Rheumatology-Immunology

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Rheumatology-Immunology@ T h e C l e v e l a n d C l i n i c 2 0 0 4

In this issue: Letter from the Chairman • Osteoporosis: Clinical Evaluation and Treatment

Through Patient Care and Clinical Research • Rheumatoid Arthritis and General Rheumatology

• Taking Care of Kids • Clinical Immunology Section • Center for Vasculitis Care and Research •

Scleroderma Care and Research • Research and Education Highlights • A Report from the

Chairman, Gary S. Hoffman, M.D., M.S. • The Rheumatology Research Support Group •

Rheumatology Newsletter Staff Directory • Department of Rheumatic and Immunologic

Diseases: Selected Recent Publications

Table of Contents

3 Letter from the Chairman

4 Osteoporosis: Clinical Evaluation,

Treatment and Clinical Research

6 Rheumatoid Arthritis and

General Rheumatology

7 Taking Care of Kids

8 Clinical Immunology Section

10 Center for Vasculitis Care and Research

11 Scleroderma Care and Research

12 Research and Education Highlights

A Report from the Chairman, Gary S. Hoffman, M.D., M.S.

13 The Rheumatology Research Support Group

14 Rheumatology Newsletter Staff Directory

15 Department of Rheumatic and Immunologic Diseases:

Selected Recent Publications

U.S.News & World ReportThe Cleveland Clinic Department of Rheumatic and Immunologic Diseases has a long history of excellence and innovation in the research and care of patients with illnesses such as arthritis, vasculitis and osteoporosis. For the past several years, U.S.News & World Reporthas consistently ranked the Department of Rheumatic& Immunologic Diseases among the nation’s top fiverheumatology programs in a survey combining physicianpolling with mortality rates and other data. The ClevelandClinic Foundation has been consistently designated as oneof the top five hospitals in America by U.S.News.

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Letter from the Chairman

The Cleveland Clinic Foundation’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

continued progress in clinical trials, outcomes research and understanding illness

at a genetic, molecular and cellular level. Both clinical and basic research hold

the promise 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 the clinical, educational and research arenas. We have

had the good fortune of growing in an environment that is primed for collaboration

in areas related to our own commitments, which include immunology, metabolic

bone disease, orthopaedics, cardiovascular medicine and surgery, pathology

and imaging.

We have benefited from extensive collaborative relationships 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 can visit with members of our Department, meet

our specialty teams and collaborators, and consider how we at the “Clinic” can

best serve you and your patients.

Gary S. Hoffman M.D., M.S.

Harold C. Schott Chair and Professor

Department of Rheumatic and Immunologic Diseases

Lerner College of Medicine

The Cleveland Clinic Foundation

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Osteoporosis: Clinical Evaluation, Treatment and Clinical Research

them at risk for fracture. The majorityof fractures occur in patients with os-teopenia, a T-score between –1.0 and–2.5. Thus the identification of the “atrisk” population depends not only onmeasurement of bone mass but identifi-cation of risk factors such as familyhistory of an osteoporotic fracture,prevalent fracture, low body weight,current smoking, glucocorticoid useand many others. The new definition of osteoporosis by consensus is “a disease characterized by low bone mass and structural deterioration ofbone tissue, leading to bone fragilityand increased risk for fracture.” This definition puts new emphasis on bone“quality,” those factors in addition tobone density that are important forstrength and resistance to fracture.

Osteoporosis: Clinical EvaluationThe National Osteoporosis Found-ation recommends a bone density test in all women over the age of 65.Postmenopausal women to age 65 with risk factors may also require testing. In 1999 only one-third ofwomen in our clinics over age 65 hadreceived a DXA (dual energy x-ray absorptiometry). In 2003 over two-thirds of women had a DXA. Thisimprovement resulted from an organ-ized effort to educate physicians andpractitioners in the Cleveland Clinicsystem as well as the placement ofDXA centers in the Cleveland Clinicsatellite offices. In 2003 more than11,000 DXAs were performed. A project to develop a DXA database that will combine bone density resultswith relevant clinical data is underwayand will enable clinical research anddrug trials to proceed at a faster pace.

In addition to osteoporosis, the Center sees patients with manymetabolic bone diseases, includingrenal osteodystrophy, transplant bone disease, steroid osteoporosis, hyperparathyroidism, osteogenesis imperfecta and others.

