ARTHRITIS AND ARTHRITIDES

DEFINITIONS
ARTHRITIS - greek Arthro (joint) itis (inflammation) ARTHRITIDES Plural form Group of disorders involving the joints which may be either inflammatory or non-inflammatory in nature

TYPES OF ARTHRITIDES
Osteoarthritis Rheumatoid Arthritis Septic Arthritis Gouty Arthritis Pseudogout Other Crystal Arthropathies Psoriatic Arthritis Juvenile Idiopathic Arthritis Adult Still Disease

RHEUMATOID ARTHRITIS
RA is the second most common form of chronic arthritis Affects approximately 1% of the adult population worldwide RA is an inflammatory disease of unknown etiology Potentially crippling disease shortens survival Significantly compromises quality of life

ETIOLOGY
Unknown but postulated causes include:
Genetic predisposition Female sex Psychological stress Immune response Hormone interaction Viral infection

CLINICAL MANIFESTATIONS
Gender: Female (3:1 ratio) Age: Late childbearing years in women (sixth to eighth decade in men) Onset: Insidious (builds up over several weeks to months) Joint symptoms must persist for at least 6 weeks

CLINICAL MANIFESTATIONS
The hands are a major site of involvement in almost all patients with RA Distribution: Symmetric small joints MCP, PIP, and MTP (spares DIP) joints Systemic: Fatigue, possible weight loss, occasional low-grade fevers Symptoms: Joint stiffness (worse in morning), pain, swelling

HAND INVOLVEMENT
Advanced rheumatoid arthritis with severe joint deformities including:
subluxation at the metacarpophalangeal joints swan-neck deformities (hyperextension at the PIP joints).

EXTRA-ARTICULAR INVOLVEMENT
Rheumatoid nodules
seen in approximately one-quarter of patients with RA almost exclusively in those patients who are seropositive for rheumatoid factor subcutaneous and typically occur on extensor surfaces and other pressure points or over joints

RHEUMATOID NODULE
Rheumatoid nodules at the elbow Rheumatoid nodules are firm and nontender

EXTRA-ARTICULAR INVOLVEMENT
Digital infarcts and leukocytoclastic vasculitis - features of RA- associated small vessel vasculitis CAD - high morbidity and mortality in patients with RA
Reasons are not entirely clear significant risk factors include:
chronic inflammation with an elevated C-reactive protein medications used, and sedentary lifestyle

EXTRA-ARTICULAR INVOLVEMENT
CARDIOVASCULAR Pericardial effusion present in 50% by echocardiography; usually asymptomatic Constrictive pericarditis may be seen in long standing cardiac involvement PULMONARY Pleural effusion Diffuse Interstitial Fibrosis

EXTRA-ARTICULAR INVOLVEMENT
Keratoconjunctivitis sicca (dry eyes) from secondary Sjgren syndrome is the most common ophthalmologic manifestation of RA Scleritis also occurs in RA and is usually painful
Severe involvement can lead to thinning of the sclera (bluish discoloration as the deep pigment shows through)

EXTRA-ARTICULAR INVOLVEMENT
NEUROLOGIC carpal tunnel syndrome tarsal tunnel syndrome Subluxations at C1C2 can produce myelopathy Rheumatoid nodules in the central nervous system are rare and usually asymptomatic

EXTRA-ARTICULAR INVOLVEMENT
FELTY SYNDROME triad of RA, splenomegaly, and neutropenia seen in patients with severe seropositive disease may be accompanied by hepatomegaly, thrombocytopenia, lymphadenopathy, and fevers

LABORATORY FINDINGS AND IMAGING

Anemia of Chronic Disease Thrombocytosis Acute Phase Reactants Elevated
ESR C-Reactive protein

WBC elevated (except in Felty syndrome)

LABORATORY FINDINGS AND IMAGING

Rheumatoid Factor
autoantibody directed against the constant (Fc) region of IgG positive in about 50% of cases at presentation additional 2035% of cases become positive in the first 6 months not unique to RA and occurs in many other diseases

Differentials of Positive Rheumatoid Factor

Rheumatic diseases RA, Sjgren syndrome, SLE Infections
Viral: Hepatitis C, EBV, parvovirus, influenza, others Bacterial: Endocarditis, osteomyelitis, others

Chronic inflammatory conditions Liver disease, inflammatory bowel disease Aging

LABORATORY FINDINGS AND IMAGING

Anti-CCP - (anticyclic citrullinated peptide antibodies) present in 6070% of patients with RA at diagnosis 9098% specific for RA present in the serum years before RA is diagnosed correlate strongly with erosive disease

LABORATORY FINDINGS AND IMAGING

Synovial Fluid Aspiration
Inflammatory white blood cell counts typically range from 500050,000 per microliter two-thirds of the cells being neutrophils No synovial fluid findings are pathognomonic of RA.

