5spondyloarthropaties seronegative arthritis
TRANSCRIPT
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Spondylo-arthritis
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Objectives
• Gain a basic understanding of the Spondylo-Arthritis
• Learn specific Characteristics from SpA • Differentiate SpA from other chronic
Arthritis ( RA, OA )• Become familiar with joints, and extra-
articular manifestations of SpA• Understand the current treatment
paradigm and medications used
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Introduction
• Spondyloarthropathies =
• Seronegative Spondyloarthritis– Absence of Rheumatoid Factor or other
autoantibody serologic abnormalities:• Psoriatic Arthritis-PsA• Ankylosing Spondylitis-AS (Prototype)• Reactive Arthritis-ReA• Enteropathic Arthritis-IBD• Undifferentiated Spondyloarthropathy-SpA
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Criteria for classification of spondyloarthropathy
• Inflammatory spinal pain or synovitis (asymmetric or predominantly in lower limbs) plus more than 1 of the following:– Positive family history– Psoriasis– Inflammatory bowel disease– Urethritis, cervicitis, or acute diarrhea < 1 mo. before arthritis– Buttock pain alternating between right and left gluteal areas– Enthesopathy– Sacroiliitis
• Sensitivity 78.4% and specificity 89.6%
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Spondyloarthropathies
• Are a diverse group of chronic inflammatory conditions linked by distinctive clinical, radiographic, and genetic features
• Refers to inflammatory changes involving the spine and the spinal joints.
• subtypes often overlap• may be considered one heterogeneous and
phenotypically diverse disease that has the potential to evolve into AS.
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Introduction
Confusion
Can often see peripheral joint symptoms in the absence of spinal symptoms
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Spondyloarthropaties
• The pathology of spondyloarthropathies is very different from that of RA. In RA, it is the synovitis that plays the major role, and the synovitis leads to bony erosions that don't heal.
• In spondyloarthritis there is some synovitis, but it's the enthesitis that is the major problem, especially in the axial disease.
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Spondyloarthropaties
• Not only is there enthesitis but also the osteitis that follows, which is different because there is reactive bone sclerosis and bone absorption, but then more bone remodeling sets in and it goes on to result in new bone formation that can result in ankylosis
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Spondyloarthropaties
• In RA, the cytokines lead to excessive osteoclastic activity resulting in bone erosions,
• In spondyloarthritis, the cytokines that are playing a major role result in osteoblastic activity
• Gradual bony bridging follows after being initiated by the inflammation
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Spondyloarthropaties
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Spondyloarthropaties
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Spondyloarthropathies
• Hallmarks of this family of disorders
• Inflammatory back pain (IBP)
• and Enthesitis: (inflammation at sites where tendons, ligaments, and joint capsule fibers attach to bone, with a strong tendency to produce fibrosis and calcifications).
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Spondyloarthropathies
• IBP: inflammatory Back Pain• worse in the late night and early morning • pain interferes with sleep to the point that the
patient gets up to walk in the middle of the night, • the discomfort can be characterized by
alternating buttock pain.• prolonged morning stiffness of greater than 30
minutes.
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Spondyloarthropathies
• Exercise alleviates the pain of IBP while rest makes it worse.
• IBP affects younger patients,
• peaking during the mid-20s
• onset before the age of 40,
• at the height of their productivity.
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Spondyloarthropathies
• IBP persists for at least 3 months.
• detrimental effects on quality of life
• increased disability, and morbidity -- equal, and in some cases exceeding, that seen in RA
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Spondyloarthropathies
• Although new bone formation is central to the pathogenesis of AS, is also associated with osteoporosis and low bone mineral density
• ectopic bone formation occurs within the inflamed vertebral enthesis
• bone resorption, (increased osteoclast activity), occurs at an unregulated rate within the vertebra and promotes weakening of the spinal column.
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Spondyloarthropathies
• The spine in the patient with AS fuses through:– ligamentous ossification and– syndesmophytosis,
• Rigid hyperkyphotic deformity develops.• Biomechanically, the fused spine acts as a
long bone incapable of appropriately dissipating the energy of a traumatic event.
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Spondyloarthropathies
• Altered spinal biomechanics• Combined with the brittle quality of the
osteoporotic bone • Increase susceptibility to vertebral column
factures,and Spinal Cord injury, even after minor, often trivial, trauma
• Significantly impaired mobility and peripheral joint arthritis:– exacerbate gait unsteadiness – increase susceptibility to falls
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Sagittal reformatted CT scan showing a highly displaced thoracic fracture. Asterisk indicates apposition of the caudal fracture fragment on the thoracic aorta
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Spondyloarthropathies
• Extra-articular manifestations including:– psoriasis,– anterior uveitis,– IBD, – as well as rarer cardiac, renal, and pulmonary
manifestations
• a wide range of clinical manifestations.
