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Page 2 of 14 Abdel-Halim et al. Vessel Plus 2022;6:8 https://dx.doi.org/10.20517/2574-1209.2021.40

Keywords: Anti-neutrophil cytoplasmic antibody, vasculitis, granulomatosis with polyangiitis, eosinophilic
granulomatosis with polyangiitis, microscopic polyangiitis, cutaneous, purpura, ulcers

INTRODUCTION
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a clinically distinct group of
severe multi-organ vasculitis involving small/medium-sized vessels with subsequent tissue damage. Vessels
involved are mainly capillaries, arterioles, and venules but small/medium-sized arteries and veins may also
be involved. According to clinical features and presence or absence of asthma and/or granulomatosis, this
group includes three diseases: granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with
[1]
polyangiitis (EGPA), and microscopic polyangiitis (MPA) .

As in many other systemic disorders, cutaneous involvement is commonly encountered in AAV and may be
the first presenting sign of the disease. Variable incidences among different reports are noted. According to
recently published data from a large international multi-center study, cutaneous manifestations at time of
presentation were present in 35% of AAV cases and were found to be more frequently encountered in
[2]
EGPA (47%) when compared to GPA and MPA (34% and 28%, respectively) . Other studies reported skin
manifestations occurring during the course of the disease in 47% of GPA cases, 44% of MPA cases, and 40%
[6]
[3-5]
of EGPA cases . Skin lesions can also mark a disease relapse .
The spectrum of skin lesions in AAV is wide and more than 50% of cases will have more than one type of
[2,6]
skin lesions at a certain time . Accordingly, knowledge of such lesions and collaboration with
dermatologists is important for physicians providing care for systemic vasculitis patients.

Being an easily accessible organ for biopsy, the presence of skin lesions may provide an easy way to confirm
the presence of vasculitis by routine histopathological and immunofluorescence studies. This can be further
substantiated by clinical examination and laboratory investigations including ANCA testing.

THE CLINICOPATHOLOGIC SPECTRUM OF CUTANEOUS LESIONS IN AAV
Understanding the underlying histopathological changes is important to appreciate the wide spectrum of
skin lesions encountered in AAV. Accordingly, skin manifestations in AAV can be classified as specific or
non-specific. The term specific does not mean lesions that occur exclusively in AAV, but rather skin lesions
that show histopathological evidence of vasculitis with or without granulomas when biopsied. They can still
be encountered in other systemic disorders or other forms of vasculitis. On the other hand, non-specific
skin lesions do not show histopathological features of vasculitis or granuloma. They may show features
reflecting the various morphologies of these lesions or just show non-specific perivascular lymphocytic
infiltrates . In either case, attributing skin lesions to AAV needs careful clinical, laboratory, and serological
[7]
correlations and exclusion of all other possible causes of similar lesions or their mimics.

In all three types of AAV, cutaneous vasculitis presents as leukocytoclastic vasculitis with fibrinoid necrosis
of vessel walls (usually involving small dermal vessels and less commonly medium-sized subcutaneous
ones), perivascular infiltrates (mainly composed of neutrophils), endothelial cell swelling, red cell
extravasation, neutrophil fragmentation, and neutrophil dust [Figure 1]. Vasculitis with granulomatosis
[8]
(perivascular collections of epithelioid histiocytes and/or giant cells-perivascular granulomatosis) is a rare
finding in skin lesions of GPA and EGPA . The term vasculitis with granulomatosis is better used to
[9]
describe such finding than granulomatous vasculitis since the term granulomatous vasculitis usually implies
the presence of granulomas inside the vessel walls as in giant cell vasculitis and Takayasu’s arteritis, which is