Bone Deficiency: Bone Summit 2004The Center, along with the Ortho-paedic Research Center, organized and hosted an international conferenceattended by 187 participants from 12

Introduction: The Osteoporosis TeamThe Center for Osteoporosis and Meta-bolic Bone Disease at The ClevelandClinic was established in 1999. Dr.Chad Deal, a rheumatologist, is Headof the Center. Dr. Miriam Delaney, As-sociate Director of the Center, and Dr.Angelo Licata, Associate Director ofClinical Trials, are endocrinologists. All three have interests in clinical evalu-ation, treatment and clinical trials. TheCenter has participated in numerousrandomized controlled trials of drugtherapy for treatment of osteoporosis.Dr. Brad Richmond, a radiologist, isDirector of Densitometry, and is incharge of 10 dedicated densitometrytechnicians.

Osteoporosis: Clinical ImpactThere are more than 1.5 million frac-tures in the United States every year. Of the 350,000 hip fractures there is a20% mortality at 1-year. It is estimatedthat more than 10 million Americanshave osteoporosis, defined as a T-scoreof less than –2.5, and another 34 mil-lion have low bone mass that places

Dr. Chad Deal

Dr. Miriam Delaney

Dr. Angelo Licata and trainee

countries and 17 states. This Summitbrought together investigators, clini-cians and industry to meet aroundissues of osteoporosis, skeletal repair,cell-based therapies for bone growthand skeletal imaging.

Osteoporosis: Clinical TrialsNumerous clinical drug trials are currently underway or completed at the Center for Osteoporosis andMetabolic Bone Disease. These include evaluation of the anabolicagent parathyroid hormone, rhPTH 1-84 and rhPTH 1-34, PTH in combi-nation with raloxifene, and PTH as atreatment in patients with low bonemass who are on TPN. Use of noveldosing of an oral bisphosphonate, ibandronate, as well as evaluation of the intravenous bisphosphonatezolendronate in men and as an agent to prevent hip fracture are also ongoing.

Osteoporosis: Basic ResearchThe Center for Osteoporosis and Metabolic Bone Disease is a multidisci-plinary clinic with participation ofrheumatologists, endocrinologists andradiologists. In addition, the Center has strong ties to the Department ofBiomedical Engineering, Department of Orthopaedic Surgery and the Orthopaedic Research Center wheremolecular mechanisms of bone forma-tion, skeletal repair and bone growthusing cell based therapies are activeareas of basic and clinical research.

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Rheumatoid Arthritis and General Rheumatology

The new biologic agentswhich attenuate the effectof tumor necrosis alfa(TNF) have revolution-ized the treatment ofrheumatoid arthritis (RA).They are efficacious andsafe compared to agents ofpast years. The anti-TNFdrugs are particularly ef-fective when combinedwith methotrexate, result-ing in remission rates ashigh as 37% after oneyear. Although this remis-sion rate is far superior to that seen with previouscombination therapy, stillmore than half of our pa-

tients never achieve remission. There is room for improvement.

Our group has participated in trials oftwo promising new biological agents.

CTLA4 IMMUNOGLOBULINCTLA-4-Immunoglobulin (CTLA-4-Ig)blocks the second signal required for T-cell activation in an immune re-sponse. Among published studies, ourgroup participated in a pilot, dose-find-ing, double-blind placebo controlled multicenter study of 214 patients. Theagent was well tolerated and proved superior to placebo when given at 2 or 10 mgs/kg. We participated in aPhase III, multicentered, double-blindcontrolled trial of CTLA-4 Ig for pa-tients whose response to etanercept orinfliximab was not acceptable. CTLA-4 Ig 10 mgs/kg was added to thepre-existing anti -TNF therapy. Results of this trial have not yet been reported.

RITUXIMABPrevious pathogenic models of RAhave emphasized the role of the T-cellas a pivotal contributor to synovitisand eventual joint destruction. Con-temporary models have demonstratedthe unique participation of the B-lymphocyte, particularly in lymphoidfollicle-like structures found inrheumatoid synovitis. Rituximab is a monoclonal antibody which atten-uates B-cell activity. Small open studiesin RA have suggested efficacy when itis combined with cyclophosphamide or methotrexate. We are currently en-rolling patients in a large multi-centered, double-blind controlled trialof rituximab added to methotrexatefor patients who have failed to respond adequately to the combination ofmethotrexate and anti-TNF agents.

EARLY ARTHRITIS CLINICSWith the introduction of agents thatmay be capable of inducing remissionand the availability of new diagnostictools, including anti-cyclic citrullinatedprotein and magnetic imaging studiesof the hands, early diagnosis of RA has been facilitated and the impetus totreat early and aggressively heightened.Our group is exploring strategies thatassess the feasibility of early arthritisclinics for all patients who have the po-tential to develop erosive joint disease.

GENERAL RHEUMATOLOGYFrom the perspective of generalrheumatology, better understandingand efficacious treatment of fibro-myalgia (FM) is a challenge. We participate in numerous double-blindcontrolled randomized multicenter trials for the treatment of FM.

