American Family Physicians

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Systemic Sclerosis/Scleroderma:

A Treatable Multisystem DiseaseMONIQUEHINCHCLIFF,MD,andJOHNVARGA,MDNorthwestern University, Feinberg School of Medicine, Chicago, Illinois

Systemic sclerosis (systemic sclero-derma)isaconnectivetissuediseaseassociated with autoimmunity, vas-culopathy, and brosis.The annualincidenceisestimatedtobe10to20casesper1millionpersons,1 whereas theprevalenceisourto253casesper1millionpersons.2Raynaud phenomenon and scleroderma(hardeningotheskin)aretheclinicalhall-marks o the disease. Pulmonary brosis

andpulmonaryarterialhypertensionaretheleadingcausesodeath.3

Epieilg Clssifcti

Patientswhohavesystemicsclerosiscanbeclassiedintodistinctclinicalsubsetswithdierentpatternsoskinandinternalorganinvolvement,autoantibodyproduction,andpatient survival.4 Themost common sub-sets are limited cutaneous (approximately60percentopatientswithsystemicsclero-sis) and diuse cutaneous (approximately

35percentopatientswithsystemicsclerosis).

Table 1includestheclinicaleaturesolim-itedanddiusecutaneoussystemicsclerosis,andTable 2 3,4presentstheclinicalassocia-tionsbetweensubtypesandautoantibodies.The limited cutaneous subset is diagnosedwhenskinthickeningislimitedtoareasdis-taltotheelbowsandknees.CREST(calcino-siscutis,Raynaudphenomenon,esophagealdysunction, sclerodactyly, telangiectasia)syndrome is a variant o limited cutane-

ous systemic sclerosis. Systemic sclerosissine scleroderma is a less common subset(approximately 5 percent o patients withsystemicsclerosis)thatisassociatedwiththecharacteristicinternalorganmaniestationsothediseasewithoutskinthickening.Localized orms o scleroderma, such as

linearscleroderma andmorphea, primarilyaect childrenand, incontrast tosystemicsclerosis, are not associated with Raynaudphenomenon or signicant internal organmaniestations. Scleroderma mimics are

uncommon conditions that are associated

Systemic sclerosis (systemic scleroderma) is a chronic connective tissue disease o unknown etiology that causes wide-spread microvascular damage and excessive deposition o collagen in the skin and internal organs. Raynaud phenome-non and scleroderma (hardening o the skin) are hallmarks o the disease. The typical patient is a young or middle-age

woman with a history o Raynaud phenomenon who presents with skin induration and internal organ dysunction.Clinical evaluation and laboratory testing, along with pulmonary unction testing, Doppler echocardiography, andhigh-resolution computed tomography o the chest, establish the diagnosis and detect visceral involvement. Patients

with systemic sclerosis can be classied into two distinct clinical subsets with dierent patterns o skin and internal

organ involvement, autoantibody production, and survival. Prognosis is determined by the degree o internal organinvolvement. Although no disease-modiying therapy has been proven eective, complications o systemic sclerosisare treatable, and interventions or organ-specic maniestations have improved substantially. Medications (e.g., cal-cium channel blockers and angiotensin-II receptor blockers or Raynaud phenomenon, appropriate treatments orgastroesophageal refux disease) and liestyle modications can help prevent complications, such as digital ulcersand Barrett esophagus. Endothelin-1 receptor blockers and phosphodiesterase-5 inhibitors improve pulmonary arte-rial hypertension. The risk o renal damage rom scleroderma renal crisis can be lessened by early detection, promptinitiation o angiotensin-converting enzyme inhibitor therapy, and avoidance o high-dose corticosteroids. Optimalpatient care includes an integrated, multidisciplinary approach to promptly and eectively recognize, evaluate, andmanage complications and limit end-organ dysunction. (Am Fam Physician. 2008;78(8):961-968, 969. Copyright 2008 American Academy o Family Physicians.)

Patient information:

A handout on sclero-derma, written by UmaJayaraman, MD,AFPEdit-ing Fellow, is provided onpage 969.

The online versiono this articleincludes supple-

mental content at http://www.aap.org/ap.

Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright 2008 American Academy of Family Physicians. For the private, noncommercial

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962 American Family Physician www.aap.org/ap Volume 78, Number 8 October 15, 2008

withskininduration,butlackRaynaudphe-nomenon, internal organ involvement, andautoantibodies.Otherdiseases,suchasmixed

orundierentiatedconnectivetissuediseaseandoverlapsyndrome,shouldbeconsideredbeoreestablishingadiagnosis(Table 3).

