South Boston Scleroderma South Boston Scleroderma and Lupus Health Studyand Lupus Health Study

Suzanne K. CondonSuzanne K. CondonAssociate CommissionerAssociate Commissioner

Director, Bureau of Environmental HealthDirector, Bureau of Environmental HealthMassachusetts Department of Public HealthMassachusetts Department of Public Health

January 2010

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OverviewOverview

▪ ▪ IntroductionIntroduction• Reasons for the Reasons for the

StudyStudy BEH/CAPBEH/CAP• Community Advisory Community Advisory

Committee (CAC)Committee (CAC)

▪ ▪ Study DesignStudy Design

▪ ▪ ResultsResults• Exposure AssessmentExposure Assessment• Spatial AnalysisSpatial Analysis• Prevalence/IncidencePrevalence/Incidence

▪ ▪ SummarySummary▪ ▪ RecommendationsRecommendations

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BackgroundBackground

In 1998, residents of South Boston and In 1998, residents of South Boston and then State Senator (now Congressman) then State Senator (now Congressman)

Stephen Lynch contacted the MDPH with Stephen Lynch contacted the MDPH with concerns of a suspected cluster of concerns of a suspected cluster of

scleroderma among women who grew up scleroderma among women who grew up in South Boston.in South Boston.

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Bureau of Environmental Health

Indoor Air Quality Community Sanitation Program

Community Assessment ProgramChildhood Lead Poisoning

Prevention Program

Environmental EpidemiologyProgram

Food Protection Program

Environmental ToxicologyProgram

Radiation Control Program

Environmental Health EducationAnd Outreach Program

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Community Assessment ProgramCommunity Assessment ProgramBureau of Environmental Health, Massachusetts Department of Public HealthBureau of Environmental Health, Massachusetts Department of Public Health

Triage phone calls regarding Triage phone calls regarding environmental and disease concernsenvironmental and disease concerns

Evaluate frequency and patterns of Evaluate frequency and patterns of disease in the populationdisease in the population

Respond to concerns about unusual Respond to concerns about unusual patterns of diseasepatterns of disease

Investigate possible associations between Investigate possible associations between environmental exposures and diseaseenvironmental exposures and disease

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Key Stakeholders and Key Stakeholders and CollaboratorsCollaborators

South Boston Community Advisory Committee (CAC)South Boston Community Advisory Committee (CAC) State Senator (now Congressman) Stephen LynchState Senator (now Congressman) Stephen Lynch Representative (now State Senator) Jack HartRepresentative (now State Senator) Jack Hart Massachusetts Department of Public Health (MDPH)Massachusetts Department of Public Health (MDPH) Co-investigatorsCo-investigators

Drs. Felson, Korn, and Desai at Boston Medical Center (Dr. Korn Drs. Felson, Korn, and Desai at Boston Medical Center (Dr. Korn passed away in 2005)passed away in 2005)

Drs. Kalish and Massarotti at Tufts Medical CenterDrs. Kalish and Massarotti at Tufts Medical Center Area hospitals and rheumatologistsArea hospitals and rheumatologists South Boston Community Health Center (SBCHC)South Boston Community Health Center (SBCHC)

Dr. Harvey BidwellDr. Harvey Bidwell Ms. Nina LevMs. Nina Lev

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Study TimelineStudy Timeline Fall 1998 MDPH first contacted by South Boston residents and Fall 1998 MDPH first contacted by South Boston residents and

Congressman LynchCongressman Lynch

1999 Began development of study protocol and sought IRB approval1999 Began development of study protocol and sought IRB approval

2000-2003 Began outreach, collaboration with co-investigators, recruiting 2000-2003 Began outreach, collaboration with co-investigators, recruiting cases and controls, and confirming diagnoses through medical examscases and controls, and confirming diagnoses through medical exams

2004 Conducted personal interviews and began data management2004 Conducted personal interviews and began data management

2005-2007 Conducted data analyses of questionnaire data and performed 2005-2007 Conducted data analyses of questionnaire data and performed exposure assessment (air dispersion modeling, hazardous waste site exposure assessment (air dispersion modeling, hazardous waste site evaluations) and spatial and temporal cluster analysesevaluations) and spatial and temporal cluster analyses

2008 External peer review2008 External peer review

2009 Response to peer review comments and preparation of final report2009 Response to peer review comments and preparation of final report

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What is Scleroderma (SSc)?What is Scleroderma (SSc)?

