Rheumatoid Arthritis Extra-articular Signs

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Epidemiology

Extra-articular findings in 20-40% of Rheumatoid Arthritis patients

Risk Factors
Extra-articular RA findings

Male Gender
Seropositive (RF, ACPA, ANA)
Tobacco Abuse

Findings
Common Extra-Articular

Rheumatoid Nodules
Profound Fatigue
Low-grade fever
Weight loss
Normochromic Normocytic Anemia

Findings
Other Extra-Articular

Cardiovascular
1. Accelerated Coronary Artery Disease (leading cause of death in RA)
2. Pericarditis
3. Myocarditis
4. Pericardial Effusion (common)
5. Rheumatoid Nodules in Great Vessel or Myocardium wall
  1. Causes Heart Block and Bundle Branch Block
6. Systemic Vasculitis
7. Cerebrovascular Disease
8. Congestive Heart Failure
Dermatologic
1. Rheumatoid Nodules (firm, painless Subcutaneous Nodules)
2. Rheumatoid nodulosis (cystic bone lesions)
3. Vasculitis skin and nail changes (nail folds, leg ulcers, Urticaria)
HemeOnc
1. Normocytic normochromic Anemia
  1. Evaluate for other Anemia causes (e.g. Gastrointestinal Bleeding with Iron Deficiency Anemia)
  2. Consider Medication Causes of Macrocytic Anemia (e.g. Methotrexate-related Folate Deficiency)
  3. Consider marrow suppression or hypersplenism
2. Mild Leukocytosis with Eosinophilia
  1. Except in Felty Syndrome (associated with Neutropenia)
3. Thrombocytosis
4. Immunocompromised state
  1. RA, its manifestations and treatments (e.g. Biologic Agents) increase the ris for opportunistic infections
5. Secondary Malignancy
  1. RA is associated with an increased risk of Lymphoma
6. Felty Syndrome
  1. Triad of RA, Splenomegaly and Neutropenia
Lung
1. Pulmonary rheumatoid Nodules
  1. Solid Nodules that are more common in men
  2. Lesions may calcify, cavitate or become secondarily infected
2. Pleural Effusion
  1. Exudative Pleural Effusions
  2. Very low Pleural Fluid Glucose and low pH
  3. More common in men, and typically small and asymptomatic
3. Caplan Syndrome (Rheumatoid Pneumoconiosis)
  1. Peripheral, rounded, encased Pulmonary Nodules (up to 5 cm) AND
  2. Occupational Pneumoconiosis (e.g. silicosis or coal worker's lung)
4. Interstitial Lung Disease
  1. Diffuse interstitial fibrosis associated with Dyspnea
  2. Risk of Cor Pulmonale
5. Bronchiolitis Obliterans
  1. Organizing Pneumonia may also be present
6. Granulomatous Pneumonitis
7. Pulmonary arteritis
  1. Rheumatoid-related Vasculitis with risk of Pulmonary Infarction
8. Rheumatoid Arthritis medications effecting lung disease
  1. Methotrexate-Induced Pulmonary fibrosis
  2. Opportunistic infections in patients on Biologic Agents (e.g. Tuberculosis)
Ophthalmologic manifestations
1. Keratoconjunctivitis Sicca or Sjogren's Syndrome (common)
2. Peripheral Ulcerative Keratitis
3. Episcleritis or Scleritis
  1. Risk of Scleromalacia perforans (orbit rupture)
4. Brown's Syndrome
  1. Superior Oblique Muscle Tendinitis results in Diplopia
Neurologic manifestations
1. Peripheral Neuropathy (e.g. Carpal Tunnel)
  1. Rheumatoid Granulomata near nerve roots result in Entrapment Neuropathy
2. Mononeuritis multiplex
  1. Secondary to Vasculitis
3. Transverse Myelitis
4. C-Spine involvement Overall (up to 80% of patients)
5. C-Spine Atlantoaxial Subluxation
  1. Cervical Spine subluxation at C1-2 (up to 25 to 40% of patients)
  2. Risk of secondary Cervical Myelopathy from central spinal stenosis
  3. Results from Rheumatoid Arthritis erosions and inflammation
    1. Affects odontoid process, transverse ligament, alar ligament, C1 lateral mass
  4. References
    1. Shlobin (2021) Neurosurg Rev 44(4): 1957-65 [PubMed]
Miscellaneous
1. Renal Disease
  1. RA is associated with Glomerulonephritis (e.g. Vasculitis, Amyloidosis)
  2. Evaluate for Nephrotoxic Drugs
2. Liver Dysfunction
  1. Associated with Hepatic Fibrosis, Hepatosplenomegaly, increased Liver Function Tests
3. Hoarseness (extreme and progressive)
  1. Rheumatoid changes in laryngeal cricoarytenoid joints

References