Cliicl Presetti

A systemic sclerosis diagnosis is based onclinicalndings,whichhavesubstantialhet-erogeneityandvaryingmaniestations.Theclassic clinical presentation is a young ormiddle-agewomanwithRaynaudphenome-nonandskinchangesaccompaniedbymus-culoskeletaldiscomortandgastrointestinalsymptoms.Table 4summarizesthesystemicmaniestationsothedisease.

Raynaud PhEnomEnon

Cold-inducedRaynaudphenomenon is themost common maniestation o systemicsclerosis,occurringinmorethan95percentopatients.Patientsngersmaychangeromwhite(vasospasm)toblue-purple(ischemia)to red (hyperemia); this is precipitated byexposuretocoldtemperatureoremotional

stress.IdiopathicorprimaryRaynaudphe-nomenontypicallyoccursinemaleadoles-cents, and is not associated with ischemiccomplications. In contrast, secondaryRay-naud phenomenon tends to occur later inlieandotenleadstotissuedamage.Table 5

presentsthecharacteristicsoprimaryandsecondary Raynaud phenomenon. Physicalndings o secondary Raynaud phenom-enonincludecyanosisandsignsoischemicdamagetothengers,suchasdigitalpitting(Figure 1A), visible capillaries on the nail

bed, ischemic ulcerations (Figure 1B), and

Tble 2. Cliicl asscitis Betwee Ssteic SclersisSbtpes Sclerer-Specifc attibies

Autoantibody

Subtype (percentage with

subtype and autoantibody) Clinical associations

Antinuclear antibody Limited cutaneous and

diuse cutaneous

(95 percent [nucleolarpattern is most specic])

Pulmonary arterial

hypertension

Interstitial lung

disease

Anticentromere

antibody

Limited cutaneous

(60 to 80 percent)

Diuse cutaneous

(2 to 5 percent)

Pulmonary arterial

hypertension

Digital ulcerations or

digital loss

Antitopoisomerase-1

antibody (anti-Scl-70)

Diuse cutaneous

(20 to 40 percent)

Rapidly progressive

skin thickening

Scleroderma renal

crisis

Pulmonary brosis

Inormation rom reerences 3 and 4.

SoRT: KEy RECommEndaTIonS FoR PRaCTICE

Clinical recommendation

Evidence

rating Reerences

Patients with signicant internal organ involvement are oten asymptomatic until the late stages o systemic

sclerosis; thereore, routine monitoring or underlying disease is essential ater the initial diagnosis.

C 11, 12

Doppler echocardiography, pulmonary unction testing, and high-resolution computed tomography o the

chest should be perormed at diagnosis o systemic sclerosis and at regular intervals thereater.

C 7, 8

Treating active interstitial lung disease with oral cyclophosphamide (Cytoxan) or one year modestly improveslung unction, dyspnea, skin thickening, and health-related quality o lie in patients with systemic sclerosis.

B 25, 27

Initiation and continuation o angiotensin-converting enzyme inhibitors are recommended in patients with

scleroderma renal crisis, even in the presence o elevated creatinine levels.

B 11, 16

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-

oriented evidence, usual practice, expert opinion, or case series. For inormation about the SORT evidence rating system, go to http://www.aap.

org/apsort.xml.

Tble 1. distigisig Cliicl Fetres LiiteCtes dise Ctes Ssteic Sclersis

Feature Limited cutaneous Diuse cutaneous

Skin brosis Areas distal to the elbows

and knees; may aect

the ace

Areas proximal or

distal to the elbows

and knees; may

aect the ace

Typical orm o lung

involvement

Pulmonary arterial

hypertension

Interstitial lung disease

Characteristic

visceral organ

involvement

Severe gastroesophageal

refux disease and

Raynaud phenomenon

Scleroderma renal

crisis

Physical examination

ndings

Telangiectasia, calcinosis

cutis, sclerodactyly, digital

ischemic complications

Tendon riction rubs,

pigment changes


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Ssteic Sclersis/Sclerer

October 15, 2008 Volume 78, Number 8 www.aap.org/ap American Family Physician 963

pterygium inversusunguis (i.e.,distal nail bedadher-encetotheventralsuraceothenailplate).