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Extra-articular manifestations
• Ocular Manifestations• Uveitis is one of the most common extra-
articular manifestations of the SpA,
• occurring in 25% to 40% of patients.
• there appears to be no correlation between the course of inflammatory eye disease and that of the arthritis.
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Extra-articular manifestations
• The uveitis typically presents as acute unilateral pain and photophobia; blurring of vision may also occur.
• Recurrence despite successful treatment is common. Cataracts and glaucoma with associated increased intraocular pressure and posterior synechiae can also be observed
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Extra-articular manifestations
• In addition, conjunctivitis is commonly observed in SpA (up to 30% to 60% of ReA), typically in a more transient and less relapsing course than uveitis
• patients who present with visual complaints in the SpA setting should be referred promptly to an ophthalmologist for thorough evaluation including slit lamp examination.
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Cutaneous Manifestations• Plaque psoriasis, characterized by scaly,
erythematous, hyperkeratotic lesions, is the most common form of psoriasis and is an important component of diagnosing PsA.
• Careful examination of the skin should be performed in SpA evaluation,
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Cutaneous Manifestations
• assessment of less conspicuous areas including the gluteal cleft, scalp and scalp line, groin, and posterior auricular regions should be performed.
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Psoriasis
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Psoriasis
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Psoriasis
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Psoriasis
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Psoriasis
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Cutaneous Manifestations
• no strict correlation between the extent of psoriasis skin disease and the extent of joint disease
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Nail Changes
• Diffuse and numerous nail pitting (plate depressions), onicholysis (separation of the nail from underlying nail bed), and crumbling of the nail plate can be observed in both psoriasis and PsA.
• The extent of nail involvement in PsA parallels both skin and joint disease
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Nail pitting/onicholysis
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Nail Pitting
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Onicholysis toe nails
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Crumbling nail/DIP joint involvement
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Pencil in Cup deformities
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Other Extra- articular Manifestations
• Aortic regurgitation is perhaps the most recognized cardiac manifestation, with scar tissue in the aorta and aortic valve cusps leading to incompetent valves.
• Conduction abnormalities and heart block have also been described, characterized by extension of the fibrosis process into the AV bundle
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Other Extra- articular Manifestations
• Apical pulmonary fibrosis, mostly asymptomatic and typically observed in patients with substantial disease duration, has been noted in a small percentage of AS patients
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Other Extra- articular Manifestations
• Renal disease beyond analgesic and nonsteroidal anti-inflammatory drug adverse effects has appeared in 2 forms in AS, both of which are rarely observed: IgA nephropathy that can manifest as proteinuria and hematuria, and secondary amyloidosis manifested by nephrotic syndrome and, if associated with renal failure, generally a poor prognosis.
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Spondyloarthropathies-Gene association
• Up to 70% of individuals suffering from SpA carry the HLA-B27 gene
• strength of the association between HLA-B27 and disease susceptibility varies among SpA subtypes and ethnic groups
• the B27 gene accounts for only 35% of the SpA genetic load.[1]
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Associations with HLA-B27
Rheumatic diseasesRheumatic diseases
Ankylosing spondylitisAnkylosing spondylitisReiter’s Reiter’s syndrome/reactive syndrome/reactive arthritisarthritisIBD related arthritisIBD related arthritisPsoriatic arthritisPsoriatic arthritis
Normal Normal AssociationsAssociationsNative AmericansNative AmericansCaucasiansCaucasiansBlacksBlacks
Degree of Degree of associationsassociations
>90%>90%>80%>80%~75%~75%~50%~50%
13%13%8%8%4%4%
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Ankylosing Spondylitis
• An inflammatory disease of the spine and axial joints
• Typically affects young men ages 15-30 • Women can be affected but much less than men
(3:1 men:women)• Affects about 1 in 1000 • women with AS may present differently from
men, complaining of neck and breast pain without the typical inflammatory low back pain
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Ankylosing Spondylitis
New York criteria for diagnosis of ankylosing spondylitis
• Definite ankylosing spondylitis If: Criterion 4 or 5 plus 1, 2, or 3.
