Differential Diagnosis for Seronegative Arthritis

In patients presenting with seronegative arthritis, the differential diagnosis can be complex, involving various autoimmune and inflammatory conditions. The evidence for testing HLA-B27 and ANA together, and how co-positivity influences the differential between reactive arthritis and early lupus-spectrum overlap syndromes, is crucial for accurate diagnosis and management.

• Single Most Likely Diagnosis
  • Reactive Arthritis: This condition is a type of seronegative arthritis that occurs after certain bacterial infections, often presenting with asymmetric oligoarthritis, enthesitis, and extra-articular symptoms like conjunctivitis and urethritis. HLA-B27 positivity supports this diagnosis, especially in the context of a recent infection.
• Other Likely Diagnoses
  • Psoriatic Arthritis: Another form of seronegative arthritis, characterized by psoriatic skin lesions and nail changes, along with arthritis. HLA-B27 can be positive in some cases, but the presence of psoriasis is key.
  • Ankylosing Spondylitis: A chronic inflammatory disease primarily affecting the spine and sacroiliac joints, often associated with HLA-B27 positivity. Early stages might present with non-specific back pain and stiffness.
  • Undifferentiated Spondyloarthritis: This diagnosis is considered when symptoms suggest spondyloarthritis but do not meet the criteria for a specific type, such as ankylosing spondylitis or psoriatic arthritis. HLA-B27 positivity and the presence of certain clinical features (e.g., inflammatory back pain, enthesitis) support this diagnosis.
• Do Not Miss Diagnoses
  • Systemic Lupus Erythematosus (SLE): Although SLE is typically seropositive, early or mild cases might present as seronegative arthritis. ANA positivity is a hallmark, but it can also be positive in other conditions. The presence of other SLE criteria (e.g., malar rash, nephritis) is crucial for diagnosis.
  • Rheumatoid Arthritis (RA): While RA is usually seropositive, seronegative RA can occur. The presence of symmetric polyarthritis, morning stiffness, and specific autoantibodies (even if initially negative) should prompt consideration of RA.
• Rare Diagnoses
  • Mixed Connective Tissue Disease (MCTD): Characterized by overlapping features of SLE, RA, scleroderma, and polymyositis, with high levels of anti-U1 RNP antibodies. It can present with seronegative arthritis and various systemic symptoms.
  • Sjögren's Syndrome: An autoimmune disorder primarily affecting exocrine glands, leading to dry eyes and mouth. It can also present with seronegative arthritis and should be considered, especially if there are symptoms of glandular dysfunction.

The co-positivity of HLA-B27 and ANA complicates the differential diagnosis, as it could suggest an overlap syndrome or an early stage of a disease where the full spectrum of symptoms has not yet developed. A thorough clinical evaluation, including a detailed history, physical examination, and additional diagnostic tests (e.g., imaging, other autoantibodies), is essential for distinguishing between these conditions and guiding appropriate management.