02 03-05-12 overview of rheumatic diseases color

8/2/2019 02 03-05-12 Overview of Rheumatic Diseases Color

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OVERVIEW OFRHEUMATIC DISEASES

Elaine M. Greifenstein, MD

Clinical Associate Professor

Internal Medicine

Susan Bruce, PharmD, BCPS

Associate Professor & Chair

Pharmacy Practice


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Concept Map


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Rheumatologic Diseases (1)

Mainly involve the musculoskeletal system May be self-limited or localized problems

improve with symptomatic treatment

ex: bursitis, tendinitis, strains, sprains

May require urgent diagnosis & treatment

ex: septic arthritis, crystal-induced arthritis, temporal arteritis

Often accompanied by systemic features

malaise & fatigue, fever, weight loss


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Often accompanied by multi-organ systeminvolvement

hematologic

skin eye

lung

kidney Challenging to diagnose

Complicated to treat at times


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May be the presenting complaint in neoplasticdiseases & endocrinopathies

Comprehensive history & physical are essential to

diagnosis! diagnosis can be made 75% of the time on H&P alone

Serologies used to support diagnosis

should be used judiciously to avoid false-positive results


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Insert figure 331-1


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COMMON RHEUMATICDISEASES

OsteoarthritisRheumatoid arthritis (RA)

Systemic lupus erythematosus (SLE)


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Osteoarthritis

Degenerative joint disease

DJD

Second leading cause of adults receiving SocialSecurity Disability payments in US

Estimated 59.4 million Americans affected by 2020 Prevalence increases with age

Caused by multiple factors: macro & micro trauma,

genetics, biochemical changes, inflammation &mechanical forces

Cartilage failure imbalance of dynamic degradative& repair process in cartilage, synovium & bone


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Rheumatoid Arthritis (RA)

An inflammatory arthritis commonly presenting as asymmetric polyarthritis

Associated with significant morning stiffness

Affects approximately 1% of the population

Significant morbidity & mortality

Women to men 3:1

Suspected familial predisposition

Etiology unknown, but inflammatory process causing

damage being elucidated


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Systemic Lupus Erythematosus (SLE)

Multi-systemic inflammatory connective tissue disease Unknown etiology, but humoral & cellular immuneabnormalities exist

Clinical manifestations range from mild to life-threatening Clinical course characterized by acute & chronicexacerbations & remissions

Most common between ages of 15 & 40 years Women to men 8:1

Prevalence of 1/1,000 population


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From: Rheumatology Image Bank byAmerican College of Rheumatology


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OTHER RHEUMATICDISEASES

Other ArthritidesConnective Tissue Diseases

Vasculitides


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Other Arthritides

Crystalline arthritis gout

pseudogout/CPPD

Seronegative spondyloarthropathies psoriatic arthritis

ankylosing spondylitis

reactive arthritis enteropathic arthritis

undifferentiated spondyloarthropathy


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Connective Tissue Diseases

Inflammatory myopathies(polymyositis/dermatomyositis)

Sjgrens syndrome

Scleroderma (systemic sclerosis/CREST syndrome) Mixed connective tissue disease

Antiphospholipid antibody syndrome

Adult-onset Stills disease

Relapsing polychondritis

Sarcoid arthropathy


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Vasculitides

Takayasus arteritis

Giant cell arteritis (Temporal arteritis)

Polymyalgia rheumatica

Polyarteritis nodosa

Wegeners granulomatosis

Churg-Strauss syndrome

Microscopic polyangiitis

Henoch-Schnlein purpura

Cryoglobulinemic vasculitis


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CLASSIFICATION OFRHEUMATIC DISEASES


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CLASSIFICATION

Inflammatory Disorders

Versus

Non-Inflammatory Disorders


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Inflammatory Disorders (1)

Characterized by: systemic symptoms

fever, stiffness, weight loss, malaise & fatigue

signs of joint inflammation on physical exam

erythema, warmth, swelling, pain

lab evidence of inflammation

elevated ESR, elevated CRP, decreased albumin, elevated platelets

joint stiffness common after prolonged rest (morning stiffness)

duration > 1 hour suggests an inflammatory disorder

improves with activity


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Inflammatory Disorders (2)

