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\begin{document}

\title{A dry gangrene signing SARS-CoV2 infection in a vulnerable patient}



\author[1]{Dorsaf Elinkichari}%
\author[2]{Faten Rabhi}%
\author[1]{Yosra Ben Ariba}%
\author[1]{Kahena Jaber}%
\author[1]{Raouf Dhaoui}%
\affil[1]{Military Hospital of Instruction of Tunis}%
\affil[2]{Hopital Militaire Principal d'Instruction de Tunis}%


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  \date{May 25, 2024}


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\begin{abstract}
Although lungs represent the main target of the SARS-CoV2, the novel
virus may affect other tissues. In the pandemic context, unexplained
cutaneous ischemic lesions would be suggestive of the infection and
should draw attention to a serious course of the disease.%
\end{abstract}%



\sloppy


\textbf{A dry gangrene signing SARS-CoV2 infection in a vulnerable
patient}

\textbf{Dorsaf Elinkichari\textsuperscript{1,3} , Faten
Rabhi\textsuperscript{1,3} , Yosra Ben Ariba\textsuperscript{2,3} ,
Kahena Jaber\textsuperscript{1,3} , Raouf Dhaoui\textsuperscript{1,3}}

\textsuperscript{1}Department of Dermatology, The Military Hospital of
Tunis, Tunis, Tunisia

\textsuperscript{2}Derpartment of Nephrology, The Military Hospital of
Tunis, Tunis, Tunisia

\textsuperscript{3}Faculty of Medicine of Tunis, University of Tunis El
Manar, Tunis, Tunisia

\textbf{Correspondence}

Dorsaf Elinkichari, Department of Dermatology, The Military Hospital of
Tunis, Tunis, Tunisia.

Email:\emph{dorsaf.elinkichari@gmail.com}

\textbf{Key Clinical message}

We believe this report will enhance our awareness of the acral ischemic
signs as a predictor of the severity of the disease in COVID-19
patients.

\textbf{Abstract}Although lungs represent the main target of the
SARS-CoV2, the novel virus may affect other tissues. In the pandemic
context, unexplained cutaneous ischemic lesions would be suggestive of
the infection and should draw attention to a serious course of the
disease.

\textbf{Key words}

SARS-CoV2, Infection, COVID-19, Acro-ischemia, Dry gangrene

Given the patient's death, written informed consent was obtained from
the patient's next of kin (Son) to publish this report in accordance
with the journal's patient consent policy.

\textbf{Introduction}

COVID-19, the disease caused by the SARS-CoV-2, have induced an
international public health emergency since its first emergence in the
last months of 2019. Although lungs are the most affected organ, the
infection can spread to other tissues causing multiorgan involvement.
The incrimination of SARS-CoV-2 infection in thromboembolic
complications due to hypercoagulability is now proven. However, its role
in arterial diseases has been less demonstrated\textsuperscript{1,2}.
Cases of acute limb ischemia and different signs of acro-ischemia in
infected patients have been reported\textsuperscript{3--6}. We report a
case of dry gangrene in a patient tested positive for SARS-CoV2 without
respiratory symptoms.

\textbf{Observation}

A 65-year-old man with a history of hypertension, ischemic
cardiomyopathy, and chronic kidney failure on dialysis presented with
painful periungual erosions appeared seven days after coronarography.
Upon physical examination, we noticed periungual and pulpal erosions
with a fibrinous center and non-infiltrated erythematous border on both
index fingers and on the left second toe (Figure 1a, 1b). Peripheral
pulses were present. The ocular fundus was normal. Cutaneous biopsy was
not performed since it could slow scarring. Doppler ultrasound showed
signs of atherosclerosis without severe arterial obstruction. The
diagnosis of cholesterol~embolization~syndrome was made based on
clinical history and physical examination. The patient was treated as
such with a good evolution after 15 days and beginning of
re-epidermalization. One month later, a worsening of the same lesions
was noted with the onset of dry gangrene (Figure 2), followed 48 hours
later by chills and fever. He had no headache, no digestive or
respiratory signs and no hypoxemia. A PCR test on nasopharyngeal swab
was positive for SARS-CoV-2. Despite the initiation of anticoagulation
therapy, the patient died after two days of disseminated intravascular
coagulation.

