Differential Diagnosis for Elevated C3 and C4
Elevated levels of complement components C3 and C4 can be seen in various conditions. Here's a categorized differential diagnosis:
Single Most Likely Diagnosis
- Acute Phase Reaction: This is the most common cause of elevated C3 and C4 levels. During an acute phase reaction, which occurs in response to inflammation, infection, or tissue damage, the liver increases the production of complement components, including C3 and C4, as part of the body's immune response.
Other Likely Diagnoses
- Chronic Infection: Chronic infections, such as endocarditis or osteomyelitis, can lead to persistent activation of the complement system, resulting in elevated C3 and C4 levels.
- Autoimmune Diseases with Active Inflammation: Conditions like rheumatoid arthritis, when actively inflamed, can cause an increase in C3 and C4 as part of the inflammatory process.
- Nephrotic Syndrome: Although more commonly associated with low levels of complement due to loss in the urine, some forms of nephrotic syndrome, especially those with significant inflammation, can have elevated C3 and C4 levels.
Do Not Miss Diagnoses
- Hemolytic Uremic Syndrome (HUS) or Thrombotic Thrombocytopenic Purpura (TTP): While these conditions are more commonly associated with low complement levels due to consumption, certain atypical forms, especially those related to complement dysregulation, might present with elevated levels. Missing these diagnoses can be fatal.
- Systemic Lupus Erythematosus (SLE) with Active Nephritis: Although SLE is often associated with low complement levels, active nephritis can sometimes present with elevated C3 and C4 levels due to acute phase reaction.
Rare Diagnoses
- Complement Component Overproduction: Rare genetic conditions can lead to the overproduction of complement components, including C3 and C4.
- Paraproteinemias: Certain paraproteins can interfere with complement regulation, potentially leading to elevated levels of C3 and C4.
- Familial C3 Glomerulopathy: A rare condition characterized by dysregulation of the complement system, which can lead to elevated C3 levels and sometimes C4, due to the underlying genetic defect affecting the alternative pathway of complement activation.