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Musculoskeletal - Pathology > Seronegative Spondyloarthropathies > Flashcards

Seronegative Spondyloarthropathies Flashcards

1
Q

Do the seronegative spondyloarthropathies show a preference for one sex or the other?

A

YES, spondyloarthropathies are more common in males

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2
Q

What disorders fall under the umbrella of Seronegative spondyloarthopaties?

A
  1. Akylosing Spondylitis
  2. Enteropathic arthritis (inflammatory bowel disease-associated arthropathy)
  3. Reactive Arthritis (Reiter’s syndrome)
  4. Psoriatic Arthritis
  5. Undifferentiated Spondyloarthropathies
  6. Juvenile Chronic Arthritis and Juvenile-onset Ankylosing Spondylitis
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3
Q

Comment on the following with regard to the seronegative spondyloarthropaties.
• Presence of RhF?
• HLA type association?
• Part of Skeleton most involved?

A
  • These disease are by definition RhF negative diseases
  • HLA-B27 is strongly associated with these diseases
  • Axial Skeleton is most involved
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4
Q

Comment on the following with regard to the seronegative spondyloarthropaties.
• Heredity?
• Presence of Subcutaneous nodules or other extra-articular manifestations of RA?
• Presence of enthesitis and dactylitis?

A
  • There is a strong **familial aggregation
  • There isNO OVERLAP** of extra-articular manifestations of RA and those of the spondyloarthropathies
  • Enthesitis and Dactylitis are present in Reactive Arthritis, Enteropathic and Psoriatic Arthritis.
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5
Q

Do the spondyloarthropathies have symmetry in common with RA?
• what joints are typically involved?

A

NO - Spondyloarthropathies are most commonly ASYMMETRIC and involve LOWER EXTREMITIES

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6
Q

What is enthesitis?
• what spondyloarthropathies are associated with this?

A
  • Inflammation at the sites where the tedons and ligaments attach to the bone
  • Spondyloarthropathies: Reiter Syndrome (reactive arthritis), Enteropathic Arthritis, Psoriatic Arthritis
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7
Q

What feature Spondyloarthropathies is this image displaying?
• specifically, which of these diseases are associated with this?

A

Dactylitis is shown here and this is associated with Reactive Arthritis, Enteropathic Arthritis, and Psoriatic Arthritis

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8
Q 
Is HLA-B27 assciated with MHC class I or II? 
• what is the difference in MHC classes?
A 
HLA-B27 is an MHC class I protein meaing it interacts with CD8+ T cells.
• MHC class I molecules differ from MHC class II in that MHC class I is found on all cells while class II is on only on APCs
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9
Q

What role the HLA-B27 play in regard to disease susceptibility and severity?

A

HLA-B27 increases BOTH susceptibility and severity of disease

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10
Q

Note: Patients with psoriasis or IBD (irritable bowel syndrome) that are HLA-B27 positive are at an increased risk for Axial (Spinal) Arthropathy

A

Note: Patients with psoriasis or IBD (irritable bowel syndrome) that are HLA-B27 positive are at an increased risk for Axial (Spinal) Arthropathy

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11
Q

Are environmental factors also important in developement of Spondyloarthropathies?

A

Yes, as with most autoimmune diseases there is is both an environmental and genetic component

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12
Q

Akylosing Spondylitis
• Typical Age at onset?
• Gender most affected?
• cause?

A

Ankylosing Spondylitis typically occurs in 1males that are around 235 years old and the 3cause is unknown

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13
Q

Akylosing Spondyltits (AS)
• how will this 35 year old man present?
• when are these symptoms the worst?
• What are 3 key pathological features?

A

Presentation of AS:
• Typically a 35 year old male presents with chronic low back pain and back stiffness that has had an insidious onset. Typically his disease is worse in the morning and improves with excercise.

3 Key Points for Pathology:
• Inflammatory cell infiltrate
• synovial fluid inflammation similar to RA
• EXCESS TNF-alpha

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14
Q

AS starts ___________ and progresses ____________.

