Page 187 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

The Clinical Approach to Patients with Vasculitis 163

optimize patient care. The symptoms, signs, and results of laboratory studies including
visceral and cerebral angiography in true vasculitis may however be mimicked by
nonvasculitic and unobvious infectious disorders. It is vitally important to exclude such
conditions since the former may not require cytotoxic therapy and administration of such
therapy to the latter will result in devastating effects due to uncontrolled infection.

While by no means exhaustive, concomitant viral, retroviral, and bacterial,
mycobacterial, spirochete, and fungal infectious agents; medications, illicit substance use,
procoagulopathy, vascular atherosclerotic, malignant and benign tumors, genetic and
vasospastic mechanisms should be considered in the differential diagnosis of suspected
vasculitis. Moreover since each of the fore mentioned mechanisms may contribute to the
etiopathogenesis of true vasculitis in selected circumstances, it is important to consider each
category in the clinical and laboratory evaluation of suspected patients.

Infection

Both hepatitis B (HBV) and C virus (HCV) infections are associated with concomitant
immune-complex (IC)-mediated vasculitis; moreover, there is a recognized relationship
between HBV and PAN. Although effective vaccine programs in the developed world have
dramatically reduced the rate of acute HBV infection, large cohort studies have found an
association between HBV and PAN in up to a third of patients [6]. Hepatitis B surface antigen
(HBsAg) and antibody (HBsAb), and core antibody (HBcAb) should be included in the
routine evaluation of such patients. Infection with HBV necessitates viral treatment in concert
a short course of corticosteroids to avoid antigen persistence, and plasma exchange (PE) to
decrease circulating pathogenic IC. Moreover, HCV contributes to the pathogenesis of mixed
cryoglobulinemic vasculitis (MCV) with IC deposition in small to medium sized vessels.
Since the formation of IC involves consumption of complement, C4 complement levels
should be assayed in addition to cryoglobulins and HCVAb. Recent data supporting the use of
rituximab without concurrent anti-viral therapy for the treatment of HCV-related
cryoglobulinemic vasculitis has shifted the treatment paradigm for severe MCV [7]. Human
immunodeficiency virus (HIV) is an associated cause of vascular inflammation in small,
medium and large vessels in less than 1% of patients, with SVV predominating [8]. In the
absence of systemic vasculitis, patients with HIV may demonstrate ANCA-seropositivity.
Thus, the diagnosis of AAV in a patient with HIV infection should be cautiously ascertain
with biopsy tissue confirmation. Although the pathogenesis of HIV-associated vasculitis is
not well understood, IC appear to play a role in development of vasculitis with CD8+ T-cells
found in affected vessel walls early in the course of HIV disease when CD4+ T-cells counts
exceed 200 cells/mm3 [9]. When the CD4+ T-cell count drops to 200 cells/mm3 or less, HIV-
infected patients become susceptible to opportunistic infection including cytomegalovirus
(CMV). The latter may be associated with true vasculitis with discernible CMV inclusions in
the inflammatory infiltrate, especially in those with established acquired immune deficiency
syndrome (AIDS), and skin, gastrointestinal, pulmonary, and CNS involvement.

Other opportunistic infections that can cause vasculitis in the immunocompromised hosts
include Pneumocystis jeroveci and Toxoplasma gondii. Endovascular infection by bacterial or
fungal agents in the course of endocarditis and mycotic aneurysms can mimic systemic
vasculitis. Koening and colleagues [10] recently identified a Burkholderia-like gram-negative

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