LABORATORY FINDINGS AND IMAGING

Typical findings occur later in the disease course and include : bony erosions, cysts osteopenia, joint space swelling calcifications narrowed joint space and deformities separations, fractures.

DIAGNOSIS
American College of Rheumatology Criteria for Rheumatoid Arthritis
Morning stiffnessa Arthritis of three joint areasa Arthritis of the handsa Symmetric arthritisa Rheumatoid nodules Serum rheumatoid factor Radiographic changes

ACR Diagnostic Criteria

The first four criteria need to be present for at least 6 weeks This time requirement was imposed because a number of conditions, most notably viralrelated syndromes, can cause self-limited polyarthritis indistinguishable from RA These also manifest with the presence of RF

DIFFERENTIAL DIAGNOSIS
Viral syndromes, especially hepatitis B and C, Epstein-Barr virus, parvovirus, rubella Psoriatic arthritis, reactive arthritis Tophaceous gout Systemic lupus erythematosus Calcium pyrophosphate disease Polymyalgia rheumatica Paraneoplastic syndromes Osteoarthritis, especially hereditary osteoarthritis of the hand Sarcoidosis, Lyme disease, rheumatic fever,

COMPLICATIONS
significant morbidity and premature mortality 50% of RA patients have had to stop working after 10 years Patients who have anti-CCP antibodies, who are rheumatoid factor positive, or who have HLA-DR alleles expressing the shared epitope have a worse prognosis with more erosions and more extra-articular disease

COMPLICATIONS
Once deformities are found on examination or erosions on radiography, the damage is largely irreversible Erosions develop in the majority of patients in the first 1 or 2 years of disease the rate of radiographic damage can be affected by early therapy

KEYS TO OPTIMAL OUTCOME

Early diagnosis DMARD therapy as early as possible Strive for remissions in all patients Recognize and treat comorbid conditions Cooperation and communication between primary care physician and rheumatologist

Juvenile Rheumatoid Arthritis

one of the more common chronic illnesses of childhood major cause of functional disability and eye disease leading to blindness in contrast to adult rheumatoid arthritis (RA), large joints such as the knees, wrists, and ankles are more prominently involved than small joints less frequent complaints of joint pain

Juvenile Rheumatoid Arthritis

Three major types of presentation:
Oligoarthritis (60 percent) Polyarthritis (30 percent) Systemic onset disease (10 percent)

Subcutaneous nodules and rheumatoid factor (RF) seropositivity are unusual antinuclear antibody (ANA) seropositivity is a hallmark of the disease

Juvenile Rheumatoid Arthritis

Characteristic : Inflammation and ankylosis of the posterior apophyseal joints of the upper cervical spine Atlantoaxial subluxation Rare neurologic sequelae 70 to 90 percent of children enter adulthood without serious disability small percentage of children will have a recurrence of arthritis as adults

Criteria for Chronic Arthritis in Children (ACR and ILAR)

CHARACTERISTIC ONSET TYPES COURSE SUBTYPES ACR (JRA) 3 9 ILAR (JIA) 7 1

AGE AT ONSET (Arthritis)

DURATION (Arthritis) INCLUDES JAS INCLUDES JPsA INCLUDES IBD INCLUDES Reactive Arthritis Exclusion of other diseases

< 16 years
> 6 weeks No No No No Yes

< 16 years
> 6 weeks Yes Yes Yes No Yes

Juvenile Rheumatoid Arthritis

Age at onset is characteristically young (1 to 3 years Girls account for the majority of patients overall at least twice as often as boys Incidence of JRA is 10 to 20 cases per 100,000 children Etiology and pathogenesis of JRA are unclear

