Updated: 7/11/2019

Rheumatoid Arthritis

Topic
Review Topic
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Questions
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Evidence
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Snapshot
  • A 35-year-old woman presents with joint stiffness and pain of the hands and wrists for the last two months. Her symptoms are most severe in the morning and improve in the afternoon. She reports an unintentional loss of 15 pounds over the course of 3 months as well as fatigue. On physical exam, there is swelling and tenderness at the metacarpophalangeal and proximal interphalangeal joints.
Introduction
  • Clinical definition 
    • a chronic autoimmune disorder that primarily affects the joints and results in an inflammatory synovitis
  • Epidemiology
    • demographics
      • sex
        • more common in women
      • age
        • 30-50 years of age
    • risk factors
      • smoking
  • Etiology
    • environmental and genetic factors play a role
  • Pathogenesis
    • T- and B-cell response after a triggering event (e.g., infection in a genetically susceptible patient) eventually results in
      • pannus formation and subsequent damage to the adjacent cartilage and bone
        • Th1 cells release interferon-γ (IFN-γ) in order to activate macrophages and synovial cells
        • Th17 cells secrete interleukin-17 (IL-17) in order to recruit monocytes and neutrophils
        • synovial plasma cells produce antibodies against self-antigens such as citrullinated peptides 
  • Genetics
    • HLA-DR4
  • Associated conditions
    • Sjogren syndrome
    • Felty syndrome 
      • seropositive rheumatoid arthritis with neutropenia
        • many patients have splenomegaly
    • Caplan syndrome
      • seropositive rheumatoid arthritis with pneumoconiosis
  • Prognosis
    • certain patients with early rheumatoid arthritis may achieve remission
Presentation
  • Symptoms
    • fatigue and depression
    • morning stiffness that lasts > 1 hour
    • pain, stiffness, and/or swelling of the joint such as the
      • metacarpophalangeal (MCP) joints
      • proximal interphalangeal (PIP) joints
      • metatarsophalangeal (MTP) joints
  • Physical exam
    • anemia of chronic disease
    • weight loss
    • decreased grip strength
    • palmar erythema
    • subcutaneous (rheumatoid) nodules
    • splenomegaly in cases of Felty syndrome
    • ulnar deviation of the fingers
    • swan neck deformity
    • bouttoniere deformities
Imaging
  • Radiography
    • indications
      • can be obtained during the initial workup to have a baseline to compare to when following disease progression
      • can be performed of the neck to rule out odontoid ligament laxity
    • modality
      • hands, wrists, and feet
    • findings
      • diffuse osteopenia
      • joint space narrowing in the carpal, metacarpal, phalangeal, and interphalangeal joints
      • periarticular bony erosions
      • ulnar deviation of the fingers
Studies
  • Labs
    • rheumatoid factor (RF) antibody testing
      • RF is an IgM antibody that targets the Fc portion of IgG 
    • anti-CCP antibody testing 
      • more specific for rheumatoid arthritis 
    • erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels
      • typically elevated
  • Diagnostic criteria
    • diagnosis is based on clinical presentation and laboratory studies
Differential
  • Systemic lupus erythematous
  • Psoriatic arthritis
  • Scleroderma
  • Polymyalgia rheumatica
  • Gout
  • Osteoarthritis
  • Parvovirus B19 
    • mild symmetric arthralgias and a viral syndrome that is self-limited
Treatment
  • Conservative
    • education, exercise, physical therapy, vaccinations, smoking cessation, and counseling
      • indication
        • a component of treatment for patients with rheumatoid arthritis
  • Medical
    • disease-modifying antirheumatic drugs (DMARDs)
      • indication
        • used to prevent, stop, or retard disease-associated damage
      • medications
        • methotrexate 
          • typically the initial DMARD used
          • side-effects include GI symptoms, oral ulcers, macrocytic anemia, and hepatotoxicity  
        • tumore necrosis factor (TNF) inhibitor such as
          • etanercept
          • adalimumab
        • leflunomide
        • sulfasalazine
        • hydroxychloroquine 
    • nonsteroidal antiinflammatory drugs (NSAIDs) and/or glucocorticoids
      • indication
        • initially given for symptomatic control while waiting for DMARD response
  • Operative
    • joint replacement surgery
      • indication
        • in patients with severe joint damage or failure to respond to conservative and medical therapy
Complications
  • Hand deformities
  • Atlantoaxial subluxation 
  • Popliteal cyst 
  • Greater risk of osteoporosis and osteopenia secondary to steroid use, inactivity, and disease process
    • bisphosphantes is an effective prophylactic therapy in these patients 
  • Nephrotic syndrome
    • result of amyloid deposition 
 