May be immune-mediated: systemic lupus erythematosus (SLE)

rheumatoid arthritis (RA)

May be reactive: reactive arthritis (ReA) / Reiters syndrome

May be infectious:

gonococcal arthritis (GC arthritis)

May be crystal-induced:

gout

pseudogout (calcium pyrophosphate deposition CPPD)


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Non-Inflammatory Disorders

Characterized by: absence of systemic symptoms

pain without erythema or warmth

pain increases with use

pain increases with weight-bearing

normal lab tests

joint stiffness

stiffness < 1 hour, typically < 15 minutes

common conditions

osteoarthritis (OA), fibromyalgia, traumatic conditions


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Inflammatory Disorders Non-Inflammatory Disorders

Symptoms

Morning stiffness Prolonged > 1 hour Brief

Peak discomfort After prolonged inactivity After prolonged use

Constitutional Present Absent

Locking/Instability Uncommon Implies internal derangement

Symmetry Common Occasional

Signs

Tenderness Over entire exposed joint +/-, unusual

Inflammation Common Unusual

Multi-organ disease Often Absent

Abnormal labs Often Absent


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CLASSIFICATION

Articular Disorders

Versus

Non-Articular Disorders


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Articular Disorders (1)

Pain may originate from articular structures: synovial membrane, cartilage, intra-articular ligaments,

capsule, juxta-articular bone surfaces

Pain may originate from periarticular structures: bursae, tendons, muscle, bone, nerve, skin

Articular disorders:

deep or diffuse pain worsens with active & passive movement

physical exam deformity, warmth, swelling, effusion,crepitus


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From: Rheumatology Image Bank by American College of Rheumatology


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From: Rheumatology Image Bank by American College of Rheumatology


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Articular Disorders (2)

Synovitis inflammation of synovial membrane that covers the joint

boggy, tender swelling around the joints

diagnosis requires palpation during physical exam can occur in any joint with a synovial lining

easiest to detect in finger & wrist joints


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Non-Articular Disorders

Non-articular disorders: usually have point tenderness

usually have increased pain with active but not passive

movement absence of deformity or swelling on physical exam


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Important History in Evaluation ofArthritis Symptoms

Classification of arthritis symptoms based onhistory:

acuteness of onset

degree of inflammation of joints number of joints involved

temporal pattern of joint involvement

distribution of joint involvement age & sex of patient


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CLASSIFICATION

Number &

Pattern of Joints Involved


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Number of Joints Involved

Acute monoarthritis suggests infection!

others gout, crystal-induced arthritis, trauma

Asymmetric oligoarticular arthritis (< 5 joints) particularly of lower extremities

typical of OA or ReA

Symmetric polyarticular arthritis (> or = 5 joints) typical of RA or SLE


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Temporal Pattern of Joint Involvement (1)

Migratory pattern present in certain joints for a few days, then remits &

reappears in other joints

examples rheumatic fever, gonococcal arthritis, earlyLyme disease

Additive pattern

begins in few joints & persists with subsequent involvementin additional joints

examples rheumatoid arthritis, systemic lupus


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Temporal Pattern of Joint Involvement (2)

Intermittent pattern

repetitive attacks of acute polyarthritis with remissionbetween attacks

examples polyarticular gout, sarcoid arthritis, Reiterssyndrome/reactive arthritis, psoriatic arthritis


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Distribution of Joint InvolvementDisease Common Joints Joints Spared

Rheumatoid arthritis Wrist, MCP, PIP, elbow,

glenohumeral, Cspine, hip,knee, ankle, MTP

DIP, thoracolumbar spine

Osteoarthritis 1st CMC, DIP, PIP, Cspine,thoracolumbar spine, hip,

knee, 1st

MTP, toe IP

MCP, wrist, elbow, ankle

Polyarticular gout 1st MTP, instep, heel,

ankle, knee

Axial, shoulder, hip

Psoriatic arthritis Knee, ankle, MTP, toe IP,wrist, MCP, hand IP, axial

Sarcoid arthritis Ankle, knee Axial


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Psoriatic Arthritis (1)