SKIn manIFESTaTIonS

Thedegreeoskinthickeningdependsonthesubtypeanddurationodisease.Earlyinthedisease,diuseswellingothengersandhands(Figure 2A)mayprecedeskinthickeningandleadtoaninitialundierentiatedarthri-

tisdiagnosis.Otherearlydermatologicchangesincludeshinyskin(Figure 2B)orpigmentchanges(Online Fig-

ure A1).Astheskinthickenson thengers(sclero-dactyly), hands and orearms (limited cutaneous

systemicsclerosis),ortrunk(diusecutaneoussystemicsclerosis), the systemic sclerosis diagnosis becomesincreasinglyapparent.Facialthickening,whichcanoccurwiththelimited

cutaneous and diuse cutaneous subsets, oten leadstodicultyopeningthemouth (Online Figure A2).Othercutaneousmaniestationsincludehairlosson

involvedskin;telangiectasiaontheace,buccalmucosa,

chest, and hands; and calcinosis cutis (Online Figures

B1 and B2).Withdiseaseprogression,ulcerationsoverjointsandfexioncontracturesothengers,wrists,andelbowsmayoccur.

muSCuLoSKELETaL manIFESTaTIonS

Musculoskeletal involvement is common in early sys-temicsclerosisandotenpromptspatientstoseekmedi-calevaluation.Puyhandswitharthralgiaandmyalgiamayleadtodicultymakingast.Palpableoraudiblerictionrubsmaybenotedovertheextensorandfexortendonsothehands,knees,andankles.Becauseric-tionrubsarehighlyassociatedwithdiusecutaneoussystemicsclerosis,5thepresenceorictionrubsshouldpromptearlydiagnosisandscreeningorcharacteristicinternalorganinvolvement.

GaSTRoInTESTInaL manIFESTaTIonS

Symptoms related to gastroesophageal refux disease(GERD)anddysphagiaorchangesinbowelhabitssecond-arytointestinaldysmotilityarecommoninpatientswithearly systemic sclerosis. Esophageal disease is virtuallyuniversalinpatientswiththelimitedcutaneoussubsetandcancauseconsiderablepathology,eveninasymptomaticpatients.Bacterialovergrowthinthesmallbowel(blindloop syndrome) with concomitant nutritional decien-cies(olateandvitaminB

12),malabsorption(steatorrhea),

andpseudo-obstructionmaybeapresentingcondition,but it ismore likely to complicate established disease.Anemiamaybeasignogastricantralvascularectasia(watermelonstomach).Watermelonstomachreerstothecharacteristicendoscopicndingolongitudinalrowsosacculatedandectaticmucosalvesselsintheantrumothestomach,whichresemblethestripesonawatermelon.

Cplictis

Internal organ complications are common in patientswithsystemicsclerosisbutareseldomsymptomaticuntilthelatestagesothedisease;thus,routinescreeningor

internalorgancomplicationsisessential.

PuLmonaRy

Dyspnea is a latemaniestation o systemic sclerosisrelatedlungdisease;however,lunginvolvementiscom-monandis theleadingcauseodeathinpatientswithsystemicsclerosis.3,6Systemicsclerosiscanaectthelungparenchyma (interstitial lung disease) and the pulmo-nary blood vessels (pulmonary arterial hypertension).Thus,routinescreeningwithpulmonaryunctiontestsandDopplerechocardiographyinallpatientsisessentialortheearlydetectionointerstitiallungdiseaseandpul-

monaryarterialhypertension,respectively.7,8

Tble 3. Sclerer Spectr disrers

Disorder Variants

Diuse cutaneous

systemic sclerosis

Limited cutaneous

systemic sclerosis

CREST syndrome

Systemic sclerosissine scleroderma

Localized

scleroderma

Linear scleroderma

En coup de sabre

Morphea

Generalized

Plaque

Mixed connective

tissue disease

Features o systemic sclerosis,

polymyositis, and SLE

Overlap syndromes Systemic sclerosis plus polymyositis,

rheumatoid arthritis, or SLE

Scleroderma

mimics

Amyloidosis

Chronic grat-versus-host disease

Diuse asciitis with eosinophilia

Eosinophilia-myalgia syndrome

Nephrogenic brosing dermopathy

Paraneoplastic syndromes

Scleredema

Scleromyxedema (papular mucinosis)

Toxic oil syndrome

Undierentiated

connective

tissue disease

Multiple nonspecic, serologic or clinical

abnormalities that do not meet ACR

criteria or rheumatic disease

ACR = American College o Rheumatology; CREST = calcinosis cutis,

Raynaud phenomenon, esophageal dysunction, sclerodactyly, telan-

giectasia; SLE = systemic lupus erythematosus.


