Page 412 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

386 Rami N. Al-Rohil and J. Andew Carlson

glomerulonephritis. Skin biopsy in patients with HSP/IgAV demonstrates neutrophilic SVV
restricted to the superficial dermis (Figure 11), although the whole dermis may eventually
become involved [38]. Patients older than age 40 years with HSP/IgAV with absent
eosinophils on histologic examination of skin tissue had a three-fold increased risk of renal
involvement compared to those younger than age 40 with tissue eosinophilia [39].

Cryoglobulinemic Vasculitis
Cryoglobulins are cold-precipitating immunoglobulins that persist in the serum and

solubilize when rewarmed. There are three types, type I, monoclonal cryoglobulins that
comprise 10% to 15% of all cases and produce non-inflammatory small vessel hyaline
thrombi; type II or mixed monoclonal IgM with RF activity and polyclonal IgG cryoglobulins
which comprise 50% to 60% of cases; and type III or mixed polyclonal IgM with RF activity
and IgG cryoglobulins comprising 30% to 40% of cases. Type II and III mixed
cryoglobulinemia are associated with CTD, hematologic malignancies and HCV infection.
Greater than 50% of HCV-seropositive patients have mixed cryoglobulins, and a lesser
frequency of vasculitis. Cryoglobulinemic vasculitis is characterized by the clinical triad of
purpura triggered by cold exposure or prolonged standing, arthralgia, and weakness in
association with mixed cryoglobulinemia. Other cutaneous manifestations include PAN-like
lesions, ulcers, splinter hemorrhages and palmar erythema. Systemic disease in CV includes
glomerulonephritis, neuropathy, and pulmonary involvement with high titers of RF and low
levels of C4. Most patients demonstrate neutrophilic SVV that equally affects vessels of the
superficial dermis and subcutis on skin biopsy with vascular IgM and complement deposits
on DIF; a minority of patients displays PAN-like histopathology [18].

Primary Medium Vessel Vasculitis

Polyarteritis Nodosa

This MVV affects men and women age 40 to 60 years without sexual preference; a
childhood form of PAN (cPAN) is well recognized [40]. There are known associations with
HBV, HCV infection, human immunodeficiency virus (HIV), cytomegalovirus, parvovirus
B19, and human T-lymphotropic virus (HTLV) with a fall in cases from 36% to 7% due to
effected vaccination programs [40]. Affected patients present with fever and weight loss
(>70%), arthritis (<75%), mononeuritis multiplex (?72%), cutaneous signs (?60%) (Figure
17), renovascular hypertension (<80%), gastrointestinal symptoms (?53%), and cardiac
failure (?30%) [40-42] suggesting multi-organ involvement.

Tissue biopsy of muscle, sural nerve, kidney, liver, testis, and rectum shows segmental
neutrophilic muscular vessel vasculitis affecting medium- and small-sized arteries. Active
vasculitic lesions are frequently associated with chronic reparative changes that show
endarteritis obliterans. Skin lesions are observed in 25 to 60% of patients [43] the commonest
of which palpable purpura and erythema of the legs [44]. Subcutaneous leg nodules ranging
from 0.5 to 2 cm are seen in proximity to blood vessels in 20% of patients. 49.7 % of the
cases, more often in non-HBV-related PAN (57.8 vs. 35 %). Purpura was the most common
type of lesion in patients with PAN with or without an associated HBV infection. Cutaneous

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