Psoriatic arthritis (PsA): occurs in up to 10% of patients with psoriasis

occurs equally in men & women

mean age of onset 35-45 years other features: enthesitis, dactylitis, skin changes, & nail

changes

one of few inflammatory arthritides that can affect the DIPjoints

enthesitis may present as heel & sole of foot pain


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Ankylosing Spondylitis (AS)

Chronic inflammatory arthritis of the back morning stiffness > 1 hour & night pain

involves articular joints of spine

sacroiliac joints (SI joints)

may be associated with peripheral arthritis of shoulders,hips, & knees

possible extra-articular manifestations: anterior uveitis,fractures of fused spine, C1-2 subluxation, restrictive lung

disease, aortic regurgitation

Male to female ratio 3-9:1

Strong association with HLA-B27


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Reactive Arthritis (Reiters Syndrome)

Reactive arthritis (ReA): non-infectious arthritis

occurs after a prior genitourinary (GU) infection or entericinfection with bloody diarrhea

implicated organisms with initial infection:

Chlamydia trachomatis

Shigella, Salmonella, Campylobacter, Yersinia

classic triad: uveitis, urethritis, arthritis (knees, ankles, feet) strongly associated with HLA-B27


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Age & Sex of Patient in Setting ofPolyarticular Symptoms

Women aged 25-50 rheumatoid arthritis, systemic lupus, osteoarthritis,

fibromyalgia

Men aged 25-50 Reiters syndrome, ankylosing spondylitis, osteoarthritis,

hemochromatosis

Patients over age 50

osteoarthritis, rheumatoid arthritis, CPPD disease,polymyalgia rheumatica, paraneoplastic syndrome


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APPROACH TOMONOARTHRITIS


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Features & Causes of Monoarthr it is (2)


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Type Features Causes

Trauma *Common*History is diagnostic*Rare in hospitalizedpatients

*Fracture*Hemarthrosis*Internal derangement

Avascular necrosis (AVN)of bone

*Uncommon*More common in hip,knee, shoulder

*Risk factors includetrauma, corticosteroid use,alcohol use/abuse

Tumors *Uncommon *Benign or malignant

*Primary or metastatic

Systemic diseases withmonoarticular onset

*Uncommon*Follow-up over time maybe necessary for diagnosis

*Psoriatic arthritis*SLE*Reactive arthritis

*RA

Features & Causes of Monoarthr it is (2)


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ARTHROCENTESIS &SYNOVIAL FLUID ANALYSIS


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ARTHROCENTESIS


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Indications for Arthrocentesis

Suspected infection Suspected crystalline disease

Post-traumatic effusion (to rule out hemarthrosis)

New effusions of uncertain diagnosis Pain relief for large or tense effusions

Intra-articular steroid injections for treatment


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Possible Complications of Arthrocentesis

Bleeding (local hematoma or hemarthrosis) Iatrogenic infection (rare; 1:50,000 procedures)

Rupture of tendon or periarticular structure

Nerve damage Allergic reaction to injected medications

Post-injection flare

SC atrophy due to steroids (more common withfluoridated steroids)


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SYNOVIAL FLUIDANALYSIS

General Evaluat ion of Synovial Flu id


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Exam Normal Non-

inflammatory

Inflammatory Septic Hemorrhagic

Viscosity High High Low Variable Variable

Color Colorless tostraw

Straw to yellow Yellow Variable Bloody

Clarity Transparent

(can readthroughfluid)

Transparent Cloudy Opaque Opaque

WBCs 50,000>95%

PMN

RBCs>>WBCs

Diff Dx OA, SLE, AVN,trauma, tumors

RA, PsA, ReA,crystal arthritis,SLE, infections

Bacteria,AFB,fungi, RA

Trauma,hemophilia,PVN

General Evaluat ion of Synovial Flu id


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APPROACH TOPOLYARTHRITIS


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Patient Case (1) 34-year-old African American woman presents with a

3-month history of joint pain, stiffness, & swelling Reports wrists, fingers, knees and feet are involved

Initially had 30 minutes of morning stiffness, but now

has progressed to 2 hours Had similar episode which lasted several weeksabout 2 months after her second pregnancy 2 years

ago treated with an Rx NSAID & acute episoderesolved

Using OTC ibuprofen 800mg tid without relief

Malar rash is present


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Patient Case (2)

