4. Drug induced vasculitis
Drug hypersensitivity reactions with changes of the vasculature or vascular pathways such as vasculitis, livedo racemosa or purpura represent a proportion of 10-20% of cutaneous reactions to drugs and can occur relatively late (7-14 days) during or even after drug exposure, but the time of onset to the related drug varies and depending on the causative drug (74 ).
Numerous drugs can induce vasculitis, which manifests primarily as cutaneous vasculitis, mediated as III hypersensitivity reactions (Table 3), i.e. immune complex deposits with antigen excess in arteries, arterioles, venules or capillaries (Fig. 8). It is of notice that some drugs might also induce antibody production (62 ).
Drug-induced vasculitis includes leukocytoclastic or hypersensitivity vasculitis, necrotizing vasculitis, Panarteritis-nodosa like vasculitis and others (62 ).
Histologic features of vasculitis are an inflammatory infiltrate in the wall of dermal or subcutaneous vessels (which can be neutrophilic, lymphocytic or granulomatous), red blood cell extravasation, variable fribrinoid necrosis of vessel walls and nuclear debris (74 ).
The number of drugs, which have been reported to be applied to COVID-19 patients all over the world is high and ranges from specific antiviral drugs, antiphlogistics, antibiotics, anti-coagulants, immunosuppressive as well as immunoregulatory drugs. All of these drugs are approved and tested for other infectious diseases or entities so that not much experience about putative side effects in COVID-19 patients exists and knowledge gained about skin lesions induced by drugs applied during other diseases can only be used and transferred to speculate on this issue.
Summing up, COVID-19 skin manifestations, could be caused for each one or a mixture of the components mentioned above i.e. reaction to the infection, drug hypersensitivity reaction, pre-existing immune state of the skin/immune system, combined with an impaired general health condition and other co-factors such as age of the individual. Therefore, it is important to discuss also putative additional trigger factors related primarily to the susceptibility to infection with SARS-CoV-2 and the risk to undergo severe courses of COVID-19 as an indirect factor predisposing subsets of patients to skin and vascular lesions.