Juvenile Rheumatoid Arthritis

LABORATORY FINDINGS: Normocytic, hypochromic anemia during periods of active disease Increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels Tests for ANAs are positive in approximately 40 percent of children Synovial fluid examination is usually typical of inflammatory fluid

Juvenile Rheumatoid Arthritis

RADIOLOGIC EXAMINATION Soft tissue swelling Juxta-articular osteoporosis Periosteal new-bone formation Marked bony overgrowth due to enlargement of the epiphyses occurs at the interphalangeal joints Widening of the phalanges from periosteal new-bone apposition

Juvenile Rheumatoid Arthritis

Juvenile rheumatoid arthritis in a 2.5year-old girl Note the extensive periosteal changes particularly in the fourth metacarpal and in all the proximal phalanges.

Juvenile Rheumatoid Arthritis

TREATMENT: Conservative management to control the clinical manifestations of the disease and to prevent deformity family-centered, community-based, and coordinated Treatment in most children is prolonged over many years

Juvenile Rheumatoid Arthritis

MEDICAL MANAGEMENT: NSAIDS Intravenous IgG Methotrexate Sulfasalazine Glucocorticoids Etanercept Hydroxychloroquine Gold compounds D-Penicillamine

PSORIATIC ARTHRITIS
chronic inflammatory arthritis that is commonly associated with psoriasis At least 5% of patients with psoriasis develop psoriatic arthritis etiology of psoriatic arthritis is unknown As in the pathogenesis of many other autoimmune disorders, an infectious trigger has been suspected

PSORIATIC ARTHRITIS
Psoriatic arthritis typically develops after or coincident with the onset of psoriasis 20% of cases, however, arthritis precedes the onset of psoriasis by as much as 2 years. asymmetric oligoarticular arthritis is the classic description articular manifestations range from an isolated monarthritis to polyarthritis to widespread destructive arthritis

CLINICAL MANIFESTATIONS
Majority of patients with psoriatic arthritis present with an oligo- or monarthritis Often the DIP joints become stiff, swollen, and tender in an asymmetric fashion When present, involvement of the DIPs helps to distinguish psoriatic arthritis from rheumatoid arthritis.

PSORIATIC ARTHRITIS

DIP involvement
Nearly always associated with nail psoriasis

CLINICAL MANIFESTATIONS
Other joints that are affected by psoriatic arthritis include the knees, hips, and sternoclavicular joints Most patients will progress to additional joint involvement in the absence of effective treatment

CLINICAL MANIFESTATIONS
Dactylitis, or "sausage digit"
complete swelling of a single digit in the hand or foot common in psoriatic arthritis, occurring in onethird to one-half of patients at some point in their disease

Dactylitis
diffuse swelling of the entire digit likely due to a combination of both arthritis and tenosynovitis.

CLINICAL MANIFESTATIONS
Enthesitis
an inflammatory process at the site of the insertion of tendons into bone occurs in up to 40% of psoriatic arthritis patients soft tissue swelling usually accompanied by tenderness to palpation and sometimes by overlying erythema and warmth common site for enthesitis is the insertion of the Achilles tendon into the calcaneus

CLINICAL MANIFESTATIONS
Skin and nail changes
All forms of psoriasis are associated with arthritis classic psoriasis vulgaris is seen most frequently erythematous plaques that produce scaling with scratching nail involvement is common in psoriatic arthritis and includes: ridging, pitting, onycholysis, and hyperkeratosis

CLINICAL MANIFESTATIONS

CLINICAL MANIFESTATIONS
Spondyloarthropathy involvement of the sacroiliac joints and axial skeleton is less common than peripheral arthritis Inflammation of the sacroiliac joints (sacroiliitis) in psoriatic arthritis is usually unilateral common site of skeletal involvement in psoriatic arthritis is the cervical spine

CLINICAL MANIFESTATIONS
Ocular Involvement Ocular inflammation
conjunctivitis, iritis, scleritis, and episcleritis

Other extra-articular involvment: oral ulcerations urethritis

LABORATORY FINDINGS
There are no laboratory tests diagnostic for psoriatic arthritis 20% of patients have hyperuricemia acute phase reactants such as the C-reactive protein and the erythrocyte sedimentation rate may be elevated Synovial fluid analysis reveals inflammatory fluid

