Editorial
COVID-19 cutaneous manifestations: simplifying the
confusion
Rokea A. el-Azhary, MD, PhD
Editor-in-Chief
Email: elazhary.rokea2@mayo.edu
The COVID-19 pandemic took all of us by surprise and literally
the whole world stood still. After 6-7 months, we are still without
a vaccine and people continue to wonder which way they
should go; take the mask off or leave it on, lockdown or not.
With the pandemic still ongoing, I thought I would share some
thoughts with our readers.
Dermatologists have been in the forefront of trying to under-
stand the varied clinical cutaneous manifestations shared during
the pandemic. Many cutaneous manifestations, particularly from
Italy and Spain, were published starting as single cases fol-
lowed by large multi-center reports describing the clinical and
pathological presentations of the skin findings. Because most of
the early descriptions were dependent on the eye of the derma-
tologist, numerous nomenclatures were used. Examples are
chilblain-like,1 pseudo-chilblain, perniosis, and just simply chil-
blain. Descriptions such as erythema and hemorrhage were
used when the diagnosis was not clear.
Although only months, it seems we have come a long way
since the beginning of the pandemic. Numerous reports were
published with descriptions of urticaria, erythema multiforme,
Kawasaki, Grover’s, morbilliform-like, vasculitis-like, vasculopa-
thy, livedo, retiform, and hemorrhage as well as others. How
can we sort out all of this? Using clinical pathological correlation
we should be able to put together a classification that is more
practical to the dermatologist. Other than the viral exanthema
that occurs with many viral diseases and not specifically for
COVID-19, the first noted cutaneous manifestations thought to
be more specific were urticarial2 and chilblain-like lesions.1
These chilblain lesions have been discussed thoroughly, yet are
still controversial in the literature. Given the fact that they
occurred mainly in very high risk areas of COVID-19, the num-
ber of chilblain reactions seemed to parallel the number of peo-
ple infected in these high risk areas and, therefore, must have
something to do with COVID-19. However, most of these acral
chilblain lesions showed negative COVID-19 PCR and serology
and they resolved on their own.3,4 With further pathology,
immunohistochemistry and electron microscopy studies,5–8 it
Chilblain, livedo Acral endothelial necrosis,
Negative PCR, negative microvascular thrombosis
serology Testing positive, moderate
Mild, resolves on its own
Figure 1 A spectrum from chilblain to coagulopathies
ª 2020 the International Society of Dermatology
was reported that these vascular lesions have endothelial dam-
age, micro thrombi, a positive SARS-CoV/SARS-CoV-2 spike
protein and viral COVID-19 particles present in the endothelial
cells. These findings occurred in the chilblain lesions as well as
in the retiform, livedo, and other vascular lesions. This patho-
physiology was also shown to be similar to that occurring in the
lung.5 The retiform-like purpuric lesions are an advanced form
of the coagulopathies with thrombi in larger vessels which could
lead to strokes, pulmonary emboli, and an elevated D-Dimer
with a poorer prognosis.5 Could the acral location of chilblain be
a flag for COVID-19 virus? Even though most of the chilblain-
like lesions are more likely to resolve on their own, it is best to
follow-up the patient and obtain a biopsy if necessary.
Given the similar pathophysiology of chilblain, livedo, and reti-
form lesions, one can consider this a spectrum (Fig. 1), starting
at the low-risk chilblain level of COVID-19 (possibly because of a
low viral load) to a very severe disease with a poorer prognosis
(a high viral load). In recent studies comparing the kinetics of the
virus load and the production of antibodies, it was shown that
virus load is low in mild cases and high in severe cases.9
Numerous types of other cutaneous manifestations were
reported: erythema, exanthema, urticarial, erythema multiforme-
like, morbilliform, and vesicular Grover’s-like lesions are some of
them.10,11 For all these clinical diagnoses confirmatory biopsies
are needed. For example, in a study of erythema multiforme-like
lesions in children the authors noted that the clinical diagnosis
was not supported by pathological manifestations, but the find-
ings were more consistent with a chilblain vasculopathy.8
As it stands at the present time, we could simplify the classifi-
cation of cutaneous manifestations of COVID-19 in two cate-
gories based on COVID-19 pathophysiology and reactive
processes:
1 Vasculopathy: Based on the pathophysiology, chilblain, livedo,
retiform or hemorrhagic presentations are all considered as a
variation of mild to moderate or severe vasculopathies. All are
vascular diseases that start with acral endothelial damage and
Coagulopathies, hemorrhage,
DIC, D-Dimer
Severe systemic disease,
poor prognosis, strokes, PE
3
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4 Editorial
microvascular thrombi that may be quite mild but can progress
to a systemic severe thrombosis in larger venous and arterial
blood vessels with poor prognosis.
2 Reactive: Urticarial, exanthemata, morbilliform and vesicular
presentations are reactive manifestations to the COVID-19
virus or to another concomitant virus or drug. They are not
part of the pathophysiology and can be controlled by antihis-
tamines or steroids. Usually these manifestations will resolve
once the infection subsides.
Similar conclusions were drawn by Marzano et al. who
emphasized the relevance and importance of dermatologists
during the pandemic.12 Indeed, dermatologists, particularly
those in the hot spots of the pandemic have shown remarkable
courage and enthusiasm and we salute them all.
References
1 Landa N, Mendieta-Eckert M, Fonda-Pasqual P, et al. Chilblain-
like lesions on feet and hands during the COVID-19 Pandemic.
Int J Dermatol 2020; 59: 739–743.
2 Recalcati S. Cutaneous manifestations in COVID-19: a first
perspective. J Eur Acad Dermatol Venereol 2020; 34: e212–
e213.
3 Le Cleach L, Dousset L, Assier H, et al. Most chilblains
observed during the COVID-19 outbreak occur in patients who
are negative for COVID-19 on polymerase chain reaction and
serology testing. Br J Dermatol 2020. https://doi.org/10.1111/bjd.
19377. Online ahead of print.
International Journal of Dermatology 2021, 60, 3–4
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retrospective study and literature review. J Eur Acad Dermatol
Venereol 2020. https://doi.org/10.1111/jdv.16665. Epub ahead of
print.
5 Magro C, Mulvey JJ, Berlin D, et al. Complement associated
microvascular injury and thrombosis in the pathogenesis of
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2020; 220: 1–13.
6 Colmenero I, Santonja C, Alonso-Riano M, et al. Sars-CoV-2
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7 Llamas-Velasco M, Mun ~oz-Herna
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8 Torrelo A, Andina D, Santonja C, et al. Erythema multiforme-like
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9 Wang Y, Zhang L, Sang L, et al. Kinetics of viral load and
antibody response in relation to COVID-19 severity. J Clin
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10 Hassan K. Urticaria and angioedema as a prodromal cutaneous
manifestation of SARS-CoV-2 (COVID-19) infection. BMJ Case
Rep 2020; 13: e236981.
11 Henry D, Ackerman M, Sancelme A, et al. Urticarial eruption in
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12 Marzano AV, Cassano N, Genovese G, et al. Cutaneous
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ª 2020 the International Society of Dermatology