Page 292 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

266 Elizabeth J. Brant, Julie G. McGregor, J. Charles Jennette et al.

Anti-idiotypic antibodies, or antibodies to anti-cPR3 antibodies, are then produced that are
reactive to PR3 [42, 43]. Complementary PR3 shows homology with proteins of multiple
microorganisms, including two proteins found in S. aureus, thus suggesting a role for
molecular mimicry in the pathogenesis of AAV. Although it remains highly controversial,
lysosome-associated membrane protein 2 (LAMP-2) has been identified as a possible
antigenic target in patients with AAV [44]. The P41-49 epitope of LAMP-2 reportedly has
significant homology with an epitope of FimH, having in common 8 of 9 amino acids [45],
but these findings were not subsequently confirmed [46].

Illicit and Prescription Drugs

Both illicit and prescription drugs have been implicated in the cause of AAV, but the
etiopathogenic mechanisms area not well understood. The ant-helminthic agent levamisole,
sometimes found in cocaine, is the most recognized drug cause of vasculitis. Affected patients
are typically MPO-ANCA positive, but may have dual positivity with MPO- and PR3-ANCA
[47, 48], and typically present with cutaneous disease. While cutaneous disease in idiopathic
AAV typically manifests as recurring crops of purpuric lower extremity lesions, the lesions
associated with levamisole are more widespread and variable in character, with necrotic
lesions involving the ears, and bullous purpura in any location. Full-thickness, large necrotic
lesions are suggestive of levamisole exposure. Affected patients can have arthralgia,
particularly of the large joints, and constitutional symptoms. Severe disease with isolated
glomerulonephritis and pulmonary-renal syndrome occurs. Patients with signs and symptoms
of AAV should be questioned regarding illicit drug use, particularly when dual MPO-ANCA
and PR3-ANCA serology is present, and urine toxicology screen for the presence of cocaine
and levamisole should be obtained.

The commonest prescription drug offenders include hydralazine and propylthiouracil
(PTU), although penicillamine, minocycline, sulfasalazine, allopurinol, and gold have all
been implicated [49]. Unlike levamisole-induced disease, the presentation of other drug-
induced forms of disease mirrors idiopathic disease, with rapidly progressive
glomerulonephritis being especially common. Serologically, patients generally have MPO
antibodies at high titers, and dual positivity to MPO and PR3 is rare. Affected patients tend to
be positive for other autoantibodies, including antinuclear antibody (ANA), anti-double-
stranded DNA (anti-dsDNA), anti-histone, anti-lactoferrin antibodies, and other forms of
ANCA, specifically anti-human neutrophil elastase (HNE). Propylthiouracil typically causes
a pauci-immune necrotizing and crescentic glomerulonephritis, but other organ systems may
be involved. While patients with PTU-induced disease tend to have high titers of MPO-
ANCA, the ANA is not usually positive. In both illicit and prescription drug-induced AAV,
cessation of the causative agent is imperative, and management is similar to that of the
idiopathic forms of disease, employing immunosuppressive medication, as well as
plasmapheresis and hemodialysis as indicated by disease severity.

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