Deformities such as these areuncommon in the modern era of rheumatology. (x-ray from a patient in 1979)

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One of the unique features of pediatricrheumatology at The Cleveland Clinicis that it is part of the Department of Rheumatic and Immunologic Diseases, and not Pediatrics, as in most academic centers in the UnitedStates. There are important advantagesto this arrangement. Most pediatricrheumatology practices are in smallunits consisting of one or two physi-cians, thereby being limited in servicesand facilities offered. As part of the Department of Rheumatic and Immunologic Diseases we share thenursing, allied medical professionals,logistic and research staff of the De-partment. Many rheumatic diseasescommon in adults are rare in children(including many types of vasculitis andsystemic sclerosis). Clinical coopera-

Taking Care of Kids

tion and sharing of expertise betweenpediatric and adult rheumatologistsspecializing in these entities improvethe care of children with these rare diseases. We also share the expertise of the bone center in the management of osteoporosis, which is often seen inchildren with rheumatic diseases, espe-cially those treated with steroids. Dueto the reputation of the Clinic, many of our patients are referred from statesoutside of Ohio and other countries.

Rheumatic diseases are less com-mon in children than adults. The mostcommon chronic rheumatic disease is juvenile idiopathic (formally rheu-matoid) arthritis with a prevalence of about 1:1000 children. Based ondata that radiographic joint damage is usually seen within two years of dis-

ease onset (earlier by MRI)and that most children witharthritis continue with dis-ease into adulthood, wetreat these children aggres-sively with early use ofmethotrexate and new “biologic” medications in children not responsiveto methotrexate.

We collaborate withother pediatric services at the Clinic, primarily orthopaedics, ophthalmol-ogy, nephrology and othersubspecialties necessaryfor treating children withrheumatic conditions. Werun a common clinic withthe Section of Pediatric Infectious Diseases in evaluating and treating

children with unexplained periodicfever syndromes. Genetic mutationshave been identified for many of thesesyndromes leading to a greater under-standing and more effective treatment.

We work closely with The Cleve-land Clinic Children’s Hospital forRehabilitation. This collaboration enables us to use their services for rehabilitation of children with arthritisand pain syndromes, particularly reflex sympathetic dystrophy or severefibromyalgia.

There is a national shortage of pediatric rheumatologists, so it is crucial to teach the principles of the discipline to pediatricians and adult rheumatologists who may en-counter these children in localitieswhere pediatric rheumatology servicesare not available. Since we are part of the Department of Rheumatic andImmunologic Diseases, adult rheuma-tology fellows are exposed to pediatricrheumatology more than in most train-ing programs.

Current research projects includeboth industry sponsored and originalresearch. We participate in trials of newmedications for the treatment of juve-nile arthritis. Newer medicines for thetreatment of juvenile arthritis are neces-sary since 10-20% of children do notrespond to methotrexate or “biologic”agents. We actively participate in na-tional research networks, necessary for effective research in pediatricrheumatology.

For more information, please contact Philip Hashkes, M.D., M.Sc., at 216/444-3250.

Dr. Philip Hashkes and one of his friends.

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The Clinical Immunology Section of the Department of Rheumatic and Immunologic Diseases carries out a number of programs in a wide array of immunologic conditions. The section, headed by Dr. LeonardCalabrese, concentrates its efforts in three main areas, each with a com-ponent of clinical care and research.These areas are 1) immunodeficiencydisorders 2) chronic viral illnesses and3) chronic fatigue syndrome.

Immunodeficiency DisordersWithin the section, a large number of adults with primary and secondaryimmune deficiencies is evaluated and treated. The main concentration of energy and resources is directed at programs of integrated care and

research in HIV disease. Dr. Calabrese,who has a joint appointment in the Department of Infectious Diseases, isactively involved in day-to-day patientcare as well as research in HIV disease.He has been doing so since 1983 andwas included in the 80 physicians andresearchers considered pioneers in theHIV epidemic, described in Voices fromthe Epidemic; an oral history (OxfordPress 2000). Together with ElizabethKirchner, M.S.N., N.P., a certified HIVspecialist, they care for a large numberof patients with HIV disease within the multi-specialty HIV clinic at The Cleveland Clinic. This clinic, whichbrings together clinical immunologists,infectious disease specialists, nurse prac-titioners, infectious disease pharmacists,social workers and other allied person-

nel, is part of the AIDS Clinical TrialGroup (ACTG). The ACTG is a systemof centers involved in clinical trials af-fording the most cutting edge researchprotocols for treatment as well as inves-tigations of pathophysiology and thenumerous co-morbidities and toxicitiesfound in the disease.

