Introduction
In the last days of 2019, severe acute respiratory syndrome
coronavirus-2 (SARS-CoV-2) caused a disease in Wuhan, China, which was
later named as coronavirus infection disease 2019 (COVID-19) and became
a global health problem (1). COVID-19 can
present with mild flu-like to severe symptoms such as acute respiratory
distress syndrome (ARDS), septic shock, poorly controlled metabolic
acidosis, coagulation dysfunction, and multi-organ failure
(2). Therefore, understanding specific and
different symptoms and signs of the disease is of great importance. To
the best of our knowledge, many of the symptoms and complications
corresponded to the COVID-19 are caused by cytokines and mediators of
the immune system induced by the infection. In this regard, cytokine
storm is the result of the overproduction of major pro-inflammatory
cytokines such as TNF-α, IL-6, and IL-1β that can produce
hypercoagulable state and multiple organ dysfunction
(3).
Similar to other types of ARDS, there is a hypercoagulable state in
COVID-19 patients. This inflammatory condition, as a result of
endovascular damage, increased platelet activity, and coagulation
cascade causes the phenomenon of immuno-thrombosis
(4). Consequently, clot formation can be
observed in large and small blood vessels, along with in situpulmonary thrombosis and also thromboembolism (PTE)
(5). In other words, overactivation of the
coagulation pathway that occurs during the time of cytokine storm may be
the result of increased thrombin activities. Furthermore, thrombin can
play other roles in the inflammatory process by proteinase-activated
receptors (PARs) (3). On the other hand,
Yan Zhang et al. reported antiphospholipid syndrome (APS) in COVID-19
(6). Livedo reticularis, that also has
been reported in COVID-19 (7), is related
to APS and cold agglutinin disease; accordingly, viral infection is one
of the causes of cold agglutinin formation
(8). Therefore, cold hemagglutinin disease
should also be considered in patients with COVID-19 who present with
this skin manifestation.
Furthermore, acrocyanosis has been described in critically ill patients
with COVID-19 because of excessive coagulation status
(9). Indeed, acrocyanosis and digital
necrosis have previously been reported in many rheumatologic disorders
and vasculitis, including ANCA-associated vasculitis, cryoglobulinemia
vasculitis, lupus-related vasculitis, vasculopathy caused by APS, and
also fingertips necrosis due to scleroderma vascular involvement as well
as Raynaud’s phenomenon (10-12). From a
physiologic point of view, gangrene may occur by impaired blood flow and
insufficient healing process of digital wounds which is associated with
the increasing levels of C-reactive protein (CRP)
(11). Here, we describe two cases of
critically ill patients with COVID-19 who developed digital acrocyanosis
and subsequently fingertips necrosis during their illness.