1.4 Virus induced vasculitis
Infectious diseases are the cause of over 20% of cutaneous vasculitis
(60 ). Most of them have a self-limiting course, but the
involvement of other organs is possible.
Vasculitis can affect small, medium and large vessels (Fig. 8).
Mechanisms might be type III or immune complex-mediated reactions to
viral antigens or part of viral antigens. In this context, large immune
complexes might precipitate and accumulate within vessels, a process
leading to vascular injury (Fig. 8A) (61 ). Histologic features
of vasculitis are an inflammatory infiltrate in wall of dermal or
subcutaneous vessels (which can be neutrophilic, lymphocytic or
granulomatous), red blood cell extravasation, variable fibrinoid
necrosis of vessel walls, and nuclear debris. Further on, deposits of
immunoglobulin, complement or fibrin in the vessel wall are detectable
by direct immunofluorescence staining (62 ). Polyarthritis
nodosa related to Hepatitis B infection is one example for a vasculitis
directly induced by a viral antigen (63 ). Interestingly,
specific virus genotypes of Hepatitis B and C Virus have been
identified, which are associated with particular forms of vasculitis,
which explains in part why only a subgroup of virus-infected patients
develops such cutaneous vascular reactions in some viral diseases
(60 ).
Cell-mediated hypersensitivity, in which exposure to viral antigens
induce recruitment of lymphocytes, which release proinflammatory
cytokines and further attract macrophages and more lymphocytes leading
to tissue damage of the vessels, has also been described as a pathway in
some infectious vasculitis types (Fig. 8B).
Furthermore, abnormal immune regulation including different expression
of adhesion molecules and cytokines in vascular endothelium by different
virus-related processes as well as direct endothelial cell invasion of
the virus (Fig. 8C) or direct stimulation of the immune system by
infectious agents might take place (62 ).
Whether and which kind of virus induced mechanisms of infectious
vasculitis play a major role in SARS-CoV-2 vascular lesions is unclear,
but immune complex mediated mechanisms are likely to be of relevance.
Furthermore, since ACE2 expression has been described for endothelial
cells (63, 64 ), it is quite speculative but still conceivable
at this time point - but even possible - that the virus directly
interacts with endothelial cells leading to tissue damage and the
resulting skin lesions.
In children an association of COVID-19 with Kawasaki-like disease with
mucocutaneous involvement, polymorphic rash, erythema of the palms and
soles, firm induration of the hands or feet, or both besides other
symptoms of Kawasakis disease has been postulated (65).Kawasaki disease is classified a systemic vasculitis of medium size
vessels (Fig. 8) and pathogens including different virus types have been
suspected as one causative factor in a rather multifactorial
pathogenesis. Further studies are needed to demonstrate a correlation of
Kawasaki disease with SARS-CoV-2 in larger patient groups and time
courses.