoughby Hills

Cleveland
Westlake

Cleveland Clinic
Beachwood

Lorain Independence Solon

Strongsville

Main Campus 9500 Euclid Avenue – Desk A50 Cleveland, Ohio 44105 216.444.562 Rheumatology Regional Medical Practices Beachwood Family Health and Surgery Center 26900 Cedar Road Beachwood, Ohio 44122 216.89.000 Independence Family Health Center 5001 Rockside Road Independence, Ohio 4411 216.986.4000 Toll Free Number: 800.544.6 Lorain Family Health Center 5700 Cooper Foster Park Road Lorain, Ohio 4405 440.204.7400 Toll Free Number: 800.272.2676

Solon Family Health Center 29800 Bainbridge Road Solon, Ohio 4419 440.519.6800 Toll Free Number: 800.648.0022 Strongsville Family Health and Surgery Center 16761 Southpark Center Strongsville, Ohio 4416 440.878.2500 Westlake Family Health Center 00 Clemens Road Westlake, Ohio 44145 440.899.5555 Toll Free Number: 800.599.7771 Willoughby Hills Family Health Center 2570 SOM Center Road Willoughby Hills, Ohio 44094 440.94.2500

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Cleveland Clinic Overview |
Cleveland Clinic, founded in 1921, is a not-for-profit academic medical center that integrates clinical and hospital care with research and education. Today, 1,700 Cleveland Clinic physicians and scientists practice in 120 medical specialties and subspecialties. Cleveland Clinic’s main campus, with 41 buildings on 10 acres in Cleveland, Ohio, includes a 1,000-bed hospital, outpatient clinic, subspecialty centers and supporting labs and facilities. Cleveland Clinic also operates 1 family health centers, eight community hospitals, two affiliate hospitals, and a medical facility in Weston, Florida. At the Cleveland Clinic Lerner Research Institute, hundreds of principal investigators, project scientists, research associates and postdoctoral fellows are involved in laboratory-based research. Total annual research expenditures exceed $150 million from federal agencies, non-federal societies and associations, and endowment funds. In an effort to bring research from bench to bedside, Cleveland Clinic physicians are involved in more than 2,400 clinical studies at any given time. In September 2004, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University opened and will graduate its first 2 students as physicianscientists in 2009. For more details about Cleveland Clinic, visit clevelandclinic.org

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Online Services |
eCleveland Clinic
eCleveland Clinic uses state-of-the-art digital information systems to offer several services, including remote second opinions through a secure Web site to patients around the world; personalized medical record access for patients; patient treatment progress access for referring physicians (see below); and imaging interpretations by the Department of eRadiology’s subspecialty trained academic radiologists. For more information, please visit eclevelandclinic.org.

DrConnect
Online Access to Your Patient’s Treatment Progress Whether you are referring from near or far, our new eCleveland Clinic service, DrConnect, can streamline communication from Cleveland Clinic physicians to your office. This new online tool offers you secure access to your patient’s treatment progress at Cleveland Clinic. With one-click convenience, you can track your patient’s care using the secure DrConnect Web site. To establish a DrConnect account, visit eclevelandclinic.org or e-mail drconnect@ccf.org.

MyConsult
MyConsult Remote Second Medical Opinion is a secure, online service providing specialist consultations and remote second medical opinions for more than 600 life-threatening and life-altering diagnoses. MyConsult remote second medical opinion service allows you to gather information from nationally recognized specialists without the time and expense of travel. For more information, visit eclevelandclinic.org/myconsult, e-mail eclevelandclinic@ccf.org or call 800.22.227, ext 422.

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Cleveland Clinic Contact Numbers |
How to Refer Patients 24/7 Hospital Transfers or Physician Consults 800.55.5056 General Information 216.444.2200 Hospital Patient Information 216.444.2000 Patient Appointments 216.444.227 or 800.22.227 Medical Concierge Complimentary assistance for out-of-state patients and families 800.22.227, ext. 55580, or email: medicalconcierge@ccf.org International Center Complimentary assistance for international patients and families 216.444.6404 or visit www.clevelandclinic.org/ic Cleveland Clinic in Florida 866.29.7866

www.clevelandclinic.org

Cleveland Clinic is determined to exceed the expectations of patients, families and referring physicians. In light of this goal, we are committed to providing accurate and timely information about our patient care. Through participation in national initiatives, we support transparent public reporting of healthcare quality data and participate in the following public reporting initiatives: • Joint Commission Performance Measurement Initiative (www.qualitycheck.org) • Centers for Medicare and Medicaid (CMS) Hospital Compare (www.hospitalcompare.hhs.gov) • Leapfrog Group (www.leapfroggroup.org) • Ohio Department of Health Service Reporting (www.odh.state.oh.us) In addition, this publication was produced to assist patients and referring physicians in making informed decisions. To that end, information about care and services is provided, with a focus on outcomes of care. For more information, please visit the Cleveland Clinic Quality Web site at clevelandclinic.org/quality.

Cover photograph by Stephen Travarca

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