Denies any other medical illnesses or

hospitalizations

Sexually active monogamous without any history

of sexually transmitted disease

Denies fevers, infections, alopecia, oral ulcers,

conjunctivitis, iritis, pleuritic chest pain, pericarditis,Raynauds, alopecia, sicca symptoms, diarrhea,blood in stool, muscle weakness, jaundice,hepatitis, blood transfusions, or illicit drug use


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Patient Case (3)

Afebrile with normal vital signs

Heart & lungs normal without rubs

Abdomen normal without hepatosplenomegaly

ENT exam normal Mild synovitis & tenderness of dorsal wrists, MCPjoints, PIP joints, & MTP joints with guarded range of

motion Painful knee ROM bilaterally with small effusions &diffuse warmth

Di C l P i i h Ch i


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Diseases Commonly Presenting with Chronic

Inflammatory Polyarticular Symptoms

Rheumatoid arthritis

Polyarticular JRA

Systemic lupus

Scleroderma Polymyositis

Polymyalgia rheumatica

Psoriatic arthritis Vasculitis

Reiters syndrome

Enteropathic arthritis Polyarticular gout

CPPD disease

Sarcoid arthritis Chronic viral hepatitis


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Diseases Commonly Presenting with Chronic Non-

Inflammatory Polyarticular Symptoms

Osteoarthritis

CPPD disease

Tophaceous gout

Benign hypermobility joint syndrome

Pagets disease

Fibromyalgia

Hemochromatosis


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LABORATORY EVALUATIONOF RHEUMATIC DISEASES


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Erythrocyte Sedimentation Rate (ESR) (1)

Measurement of rate of erythrocyte settling inanticoagulated blood

Nonspecific marker of tissue inflammation

ESR cannot distinguish if underlying cause is:

Infectious

Inflammatory

Paraneoplastic

Patients with ESR > 100 mm/hr generally have one of thefollowing:

connective tissue disease

infection (classically TB or osteomyelitis)

malignancy (often metastatic)


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Erythrocyte Sedimentation Rate (ESR) (2)

Sometimes used to monitor activity of inflammatoryconditions like RA or SLE

Variables which tend to raise the ESR include:

Renal disease

Diabetes

Female sex

Pregnancy

Increasing ageESR may be lowered by:

Heart failure

Sickled erythrocytes


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C-Reactive Protein (CRP)

Acute phase protein synthesized in response to tissueinjury

Serum concentration change more quickly than ESR (mayincrease within 4-6 hours and normalize in a week)

May provide prognostic information in patients with RAwhen sustained elevations present

associated with radiographic progression

associated with long-term disability

May be elevated in obesity, diabetes, CAD, & malignancy


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Antinuclear Antibodies (ANA)

Diverse group of autoantibodies that react withantigens in the cell nucleus

Different patterns reflect different nuclear components

Should only be ordered after complete history &physical examination & differential diagnosis generated

Presence or absence must be interpreted within theclinical context of the patient

Titers do not necessarily correlate with disease activity


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ANA Sensitivity

SLE - >95%

MCTD - >95%

Sjgrens syndrome 75%

Polymyositis/dermatomyositis - >75% Scleroderma - >60-90%

RA 15-35%

Anti-centromere staining pattern CREST >90%

Absence of ANA virtually excludes diagnosis of SLE,but presence does not establish diagnosis


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Significance of Positive ANA in


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Significance of Positive ANA inChronic Polyarticular Symptoms (2)

Medication history may reveal medicationsassociated with drug-induced lupus (examples:procainamide, hydralazine)

Other diseases associated with positive ANA: autoimmune thyroid disease

chronic viral hepatitis


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Specific Autoantibodies (1)

Type Description Clinical Association

Anti-dsDNA Antibodies to doublestranded DNA

SLE (often correlates with more active,severe disease)

Anti-histone 5 types exist SLE, drug-induced SLE

Anti-ENA Sm (Smith)

RNP (ribonucleoprotein)RNA-protein complexes

SLE

Mixed connective tissue dxHigher prevalence in AA and Asian

patients

Anti-SSA (Ro) Ribonucleoproteins SLE, Sjogrens syndrome

Anti-SSA (La) Ribonucleoproteins Sjogrens syndrome, SLE

Anti-centromere Antibody to centromereregion of chromosome

Limited scleroderma


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Specific Autoantibodies (2)

