Introduction to rheumatology Flashcards

1
Q

What is Rheumatology?

The 100 rheumatology diseases that exist are broadly divided into waht to subcategories?

A

–>The study, diagnosis, and treatment of conditions that may (but not always) affect the joint.

–>Many of the diseases that cause arthritis are immune-mediated (which is why it is included in this block) and can involve multiple organ systems.

  • Rheumatologists need to master internal medicine and know about many other medicine specialties.
  • Adult and pediatric rheumatology are different specialties

There are over 100 rheumatologic diseases; they are broadly divided into inflammatory/immune and non-inflammatory categories.

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2
Q

History inflammatory vs Mechanical

For_________, activity may improve symptoms.

For _________, activity may worse symptoms.

For ______, rest may improve symptoms.

For_________, rest may worsen symptoms.

A
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3
Q

Joint exam: Way to evaluate patient

What do red joints indicate?

In what diseases can cool swelling occur?

A

–>Untreated or inadequately controlled inflammatory arthritis typically results in synovial distention, warmth and decreased range of motion.

-Red joints typically indicate infection or crystal disease.

–>Cool swelling can occur in non-inflammatory diseases such as osteoarthritis.

–>It is key to note which joints (including feet with shoes off) are abnormal since the pattern of joint involvement is major clue to the correct diagnosis.

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4
Q

Difference in presentation between osteoarthritis and rheumatoid arthritis?

A
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5
Q

Patient evaluation: lab testing of inflammation

Indirect assessment of inflammatory response is done with______.

Direct assessment of inflammatory response is done with _______.

A
  • Helps with diagnostic process and following response to therapy.
  • Not specific to rheumatologic diseases.
  • Non-specific indicators of inflammation: Platelet count and ferritin.
  • Negative acute phase reactants: albumin and hematocrit.
  • Indirect assessment of inflammatory response: Erythrocyte sedimentation rate (ESR)
  • Direct assessment of inflammatory response: C-reactive protein (CRP).
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6
Q

Lab testing to autoantibodies

Which factors are associated with RA?

A
  • Ordered to confirm clinical impression.
  • High titer antinuclear antibodies (ANAs) are associated with lupus and related diseases.
  • Poor positive predictive value of low titer ANA.
  • There are disease specific autoantibodies that are more specific for disease states.
  • Rheumatoid factor and anti-CCP are associated with RA.

RF is often false +

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7
Q

Patient evaluation: synovial fluid analysis

A

X-ray usage

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8
Q

Monoarticular arthritis

A

Polyarticular Arthritis

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9
Q

Non-inflammatory diseases: Osteoarthritis

What kidn of joints does it affect the most?

Pathophysiology is due to imbalance of ____ and _____.

How are the ESR/CRP levels? What about WBCs in sinovial fluid?

Do x-rays show simmetric or asymmetric joint space loss?

A

-Most common form of arthritis

  • Predilection for spinal, weight-bearing, and pinch grip joints
  • Pathophysiology is imbalance between production and destruction of articular cartilage
  • Symptoms: **pain with activity
  • Exam: crepitus, deformity, limited range of motion, Heberden’s and Bouchard’s nodes
  • Labs: normal levels of ESR/CRP, low WBC in synovial fluid
  • X-rays: Asymmetric joint space loss & osteophytes
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10
Q

Other non-inflammatory disease:

What could cause avascular necrosis?

A
  • Secondary OA is related to other diseases. It often involves joints not usually affected by OA.
  • Avascular necrosis refers to the ischemic death of cellular bone components. It happens at the end of long bones with tenuous blood supply. **High dose corticosteroids can cause this at the femoral head.

Fibromyalgia is a controversial disease in which psychological factors and _increased central pain processin_g result in diffuse pain.

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11
Q

Inflammatory diseases: Rheumatoid arthritis

Which joints are not affected in rheumatoid arthritis?

What are the symptoms?

Symmetric or asymmetric sinovitis?

A
  • Approximately 1% US adults
  • Small joints except **DIP joints - no thoracic or lumbar spine involvement
  • Inflamed synovial tissue can erode into bone causing deformity and impaired function

**Symptoms: fatigue, pain, swelling and morning stiffness.

Exam: Symmetric synovitis, +/- nodules

  • Labs: + RF/CCP, high ESR/CRP, inflammatory joint fluid
  • X-rays: periarticular osteopenia, symmetric joint space loss and +/-marginal erosions
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12
Q

inflammatory diseases: Gouty Arthritis

Characterized by:

What enzyme do we lack that helps oxidize uric acis to allantoin?

A
  • Episodic, very painful arthritis with swelling, redness and warmth often in lower extremity joints
  • Humans lack the enzyme uricase, which oxidizes uric acid to allantoin. Loss of uricase helped early hominids adjust to upright posture by ↑ sodium retention.
  • Gout is caused by high levels of uric acid, supersaturation and an inflammatory response to crystals.
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13
Q

Inflammatory diseases: Pseudogout

Synovial fluid is inflammatory with ______ crystals.

A
  • Episodic intensely painful arthritis of large joints in older patients with swelling, redness and warmth.
  • Synovial fluid is inflammatory with Ca++ pyrophosphate crystals
  • Not due to high serum levels of calcium or pyrophosphate.
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14
Q

Inflammatory dx: Spondyloarthropathies

What are some key manifestations?

What kind of inflammatory pain do patients usually have?

Association with what antigen?