Rare, chronic connective tissue diseaseRare, chronic connective tissue disease

Characterized by hardening of the skin and Characterized by hardening of the skin and internal organsinternal organs

Mainly affects women during child-bearing years Mainly affects women during child-bearing years and early menopausal years (peak incidence is and early menopausal years (peak incidence is between 45 to 54 years of age)between 45 to 54 years of age)

Recent studies suggest African American Recent studies suggest African American women may be more likely to develop SScwomen may be more likely to develop SSc

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What is Lupus (SLE)?What is Lupus (SLE)?

A rare, chronic inflammatory diseaseA rare, chronic inflammatory disease

Characterized by inflammation of various parts Characterized by inflammation of various parts of the body (skin, joints, kidneys, blood vessels)of the body (skin, joints, kidneys, blood vessels)

90% of patients are women and usual age at 90% of patients are women and usual age at onset is between 15 and 40onset is between 15 and 40

African American women are 3-4 times more African American women are 3-4 times more likely to develop lupus than white womenlikely to develop lupus than white women

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What do we know about SSc and What do we know about SSc and SLE?SLE?

More common in womenMore common in women Genetic predisposition + environmental Genetic predisposition + environmental

triggertrigger Genetics, hormones, environmental Genetics, hormones, environmental

exposures such as silica dust and organic exposures such as silica dust and organic solvents thought to be involvedsolvents thought to be involved

More research is needed to identify More research is needed to identify cause(s)cause(s)

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Study ApproachStudy Approach

Statistical challenges when conducting a Statistical challenges when conducting a study of a disease with relatively low study of a disease with relatively low prevalence (like scleroderma)prevalence (like scleroderma)

Similarities in some factors associated Similarities in some factors associated with both scleroderma and lupuswith both scleroderma and lupus

Combining SSc and SLE in one Combining SSc and SLE in one investigation might increase the chances investigation might increase the chances of determining environmental contributions of determining environmental contributions in South Bostonin South Boston

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Study AimsStudy Aims

1)1) To identify current/former residents of To identify current/former residents of South Boston with SSc or SLE in order to South Boston with SSc or SLE in order to calculate more accurate calculate more accurate prevalence/incidence rates for South prevalence/incidence rates for South BostonBoston

2)2) To identify possible contributing factors To identify possible contributing factors (environmental and non-environmental) (environmental and non-environmental) among individuals with SSc and SLEamong individuals with SSc and SLE

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Outreach EffortsOutreach Efforts

Creation of the CACCreation of the CAC Contact with local hospitals and rheumatologistsContact with local hospitals and rheumatologists Fliers to community organizations and centers, Fliers to community organizations and centers,

churches, schools, local businesses and media churches, schools, local businesses and media outlets outlets

Community fundraisers and events including Community fundraisers and events including local charity walks and road raceslocal charity walks and road races

Community talk show for cable television with Community talk show for cable television with CAC members and researchersCAC members and researchers

Features on ABC Nightline and in Features on ABC Nightline and in SelfSelf Magazine Magazine

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Study DesignStudy Design

Retrospective case-control studyRetrospective case-control study People with SSc and SLE identified People with SSc and SLE identified

through area hospitals, rheumatologists, through area hospitals, rheumatologists, death record searches and self-reportdeath record searches and self-report

Controls recruited through residential listsControls recruited through residential lists ““Matched” to cases by gender, age, and Matched” to cases by gender, age, and

residential historyresidential history

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Study DesignStudy Design

Medical examination to confirm diagnosisMedical examination to confirm diagnosis Standardized questionnaire:Standardized questionnaire:

DemographicsDemographics Residential, occupational, family, medical, and Residential, occupational, family, medical, and

reproductive historiesreproductive histories Questions regarding hobbies and recreational Questions regarding hobbies and recreational

activities in South Bostonactivities in South Boston

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Information Gathered Through Personal Information Gathered Through Personal InterviewsInterviews

Medical historyMedical history Diseases such as cancer, Parkinson’s disease, rheumatoid Diseases such as cancer, Parkinson’s disease, rheumatoid

arthritis, hypertension, etc.arthritis, hypertension, etc. MedicationsMedications

