Differential Diagnosis for Joint Pain with Elevated ESR and CRP, Negative RF and ANA

• Single Most Likely Diagnosis

  • Seronegative Spondyloarthritis: This condition is characterized by joint pain, elevated inflammatory markers (ESR and CRP), and the absence of rheumatoid factor (RF) and antinuclear antibodies (ANA). It encompasses a group of diseases including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis associated with inflammatory bowel disease. The negative RF and ANA, along with elevated ESR and CRP, point towards an inflammatory process not typical of rheumatoid arthritis or systemic lupus erythematosus, making seronegative spondyloarthritis a leading consideration.

• Other Likely Diagnoses

  • Osteoarthritis with Inflammatory Component: While osteoarthritis is primarily a degenerative condition, some patients may exhibit an inflammatory component, leading to elevated ESR and CRP. The absence of RF and ANA helps to distinguish it from autoimmune causes.
  • Crystal Arthropathies (Gout or Pseudogout): These conditions can cause acute joint pain and elevate inflammatory markers. The diagnosis is typically made by identifying crystals in the joint fluid.
  • Infectious Arthritis: Bacterial, viral, or fungal infections can cause joint pain and inflammation. The absence of RF and ANA does not rule out infectious causes, and joint aspiration is crucial for diagnosis.

• Do Not Miss Diagnoses

  • Lyme Arthritis: Caused by Borrelia burgdorferi, Lyme disease can present with joint pain and elevated inflammatory markers. It is crucial to consider this diagnosis, especially in endemic areas, as it is treatable with antibiotics.
  • Septic Arthritis: This is a medical emergency that requires prompt diagnosis and treatment. The presence of joint pain and elevated ESR and CRP, regardless of RF and ANA status, necessitates consideration of septic arthritis.
  • Malignancy-associated Arthritis: Certain malignancies, like lymphoma, can cause arthritis that mimics other forms of joint disease. A high index of suspicion is necessary, especially in older adults or those with risk factors for cancer.

• Rare Diagnoses

  • Relapsing Polychondritis: A rare autoimmune disorder characterized by recurrent episodes of cartilaginous inflammation, which can affect joints among other structures.
  • Sarcoid Arthritis: Part of sarcoidosis, a systemic granulomatous disease that can affect joints, among other organs, and may present with elevated inflammatory markers and negative autoimmune tests.
  • Whipple's Disease: A rare, systemic bacterial infection that can cause joint pain, among other symptoms, and may have a presentation that overlaps with other forms of arthritis.