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Tble 4. Sste-Specifc Ivlveet Ssteic Sclersis

System Maniestation History and physical examination fndings

Cardiovascular Abnormal cardiac conduction

Congestive heart ailure

Diastolic dysunction (secondary to let

ventricular brosis)

Pericardial eusion

Edema, extra heart sound (S3)

Digital ischemic changes Abnormal capillaries on the nail old

Acro-osteolysis

Digital pitting or ulceration

Pterygium inversus unguis (i.e., distal nail bed adherence

to the ventral surace o the nail plate)

Raynaud phenomenon Color changes in the ngers precipitated by exposure to cold

temperature or emotional stress: white (vasospasm), blue-purple

(ischemia), and red (hyperemia)

Gastrointestinal Bacterial overgrowth Anemia

Barrett esophagus or strictures

Gastric antral vascular ectasia

(watermelon stomach)

Anemia

Gastrointestinal bleedingGastroesophageal refux disease Chronic cough

Dental erosions

Dysphagia

Halitosis

Pharyngitis

Intestinal malabsorption Wasting, diarrhea

Pseudo-obstruction Obstructive symptoms

Genitourinary Sexual dysunction Dyspareunia, impotence

Musculoskeletal Flexion contractures Prayer or steeple sign (inability to directly bring hands together

because ngers will not ully extend)

Muscle atrophy (secondary to myositis[overlap syndrome] or deconditioning) Weakness

Puy hands Diusely swollen hands without synovitis

Inability to make a tight st

Tendon riction rubs Palpable or audible rubs with active fexion or extension o ngers,

wrists, knees, or ankles

Pulmonary Interstitial lung disease Basilar, course crackles

Cough

Dyspnea on exertion

Pulmonary ar terial hypertension Dyspnea on exertion

Extra heart sound (right-sided S3)

Fixed splitting o S2

Right ventricular heaveSyncope

Renal Renal crisis Abnormal unduscopy examination ndings

Hypertension

Schistocytes on peripheral smear

Skin Calcinosis Calcium deposits along extensor tendons and on digits

Hyper- or hypopigmentation Tanned skin on sun-exposed and unexposed areas or loss o pigmentation

Pruritus Excoriations, scabbing

Telangiectasias Matte-like vascular abnormalities that blanche on palpation

Thickened skin Reduced oral aperture

Sclerodactyly

Tight skin

S2 = second heart sound; S3 = third heart sound.


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REnaL

Beore the introduction o angiotensin-convertingenzyme (ACE)inhibitors, sclerodermarenalcrisiswas

themostatalcomplicationosystemicsclerosis.Sclero-dermarenalcrisisdevelopsin3to10percentoallpatientswithsystemicsclerosisandin10to20percentothosewithrapidlyprogressivediusecutaneoussystemicscle-rosis;thegreatestriskoccurswithintherstthreeyearsothe disease.11,12 Other risk actors include high-dosecorticosteroid use (greater than 15 mg o prednisonedaily),13thepresenceotendonrictionrubs,asymptom-aticpericardialeusion,new-onset anemia,older age,andpregnancy.11,14Althoughantitopoisomerase-1(anti-Scl-70)antibodiesareamarkerodiusecutaneoussys-temicsclerosis,theirpresencedoesnotincreasetherisko renal crisis.15 Patientswith scleroderma renal crisischaracteristicallypresentwithsudden-onsetacceleratedhypertension that is oten associatedwithprogressiveoliguricrenalailurewithproteinuria,microangiopathicanemia,andmicroscopichematuria.Tento15percentopatientswithsclerodermarenalcrisisarenormoten-sive,buthypertensivewhencomparedwiththeirbase-linebloodpressuremeasurements.16Thus,regularbloodpressuremonitoring is essential or early detection osclerodermarenalcrisis.