Reproductive historyReproductive history Number and timing of childrenNumber and timing of children Timing of menarche and menopauseTiming of menarche and menopause Hormone useHormone use

Lifestyle factorsLifestyle factors Smoking, alcohol useSmoking, alcohol use

DemographicsDemographics Race/ethnicityRace/ethnicity Socio-economic statusSocio-economic status EducationEducation

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Information Gathered Through Personal Information Gathered Through Personal InterviewsInterviews

Complete residential history to determine likelihood of individuals Complete residential history to determine likelihood of individuals diagnosed with SSc/SLE sharing common exposure opportunities in diagnosed with SSc/SLE sharing common exposure opportunities in South BostonSouth Boston

Complete occupational historyComplete occupational history Working in dry cleaning, textiles, film developing, etc.Working in dry cleaning, textiles, film developing, etc. Contact with specific chemicals such as benzene, diesel oil, silica, etc.Contact with specific chemicals such as benzene, diesel oil, silica, etc.

HobbiesHobbies Pottery, stone sculpting, automotive repair, etc. (due to silica/solvent Pottery, stone sculpting, automotive repair, etc. (due to silica/solvent

exposure concerns)exposure concerns) Environmental factorsEnvironmental factors

Proximity to Coastal Oil, Boston Edison, other hazardous waste sites to Proximity to Coastal Oil, Boston Edison, other hazardous waste sites to determine possible exposures to solventsdetermine possible exposures to solvents

MaDEP provided information on air emissions related to BECoMaDEP provided information on air emissions related to BECo Swimming at various beaches (Carson, Pleasure Bay, Castle Island, L Swimming at various beaches (Carson, Pleasure Bay, Castle Island, L

Street, Reserve Channel)Street, Reserve Channel)

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Study Results:Study Results:Participation/Response RateParticipation/Response Rate

45 individuals identified with a confirmed 45 individuals identified with a confirmed diagnosis of scleroderma or lupusdiagnosis of scleroderma or lupus 41 agreed to participate41 agreed to participate

830 individuals selected as potential controls830 individuals selected as potential controls 219 agreed to participate219 agreed to participate 154 met study eligibility criteria154 met study eligibility criteria

Total study population = 195Total study population = 195 Individuals with SSc or SLE = 41Individuals with SSc or SLE = 41 Controls = 154Controls = 154

Overall participation rate = 22% (195 study Overall participation rate = 22% (195 study participants/875 eligible individuals)participants/875 eligible individuals)

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Prevalence versus IncidencePrevalence versus Incidence

Prevalence = the number of individuals Prevalence = the number of individuals with a disease at a specified with a disease at a specified pointpoint in time in time

Incidence = the number of Incidence = the number of newnew diagnoses diagnoses of a disease reported during a defined of a disease reported during a defined periodperiod of time of time

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ResultsResultsScleroderma Prevalence and IncidenceScleroderma Prevalence and Incidence

SB Study SB Study PopulationPopulation

Estimates Estimates Reported in Reported in

Medical Medical LiteratureLiterature

PrevalencePrevalence

(cases per (cases per 100,000)100,000)

33.433.4 27.627.6

IncidenceIncidence

(cases per (cases per 100,000 100,000 annually)annually)

1.131.13 0.96-1.930.96-1.93

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ResultsResultsLupus Prevalence and IncidenceLupus Prevalence and Incidence

SB Study SB Study PopulationPopulation

Estimates Estimates Reported in Reported in

Medical Medical LiteratureLiterature

PrevalencePrevalence

(cases per (cases per 100,000)100,000)

26.726.7 14.6-149.514.6-149.5

IncidenceIncidence

(cases per (cases per 100,000 100,000 annually)annually)

1.411.41 1.51-5.561.51-5.56

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ResultsResultsExposure AssessmentExposure Assessment

Participants with a family history of specific Participants with a family history of specific rheumatic diseasesrheumatic diseases11, particularly parents, , particularly parents, had a 2-fold increase in SSc/SLE riskhad a 2-fold increase in SSc/SLE risk

Findings consistent with previous reports Findings consistent with previous reports of a positive family historyof a positive family history

1 1 Includes Rheumatoid Arthritis, Raynaud’s Disease, Lupus, Includes Rheumatoid Arthritis, Raynaud’s Disease, Lupus, Scleroderma, Mixed Connective Tissue Disease, or Thyroid Disease Scleroderma, Mixed Connective Tissue Disease, or Thyroid Disease