\textbf{Discussion}

The main target of the SARS-CoV2 is the respiratory system. Typical
manifestations include fever, sore throat, dry cough, fatigue, diarrhea,
hyposmia and hypogeusia\textsuperscript{7}. Simultaneously, the
infection can be associated with multiorgan dysfunctions. The viruses
bind to angiotensin-converting enzyme 2 receptors, which are present~in
all cells, including in endothelial cells leading to microvascular
dysfunction\textsuperscript{8}.~Upon entering host cells, the viruses
replicate and destroy them.~This process induces organ damage, release
of proinflammatory cytokines, chemokines, and activation of the
complement system which all lead to the hyperinflammation state known as
``cytokine storm''\textsuperscript{2}.~Both microvascular dysfunction
and cytokine storm are involved in thrombotic and ischemic
manifestations\textsuperscript{3}. Several studies have reported
different signs of acral ischemia such as pseudo-chilblains, livedo
reticularis and dry gangrene\textsuperscript{4--6}. Chilblains occur
more commonly in young patients with mild or asymptomatic form of the
disease\textsuperscript{4,6}. However, as in our case, the other
manifestations of acral ischemia, including gangrene and livedo
reticularis often occur in patients with severe disease, with a
mortality rate of 10\%\textsuperscript{6}. This group of patients may
present with a misleading form of the disease in a context of a
confusing hidden severity. Thus, they don't always develop signs that
require hospitalization, like the case of our patient who did not
develop respiratory signs or asymptomatic hypoxemia.

The particularity of our case consists in the appearance of ischemic
skin manifestations of SARS-CoV2 infection and in the severe course of
the disease leading to death without any respiratory signs. Considering
the arteriopathy and the cholesterol~embolization~syndrome, the
infection precipitated the evolution of lesions that would heal towards
dry gangrene.

\textbf{Conclusion}

In the pandemic context, the appearance of unexplained cutaneous
ischemic signs, even if isolated, would be suggestive of the infection.
Acro-ischemic signs may indicate a state of severe systemic
hypercoagulability and should draw attention to a serious course of the
disease.

\textbf{CONFLICT OF INTEREST}

None. This research received no specific grant from any funding agency
in the public, commercial, or not-for-profit sectors.

\textbf{AUTHOR CONTRIBUTIONS}

D. Elinkichari is the guarantor of the content of the manuscript,
including the data and analysis. F. Rabhi contributed to acquisition of
data, conception, and interpretation of information, revised it
critically for important intellectual content, and gave final approval
of the version to be submitted. Y. Ben Ariba contributed to acquisition
and analysis of data. K. Jaber revised data critically for important
intellectual content. MR. Dhaoui contributed to interpretation of data
and revision of the manuscript.

\textbf{ETHICAL STATEMENT}

Written informed consent was obtained from the patient's next of kin
(Son).

\textbf{References}

1. Ward A, Sarraju A, Lee D, et al. COVID-19 is associated with higher
risk of venous thrombosis, but not arterial thrombosis, compared with
influenza: Insights from a large US cohort. \emph{medRxiv} . Published
online October 18, 2021:2021.10.15.21264137.
doi:10.1101/2021.10.15.21264137

2. Loo J, Spittle DA, Newnham M. COVID-19, immunothrombosis and venous
thromboembolism: biological mechanisms. \emph{Thorax} .
2021;76(4):412-420. doi:10.1136/thoraxjnl-2020-216243

3. Santosa YP, Yuwono A. Two Different Clinical Presentations of Acute
Limb Ischemia Caused by Acute Thrombotic Events in
COVID-19.\emph{Cureus} . 13(9):e17916. doi:10.7759/cureus.17916

4. Alramthan A, Aldaraji W. Two cases of COVID-19 presenting with a
clinical picture resembling chilblains: first report from the Middle
East. \emph{Clin Exp Dermatol} . 2020;45(6):746-748.
doi:10.1111/ced.14243

5. Bouaziz JD, Duong TA, Jachiet M, et al. Vascular skin symptoms in
COVID-19: a French observational study. \emph{J Eur Acad Dermatol
Venereol} . 2020;34(9). doi:10.1111/jdv.16544

6. Galv\selectlanguage{ngerman}án Casas C, Català A, Carretero Hernández G, et al.
Classification of the cutaneous manifestations of COVID \selectlanguage{english}-19: a rapid
prospective nationwide consensus study in Spain with 375 cases.\emph{Br
J Dermatol} . 2020;183(1):71-77. doi:10.1111/bjd.19163

7. Azer SA. COVID-19: pathophysiology, diagnosis, complications and
investigational therapeutics. \emph{New Microbes and New Infections} .
2020;37:100738. doi:10.1016/j.nmni.2020.100738

8. Becker RC. COVID-19 update: Covid-19-associated coagulopathy. \emph{J
Thromb Thrombolysis} . Published online May 15, 2020:1-14.
doi:10.1007/s11239-020-02134-3\selectlanguage{english}
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