– 1. Limited lumbar motion– 2. Low back pain for 3 months improved with exercise
not relieved by rest– 3. Reduced chest expansion– 4. Bilateral, grade 2 to 4, sacroiliitis on X-ray– 5. Unilateral, grade 3 to 4, sacroiliitis on X-ray
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Ankylosing Spondylitis
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Previous Picture Hx
• A photographic series of a patient with ankylosing spondylitis was taken over a period of 26 years. By 1957 a thoracic kyphosis has become apparent, and loss of the normal lumbar lordosis has occurred. There are early flexion contractures of the hips and knees. In the next two sequences, increasing flexion contractures of the hips and knees have occurred along with progressive ankylosis of the spine. In 1973, bilateral total hip arthroplasties were performed, which improved the patient's posture.
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Ankylosing spondylitis: lumbar vertebrae, bamboo spine (radiograph)
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• This anteroposterior projection of the lumbar spine shows the characteristic changes of syndesmophyte formation or "bambooing." Ossification is present deep to the lateral collateral ligaments, and it follows the contour of the intervertebral disc spaces. This ossification involves the outer layers of the intervertebral disc (annulus fibrosus). In contrast, degenerative spurs will extend almost at right angles to the vertebral bodies, rather than snugly following the contour of the disc as in ankylosing spondylitis.
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Sacroiliitis grading0-normal 1-possible2-minimal3-moderate4-ankylosing
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Ankylosing Spondylitis
• Begins in the Sacroiliac Joints and progresses upwards and can involve the entire spine
• Beyond the spine, axial joints including the shoulders and hips can be involved with varying degrees of severity particularly in AS.
• Shoulder involvement can be detected radiographically with characteristic erosive changes at the rotator cuff insertion.[
• Hip involvement is considered a poor prognostic factor in AS
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Ankylosing Spondylitis
• Inflammatory Stages– Can be extremely painful (flares)– Prolonged morning stiffness (hours)– Fatigue (pain & lack of sleep)
• Ankylosis– Stiffness increases – Significantly reduced ROM– Abnormal posture
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Enthesitis
• Inflammation at the insertion of tendon, ligament, or articular capsule into bone
• Lower limb entheses are more commonly involved than the upper limb
• Patients with AS get “funny” pains
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Achilles Enthesopathy
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Enthesitis
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Enthesitis• Common sites for Enthesitis
– Heel – Most Common (Achilles)– Patella– Tibial Tubercle– Base of the 5th metatarsal– Plantar Fascia– Other sites include:
• Anserine Bursa• Greater Trochanter• Iliac Crest• Rotator Cuff (Common in Ankylosing Spondylitis)• Costochondral
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Physical Examination
• Peripheral Entheseal Involvement
• Spinal Involvement
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Spinal Involvement
• Measure the Occiput to Wall distance• Chest Expansion
– Place the tape measure at the xiphisternum– Deep inhalation, exhalation, then inhalation– Measurement is age and sex dependant– Useful for following patients over time
• Modified Schober Test– Potentially useful diagnostically– Unsure of benefit over time (insensitive)
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Modified Schober Test
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Occiput to Wall Test
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Spinal Involvement
• Finger Tip to Floor Distance– Feet at specified distance apart– Measure fingertips to floor– Useful for following patients over time
• Lateral Flexion– Stand with back against the wall and feet at specified
distance apart– Make a mark where the finger tips touch the thigh– Ask the patient to flex laterally and place a second
mark at the maximal extent of the fingertips– Measure the distance between the two marks– Useful for following patients over time
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Finger Tip to Floor Distance
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Spinal Involvement
• SI Compression Testing
• Cervical Spine– Examine!– Can have Cervical Spine involvement alone– Can result in Atlanto-Axial Instability
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Laboratory Investigations
• Evidence of Inflammation– CBC Normochromic normocytic anemia
– Elevated ESR/CRP– Reactive thrombocytosis
• HLA-B27 found in 90-95% of patients with Ank Spond vs 6% of general population
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Juvenile Ankylosing Spondylitis
Onset 8 to 14 Sex Ratio M:F 7 to 1 HLA-B27 91 % Systemic symptoms rare Iritis 10 to 27 % Polyarticular 97% Prognosis Probably good
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PSORIATIC ARTHRITIS
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Case #1
• 50 y.o. man presents to the office with painful, swollen fingers
• Intermittent flares over the last year with limited morning stiffness and slight loss of energy
• Presents with the following findings:
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Case #1
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Case #1
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Case #2
• 48 year old woman originally from Russia, moved to Canada 1 year ago.
• Has complained of persistent arthritis and deformities in hands for years.
