Page 407 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

Dermatologic Aspects of Systemic Vasculitis 381

a history of cardiac septal defect; cytokines IL-6, TNF?, C-reactive protein (CRP), activated
coagulation marker complex thrombin–antithrombin III, functional endothelial markers
endothelial microparticles and thrombomodulin; and ANCA serology when SVV (MPA,
EGPA, GPA) is suspected. Perinuclear pattern of ANCA (pANCA) with myeloperoxidase
(MPO) antibodies as well as lactoferrin and cathepsin, occurs most often in MPA and EGPA.
Cytoplasmic (cANCA) with proteinase-3 (PR3) is strongly associated with GPA. However,
the presence of ANCA is not diagnostic of systemic vasculitis since up to 60% of patients
with cutaneous LCV can be ANCA-positive with disease limited to the skin. Positive ANCA
serology so noted in diverse systemic inflammatory and pulmonary disorders that mimic
vasculitis [16] usually demonstrates atypical indirect immunofluourescent patterns with
negative antibodies to PR-3 and MPO by antigen specific enzyme-linked immunosorbent
assays (ELISA).The absence of IC and the presence of minimal IgG and C3, so-called pauci-
immune vasculitis, are expected findings in GPA, EGPA and MPA. Those with suspected
secondary vasculitis with biopsy-proven cutaneous vasculitis in association with a
serologically specific CTD, so suggested by dry eyes and mouth, arthritis, sclerosis,
photosensitivity, should undergo ANA, rheumatoid factor (RF), anti-phospholipid (aPL), Ro
(SSA), La (SSB), ribonucleoprotein (RNP) or Sm (Smith) antibody assays [1, 17, 18]. The
secondary vasculitides in association with CTD can involve multiple organs and vessels of
variable caliber. Extravascular histologic findings can provide a clue to diagnosis of
associated CTD such as interface dermatitis with dermal mucin deposition so noted in SLE
and dermatomyositis, dermal or subcutaneous sclerosis in scleroderma, palisaded neutrophilic
and granulomatosis dermatitis in RA or SLE, and tissue neutrophilia, not a neutrophilic
dermatosis, in SLE and Sjögren syndrome [2].

Primary Small Vessel Vasculitides

ANCA-Associated

Microscopic Polyangiitis
This neutrophilic necrotizing SVV characteristically involves arterioles, capillaries, and

venules and occasionally small and medium arteries of the kidney and lung resulting in
pulmonary capillaritis and necrotizing glomerulonephritis. It typically affects patients older
than 50 years old, with a male to female ratio of 1:1.5 and a greater prevalence in Asians [19].
The largest cohorts ascertained in departments of medicine or nephrology render a bias
toward certain spectrums of the disease [20] and may underestimate the true incidence of
cutaneous manifestations [21]. Agard and coworkers [22] found skin lesions, primarily
purpura, at presentation in 14% of 36 patients, compared to 4% by Cupps and Fauci [23].
Kluger and colleagues [21] [24] ascertained skin manifestation in 44% of 162 patients
comprised of palpable purpura in of the legs in 26%, livedo racemosa in 12%, nodular lesions
in 10%, ulcer/necrosis in 6%, urticaria in 1.2%, oral and genital ulcers each in 0.6%;
arthralgia, mononeuritis multiplex and ocular symptoms occurred more often as well.
Guillevin and coworkers [25] observed cutaneous involvement, primarily purpura, in 62.4 %
of 85 patients.

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