Updated: 9/29/2018

Rheumatoid Arthritis

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Snapshot
  • A 36-year-old woman presents to her physician's clinic with pain and swelling in the hands and wrists. She reports morning stiffness that lasts for approximately 1 hour which later improves. She also states to be experiencing symptoms of depression and fatigue. On physican exam, there is decreased grip strength and 4/5 strength on wrist extension. There is tenderness to palpation and swelling of the proximal interphalangeal joints and metacarpophalangeal joints.
Introduction
  • 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) levels
      • typically elevated
    • 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
Treatment
  • Conservative
    • education, exercise, physical therapy, vaccinations, smoking cessation, and counseling
      • indication
        • a component of treatment for patients with rheumatoid arthritis
  • Pharmacologic
    • disease-modifying antirheumatic drugs (DMARDs)
      • indications
        • used to prevent, stop, or retard disease-associated damage
      • medications
        • methotrexate
          • typically the initial DMARD used
        • tumor necrosis factor (TNF) inhibitor such as
          • etanercept
          • adalimumab
        • leflunomide
        • sulfasalazine
        • hydroxychloroquine
    • nonsteroidal antiinflammatory drugs (NSAIDs) and/or glucocorticoids
      • indications
        • 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
 

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Questions (10)
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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(M1.MK.4666) A 35-year-old woman presents with a 4-month history of hand pain that is worse when awakening in the morning. She reports that her pain improves throughout the morning. Both hands are equally affected. Findings from a physical examination are shown in Figure A. Which of the following autoantibodies is highly specific for this patient's disorder? Review Topic

QID: 107096
FIGURES:
1

Anti-Smith antibodies

0%

(0/16)

2

Antihistone antibodies

0%

(0/16)

3

Anticentromere antibodies

0%

(0/16)

4

Anti-IgG antibodies

0%

(0/16)

5

Anti-citrullinated protein antibodies

94%

(15/16)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(M1.MK.15) A 38-year-old female visits your office complaining of several years of joint swelling and stiffness that is worse in the morning and improves throughout the day. Physical examination reveals bilateral deformities at her proximal interphalangeal and metacarpophalangeal joints. The presence of which of the following in this patient’s serum would most help 'rule in' a diagnosis of rheumatoid arthritis: Review Topic

QID: 100436
1

Rheumatoid factor

16%

(22/141)

2

Anti-nuclear antibody

6%

(9/141)

3

Anti-citrullinated protein antibody

73%

(103/141)

4

Anti-centromere antibody

3%

(4/141)

5

Anti-smooth muscle antibody

0%

(0/141)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3
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