mackenzie lind, epid 624 presentation, 3/30/15. affects 52.5 million adults in the us (includes...

Rheumatoid arthritis, osteoarthritis, and traumatic arthritis

Mackenzie Lind, EPID 624 Presentation, 3/30/15

Arthritis: Prevalence/Basic Epidemiology

Affects 52.5 million adults in the US (includes rheumatoid arthritis, gout, lupus, other arthritis, fibromyalgia) Projected to increase to 67 million by 2030

22.7% of adults- arthritis diagnosed by a doctor Jumps to ~30% for age 45-64 and ~50% for adults >

65 Most common cause of disability among US

adults!!! Many have activity limitations, work limitations, and

report lower quality of life Costs: 128 billion dollars (2003)

http://www.cdc.gov/arthritis/data_statistics/arthritis_related_stats.htm

Arthritis: Prevalene

http://www.terraclouds.com/images/Global-Arthritis-Statistics.gif

Arthritis: Prevalence

http://www.cdc.gov/arthritis/data_statistics/race.htm

Arthritis: Disability

http://www.cdc.gov/arthritis/data_statistics/national-statistics.html

Arthritis: Impairment

http://www.cdc.gov/arthritis/data_statistics/national-statistics.html

Arthritis: Cost

Arthritis: Comorbidities

http://www.cdc.gov/arthritis/data_statistics/comorbidities.htm

Rheumatoid arthritis (RA) Chronic systemic inflammatory disease Autoimmune Cause is mostly unknown, but thought to

be due to the presence of specific antibodies Antibodies to rheumatoid factor (RF), anti-

citrullinated protein antibodies (ACPA) Key features: Synovitis -> pannus

formation (thick layer of granulation tissue, releases inflammatory cytokines) -> destruction of cartilage and bone

Information from Sattar HA, Fundamentals of Pathology, 2011

RA: Pathophysiology

http://www.medical-artist.com/assets/images/Stages-of-rheumatoid-arthritis.jpg

RA: Clinical presentation

Arthritis Stiffness in the morning, improves with activity, as day

continues Symmetric involvement of joints, polyarthritis▪ Commonly the PIP joints (fingers), wrists, elbows, ankles

knees (in contrast to osteoarthritis) Systemic symptoms (e.g. fever, weight loss,

muscle pain) Rheumatoid nodules Vasculitis Baker cyst (in knee) Also: Pleural effusions, lung fibrosis,

lymphadenopathyInformation from Sattar HA, Fundamentals of Pathology, 2011

RA: Basic Epidemiology

1.5 million adults with RA (2007) 75% women! Most commonly occurs in middle age (40-60),

onset=highest in 60s Population prevalence: 0.5-1% Lifetime risk: 4% (women), 3% (men) Incidence: 41/100,000 Increased mortality in RA (2.3x)

higher in individuals with ACP and RF antibodies 40% of deaths due to heart disease

Individuals with RA have increased risk for depression, 1.7x greater (Lin et al. 2015)Information from Sattar HA, Fundamentals of Pathology, 2011

American College of Rheumatology fact sheethttp://www.cdc.gov/arthritis/data_statistics/arthritis_related_stats.htm

RA: Epidemiology

RA=19th most common for years lost to disability

Individuals with RA report more loss of function, worse functional status (even more than OA),worse quality of life

RA accounts for ~22% of all arthritis-related deaths

Costs: $2785/year (US 2000) (more than OA) Lifetime $61,000-122,00 (US 1995)

http://www.cdc.gov/arthritis/basics/rheumatoid.htm

RA: Epidemiology

Helmik et al. 2008

RA: Epidemiology

http://buyprovailencheap.org/wp-content/uploads/2013/10/Rheumatoid-arthritis-country.jpg

RA: Genetics

RA is heritable Estimate from twin and family studies is ~60% due to additive

genetic effects (Frisell et al. 2013, MacGregor et al. 2000, van der Woude et al. 2009)

Identification of specific genes that confer risk First genes were in the Human Leukocyte Antigen (HLA) group

of the Major Histocompatibility Complex (MHC) (Kochi, Suzuki, & Yamamoto 2014)