CaRdIaC

Increasing evidence suggests that systemic sclerosiscommonly aects the heart. Cardiac involvement insystemicsclerosisincludesmyocardialdisease,conduc-tionsystemdeects,arrhythmias,orpericardialdisease.Scleroderma renal crisis and pulmonary disease canalsoleadtocardiacdysunction. 17Single-photonemis-sionCToasymptomaticpatientscandetectabnormalmicrocirculationandvasoreactivityomyocardialves-sels.18Cardiacbrosiscannowbeassessedusingcardiacmagneticresonanceimaging,butnolong-termstudieshave assessed the incidence andoutcomes opatients

withcardiacbrosis.

dIFFEREnTIaL dIaGnoSIS

Theinitialevaluationopatientswithsuspectedsystemicsclerosis includes a complete blood count; a compre-

hensivechemistrypanel;andserologicstudies,includ-ingantinuclear,anticentromere,andantitopoisomeraseantibodies.Creatinekinasemeasurements,erythrocytesedimentation rate, and C-reactive protein measure-mentsmaybeuseul;elevatedresultssuggestmyositis,vasculitis, malignancy, or overlap o systemic sclero-siswithanotherautoimmunedisease. Table 3includessclerodermaspectrumdisorders.

Tretet

Becauseo theheterogeneity o systemic sclerosis andpotentialtreatmenttoxicity,therapymustbeindividual-izedtoeachpatientsclinicalpresentationandneeds.Nodisease-modiyingagenthasbeenproventopreventorreversebrosis,althoughretrospectivestudiesandcaseseries show that d-penicillamine (Cuprimine), myco-phenolate moetil (Cellcept), and cyclophosphamide(Cytoxan)maybeeectiveinsomepatients.Therehasbeensignicantimprovementintreatmentsororgan-speciccomplications(Table 6),especiallyRaynaudphe-nomenon,sclerodermarenalcrisis,andgastrointestinalandpulmonarycomplications.

Raynaud PhEnomEnon

Digital amputationbecauseo ischemic complicationsusually is not necessary i aggressive oral vasodilatortherapyisinitiatedinpatientswithrequentorsevereepisodes o Raynaud phenomenon. Commonly usedagents include long-acting calcium channel blockers(e.g.,niedipine[Procardia])19andangiotensin-IIrecep-torblockers (e.g., losartan [Cozaar]).20 There are lim-iteddata on theuseophosphodiesterase-5 inhibitors(e.g.,sildenal[Revatio])ortreatingsecondaryRaynaudphenomenon.21Patientswithrecurrentischemiculcersmaybenetrombosentan(Tracleer),anoralendothe-

lin-1 receptor inhibitor. In one recent study, patients

a

Figre 2. Early dermatologic manifestations of systemic sclerosis. (A) Diffusely puffy hands are a common initial pre-sentation. (B) Shiny skin suggests impending skin thickening.

B


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withischemiculcerswhoweretreatedwithbosentan had a 48 percent reduction innewulcerormation;however,therewasno

improvementinexistingulcers.22

Autonomicnervoussystemmodulationwithsympatho-lytic agents (e.g., prazosin [Minipress]) ismodestly benecial andmay be associatedwithadverse eects.23 Patients with symp-tomatic relie rom sympathetic ganglionicblockademay benet rom surgical digitalsympathectomy,althoughtherearenocon-trolledtrialsoitseectiveness.

GaSTRoInTESTInaL ComPLICaTIonS

In addition to therapies to control gastro-

intestinal symptoms and prevent GERDcomplications, patients with systemic scle-rosis and gastric antral vascular ectasiamay require endoscopic laser coagulationtodecrease the riskobleeding. Intestinalpseudo-obstructionotenisdiagnosedatthetime o laparotomy, although conservativenonsurgical management with bowel rest,antibioticstotreatbacterialovergrowth,andjudicious useo promotilityagentsmay beeective. Antibiotics, including riaximin(Xiaxan), and correction o nutritionaldecienciesarethemainstaysotherapyorintestinalovergrowth.24

PuLmonaRy ComPLICaTIonS

Resultsromtworecentrandomizedtrialssuggestthatoralorintravenouscyclophosphamideisbenecialinpatientswith early and progressive interstitial lung disease.25-27Lung physiology (FVC) and health-related outcomes(dyspnea,skin thickening,qualityolie,and unction)improvedmodestlyateroneyearocyclophosphamidetherapywithorwithoutsubsequenttreatmentwithaza-

thioprine(Imuran)andprednisone.25-27

Itisimportanttonotethatalthoughcyclophosphamidehasmodestbenetsorlungunction,thereisariskohemorrhagiccystitisandbladdercancer,bonemarrowsuppression,inection,inertility, and possibly late hematologic malignancies.Althoughseveralsmallstudiessuggestapotentialroleortheimmunomodulatory,antibroticdrugmycophenolatemoetilinthetreatmentointerstitiallungdisease,con-trolledtrialsarelacking.28Oralbosentan,sildenal,paren-teralepoprostenol(Flolan)andtreprostinil(Remodulin),andinhalediloprost(Ventavis)are usedto treat symp-tomaticpulmonaryarterialhypertension.29-34Inpatients

withhypoxemia,continuousoxygenmaybeneeded.