A

AS starts in the LOWER SPINE and progresses UP THE SPINE

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15
Q

Do you ever see peripheral joint involvment with AS?
• If so, which joints?

A

YES, 1/3 of patients have involvment of hips, shoulders, knees, and ankles

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16
Q

Excluding spinal involvment, how can you differentiate AS from RA on the basis of a physical?

A

Joint involvement in AS is typically asymmetric joint involvment. Enthesitis may also be present

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17
Q

What 6 physical findings will you often see in Ankylosing Spondylitis?

A
  1. Sacroiliac Tenderness
  2. Limited Spine ROM
  3. Loss of Lumbar Lordosis, Thoracic, and cervical kyphosis
  4. Abnormal Schober’s test
  5. Reduced Chest expansion (less than 2.5cm at 4th intercostal space)
  6. Increased Occiput to wall distance
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18
Q

What defines a negative Schober’s Test?
• What is this test?

A

Schober’s tests is placing a mark at the level of the iliac spine and measuring up 10cm and placing another mark. When the patient bends forward the distance between the two marks should go up to around 5 more cm.

• In patients with Ankylosing Spondylitis you won’t expand more than 3 cm.

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19
Q

Note: In AS patients you’re more likely to see diaphragmatic breathing

A
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20
Q

What is shown on the left and right?

A

Sacroiliitis - this shows fusion of sacrum to the illium
• Left: earlier findings in AS
• Right: Findings in late stage disease

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21
Q

What complication of what disease is shown here?

A

Bamboo Spine is a complication of Ankylosing Spondylitis

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22
Q

What are some X-ray findings that are common in AS?

A
  • Generalized Spinal Osteopenia
  • Boney Ankylosis
  • Vertebral Fractures after minimal trauma
  • Subluxation of atlas and axis or of atlas and occipital bone
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23
Q

What are the Extra-articular Features of AS?

A
  1. ANTERIOR UVEITIS
  2. CARDIAC ISSUES (aortic regurgitation most common, Heart Block)
  3. APICAL LUNG FIBROSIS and Thoracic Cage Restriction
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24
Q

What is a major risk factor for people with AS to develop aortic regurgitation or heart block?

A

People with AS that have peripheral joint involvment are twice as likely to experience aortic regurg. or heart block

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25
Q

What method of treatment should you use for patients with AS?

A
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26
Q

What triad are you looking for in Reactive Arthritis?

A
  • Conjunctivitis, Urethritis, Arthritis
  • Can’t see, can’t pee, can’t climb a tree
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27
Q

What pathogens are associated with causing Reactive Arthritis?

A

GI:
• Salmonella
• Yersinia Enterocolitica
• Shigella Flexneri
• Clostridium Difficile

GU:
• Chlamydia trachomatis

28
Q

How common is reactive arthritis?
• who is most commonly affected?

A

1Men (5:1) who are 2HLA-B27 positive and 3HIV positive are most likely to get this disease

29
Q

How does the disease progression of reactive arthritis compare in an HIV patient vs. a normal patient?

A

HIV patients have MORE SEVERE arthritis that is Resistant to Therapy

30
Q

What are the Key clinical features of reactive arthritis?

A
  1. Arthritis
  2. Conjuctivitis, Uveitis, Keratitis
  3. Urethritis (sterile, mucopurulent discharge => BOTH GI and GU trigger)
    ___________________________________________________
  4. Enthesitis (achilles, plantar fascia, symphisis pubis, Ribs)
  5. Cardiac Involvment (rare)
  6. Skin - Keratoderma blennorrhagic, onchyoysis of NAILS
  7. Oral Ulcerations
31
Q

What 2 features of reactive arthritis are shown here?

A 
Keratoderma blennorrhagica (right) 
Onycholysis (Lef)
32
Q

What lab tests are significant for Reactive Arthritis?