LABORATORY FINDINGS
Rheumatoid Factor Patients with psoriatic arthritis usually do not have rheumatoid factor But up to 10% of patients with psoriatic arthritis will test positive Antibodies to cyclic citrullinated peptides have only rarely been reported in patients with psoriatic arthritis

IMAGING STUDIES
The most common radiographic findings in psoriatic arthritis are:
joint space narrowing and erosions involving the distal interphalangeal and proximal interphalangeal joints asymmetric, paralleling the pattern of the clinical arthritis

metacarpophalangeal joints and wrists are usually spared, in contrast to rheumatoid arthritis

IMAGING STUDIES
Arthritis mutilans describes the end stage of the destructive process loss of bony architecture allows complete subluxation and telescoping of the involved digit Occurs in about 5 % of cases

DIFFERENTIAL DIAGNOSIS
The diagnosis of psoriatic arthritis may be difficult when the skin manifestations are subtle or the arthritis antedates the onset of skin lesions
rheumatoid arthritis, (reactive arthritis, ankylosing spondylitis, and enteropathic arthritis). the crystal arthropathies (gout and pseudogout) septic arthritis,

TREATMENT
NSAIDS Disease modifying anti-rheumatic drugs
methotrexate, sulfasalazine, azathioprine, antimalarials ( hydroxychloroquine), and cyclosporine

Biological Therapies
Tumor necrosis factor- (TNF-) Alefacept

Juvenile Idiopathic Arthritis (JIA)

Refers to the group of disorders that cause chronic arthritis in children Chronic synovitis is present in any one joint for more than 6 weeks in a child less than 16 years of age Chronicity of the joint involvement in JIA distinguishes this group of disorders from the many short-term causes of joint pain and swelling that can occur in childhood.

Juvenile Idiopathic Arthritis (JIA)

Incidence of 122 children per 100,000 Prevalence of anywhere from 8150 per 100,000 Most common chronic rheumatic disease of childhood Significant cause of both short-term and long-term disability

Types of JIA
Systemic onset JIA (SOJIA) Oligoarticular (previously known as pauciarticular) JIA Polyarticular rheumatoid factor positive JIA Polyarticular rheumatoid factor negative JIA Juvenile psoriatic arthritis Enthesitis-related arthritis "other."

Oligoarticular JIA
Occurs in very young children Asymmetric pattern of joint involvement is common Fewer than five joints total can be affected Morning stiffness is a prominent finding Affected joint is often swollen and quite large, the child frequently has less pain than one would anticipate Knees are the most commonly involved joints

Polyarticular JIA
Affects children whose arthritis begins in five or more joints at onset Rheumatoid factor test is a useful prognosticator Rheumatoid factor positive patients are usually teenage girls with symmetric smalljoint arthritis involving hands and feet These girls may have rheumatoid nodules, with aggressive erosive joint disease

Polyarticular JIA
Polyarticular rheumatoid factor negative JIA affects younger children More girls are affected than boys Arthritis may or may not be symmetric Usually affects large joints predominantly no associated extra-articular features and uveitis is rare Affected patients have active arthritis for many years without erosive change on xray.

Systemic onset JIA (SOJIA)

High daily spiking fever Evanescent rash present during febrile episodes that disappears when the temperature is back to normal Severe myalgias Polyserositis Affects children and adults at any age, without preference for girls or boys.

Systemic onset JIA (SOJIA)

Hallmarks of this disorder are the daily spiking fever in a "rabbit ears" pattern in association with an evanescent, salmoncolored, macular rash on the trunk and extremities Marked leukocytosis, very high sedimentation rates, and elevated ferritin levels are the rule in this disease

Juvenile Psoriatic Arthritis

Presents with any of the following signs and symptoms:
sacroiliitis distal interphalangeal joint synovitis dactylitis, "sausage" digit nail pitting psoriatic rash positive family history of psoriasis

Enthesitis-related JIA
Patients with juvenile onset spondylitis, reactive arthritis, and the arthritis associated with inflammatory bowel disease Boys from 8 years of age onward are most often affected Pain, stiffness, and loss of flexibility in the spine, in addition to synovitis of peripheral joints, predominantly in lower extremities.