REnaL ComPLICaTIonS

Allpatientswithsystemicsclerosisshouldbeadvisedtochecktheirbloodpressureathomeona regularbasis.Anypersistentelevationsshouldpromptamedicaleval-uationandtreatmentwithACEinhibitorsisclerodermarenalcrisisissuspected.ACEinhibitorsshouldbeusedtocontrolhypertensiondespiterisingserumcreatininelevelsortheinitiationodialysisbecausetheyareessen-

tialorpreservingandrestoringrenalunction.35

Prgsis

Lie expectancy in patients with systemic sclerosis isdeterminedbasedontheextentandseverityointernalorganinvolvement.Propermanagementrequiresregularmonitoringandjudicioususeoorgan-specictherapies.Patientsmay benet rom reerral to specialty centerswithexpertiseintreating thevariouscomplicationsothedisease. Sel-help resources are available rom theSclerodermaFoundation(http://www.scleroderma.org)andtheSclerodermaResearchFoundation(http://www.

sclerodermaresearch.org).

Tble 6. Tretets r org-Specifc Cplictis Ssteic Sclersis

Complication Treatment

Raynaud

phenomenon

-Adrenergic blockers

Angiotensin-II receptor blockers

Long-acting calcium channel blockers (dihydropyridines)

Pentoxiylline (Trental)

Stellate ganglionic blockades, digital sympathectomy

Skin brosis Immunomodulatory drugs (d-penicillamine

[Cuprimine], mycophenolate moetil [Cellcept],

cyclophosphamide [Cytoxan])

Gastroesophageal

refux disease

Antacids

Histamine H2

blockers

Proton pump inhibitors

Intestinal dysmotility

or bacterial

overgrowth

Antibiotics

Correction o nutritional deciencies

Promotility agents

Pulmonary brosis

or alveolitis

Immunomodulatory drugs

Initial therapy with oral or intravenous cyclophosphamideMaintenance therapy with azathioprine (Imuran)

Pulmonary arterial

hypertension

Diuretics

Endothelin-1 receptor inhibitors (bosentan [Tracleer])

Oxygen

Phosphodiesterase-5 inhibitors (sildenal [Revatio])

Prostacyclin analogues (epoprostenol [Flolan],

treprostinil [Remodulin], iloprost [Ventavis])

Wararin (Coumadin) is sometimes used in patients

with recurrent pulmonary thromboembolic disease

secondary to pulmonary arterial hypertension

Scleroderma renal

crisis

Dialysis

Short-acting angiotensin-converting enzyme inhibitors

NOTE: Complications are listed in descending order o requency.


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Te atrs

MONIQUE HINCHCLIFF, MD, is a clinical instructor o rheumatology atNorthwestern Universitys Feinberg School o Medicine, Chicago, Ill., and

is associate clinical director o the universitys Scleroderma Program. Dr.Hinchcli received her medical degree rom Rosalind Franklin Universityo Medicine and Science, Chicago. She completed an internal medicineresidency at Norwalk (Conn.) Hospital, an afliate o the Yale UniversitySchool o Medicine, and a rheumatology ellowship at Northwestern Uni-versitys Feinberg School o Medicine.

JOHN VARGA, MD, is a proessor o medicine at Northwestern UniversitysFeinberg School o Medicine and is director o the universitys SclerodermaProgram. He is chair o the Scleroderma Foundations Medical and ScientifcAdvisory Board. Dr. Varga received his medical degree rom New York Uni-versity School o Medicine, New York. He completed an internal medicineresidency at Brown University School o Medicine, Providence, R.I., and arheumatology ellowship at Boston (Mass.) University School o Medicine.

Address correspondence to Monique Hinchcliff, MD, 240 E. Huron Ave.,McGaw Pavilion, M300, Chicago, IL 60611 (e-mail: [email protected]). Reprints are not available from the authors.

Author disclosure: Nothing to disclose.

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