In addition to the ACTG protocols,the multispecialty HIV clinic is involvedwith a number of investigator designedinitiatives, which emphasize the studyof HIV-associated rheumatic diseases.Since 1989, Dr. Calabrese has prospec-tively followed a cohort now of morethan 400 HIV infected patients. He andhis team have found that, with the intro-duction of combination antiretroviraltherapy and the attendant decrease inmortality, there has been a dramaticchange in the pattern of rheumaticcomplications. Other projects includetherapeutic and pathophysiologic stud-ies in metabolic bone disease as well asstudies of psychosocial issues affectingadherence to medications.

Dr. Calabrese led a team of investi-gators in publishing their experience ofperforming the first successful cardiactransplantation in an HIV-infected patient (Calabrese et. al. New EnglandJournal of Medicine 348:2319-2324,2003).

Chronic Viral IllnessThe Clinical Immunology Section hasalso focused increasing efforts on theevaluation and treatment of patients infected with hepatitis C virus (HCV).HCV is the most common bloodborneinfection in the United States and posesa major public health problem. HCVinfects nearly one-third of all HIV-

Clinical Immunology Section

Dr. Calabrese and Elizabeth Kirchner

infected patients and is particularly aggressive in that population. In addi-tion to being a leading cause of liverdisease, HCV is associated with a widevariety of extra-hepatic rheumatic andimmunologic manifestations, especiallyvasculitis. Dr. Calabrese is interested infurther understanding why only somepatients are afflicted with these im-munologic complications and findingnew and better therapies for both thevirus as well as its immunologic mani-festations. (Vassilopoulos D, CalabreseLH. Hepatitis C virus infection and vasculitis: Implications of antiviral andimmunosuppressive therapies. Arthritisand Rheumatism 46:585-597, 2002.)

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the HIV virion

Leukocytoclastic vasculitis in a patient with hepatitis Cvirus infection with cryoglobulinemia

Investigators from the Lerner Research Institute performing neurophysiolog-ic studies as part of a three year Department of Defense grant to investigate veterans with Gulf War Syndrome and patients with chronic fatigue syn-drome done jointly with Dr. Calabrese.

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The Department includes the Centerfor Vasculitis Care and Research whichwas initiated by Dr. Hoffman, whoserved as its Director through 2004. Dr. Carol Langford, from the NationalInstitutes of Health, assumed responsi-bility as Director of the Center inAugust 2004. Several other facultywithin the Department have special expertise in vasculitis and participate in providing care for vasculitis patientsand enrolling patients in multicenterstudies. The Center enjoys numerousvisiting faculty, on sabbatical, fromthroughout the world who come tostudy and participate in clinical trialsand basic research. Extensive collabo-rations with other departments havebeen established to bring complemen-tary skills to both service and research,e.g., Dr. Stanley Hazen, Dr. Marie-Luise Brennen, (Diagnostic Cardi-ology and Cell Biology), Dr. TomHamilton and Dr. Rula Hajj-Ali (Immunology), Dr. Richard Prayson(Pathology), Drs. Kosmorsky, Perez,Perry and Lowder (Ophthalmology),Dr. Rob Lorenz (ENT) and others.

The Center also has thrived be-cause of collaborative relationships

with longstanding partners at theMayo Clinic, Johns Hopkins andBoston University. Secondary collabo-rations have been developed with morethan 30 other centers when it has beennecessary for large randomized con-trolled trials. During the past 10 years,the Center and its collaborators in theUnited States and abroad have ledsome of the first randomized controlledtrials in vasculitis and are currentlyconducting randomized controlled trials using biologic agents. Unprece-dented studies are ongoing with agentsthat block TNF, IL1 and B cell propa-gation. Linked to clinical trials arestudies that evaluate the genetic predis-position and susceptibility to a varietyof vasculitides. In collaboration withcolleagues at the University of Al-abama, the first genetics repositoryusing immortalized cell lines has beenestablished and will be made availableto geneticists throughout the UnitedStates to further evaluate disease sus-ceptibility profiles. All of these studiesare NIH funded or investigator initiatedand funded with industry partners.Listed at left is a sample of recent and ongoing studies.

Center for Vasculitis Care and ResearchProjects

Pathogenesis of WG. Analysis ofcytokine gene polymorphismsInvestigators: Yihua Zhou, DeRen Huang,Gary Hoffman

Utilization of infliximab therapyin giant cell arteritisInvestigators: Karen Rendt, Gary Hoffman

Utilization of anti-TNF therapyin Takayasu’s arteritisInvestigators: Gary Hoffman, Patrick Liang

Molecular and genomic analysis ofvessel wall in GCA Investigators: Rula Hajj-Ali, Gary Hoffman

Wegener’s Granulomatosis EtanerceptTrial (WGET) Investigators: Gary Hoffman, John Stone(PI- Hopkins)