Type Description Clinical Association

Anti-Scl 70 Antibodies to DNAtopoisomerase 1

Diffuse scleroderma

Anti-Jo 1 Antibody to histidyl tRNA

synthetase

poly/dermatomyositis; patients tend to

have interstitial lung disease, Raynauds,

arthritisAnti-SRP Antibody to signal

recognition proteinCardiomyopathyPoor prognosis

Anti-PM-Scl Antibody to nucleolargranular component

Polymyositis/scleroderma overlapsyndrome

Anti-Mi-2 Antibodies to nucleolarantigen of unknownfunction

DermatomyositisFavorable prognosis

Antineutrophil Cytoplasmic Antibody


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Antineutrophil Cytoplasmic Antibody

(ANCA)

2 staining patterns:

Cytoplasmic (C-ANCA)

Highly sensitive and specific for Wegeners granulomatosis

Perinuclear (P-ANCA)

Associated with miscroscopic polyangiitis & Churg-Strauss Syndrome

Correlate with disease activity

Positive results may be caused by:

Infection Medications (propylthiouricil)

Other autoimmune diseases


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Rheumatoid Factor

Polyclonal autoantibodies directed against Fc portion ofimmunoglobulins (IgG)

Most commonly an IgM directed against IgG

Associated with chronic inflammatory diseases

80% sensitivity RA50% sensitivity scleroderma

also seen in:

Wegeners granulomatosis

endocarditis

chronic hepatitis

chronic infection

sarcoidosis

malignancy

Significance of Rheumatoid Factor in Chronic


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Significance of Rheumatoid Factor in Chronic

Polyarticular Symptoms

RF positive eventually in 75-85% of patients withrheumatoid arthritis

RF may only be seen in 25% of patients with early

rheumatoid arthritis (consider anti-CCP anticycliccitrullinated peptide)

RF has low sensitivity & specificity for rheumatoid

arthritis in ACUTE polyarticular syndromes RF can be positive in acute infections (hepatitis B,hepatitis C, EBV)

Anti-Cyclic Citrullinated Peptide


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Anti Cyclic Citrullinated Peptide

(anti-CCP)

Autoantibodies directed against the amino acids formedby the posttranslational modification of arginine

Role in the pathogenesis of RA?

35% of patients will be positive in early rheumatoidarthritis when RF is negative

A positive anti-CCP test can rule in rheumatoid arthritis,

but a negative test cannot rule out rheumatoid arthritis

For rheumatoid arthritis, specificity 95%, sensitivity 70%


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Myositis

Creatinine phosphokinase (CPK)

Myositis-specific antibodies

sensitivities for inflammatory myopathies is low anti-Jo-1

anti-signal recognition particle (anti-SRP)

anti-Mi-2


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RAYNAUDSPHENOMENON


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Raynauds Phenomenon (1)

Raynauds phenomenon:

characterized by episodic digital ischemia

sequential development of digital blanching, cyanosis &rubor (triphasic color response) following cold exposure &

subsequent rewarming typically one or more digits will appear white on cold

exposure

separated into two categories: primary or idiopathic Raynauds disease

secondary associated with other disease states or known causes ofvasospasm


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Raynaud

s Disease: women are affected 5x more than men

usually between age 20 & 40

fingers involved more frequently than toes

have milder forms of Raynauds phenomenon

between attacks, digits may appear normal

secondary causes of Raynauds phenomenon have been

ruled out first


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Secondary Raynauds phenomenon causes:

connective tissue diseases arterial occlusive disease

pulmonary hypertension

neurologic disorders blood dyscrasias

trauma

drugs ergots

bleomycin, vinblastine, cisplatin

beta-blockers


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Raynauds phenomenon treatment:

reassurance if mild

avoid unnecessary cold exposure

warm clothing; gloves, mittens & hat

tobacco use is contraindicated

drug treatment if local measures unsuccessful calcium channel blockers (ex: nifedipine)

alpha-1 adrenergic antagonists (ex: prazosin) surgical sympathectomy, if unresponsive to other

measures

02 03-05-12 overview of rheumatic diseases color

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