A
  1. Inflammatory Markers - ESR elevated, CRP elevated
  2. Culture - usually not positive
  3. HLA-B27

***Look for HIV and Serology of pathogen too***

33
Q

After someone presents to you with reactive arthritis, what can you tell them with regard to the duration of their symptoms?
• will their symptoms ever recur?

A

Symptoms of reactive arthritis typically resolve after 2 to 3 months. However, recurrences are common and 20-50% of people end up with chronic disease.

34
Q

What are 5 key factors that shoul tip you off to psoriatic arthritis?

A
  • *1. Asymmetric** joint involvment (key to all the spondyloarthropathies)
  • *2. Dactylitis
    3. Enthesitis
    4. Inflammatory-type back pain
    5. RhF negative**
35
Q

What are two important prognositic indicators in Psoriatic Arthritis?

A
  1. ESR elevated is a poor prognostic indicator (remember this is a normal feature of reactive arthritis)
  2. Polyarticular Disease is also a poor prognostic indicator
36
Q

What are 2 features too look for on a biopsy of synovium from a patient with Psoriatic Arthritis that may help you differentiate it from RA?

A

Psoriatic Arthritis has increased vascularity with a thinner synovium lining layer than RA. Also, there is presence of neutrophils on biopsy of the synovium in PsA.

37
Q

Prominent entheseal involvement with ________________ at entheseal insertions on magnetic resonance imaging has prompted the hypothesis that psoriatic arthritis may originate at the enthesis.

A

1.Prominent entheseal involvement with bone marrow edema at entheseal insertions on magnetic resonance imaging has prompted the hypothesis that psoriatic arthritis may originate at the enthesis.

38
Q

What T cells are thought to be most important to the pathogenesis of Psoriatic Arthritis?

A

CD8+, this makes sense b/c its all of these seronegative spondyloarthropathies are associated with HLA-B27 which is an MHC I type so it interacts with CD8+ T-cells

39
Q

Do TNF-alpha drugs work for Psoriatic Arthritis?

A

YES, TNF-alpha inhibitors have proven useful for patients with psoriatic arthritis that present with skin and joint disease

40
Q

What features should you look for in the nailbeds of a person with Psoriatic Arthritis?

A

A. Nail Pitting
B. Onycholysis
C. Severe Destructive change with nail loss and pustule formation

41
Q

What are some key factors expressed on T cells in Psoriatic Arthritis?

A
  1. HLA-DR molecule
  2. IL-2 receptors and Adhesion molecules
  3. IL-6 and other proinflammatory Cytokines
42
Q

What is the Synovial Cytokine Profile for Psoriatic Arthritis?
• what SERUM cytokines are upregulated?
• How does the synovial cytokine profile in PsA differ from RA?

A

Synovial Cytokines:
• TNF-alpha, IL-1, IL-6, IL-8 (notice the similarity to RA)

Serum Cytokines:
• IL-10, IL-13, IFN-alpha, VEGF, FGF

Compared to RA:
• PsA patients have MORE TNF-alpha, IL-1ß, IL-2, IL-10, INF-gamma
• PsA patients have LESS IL-4
• IL-5

43
Q

What is the role of IL-18 in PsA?

A

IL-18 => 1Stimulates Angiogenesis, 2Upregulates Chemokine Expression on synovial fibroblasts, 3Increases Mononuclear Recruitment

***Note: in PsA this cytokine is increased in BOTH serum and synovial tissue***

44
Q

What 5 pattens of Joint involvment do we see in PsA?

A
  1. Polyarticular Pattern (more than 4 joints involved)
  2. Oligoarticular Pattern (less than 4 joints involved)
  3. DIP involvment Pattern
  4. Arthritis Mutilans
  5. Axial involvment
45
Q

What is shown here?

A

PsA mutilans - causes Joint Retraction

46
Q

What extraarticular features of PsA should you look for?

A

• Conjunctivitis and Iritis (like all of the other seronegative spondyloarthropathies)

47
Q

What should you suspect if you see a patient suffering from very severe PsA symptoms?

