Introduction to rheumatology Flashcards
What is Rheumatology?
The 100 rheumatology diseases that exist are broadly divided into waht to subcategories?
–>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.
History inflammatory vs Mechanical
For_________, activity may improve symptoms.
For _________, activity may worse symptoms.
For ______, rest may improve symptoms.
For_________, rest may worsen symptoms.
Joint exam: Way to evaluate patient
What do red joints indicate?
In what diseases can cool swelling occur?
–>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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Difference in presentation between osteoarthritis and rheumatoid arthritis?
Patient evaluation: lab testing of inflammation
Indirect assessment of inflammatory response is done with______.
Direct assessment of inflammatory response is done with _______.
- 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).
Lab testing to autoantibodies
Which factors are associated with RA?
- 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 +
Patient evaluation: synovial fluid analysis
X-ray usage
Monoarticular arthritis
Polyarticular Arthritis
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?
-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
Other non-inflammatory disease:
What could cause avascular necrosis?
- 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.
Inflammatory diseases: Rheumatoid arthritis
Which joints are not affected in rheumatoid arthritis?
What are the symptoms?
Symmetric or asymmetric sinovitis?
- 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
inflammatory diseases: Gouty Arthritis
Characterized by:
What enzyme do we lack that helps oxidize uric acis to allantoin?
- 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.
Inflammatory diseases: Pseudogout
Synovial fluid is inflammatory with ______ crystals.
- 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.
Inflammatory dx: Spondyloarthropathies
What are some key manifestations?
What kind of inflammatory pain do patients usually have?
Association with what antigen?
- 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
Inflammatory dx: Autoimmunity/Systemic Lupus Erythematosus (SLE)
In the labs you can observe strongly high _____, and low complemente __ and __.
- 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
Inflammatory dx: Autoimmunity/others
SjÖgren’s Syndrome
-middle aged women with autoimmune exocrine gland dysfunction
Systemic Sclerosis
-fibrosis of skin with vascular and inflammatory signs and symptoms
Inflammatory dx: Vasculitis
Antibodies to ______ seen in some cases.
–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.
Inflammatory dx: Poly- & Dermatomyositis
- 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.
Treatments
Non-Steroidal Anti-Inflammatory Drugs (NSAIDS):
- 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
Glucocorticoid Therapy: Benefits
Used in ____ therapy in almost all inflammatory arthritic diseases but avoiding long-term, high-dose use.
- 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.
Disease modifying anti-rheumatic agents (DMARDS) and other oral agents
- 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
Biologic agents
- 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
Biologic Agents: anti-TNF agent
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.
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.
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.
