Differential Diagnosis for Elevated ESR with Normal CRP and Anemia

• Single Most Likely Diagnosis
  • Chronic disease (e.g., chronic kidney disease, chronic liver disease): Elevated ESR can be seen in chronic diseases due to chronic inflammation, while CRP may remain normal. Anemia is also common in these conditions due to various mechanisms such as decreased erythropoietin production or chronic blood loss.
• Other Likely Diagnoses
  • Chronic infections (e.g., tuberculosis, osteomyelitis): These conditions can cause a chronic inflammatory response, leading to an elevated ESR. CRP may not always be elevated, especially in the chronic phase of the infection. Anemia of chronic disease is also a common finding.
  • Autoimmune disorders (e.g., rheumatoid arthritis, systemic lupus erythematosus): Although CRP is often elevated in these conditions, it can be normal, especially if the disease is not very active. ESR is typically elevated due to chronic inflammation, and anemia is common due to the disease process or treatment side effects.
  • Malignancy (e.g., lymphoma, multiple myeloma): Some cancers can cause an elevated ESR due to paraproteins or chronic inflammation. CRP may be normal, and anemia is common due to bone marrow infiltration, chronic disease, or treatment effects.
• Do Not Miss Diagnoses
  • Multiple myeloma: This condition can cause an elevated ESR due to paraproteins and rouleaux formation of red blood cells. CRP may be normal, and anemia is common. Missing this diagnosis can lead to delayed treatment and poor outcomes.
  • Temporal arteritis/giant cell arteritis: Although less common, this condition can cause an elevated ESR with normal CRP. Anemia may be present due to chronic disease. Missing this diagnosis can lead to vision loss or other serious complications if not treated promptly.
• Rare Diagnoses
  • Paraproteinemias (e.g., Waldenström's macroglobulinemia): These conditions can cause an elevated ESR due to paraproteins. CRP may be normal, and anemia is common. These diagnoses are less common but should be considered in the appropriate clinical context.
  • Sickle cell disease: Although typically associated with a low ESR due to sickled red blood cells, some patients with sickle cell disease may have an elevated ESR. CRP may be normal, and anemia is a hallmark of the disease. This diagnosis is rare in populations without African ancestry.