Despite of rapid pulmonary failure, vascular complications due to coagulopathy, endotheliopathy and vasculitis significantly contribute to the high mortality rates of patients infected with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2) [7]. Recent observations also showed that infections with SARS-CoV-2 may go along with mild to fulminant dermal diseases [8]. Until now, data on pathogenesis and clinical manifestations of COVID-19 support the hypothesis of three distinct phases of the disease: viral phase, immunological phase and haemo-vascular phase [9, 10]. In October 2020 Manzo discussed COVID-19 as a trigger for an immune complex hypersensitivity reaction [11]. He highlighted the significant antigen excess in the second phase of COVID-19 disease that may lead to the formation of soluble antigen-antibody immune complexes, which cannot be removed by phagocytes anymore. These may settle and persist in tissue places, e.g., skin where they can induce persistent inflammation. In general, multiple infectious diseases are known to be facultative triggers of immune complex diseases, e.g., beta-hemolytic streptococcal bacteria that precede purpura Schoenlein-Henloch disease in pediatric patients [12], an example of type three hypersensitivity. Interestingly, a recent letter to the editor of Roncati et al. discussed COVID-19 preceding a type three hypersensitivity vasculitis by inducing a severe inflammatory state by an interleukin-6 mediated cytokine release syndrome [13].
As vaccines are supposed to induce antigen-antibody reactions, novel COVID-19 vaccines mediated by the SARS-CoV2-spike-protein may trigger similar pathogenic effects. So far, cutaneous immune complex vasculitis have been seen in older patients after receiving seasonal influenza vaccinations [14]. Until now, data on the range of side effects of the novel COVID-19 vaccines are rare, but especially severe thrombotic [15] and anaphylactic reactions [16] drew scientific and general society’s’ attention. Recently, Bomback et al. published a summary of reported glomerular diseases after COVID-19 vaccination, including ten cases of IgA nephropathies [17]. MRNA-based vaccines have never been licensed for application in humans before this pandemic. Therefore, effects and side effects of BNT162b2 and its related agents are of great scientific interest. In current literature safety and efficacy of BNT162b2 was similar to other viral vaccines [18].
Our case report is the first to describe a cutaneous and gastrointestinal immune complex vasculitis after a mRNA-based vaccination with BNT162b2, in a cirrhotic patient without any history of autoimmune or vasculitis predisposition. Immune complex related extrahepatic conditions can be seen in patients with chronic liver disease. However, the majority of these cases are described in patients with liver disease due to hepatitis C or B infection [19, 20] or florid bacterial infection [21]. One can assume that a chronic liver disease may have precipitating effects of the deposition of immune complexes with defective liver metabolism of IgA circulating immune complexes, but we interpret the mRNA-vaccination as the main trigger of this phenomenon in our patient.
In general, most cases of cutaneous immune complex vasculitis are self-limited [22]. As our patient presented with pronounced skin involvement, additional gastrointestinal inflammation and bleeding signs we decided to treat him with oral anti-inflammatory steroids. Thereby, we achieved fast relief and restoration of our patient’s health. In patients with severe organ failure, strong immunosuppressive therapy and plasmapheresis may be necessary [23].
We acknowledge that the link between BNT162b2-vaccine and cutaneous and gastrointestinal immune-complex vasculitis cannot be confirmed by a single case. However, our theory is supported by: (1) the fact that the patient did not have any history of vasculitis before—and no dermal lesion was seen 2 days prior the second vaccination, (2) the suitable time span of 12 days between exposition and appearance of type three hypersensitivity reaction without any hints of an alternative cause—no changes in medication, alimentary habits or sign of another infection (3) interleukin-6 mediated inflammatory response and (4) data on COVID-19 infections that trigger immune complex vasculitis.
Worldwide, more than one billion COVID-19 vaccines doses have been injected to control the SARS-CoV-2 pandemic [5]. Among these, novel mRNA-based vaccines are administered on large scale for the first time in history. So far, serious adverse events reported with mRNA-vaccines, especially BNT162b2 are rare and efficacy rates are high [18]. However, clinical trials will not be able to detect rare clinical side effects. We are the first to describe the event of an immune complex vasculitis in a patient with liver cirrhosis without known predispositions for type 3 hypersensitivity. The purpose of this case report is to raise awareness of possible side effects in healthcare professionals in the so far world’s fastest and biggest vaccination program. We aim to highlight the importance of further scientific and clinical vigilance and surveillance.