• Presents with the following findings:
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Case #2
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Case #2
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Case #3
• 51 year old man has had pain, stiffness, and progressive deformity in the hands for many years
• Presents with the following findings:
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Case #3
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Case #4
• 28 year old man presents with pain and stiffness in both wrists and the left knee
• Also has intermittent swelling of the toes
• Has the following findings:
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Case #4
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Case #4
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Case #5
• 35 year old man presents with low back pain and stiffness which improves with exertion
• He has the following findings:
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Case #5
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What is the Diagnosis?
• In all of these cases the diagnosis is Psoriatic Arthritis!
• 5 Presentations– DIP Involvement (Case #1)– Arthritis Mutilans (Case #2)– Symmetric Polyarthritis (Case #3)– Oligoarthritis (Case #4)– Spondylitis (Case #5)
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What is the Diagnosis?
Confusion
Psoriatic Arthritis is a heterogenous disease which can present in a multitude of ways
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Psoriasis/Nail changes/arthritis DIPs and Sausage deformity
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Psoriatic Arthritis PsA
• Subchondral bone resorption of the distal interphalangeal joint of the thumb and middle fingers has resulted in the "pencil-in-cup" appearance. A flexion deformity of the distal interphalangeal joint of the small finger is present, and the corresponding joint of the ring finger has fused.
• (Next slide)
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Fusion
Pencil in Cup deformity
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Who Gets Psoriatic Arthritis?
• Most common age of onset is 30-50 years old
• 1-3% of the population has psoriasis
• 6-42% of people with psoriasis get psoriatic arthritis
• Therefore, it is rare (about 1 in 1000)
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History – Initial Presentation
• Typical presentation is a peripheral inflammatory joint disease – usually a mono or oligo arthritis– Knees– Wrists
• May occasionally present with polyarthritis
• Initial presentation of inflammatory spinal disease is rare
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History - Progression
• Oligoarticular in 40-50%
• Polyarticular in 30-50%– Like Rheumatoid Arthritis
• Predominant Spinal Disease in 5%– Spinal symptoms usually occur after many
years of peripheral arthritis
• DIP involvement in 5%
• Arthritis Mutilans in 5%
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PSORIATIC ARTHRITIS
Possible Indicators of Bad Prognosis
Younger age at onset, including children
Presence of certain HLA antigens:
HLA-B27 correlates with spondylitic involvement
HLA-DR3, DR4 correlates with erosive disease
Extensive skin involvement
Polyarticular involvement
Lack of clinical response to NSAIDs
Association with HIV infection
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History - Progression
• Sacroiliac Involvement– Sacroiliitis in 1/3 of patients– Usually asymmetric (unilateral)– May be asymptomatic
• Spinal Involvement– May affect any part of the spine in a random
fashion– Different from ankylosing spondylitis
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History – Rheumatologic Review of Systems• Mucocutaneous Involvement
– Psoriatic skin lesions– Psoriatic Nail lesions
• Entheseal Involvement
• Dactylitis
• Ocular Involvement
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History - Psoriasis
• Do you have Psoriasis?– Psoriasis present before the onset of joint disease
(70%)– Psoriasis comes with the arthritis (15%)– Psoriasis comes after the arthritis (15%)
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Umbilical Psoriasis
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Psoriasis Behind the Ear
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Psoriasis in the Crease
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Psoriasis in the Nails
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History - Dactylitis
• Have you ever had a finger or toe swell up on you like a sausage?
• Entire digit is involved compared to “fusiform” swelling around a joint
• Dactylitis – represents inflammation of the flexor tenosynovium – “flexor tenosynovitis”
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History - Dactylitis
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History – Family History
• Family studies suggest a 50-fold increase in the risk of psoriatic arthritis in 1st degree relatives
• Fathers are twice as likely to transmit the disease
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Physical Examination
• Skin and Nail Involvement• Peripheral Joint Involvement• Peripheral Entheseal Involvement• Spinal Involvement
– Modified Schober Test– Occiput to Wall Distance– Cervical Spine ROM– Finger tip to floor distance– Lateral flexion
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Peripheral Joint Involvement
• Inflammatory Joint Count– Number of Joints Involved
• Prognostic Importance• Therapeutic Importance
– Pattern of Joints Involved• Diagnostic Importance
– Evidence of Damage– Dactylitis
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How to Tell the Difference
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Red Flags – When to Call the Rheumatologist• Cervical Spine Instability
– Acute onset neck pain or headache– Weakness or sensory change in extremities– Hyper-reflexia
• Flare of disease activity
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Radiology
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Reiter’s Syndrome: Diagnostic Criteria
Seronegative asymmetric arthropathy
And at least 1 of the following:
Urethritis or cervicitis
Diarrhea
Inflammatory eye disease
Mucocutaneous diseaseBalanitis, oral ulceration, or keratoderma
Other spondyloarthropathies and rheumatic disease excluded
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BACTERIA MOST COMMONLY FOUND TRIGGERING REACTIVE ARTHRITIS
Borrelia burgdorferi
Campylobacter jejuni
Chlamydia trachomatis
Neisseria gonorrhoeae
Salmonella species
Shigella flexneri
Streptococcus pyogenes
Yersinia enterocolitica
Yersinia pseudotuberculosis
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Reiter’s SyndromeFrequency Difficult to
define
Male – Female ratio 4 to 1
HLA-B27 90 %
Onset Simultaneous or
over 3 – 4 weeks
Course Self limited
Relapsing
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Reiter’s SyndromeClinical Manifestations
Arthritis Oligoarticular, Lower extremities.
