Page 258 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

232 Clodoveo Ferri, Dilia Giuggioli and Marco Sebastiani

petechiae and severe vasculitic lesions, complicated by torpid ulcers of the legs and malleoli.
Repeated episodes of purpura lead to stable, sock-like ochraceous discoloration of the legs [1,
4]. Humoral cofactors and vascular disturbances stemming from increased cryocrit levels,
chronic venous insufficiency and physical stress all contribute to vasculitic alterations. Higher
purpuric pressures occur in the afternoon when cryocrit levels are highest and standing is
more prolonged, especially in muggy weather conditions. Arthralgia, non-erosive
oligoarthritis, and less frequently frank arthritis were noted. When CV occurs in association
with the sicca syndrome, there was mild xerostomia and xerophthalmia in up to one-half of
patients [1, 4].

Peripheral nervous system involvement includes small fiber neuropathy of the legs with
painful, burning paresthesia that worsens at night and is often resistant to treatment. A
minority of patients develops large fiber sensorimotor involvement, but when present, most
often occur with abrupt asymmetric onset of mononeuritis. Peripheral neuropathy may also be
triggered or exacerbated during the first several weeks of treatment with interferon-alpha
(IFN-?) in patients so disposed [1, 4]. Central nervous system (CNS) vasculitis, albeit rare,
presents with focal deficits such as dysarthria and hemiplegia, which may be difficult to
distinguish from more common atherosclerotic vascular sequela.

Systemic liver involvement is rarely observed in other systemic vasculitides, but is
present in CV, and generally preceded by mild to moderate chronic hepatitis that is apparent
at presentation or develops in two-thirds of patients particularly those with HCV-related CV
[1, 4]. Clinically-overt liver cirrhosis occurs in one-quarter of patients but is only rarely
associated with hepatocellular carcinoma. Life-threatening hepatorenal syndrome occurs in
association with progressive CV [9]. The overall outcome of CV-associated chronic hepatitis
seems to be more favorable than HCV-related hepatitis without MCs, whereas hepatocellular
carcinoma is less frequently observed in HCV-related CV compared to the overall population
of HCV-infected individuals. Such differences are difficult to fully explain however, the
relatively low prevalence of the 1b HCV genotype in those that develop CV, along with a
lower median consumption of alcohol predicts a more benign clinical course of liver
involvement [1, 4]. Immune complex-mediated glomerulonephritis, most often seen in type 1
MPGN, affects the prognosis and survival of patients with CV due to hypothesized immune
mechanisms [1, 4]. Intestinal vasculitis presents with severe life-threatening acute abdominal
pain necessitating prompt diagnosis and aggressive treatment [1, 4]. There are reported
associations of glomerulonephritis and skin ulcers, and increased cryocrit levels in hemolytic
complement [1, 4].

Interstitial lung disease characterized by subclinical alveolitis has been described in those
with CV and in association with isolated HCV infection [1, 4]. When present, it can be a
predisposing condition to the complications associated with acquired pulmonary infection,
and in rare instances, can lead to clinically manifest interstitial lung fibrosis. Capillaritis
complicated by severe cough and hemoptysis, are other rare manifestations of CV-related
lung involvement, as well as the hyperviscosity syndrome due to high levels of serum
cryoglobulins [1, 4].

A low or undetectable C4 level with a normal C3 fraction occurs in patients with CV
regardless of disease activity. In vitro consumption of hemolytic complement is due to the
anti-complement activity of cryo-Ig [1, 4]. A sudden increase in C4 from low to abnormally
high levels can precede the development of B-NHL [1].

Complimentary Contributor Copy