Most well known= HLADR-4, HLADRB-1 Many others, also involved in immunological functions: PTPN4,

CTLA-4, PADI4, MIF (Orozco, Rueda, & Martin, 2006)

Genome-Wide Association Studies (GWAS) have identified 101 risk loci for RA (Kochi, Suzuki, & Yamamoto 2014)

Also, some genetic overlap with other autoimmune disorders as well as chronic diseases (psoriatric arthrtis, cancer, diabetes, heard disease)

RA: Environmental risk factors Smoking *Most widely accepted*

Accounts for 1 of every 6 new cases of RA▪ Also have gene x environment interactions (complex)

1.3-2.4x increased risk to develop arthritis Relationship is most significant among individuals with the

ACPA antibody Other air pollutants

Occupation exposures, silica Reproductive

Oral contraceptives, breast feeding (decreased risks) Alcohol

Moderate amounts protective Socioeconomic status

Will discuss more at the end!Hoovestol and Mikuls, 2011

RA: Prevention

Primary prevention: This is challenging for RA, since genetics

play a significant role but many specific RFs are unknown

Don’t smoke Secondary prevention??? Tertiary prevention

Medication to control/delay the progression of the disease

RA: Treatment

NSAIDs and corticosteroids Disease-modifying anti-rheumatoid

drugs (DMARDs) [non-biologic] Biologic drugs: e.g. anti-TNF alpha

drugs (adalimumab, infliximab, etanercept)

Also PT and OT

http://www.cdc.gov/arthritis/basics/rheumatoid.htm

Osteoarthritis (OA)

Most common! Also known as degenerative joint

disease Generally develops after age 40 Cause unknown

“wear and tear” Defined by changes on radiography

as well as symptoms (pain/swelling)


OA: Clinical Presentation

Arthritis Joint stiffness in the morning, gets worse

throughout the day Oligoarticular Knees, hips, lumbar spine, distal interphalangeal

joints (DIPs), proximal interphalangeal joints (PIPs) Progression: disruption of cartilage,

eburnation- bone on bone, osteophytes (bony growths) can form, often in fingers (Heberden nodes in DIPs, Bouchard nodes in PIPs)


OA: Pathology

http://arthro.wpengine.netdna-cdn.com/wp-content/uploads/2014/01/image001-1.jpg

OA: Pathology

http://img.webmd.com/dtmcms/live/webmd/consumer_assets/site_images/media/medical/hw/h9991469_003.jpg

http://upload.wikimedia.org/wikipedia/commons/9/9c/Heberden-Arthrose.JPG

OA: Epidemiology

Affects 27 million Americans >25 y/o (Lawrence et al. 2008)

<50 y/o- more common in men, then switches to women

13.9% (25 or older), 33.6% (65 or older)

Approximately 1 in 2 people develop OA in knee by age 85

For obese individuals: 2/3 risk of lifetime knee OA

1 in 4 develop hip OA

http://www.niams.nih.gov/Health_Info/Osteoarthritis/default.asp

http://www.cdc.gov/arthritis/basics/osteoarthritis.htm

OA: Disease Impact

Increased mortality (~2x) But only ~6% of all arthritis deaths Significant effect on quality of life

Knee OA among top 5 leading causes of disability in adults

High in DALYs and YLDs 80% of patients with OA have limitations to movement Poor health, lost work

70% of all arthritis hospitalizations! Cost: in part due to high cost of surgery

28.5 billion (knee replacements), 13.7 billion (hip) 13 million in job-related costs

http://www.cdc.gov/arthritis/basics/osteoarthritis.htm

OA: Risk factors

Age Trauma (joint injury),

overuse/repetitive use Occupational

Construction, cleaning…hard labor Obesity (for knee especially)

Excess pressure on joints Certain deformities *Hand RA=risk for knee RA

http://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Osteoarthritis/

OA: Genetics

Genetic contributions to OA Heritability estimated at 35-65% Genes implicated:

Collagen genes (joint structure) for early onset▪ E.g. COL11A1/A2, Col1A1

Immune system▪ Interleukins, e.g. IL-1, IL-6, IL-4

Estrogen (women)▪ Estrogen receptor

Vitamin D▪ Vitamin D receptor

New findings: novel loci (NCOA3, ALDH1A2), in regulatory genes, alters gene expression (Loughlin, 2015)