Enthesitis Calcaneous, patella.
Urethritis Dysuria more common
30 % urethritis
Conjuntivitis 2/3 at onset
Mucocutaneous
Manifestations Less frequent
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Arthritis Conjunctivitis
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Cervicitis
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Urethritis
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Circinate Balanitis. Meatitis, mild balanitis, severe balinitis
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• Left, previous photograph demonstrates meatitis and early balanitis. The lesion is erythematous, moistened by the urethral discharge, and, like the later stages, painless.
• Center, A discrete, moist, well-circumscribed lesion is seen on the glans. Such lesions often begin as small vesicles or pustules.
• Right, More advanced lesions are dry, scaly, and painless. In circumcised patients, the lesions on the glans may become crusted and hyperkeratotic, similar to those seen on the skin, or they may remain moist and weeping.
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ReA superficial erosions of the tongue
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Superficial oral ulcers can be seen in ReA and are typically painless
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• ReA has as part of its constellation of symptoms characteristic lesions including keratoderma blennorrhagica characterized by hyperkeratotic skin lesions on soles and palms and genital lesions such as circinate balanitis, an erythematous and painless lesion of the glans penis.
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Keratoderma Blenorrhagicum
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Pustules ReA KB incipient
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Advanced KB
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ARTHRITIS AND INFLATORY BOWEL DISEASECrohn’s Disease
Ulcerative Colitis
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IBD associated arthritis
Arthritis Peripheral Specially lower extremities
Self limited 4 to 6 weeks
Central SI joints and enthesitis
Frequency 7 to 21 %
No relation between the activity of the Arthritis and the IBD.
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In IBD-associated SpA, erythema nodosum can be
observed in Crohn's disease
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pyoderma gangrenosum can be associated with ulcerative colitis.
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SINDROME DE SAPHOSYNOVITIS
ACNE CONGLOBATA, FULMINANS E HIDRAENITIS SUPURATIVA
PUSTULOSIS PALMO PLANTAR
HYPEROSTOSIS ESTERNO-CLAVICULAR Y ESPINAL
OSTEOMIELITIS ESTERIL MULTIFOCAL RECURRENTE
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Management - Overview
• Goals of Treatment– Improve pain– Improve Function– Prevent Long-term Damage– Safely
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Management
• NSAIDs– Can be useful in some cases of mono/oligo
arthritis– Useful for enthesitis– Useful for spinal disease
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Management: DMARDs
Medication PsoriaticAnkylosing Spondylitis
Hydroxychloroquine (Plaquenil®)
Rarely with little evidence
NO
MethotrexateYES
Rarely with poor efficacy in spinal
disease
Sulfasalazine YES YES
Leflunomide (Arava®)YES NO
Gold YES NO
Steroids YES YES
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Management: Biologics
• Biologics Approved for Psoriatic Arthritis and Ankylosing Spondylitis– Etanercept (Enbrel®) – Infliximab (Remicade®)– Adalimumab (Humira®)
• Biggest advance in the treatment of spondyloarthropathies in decades!
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Management: Biologics
• Dramatic clinical efficacy with the greatest amount of data to date coming from studies of ankylosing spondylitis and psoriatic arthritis.
• Substantially improve both peripheral and axial arthritis, as well as various other clinical parameters, and has also slowed the progression of joint damage.
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SPONDYLOARTHOPATHIES Summary
Absence of rheumatoid factorInvolvement of sacroiliac andspinal jointsPeripheral arthritis(predominantly lower limb)EnthesopathyFamilial clusteringIncreased incidence of HLA-B27Common spectrum of extra-articular features
(predominantly muco-cultaneous)