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ResultsResultsExposure AssessmentExposure Assessment

Previous participant diagnosis of Previous participant diagnosis of rheumatoid arthritis (RA) resulted in 4-fold rheumatoid arthritis (RA) resulted in 4-fold increase in SSc/SLE riskincrease in SSc/SLE risk

However,However, Inflammatory arthritis is one of 11 ACR Inflammatory arthritis is one of 11 ACR

criteria for diagnosis of SLE and possibly a criteria for diagnosis of SLE and possibly a pre-cursor/early stage of SScpre-cursor/early stage of SSc

More common osteoarthritis often More common osteoarthritis often mistaken for RAmistaken for RA

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ResultsResultsExposure AssessmentExposure Assessment

Hobby-related Hobby-related possible possible silica exposures silica exposures showed association with increased risk of showed association with increased risk of SSc/SLESSc/SLE

However,However, Detailed analysis of hobby-related Detailed analysis of hobby-related

exposures to silica (including types of exposures to silica (including types of silica exposures and frequency of silica exposures and frequency of exposure) and/or solvents did not show exposure) and/or solvents did not show increased risk associated with SSc or SLEincreased risk associated with SSc or SLE

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ResultsResultsOpportunities for environmental exposureOpportunities for environmental exposure

Detailed analyses showed no increased Detailed analyses showed no increased risk associated with swimming at Carson risk associated with swimming at Carson Beach, Pleasure Bay, Castle Island, L St. Beach, Pleasure Bay, Castle Island, L St. Beach, or Reserve ChannelBeach, or Reserve Channel

No increased risk seen in relation to No increased risk seen in relation to modeled emissions from BECo plantmodeled emissions from BECo plant

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ResultsResultsResidential clustering/opportunities for environmental Residential clustering/opportunities for environmental

exposureexposure

No indication of any unusual geographic No indication of any unusual geographic or time patterns of residential addresses or time patterns of residential addresses between 1950 and 2000between 1950 and 2000

Case distribution followed population Case distribution followed population density patternsdensity patterns

No increased risk seen in relation to No increased risk seen in relation to residential proximity to hazardous waste residential proximity to hazardous waste sites including Coastal Oilsites including Coastal Oil

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Study LimitationsStudy Limitations

Low participation rate of 22% (primarily Low participation rate of 22% (primarily due to control participation)due to control participation)

Small sample sizeSmall sample size Limited statistical powerLimited statistical power Imprecise estimatesImprecise estimates

Exposure assessment limited by historical Exposure assessment limited by historical nature of the studynature of the study

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SummarySummary The prevalence of scleroderma in South Boston was The prevalence of scleroderma in South Boston was

higher than expected.higher than expected. A family history of specific rheumatic diseases was the A family history of specific rheumatic diseases was the

factor most statistically significantly associated with factor most statistically significantly associated with increased risk of scleroderma and lupus.increased risk of scleroderma and lupus.

A previous diagnosis of rheumatoid arthritis was A previous diagnosis of rheumatoid arthritis was associated with scleroderma and lupus among current/ associated with scleroderma and lupus among current/ former South Boston residents.former South Boston residents.

The study did not find any geographic or temporal The study did not find any geographic or temporal clustering of cases in South Boston.clustering of cases in South Boston.

No associations were found linking the risk of developing No associations were found linking the risk of developing SSc or SLE with potential environmental exposures SSc or SLE with potential environmental exposures either as a result of living in South Boston or due to either as a result of living in South Boston or due to hobbies or recreational activities.hobbies or recreational activities.

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RecommendationsRecommendations

Research is currently underway involving clinical Research is currently underway involving clinical registries that may better evaluate the nature of registries that may better evaluate the nature of gene-environment interactions and characterize gene-environment interactions and characterize the role of environmental factors the role of environmental factors

No further MDPH study in South Boston is No further MDPH study in South Boston is planned, however, Boston Medical Center planned, however, Boston Medical Center recently became a recruitment site for the NIH recently became a recruitment site for the NIH national scleroderma registrynational scleroderma registry

Registration is open to all individuals who meet Registration is open to all individuals who meet eligibility criteria for the registryeligibility criteria for the registry