Wegener’s Granulomatosis Genetic Reposi-tory, (WGGER)Investigators: Gary Hoffman, Jeffrey Edberg(PI-UAB), John Stone (Hopkins)

Search for Infectious Etiology ofWegener’s DiseaseInvestigators: Gary Hoffman, Herbert Vir-gin, (Wash U- PI), John Stone (Hopkins)

Short Term Cyclophosphamide followed by alternative therapy in WG Investigators: Alexandra Villa Forte, Gary Hoffman

Rituximab in ANCA-Associated VasculitisInvestigators: John Stone (Hopkins), Ulrich Specks (Mayo) – PIs; Gary Hoffman, Carol Langford, site PIs

Vasculitis Clinical Research ConsortiumInvestigators: Peter Merkel (PI-BUMC),Carol Langford, site PI; Gary Hoffman, site co-PI

Vasculitis Outcome MeasuresInvestigators: Gary Hoffman, site co-PI Development and Validation; Carol Langford, site PI

Utility of rituximab in HCV-associated cryoglobulinemiaInvestigators: Leonard Calabrese, Carol Langford

Surrogate markers of disease activityin vasculitisInvestigators: Gary Hoffman, StanleyHazen, Marie-Luise Brennen, Carmen Gota

Carol Langford, M.D., M.H.S.Director, Center for VasculitisCare and Research

The Center has derived great benefits from multi-diciplinary collaborations, such as in studies ofsurrogate markers. Pictured are Drs. Hazen andBrennen (Diagnostic Cardiology) and Drs. Gotaand Hoffman (Rheumatology).

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Dr. Soumya Chatterjee directs sclero-derma research in the Department ofRheumatic and Immunologic Diseases.He joined the Department in January2004. Dr. Chatterjee trained inrheumatology in England before moving to the United States in 1996.Formerly, he was a rheumatology fac-ulty member at Wayne State University,where his mentor, Dr. Maureen Mayes,inspired his interest in scleroderma.

Dr. Chatterjee has been involved in the following research projects:

1. An NIH/NIAMS sponsored ran-domized, double-blind, placebo-controlled multi-center phase II trial of oral type I bovine collagen (CI) as a toleragen in scleroderma.

2. A double-blind, randomized,placebo-controlled study of 122 patients at 17 centers in Europe andNorth America, to assess the effect of Bosentan on the prevention of ischemic digital ulcers in systemic sclerosis (RAPIDS 1).

3. A double-blind randomizedplacebo-controlled study looking at the efficacy of Bosentan in patientswith interstitial lung disease associatedwith systemic sclerosis [BUILD-2].

Bosentan, an orally active dual endothelin receptor antagonist, has been shown to antagonize the deleterious effects of endothelin, e.g.,vasoconstriction, hypertrophy, fibrosisand inflammation. It is FDA-approved for the treatment of severe pulmonaryarterial hypertension (PAH).

4. Dr. Chatterjee is establishing a scle-roderma database that will collect dataon patients who are followed by CCFphysicians in internal medicine and thevarious sub-specialties. Data will be usedto conduct epidemiologic, translationaland outcomes research and help in recruitment of patients for future trials.

5. Endothelial dysfunction plays a important role in the pathogenesis of vasculopathy in scleroderma. Dr.Chatterjee is collaborating with thebasic scientists at the CCF Lerner Research Institute to evaluate the microcirculation in scleroderma andthe effect of various pharmacologic interventions on microcirculatoryblood flow.

Scleroderma Care and Research

CREST variant of scleroderma

Scleroderma and severe Raynaud’s vasospasm

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Education is a cornerstone of TheCleveland Clinic’s overall mission, and members of our department are extremely active in multiple areas ofmedical education. Several of ourphysicians serve the American Collegeof Rheumatology, performing work on behalf of the Board of Directors andmany committees, including medicaleducation, annual meeting planning,professional meeting planning, work-force training and research. A numberof our faculty and one of our fellows repeatedly serve in “Meet the Profes-sor” sessions during the national ACRannual meeting.

Members of our faculty are fre-quently invited visiting professors bothnationally and internationally. Ourphysicians also have provided literaturebeyond that linked to research, servingas journal reviewers, journal and bookauthors and sitting on numerous edito-rial boards.

A key goal of the department in-cludes training the next generation of rheumatologists. Consequently, we emphasize our faculty’s role in being leaders in medical education at a departmental, institutional and international level.

Our two-year fellowship accom-modates five to six fellows (two tothree per year). An option for a thirdpost-graduate year is available andlinked to aquiring either an MPH orMSc degree. Fellows have rotations in metabolic bone disease, pediatricrheumatology, orthopaedics, spine, podiatry, the vasculitis clinic and musculoskeletal radiology. We offer a one-year vasculitis fellowship for exceptional board-eligible or board-certified rheumatologists who have a primary interest in clinical or basicscience research aspects of inflamma-tory vascular disease.