A

Suspect HIV in patients with extremely severe PsA

48
Q

What is shown on this X-ray?

A

Pencil-in-Cup deformity on the 4th digit.

49
Q

Other than asymmetry, what aspect of joint involvment should help you differentiate PsA and RA?

A

PsA involves the DIPs while RA doen’t

50
Q

Note: Axial Disease in PsA makes is rememble AS while the Erosive and Proliferative aspects of the disease make it resemble RA.

A
51
Q

Erosive Process in PsA

A
52
Q

Are TNF-alpha antagonists useful in treating PsA?

A

Yes, TNF-alpha antagonists are effect for people with PsA

53
Q

T or F: Genetic Polymorphisms in Crohn’s Disease can result in relative immune deficiency.

A

True, this may put you at increased risk for enteropathic arthritis

54
Q

Patients with what prior exisiting inflammatory conditions are at an increased risk of getting enteropathic arthritis?

A
  • Crohn’s Disease
  • Ulcerative Colitis
  • Whipple’s Disease
  • Irritable Bowel Disease
55
Q

Does Eteropathic Arthritis have a gender preference?
• what additional problems are seen with people possessing the HLA-B27 phenotype?

A

No, M=F

• People with HLA-B27 are more likely to experience Axial Involvment with their enteropathic arthritis (NOT PERIPHERAL)

56
Q

What is the pathogenesis of Enteropathic Arthritis?

A
  • *1. Inflammation in the Gut Draws in Lymphocytes
    2. B-cells produce Ig’s
    3. Immune complexes form and deposit in the joints** (if HLA-B27+ then it will deposit in your spine)
57
Q

What joints are typically involved in Peripheral Enteropathic Arthritis and Axial Enteropathic Arthritis?
• Do arthritic flare-ups parallel GI flareups?

A

Peripheral:
• Peripheral Joint disease typically involves the LOWER extremities and is ASYMMETIC
• GI inflammation parallels arthritis

Axial (HLA-B27 ppl):
• Lower spinal involvment that progresses up (clinically and radiographically this is identical to AS)
• Arthritis does NOT correlate with GI inflammation

58
Q

Are Dactylitiis and Enthesitis features of Enteropathic Arthritis?

A

Yes

59
Q

Notice the Asymmetry (right more affected than left) and lack of joint space in this person with Enteropathic Arthritis.

A
60
Q

What progression of Treatment is tyically used in Enteropathic Arthritis?

A
  1. Symptomatic Tx with NSAIDs (both spinal and peripheral dz)
  2. Sulfasalazine (good for Ulcerative Colitis (UC), NOT for Crohn’s Disease (CD))
  3. Gulcocorticoids (good for UC and CD, local injections if few joints involved)
  4. Azathioprine (good for UC and CD)
  5. Infliximab (CD and UC) or Adalimumab (CD) only
61
Q

What causes Arthritis of Celiac Disease?

A

• Autoimmune Reaction to partially digested wheat gluten by T lymphocytes in people with HLA-DQ2 or HLA-DQ8

62
Q

What are the typical symptoms of Celiac Disease in 2/3 of people?

A
  • Irritated Bowel
  • Fatigue
  • Headache
  • ARTHRALGIAS

(25% of people progress to get diabetes, anemia, osteoporosis, neuropathies, and joint symptoms)

63
Q

How do Arthralgias in Celiac Disease Typically Present?
• how do you treat these patients?

A
  • Asymmetric, Oligoarthritis/Polyarthritis/Axial Arthritis => basically the same as all of these diseases
  • Treatment - eliminate gluten from the diet
64
Q

How do you diagnose Celiac Disease?

A

• IgA antiitissue Tranglutaninase
• IgA antiedomysial Antibodies

65
Q

What disease is associated with IgA deficiency?

A

Celiac - 10% of pts. with IgA deficiency Get Celiac

66
Q
A
67
Q

What has caused the appearance of these spines?

A

Musculoskeletal - Pathology (17 decks)

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