 

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Questions (11)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M2.RH.62) A 67-year-old male with no significant medical history comes to your office complaining of pain and stiffness in his hands upon wakening in the morning. You perform an x-ray (Figure A). What is the most likely diagnosis? Review Topic

QID: 106427
FIGURES:
1

Gouty arthritis

0%

(0/20)

2

Osteoarthritis (OA)

50%

(10/20)

3

Rheumatoid arthritis (RA)

15%

(3/20)

4

Psoriatic arthritis

30%

(6/20)

5

Systemic lupus erythematosus (SLE)

0%

(0/20)

M2

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SUBMIT RESPONSE 2

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(M2.RH.62) A 45-year-old male with no significant medical history comes to your office complaining of pain and stiffness in his hands upon wakening in the morning for the past several months. The stiffness generally lasts one to two hours, per the patient. You perform an x-ray (Figure A). What is the most likely diagnosis? Review Topic

QID: 106428
FIGURES:
1

Gouty arthritis

0%

(0/21)

2

Osteoarthritis (OA)

5%

(1/21)

3

Rheumatoid arthritis (RA)

90%

(19/21)

4

Psoriatic arthritis

0%

(0/21)

5

Systemic lupus erythematosus (SLE)

0%

(0/21)

M2

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SUBMIT RESPONSE 3

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(M2.RH.32) A 35-year-old woman presents to her family physician with a complaint of painful joints for the past 2 weeks. She reports symmetric bilateral joint pain in her hands, knees, and ankles. She has never had this before, and her past medical history is notable only for asthma. She states the pain is worse in the morning and improves throughout the day. Review of systems is notable for a recent low-grade fever with malaise. She works as a school teacher and is sexually active with men and women. Her temperature is 97.9°F (36.6°C), blood pressure is 120/84 mmHg, pulse is 70/min, respirations are 14/min, and oxygen saturation is 97% on room air. The patient is instructed to take ibuprofen and acetaminophen for her joint pain. She returns 1 month later stating that she has not needed to take the medications as her pain has been absent for the past 3 days. Which of the following is the most likely diagnosis? Review Topic

QID: 104917
1

Osteoarthritis

3%

(1/36)

2

Parvovirus

0%

(0/36)

3

Reactive arthritis

61%

(22/36)

4

Rheumatoid arthritis

14%

(5/36)

5

Transient synovitis

19%

(7/36)

M2

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SUBMIT RESPONSE 2

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(M2.RH.95) A 50-year-old female presents to clinic complaining of joint pain. She reports stiffness is her knees, wrists, and hands, that is worst in the morning. Her symptoms have been present for many years. On physical exam, her vital signs are stable, and she has tenderness when her knees, hands, and wrists are articulated. You closely examine her hands (Figure A). Serum rheumatoid factor is positive. Which of the following is true regarding this patient's disease? Review Topic

QID: 106064
FIGURES:
1

High titers of rheumatoid factor are usually associated with a better prognosis

9%

(2/22)

2

Exercise is discouraged as it may worsen range of motion

0%

(0/22)

3

The patient is at increased risk of developing osteopenia and osteoporosis

77%

(17/22)

4

Opioids are the drugs of choice for pain control in this disease

5%

(1/22)

5

Disease modifying drugs such as methotrexate should only be started one year after diagnosis

5%

(1/22)

M2

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