In addition, all residents in theClinic’s Internal Medicine program rotate through the Department ofRheumatic and Immunologic Diseases.

Department members are playing a vital role in the new Cleveland ClinicLerner College of Medicine of CaseWestern Reserve University. Drs.Leonard Calabrese, Chad Deal andBrian Mandell are deeply involved in providing the immunology and musculoskeletal curriculae.

Research is a crucial component of our mission. The department is oneof four major medical centers across the country involved in a VasculitisClinical Research Consortium, part of the NIH’s Rare Diseases Clinical Diseases Network. The consortium is fostering and facilitating clinical investigation in the vasculitides, whichhas been a major area of interest in our department.

Currently, the department’s researchgroup is recruiting for numerous clinical trials. Several areas of interestinclude rheumatoid arthritis in adultsand children, osteoporosis, HIV, hepa-titis C, cryoglogulinemia, scleroderma,giant cell Arteritis, Wegener’s granulo-matosis, microscopic polyangiitis andTakayasu’s arteritis. Translational re-search is ongoing in vasculitis, especiallyin regards to studies of surrogate markers of disease activity, pathogendiscovery, genetic profiles of susceptiblepatients and gene expression analyses oftargeted vessels in an attempt to identifysubstrate vulnerability to disease.

Dr. Hoffman, chairman of the Department of Rheumatic and Im-munologic Diseases, can be reacheddirectly at 216/445-6996 or 800/553-5056, ext. 56996.

Research and Education HighlightsA Report from the Chairman, Gary S. Hoffman, M.D., M.S.

Co-directors of RheumatologyEducation, Drs. Brian Mandell,Abby Abelson, and Karen Rendt

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The Rheumatology Research Support Group

From left to right: Sonya Crook, Sharon Farkas, Debora Bork and Tiffany Clark (Elizabeth Kirchner not pictured)

The Rheumatology Research SupportGroup (RRSG) helps develop, plan andadminister all clinical research projectswithin the Department of Rheumaticand Immunologic Diseases. RRSG includes Debora J. Bork, Research Administrator; Sonya Crook, R.N.,Research Nurse; Tiffany Clark, C.N.P.,Research Nurse Practitioner; SharonFarkas, R.N., Research Nurse; Eliza-beth Kirchner, C.N.P., Research NursePractitioner. The research nurses in theRRSG are experts in clinical research,having been involved in clinical trialsfor many years. They can take a studyfrom start to finish. During the study,they plan and implement patient re-cruitment strategies, educate potentialstudy participants, schedule and per-form patient visits and complete datacollection forms.

Tiffany Clark, C.N.P., is a co-investigator and study coordinator for the vasculitis research projects inthe Department.

Elizabeth Kirchner, C.N.P., hasprovided clinical research support forHIV studies, including those sponsoredby the AIDS Clinical Trials Group(ACTG). Her contributions includecollaborative relationships with col-leagues in Infectious Diseases and theACTG unit at the Case Western Re-serve University School of Medicine.

Debora Bork provides administra-tive oversight for the entire Depart-ment’s research efforts. She is a liaison

with study sponsors and a consultantproviding advice regarding study design and operational issues.

The group has many ongoing clinical trials in several different sub-specialty areas including rheumatoidarthritis in adults and children, osteo-porosis, scleroderma, large vesselvasculitis, microscopic polyangitis, Wegener’s granulomatosis, cryoglobu-linemia and hepatitis. The Departmentis one of four major medical centers

involved in the Vasculitis Clinical Re-search Consortium, a part of NIH’sRare Diseases Clinical Diseases Net-work. The Department Chairman isalso the founder of the InternationalNetwork for the Study of Systemic Vasculitides. Basic and translational research has focused on immune susceptibility profiles, target organ vulnerability in vasculitis, as well asbiochemical mediators and surrogatemarkers of vessel injury.

Gary Hoffman, M.D., M.S.Chairman, Department ofRheumatic & ImmunologicDiseases. Professor and Harold C. Schott Chair, inRheumatic & ImmunologicDiseasesOffice: 216/445-6996Specialty Interest: Vasculitis

Matthew Bunyard, M.D.Senior Staff PhysicianOffice: 216/445-3460Specialty Interest: Generalrheumatology

Leonard Calabrese, D.O.Vice Chairman, Department ofRheumatic & ImmunologicDiseases. Professor and R.J. Fasenmyer Chair in Clinical ImmunologyOffice: 216/444-5258Specialty Interests: AIDS, vasculitis, myositis, chronicfatigue syndrome

