Page 189 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

The Clinical Approach to Patients with Vasculitis 165

Atherosclerosis

Patients with MVV and LVV can present with ischemic limb pain and claudication.
Atherosclerotic peripheral arterial disease is by far the most common cause of claudication,
affecting an estimated 5% to 25% of the adult population [13]. Angiography and cross-
sectional imaging demonstrates segmental arterial involvement with stenosis similar to that of
systemic vasculitides. Assessment of cardiovascular risk factors, such as age, diabetes,
hyperlipidemia, hypertension and tobacco use is useful in predicting atherosclerosis before
studies for vasculitis are performed. Such patients in turn lacking traditional cardiovascular
risk factors or in younger age groups should be at a higher suspicion for vasculitis.
Notwithstanding, either may have constitutional symptoms and signs, and elevated
inflammatory markers. Patients with atherosclerosis are additionally at risk for
atheroembolism and cholesterol crystal embolism, further demonstrable as arteriolar
cholesterol clefts in tissue biopsy of skin, muscle, and cutaneous nerve specimens [14]. Distal
embolization of atherosclerotic plaque occurs spontaneously in the setting of anticoagulation,
and during endovascular instrumentation leading to livedo skin rash, digital ischemia, visual
changes and renal impairment. Thromboangiitis obliterans, a non-atherosclerotic disease of
peripheral arteries, also presents with claudication, digital ulceration and ischemia however
the prototypical patient is a male smoker under the age of 45 years with involvement of two
or more extremities, and in contrast to the vasculitides, markers of inflammation and
autoantibodies are typically unrevealing and imaging demonstrates segmental arterial
occlusion and corkscrew collaterals. Tissue biopsy of involved vessels reveals an occlusive
thrombus with inflammatory cell infiltration that does not extend into the vessel wall.

Malignancy

The majority of malignancy-associated vasculitides occur in conjunction with
hematologic malignancies and myelodysplastic syndromes. A reported 4.5% to 8% of patients
with lymphoproliferative disease develop vasculitis with renal, cerebral, pulmonary, and
cutaneous involvement [15] and reports of homology between the genetic sequences of serine
proteinase-3, the antigenic target in GPA, and myeloblastin a protein found in certain human
leukemic cells, in part explaining the association between hematologic malignancy and
systemic vasculitis [16]. One rare lymphoproliferative disorder of mature B-cells, hairy cell
leukemia (HCL), can be the proximate cause of necrotizing systemic vasculitis.

Other tumors can cause constitutional symptoms mimicking vasculitis and embolic
phenomena including atrial myxomas, so noted in more than 30% of patients that manifested
fever, arthralgia and weight loss in association with laboratory features of acute inflammation
[17].

These benign tumor express increased levels of IL-6, a pro-inflammatory cytokine
implicated in the pathogenesis of LVV such as GCA.

Careful cardiac auscultation for the characteristic “plop” sound heard in early diastole
and a murmur that comes-and-goes are clues to this diagnosis further supported by cardiac
echocardiography that identifies its origin from the left atrial septum.

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