Fernandez-Moreno, Rego, Carreira-Garcia, & Blanco, 2008

OA: Prevention

Primary: Diet/exercise▪ Obesity and knee OA

Secondary: Diet/exercise

Tertiary Pain management Exercise Weight control Surgery (if severe) *Treatment primarily consists of managing pain,

maintaining activity, and weight control

Post-traumatic arthritis (PTA) Form of osteoarthritis

~12% of individuals with OA have PTA 5.5 million people

Occurs following joint injury (e.g., sports, accident, etc)

The injury damages cartilage/bone Need to prevent injuries! Treatment- exercise, medicine, maintain

proper weight Possibly surgery- for debriding, reconstruction,

or replacement, if severe.http://my.clevelandclinic.org/health/diseases_conditions/hic_Arthritis/hic-post-traumatic-arthritis

Other types of arthritis and related disorders

Ankylosing spondylitis Involves axial skeleton

Psoriatic arthritis Psoriasis and joint pain

Reactive arthritis Develops after STI (Chlamydia), GI infection (e.g. Salmonella,

Campylobacter) Can’t see, can’t pee, can’t climb a tree

Infectious arthritis Bacterial infection- N. gonorrhoae (sexually active young

adults), S. aureus (kids) Gout

Deposits of monosodium urate crystals in joints Due to hyperuriciemia, often pain in big toe


Osteoporosis

Defined as a reduction in bone mass (trabecular), as compared to a reference group’s bone mineral density (BMD) Measured via DXA scans

Instead, bone is porous- which increases the risk of fracture (compression fractures)

‘Silent Disease’ Often undetected until a broken bone occurs

After age 30: lose bone mass each year (~1%) Accelerated with poor diet, no weight-bearing

exercise, low estrogenSattar HA, Fundamentals of PathologyCDC

Osteoporosis

https://www.arthritiswa.org.au/useruploads/images/osteoporosis_diagram-64.gif

Hip fractures

Common with osteoporosis (from falls, etc)

Dangerous- public health concern! Increased risk of death during 12 months

following hip fracture Afterwards- hard to get around, lose mobility,

etc Costly

Most expensive of all osteoporosis fractures

Info from NHANES fact sheethttp://www.cdc.gov/nchs/data/nhanes/databriefs/osteoporosis.pdf

Osteoporosis: Epidemiology 54 million Americans have low bone mass and

osteoporosis 43.4 million: low bone mass 10.2 million: osteoporosis The total number is estimated to increase to 64.4

million by 2030 1 in 2 women and 1 in 4 men > 50 y/o will

break a bone due osteoporosis Costs: $19 billion dollars every year, up to 25.3

billion by 2010 Medicare pays for 80% of broken bones due to

osteoporosisInfo from National Osteoporosis Association

Projected increases in osteoporosis

http://nof.org/files/nof/public/content/file/2833/upload/923.pdf

Osteoporosis: Epidemiology

Data from NHANEShttp://www.cdc.gov/nchs/data/nhanes/databriefs/osteoporosis.pdf

Osteoporosis: Risk factors

Age Gender (women more than men) Ethnicity (White/Asian) Body type/size Family history (genetics) Other

Alcohol, smoking, activity level, medications, calcium/Vit D levels, low estrogen, anorexia

Info from NIH fact sheethttp://www.niams.nih.gov/Health_Info/Bone/Osteoporosis/osteoporosis_ff.asp

Osteoporosis: Prevention (and treatments)

Primary prevention Diet- adequate calcium and Vitamin D Exercise Avoid smoking and excess alcohol consumption Bone density scans at appropriate age

Secondary prevention Also diet/exercise Medications, such as bisphosphonates like Alendronate

(antiresorptive) or anabolic drugs like Teriparatide (similar to parathyroid hormone), that can increase bone formation

Tertiary prevention Taking measures to prevent falls, important in the elderly Medications

Vitamin D Recommendations

http://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

Calcium recommendations

http://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/

Research

mackenzie lind, epid 624 presentation, 3/30/15. affects 52.5 million adults in the us (includes...

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