John Joseph Carey, M.D.Clinical AssociateOffice: 216/445-6996Specialty Interests: Generalrheumatology and metabolicbone disease

Soumya Chatterjee, M.D., M.S.Senior Staff PhysicianOffice: 216/444-9945Specialty Interests: Scleroderma, rheumatoidarthritis, lupus, myositis

John Clough, M.D.Senior Staff PhysicianOffice: 216/444-5627Specialty Interests: Systemiclupus, immune deficiencydisease, rheumatoid arthritis

Chad Deal, M.D. Head, Center for Osteoporosisand Metabolic Bone DiseaseOffice: 216/444-6575Specialty Interest: Osteoporosis, metabolicbone disease

Miriam Delaney, M.D.Associate Head, Center for Osteoporosis & MetabolicBone DiseaseOffice: 216/444-9654Specialty Interests: Osteoporo-sis, transplant bone disease,metabolic bone disease, disor-ders of calcium homeostasis,steroid osteoporosis

Philip Hashkes, M.D., M.Sc.Head, Section of PediatricRheumatologyOffice: 216/445-8525Specialty Interests: Pediatricrheumatology, drug therapyof arthritis, periodic fever syndromes

Anna Koo, M.D.Senior Staff Physician Office: 216/444-3247Specialty Interests: Therapeu-tic apheresis, generalrheumatology

Carol Langford, M.D., M.H.S.Director, Center for VasculitisCare and ResearchOffice: 216/445-6056Specialty Interest: Vasculitis

Brian Mandell, M.D., Ph.D.Program Co-Director,Rheumatic and ImmunologicDiseases. Professor ofMedicine, Vice Chairman ofMedicine for EducationOffice: 216/445-6580Specialty Interests: Vasculitis,cyrstal induced arthritis, systemic lupus, myositis, multisystem involvement fromautoimmune disease

Staff Directory

Daniel Mazanec, M.D.Cleveland Clinic Spine Institute,Rheumatic and ImmunologicDiseasesOffice: 216/444-6191Specialty Interest: Medical spine

Karen Rendt, M.D.Program Co-Director,Rheumatic and ImmunologicDiseasesOffice: 216/445-4236Specialty Interests: Vasculitis,systemic lupus erythematosus,rheumatoid arthritis, psoriaticarthritis, other inflammatoryarthritides, other autoimmuneillnesses

Raymond Scheetz, M.D.Senior Staff PhysicianOffice: 216/444-5625Specialty Interests: Metabolicjoint disease, rheumatoidarthritis, lupus, relapsing polychondritis, myositis

William Wilke, M.D.Senior Staff PhysicianOffice: 216/444-5624Specialty Interests: Drug treat-ment of rheumatoid arthritis,giant cell arteritis, polymyalgiarheumatica, fibromyalgia,chronic fatigue syndrome, Sjogren’s syndrome

Abby Abelson, M.D.Associate Staff PhysicianOffice: 216/839-3840Specialty Interests: Generalrheumatology, metabolicbone disease

Rula Hajj-Ali, M.D.Clinical AssociateOffice: 216/444-9643Specialty Interests: Generalrheumatology, vasculitis

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Calabrese LH, Albrecht M, Young J, McCarthyP, Haug M, Jarcho J, Zackin R. Successful car-diac transplantation in an HIV-1-infected patientwith advanced disease. N Engl J Med2003;348:2319-2324.

Hoffman GS, Cid MC, Hellmann DB, et al. Amulticenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexatetreatment for giant cell arteritis. Arthritis Rheum2002;46:1309-18.

Gota C, Calabrese LH. Induction of clinical au-toimmune disease by therapeuticinterferon-alpha. Autoimmunity 2003;36:511-518.

Maksimowicz-McKinnon K, Bhatt DL, Cal-abrese LH. Recent advances in vascularinflammation: C-reactive protein and other in-flammatory biomarkers. Curr Opin Rheumatol2003;16:18-24.

Hajj-Ali RA, Furlan A, Abou-Chebel A, Cal-abrese LH. Benign angiopathy of the centralnervous system: Cohort of 16 patients with clini-cal course and long-term followup. ArthritisRheum 2002;47:662-669.

Deal C. The use of intermittent human parathy-roid hormone as a treatment for osteoporosis.Curr Rheumatol Rpts 2004;6:49-58.

Kifor O, Moore FD, Delaney M, Garber J,Hendy GN, Butters R, Gao P, Cantor T, Kifor I,Brown EM, Wysolmerski J. “Autoimmune” Fa-milial Hypocalciuric Hypercalcemia (FHH)Caused by Blocking Autoantibodies to the Cal-cium-Sensing Receptor (CaR). J Clin EndocrinolMetab 2003;88:60-72.