Enthesitis-related JIA
Heel pain, rash including pyoderma gangrenosum or ulcers, and acute, painful uveitis can occur HLA-B27 gene can be found in many patients in this category, but is not diagnostic.

Adult-onset Still disease (AOSD)

Multisystem inflammatory disease that typically begins with a sore throat Fever that spikes in "rabbit ears" pattern with daily return to normal. Salmon-colored macular rash only occurring with fever. Arthritis, splenomegaly, pleuritis, pericarditis, and marked leukocytosis common. Pharyngitis often the initial symptom

Adult-onset Still disease (AOSD)

Other constitutional symptoms soon follow, including profound fatigue, weight loss, and anorexia Malignancy and infectious causes of these symptoms must be excluded cause of AOSD has yet to be identified

Adult-onset Still disease (AOSD)

AOSD is rare Incidence of 0.16 cases per 100,000 population Women and men are equally affected Peak onset is between ages 20 and 45 Pediatric patients with systemic-onset juvenile idiopathic arthritis can have a recurrence of active Still disease at any age into adulthood.

Adult-onset Still disease (AOSD)

Laboratory Work-up: No definitive lab test for AOSD Marked leukocytosis (>15,000/L) with a predominance of neutrophils (>80%) Markedly elevated erythrocyte sedimentation rate (>90) Marked elevation of the serum ferritin (above 3000 mg/mL) is seen in over 70% of AOSD patients

Arthritis Associated with Systemic Disease

Arthropathy of Acromegaly Excessive production of growth hormone by an adenoma in the anterior pituitary gland
Proliferation of cartilage, periarticular connective tissue, and bone Results in several musculoskeletal abnormalities, including osteoarthritis, back pain, muscle weakness, and carpal tunnel syndrome.

Arthropathy of Acromegaly
Arthropathy resembling osteoarthritis is a common feature Affects most often the knees, shoulders, hips, and hands Single or multiple joints may be affected Carpal tunnel syndrome occurs in about half of patients
median nerve is compressed by the excessive growth of connective tissue in the carpal tunnel

Arthropathy of Hemochromatosis
Disorder of iron storage Excessive amounts of iron are absorbed from the intestine Leads to iron deposition in parenchymal cells, which results in tissue damage and impairment of organ function

Arthropathy of Hemochromatosis
Arthropathy is an osteoarthritis-like disorder Affects the small joints of the hands, followed later by larger joints such as knees, ankles, shoulders, and hips The second and third metacarpophalangeal joints of both hands are often the first joints affected
provide an important clue to the possibility of hemochromatosis.

Arthropathy of Hemochromatosis
Treatment of hemochromatosis is repeated phlebotomy Little effect on the arthritis Administration of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs)

Hemophilic Arthropathy
Sex-linked recessive genetic disorder characterized by
the absence or deficiency of factor VIII (hemophilia A, or classic hemophilia) or the absence of factor IX (hemophilia B, or Christmas disease)

Hemophilia A is by far the more common type, constituting 85% of cases

Hemophilic Arthropathy
Spontaneous hemarthrosis is a common problem with both types of hemophilia and can lead to a chronic deforming arthritis Hemarthrosis is not common in other inherited disorders of coagulation, such as von Willebrand disease or factor V deficiency The frequency and severity of hemarthrosis are related to the degree of clotting factor deficiency

Hemophilic Arthropathy
Hemarthrosis appears after 1 year of age, when the child begins to walk and run Joints most commonly affected are the knees, ankles, elbows, shoulders, and hips Small joints of the hands and feet are occasionally involved Characterized by warm, tensely swollen, and painful joint

Hemophilic Arthropathy
The patient holds the affected joint in flexion and guards against any movement Blood in the joint remains liquid because of the absence of intrinsic clotting factors
Resorbed over a period of a week or longer

Joint function usually returns to normal or baseline in about 2 weeks Recurrent hemarthrosis leads to the development of a chronic arthritis

Hemophilic Arthropathy
TREATMENT: Immediate infusion of factor VIII or IX at the first sign of joint or muscle hemorrhage patient is placed at bed rest Analgesic doses of an NSAID and local icing may help with the pain

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