A
  • Ankylosing spondylitis, reactive arthritis, psoriatic arthritis and inflammatory bowel disease arthropathy.
  • Key manifestations are *spinal arthritis & *enthesitis
  • Patients have inflammatory low back pain.
  • There is a strong genetic association with the HLAB27 antigen but these diagnoses are made based on clinical findings not labs.

What is enthesitis?

  • Inflammation of ligamentous-osseous junctions
  • What does Inflammatory back pain mean?
  • insidious onset of pain (months)
  • prolonged morning stiffness
  • pain improves with exercise
  • no neurologic sequelae
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15
Q

Inflammatory dx: Autoimmunity/Systemic Lupus Erythematosus (SLE)

In the labs you can observe strongly high _____, and low complemente __ and __.

A
  • 1/1000 young women
  • More common in non-whites
  • Symptoms from involvement of multiple organ systems: Skin, joints, serosa, kidneys, central nervous system, lungs and blood cells
  • Labs: strongly + ANA, CRP not always high, low complement 3 and 4
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16
Q

Inflammatory dx: Autoimmunity/others

A

SjÖgren’s Syndrome

-middle aged women with autoimmune exocrine gland dysfunction

Systemic Sclerosis

-fibrosis of skin with vascular and inflammatory signs and symptoms

17
Q

Inflammatory dx: Vasculitis

Antibodies to ______ seen in some cases.

A

–Rare disorders with constitutional and poly-systemic manifestations.

–Potentially life-threatening (especially alveolar hemorrhage) and often require aggressive therapy

–Labs reflect systemic inflammation. Anti-neutrophil cytoplasmic antibodies in some cases.

18
Q

Inflammatory dx: Poly- & Dermatomyositis

A
  • Rare autoimmune muscle diseases
  • Constitutional and systemic manifestations.
  • Exam: **proximal weakness**
  • Labs: Elevated muscle enzymes, +ANA (70%), Myositis specific antibodies only in 20%
  • Diagnosed with electromyography (EMG) and muscle biopsy.
  • Sometimes associated with cancer.
  • PM and DM have very different pathophysiology.
19
Q

Treatments

Non-Steroidal Anti-Inflammatory Drugs (NSAIDS):

A
  • Used for joint pain in almost all rheumatologic diseases.
  • Beneficial Effects of inhibition of prostaglandin production

Analgesia

Anti-pyresis

Anti-inflammatory

What are some of the negative effects of NSAIDs?

  • GI mucosal damage
  • Exacerbation of asthma
  • Platelet inhibition
  • Nephrotoxicity
20
Q

Glucocorticoid Therapy: Benefits

Used in ____ therapy in almost all inflammatory arthritic diseases but avoiding long-term, high-dose use.

A
  • Suppression of inflammatory cascade
  • Modification of the immune response through decreased neutrophil margination/migration, macrophage cytokine (IL-1, TNF) production, decreased T cell proliferation.
  • Used as initial therapy in almost all inflammatory arthritic diseases with goal of avoiding long-term, high-dose use.
21
Q

Disease modifying anti-rheumatic agents (DMARDS) and other oral agents

A
  • Exact mechanisms of action for many are nebulous even though most have been used for decades
  • All have their own toxicities and monitoring requirement
  • Many are highly teratogenic (can disturb development of fetus)
  • Most are generic and not expensive

Some examples:

  • Hydroxychloroquine
  • Sulfasalazine
  • Methotrexate
  • Azathioprine
  • Mycophenolate
  • Leflunomide
  • Cyclophosphamide
22
Q

Biologic agents

A
  • Have very specific targets
  • Given by injection or infusion
  • Revolutionized the lives of people with RA and other conditions in the past 1-2 decades.
  • All are patented and are extremely expensive (>$10K per year)
  • Also have many risks and potential toxicities
23
Q

Biologic Agents: anti-TNF agent

A

Agents: Entanercept , adalimumab, infliximab, certolizumab pegol, golimumab

Rationale: TNFα is a key cytokine in the pathophysiology of synovitis and bone destruction in rheumatoid arthritis

Mechanism of action: Enbrel is a dimeric soluble TNF receptor that bind soluble TNF α & β. Others are monoclonal antibodies.

24
Q

Biologic agents: other

**Rituximab mainly attacks _____ not plasma cells.

*Toclizumab is an anti-______ receptor antibody that competes for human IL-6 receptor, inhibiting binding of IL-6 to its receptor.

Abatacept is a soluble fusion protein of extracellular domain of ______ and Fc portion of IgG1. It acts as a _______ inhibitor of the CD28-CD80(B7) signal for T cell activation.

A

Rituximab - B cell depleting monoclonal anti-CD20 antibody (molecule expressed on pre-B cells but not plasma cells).

Belimumab – monoclonal antibody that targets B-lymphocyte stimulator (BLyS).

Toclizumab -anti-IL-6 receptor antibody competes for human IL-6 receptor, inhibiting binding of IL-6 to its receptor.

Abatacept - Soluble fusion protein of extracellular domain of CTLA4 and Fc portion of IgG1. It acts as a competitive inhibitor of the CD28-CD80 (B7) second signal.

–>Rationale: T cells have a proven role in RA disease pathogenesis. Activation of T cells by antigen-presenting cells requires two distinct signals: 1) APC’s MHC II molecule with antigen and TcR, 2) binding of T cell’s CD28 to APC’s CD80 (B7)

Mechanism of action: Soluble fusion protein of extracellular domain of CTLA4 and Fc portion of IgG1. It acts as a competitive inhibitor of the CD28-CD80 (B7) second signal.

25
Q

Non-pharmacologic therapies

A