Diagnostic significance of hypocomplementemia

Certain immune complex (IC)-mediated diseases frequently cause hypocomplementemia as assessed by measurement of serum or plasma C3, C4 or CH50 (third component of the complement system, fourth component of the complement system and hemolytic complement activity, respectively). Thus, the measurement of serum or plasma C3, C4 and CH50 is used commonly to assess for the presence of an IC-mediated disease or, in patients with a known IC disorder, to assess for disease activity [1]. However, there are numerous non-immunologic conditions that also can cause hypocomplementemia. It is important for the clinician to be aware of the non-immunologic conditions that cause hypocomplementemia because some can induce a systemic disorder that can easily be confused with an IC-mediated vasculitis. In addition, a non-immunologic condition that causes hypocomplementemia could develop in a patient with an IC-mediated disease that is inactive. If the physician does not recognize that the hypocomplementemia is the result of the nonimmunologic condition, this could lead to incorrect treatment of the patient. Although the literature on complement is voluminous and includes excellent recent reviews of disorders of complement metabolism [2, 3] and its importance in the diagnosis of renal disease [4], to our knowledge there is no previous publication that attempts to provide a comprehensive listing of the causes of hypocomplementemia and its differential diagnosis. It is the purpose of this work to provide that listing, with annotations regarding differential diagnosis, and to discuss several other issues relevant to the evaluation of the hypocomplementemic patient