Delaney MF, Hurwitz S, Shaw J, LeBoff MS.Bone density changes with once-weekly rise-dronate in postmenopausal women. J ClinDensitom 2003 Spring;6(1):45-50.

Furspan PB, Chatterjee S, Freedman RR. In-creased tyrosine phosphorylation mediates thecooling-induced contraction and increased vascu-lar reactivity of Raynaud’s disease. ArthritisRheum 2004;50:1578-1585.

Hashkes PJ. Profile of a pediatric rheumatologypractice in Israel. Clin Exp Rheumatol2003;21:123-128.

Hashkes PJ, Friedland O, Jaber L, Cohen HA,Wolach B, Uziel Y. Decreased pain threshold inchildren with growing pains. J Rheumatol2004;31:610-613.

Hoffman GS, Calabrese LH. Vasculitis 2003: Ed-itors. Clinical and Experimental Rheumatology2003;21(6)(Suppl 32):S1-S139.

Hoffman GS, Thomas-Golbanov CK, Chan J,Akst LM, Eliachar I. Treatment of subglotticstenosis, due to Wegener’s granulomatosis, withintralesional corticosteroids and dilation. JRheumatol 2003;30:1017-1021.

Hoffman GS, Calabrese LH, Liang P. Vasculitis.In: Smolen JS, Lipsky PE, eds. Targeted therapiesin rheumatology. London; New York: MartinDunitz; 2003:583-601.

Hoffman GS. Large-vessel vasculitis: unresolvedissues. Arthritis Rheum 2003;48:2406-2414.

Hoffman GS, Markel PA, Brasington RD,Lenschow DJ, Liang P. Anti-tumor necrosis factor therapy in patients with difficult to treatTakayasu’s arteritis. Arthritis Reum 2004;50:2296-2304.

Langford CA, Sneller MC. Biologic therapies inthe vasculitides. Curr Opin Rheumatol2003;15:3-10.

Langford CA, Talar-Williams C, Barron KS,Sneller MC. Use of a cyclophosphamide induc-tion methotrexate maintenance regimen for thetreatment of Wegener’s granulomatosis: ex-tended follow-up and rate of relapse. Am J Med2003;114;463-9.

Langford CA, Balow JE. New insights into theimmunopathogenesis and treatment of small ves-sel vasculitis of the kidney. Curr Opin NephrolHypertens 2003;12:267-72.

Langford CA. Wegener’s granulomatosis: currentand upcoming therapies. Arthritis Res Ther2003;5:180-191.

Robinson MR, Lee SS, Sneller MC, Lerner R,Langford CA, Talar-Williams C, Cox TA, ChanCC, Smith JA. Tarsal-conjunctival disease associ-ated with Wegener’s granulomatosis.Ophthalmology 2003;110:1770-1780.

Liang P, Tan-Ong M, Hoffman GS. Takayasu’sarteritis: vascular interventions and outcomes. J Rheumatol 2004;31:102-106.

Maksimowicz-McKinnon K, Hoffman GS.Crohn’s disease plus Takayasu’s arteritis: morethan coincidence? Ann Med Interne2003;154:75-76.

Vassilopoulos D, Younossi ZM, Hadziyannis E,Boparai N, Yen-Lieberman B, Hsi E, Villa-ForteA, Ball E, Kimberly RP, Calabrese LH. Study ofhost and virological factors of patients withchronic HCV infection and associated laboratoryor clinical autoimmune manifestations. Clin ExpRheumatol 2003;21(Suppl 32):101-111.

Vassilopoulos D, Niles JL, Villa-Forte A, ArroligaAC, Sullivan EJ, Merkel PA, Hoffman GS. Preva-lence of antineutrophil cytoplasmic antibodies inpatients with various pulmonary diseases or mul-tiorgan dysfunction. Arthritis Rheum2003;49:151-155.

Vassilopoulos D, Calabrese LH. Rheumatic as-pects of human immunodeficiency virus infectionand other immunodeficient states. In: HochbergMC, ed. Rheumatology. 3rd ed. Edinburgh; St.Louis: Mosby; 2003;2:1115-1129.

Zhou Y, Huang D, Farver C, Hoffman GS. Rela-tive importance of CCR5 and antineutrophilcytoplasmic antibodies in patients with We-gener’s granulomatosis. J Rheumatol2003;30:1541-1547.

Recent Books and Symposia:Hoffman GS, Weyand CM, eds. InflammatoryDiseases of Blood Vessels. New York: MarcelDekker, Inc.; 2002.

Hoffman GS, Stone JH, eds. Proceedings of the 10th International Vasculitis and ANCAWorkshop. Cleve Clinic J Med; 2002;69(Suppl 2):SII1-192.

Department of Rheumatic and Immunologic Diseases: Selected Recent Publications

15

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