Fig. 3. Histopathology examination: a) Hyperkeratosis, well-defined
epidermal hyperplasia (defined between red arrows), and horn cysts
(hematoxylin and eosin stain, 40 ×); b) Hyperkeratosis, epidermal
hyperplasia, horn cyst (blue arrow), surrounded by basaloid cells (green
arrow), and basal melanosis (hematoxylin and eosin stain, 100 ×); c)
Epidermal acanthosis, predominantly composed of basaloid cells (black
arrows) and some squamoid cells. Increased melanin is seen mostly in the
dermo-epidermal junction (hematoxylin and eosin stain, 400 ×).
Discussion
The etiology of the Leser-Trélat sign is still unknown, although it has
been considered as a paraneoplastic phenomenon. Some cases with the
Leser-Trélat sign have occurred in non-malignant patients, including
patients with underlying infections like viral infections (7),
lepromatous leprosy, (4), in association with erythrodermic pityriasis
rubra pilaris, (5),In addition, a case has been reported in a heart
transplant patient treated with immunosuppressive drugs (9).
In addition, some observations have indicated that the Leser-Trélat sign
may develop following viral infections. Inamadar and Palit (6) have
reported a case with human immunodeficiency virus infection who
developed the Leser-Trélat sign. In a study by Tsambaos et al., human
papillomavirus (HPV) DNA was positive in 34 patients from among 173
cases with non-genital seborrheic keratosis. (7).
Some theories have associated its development to transforming growth
factor-alpha and epidermal growth factors secreted from tumor cells.
According to previous studies, TGF-alpha is overexpressed in seborrheic
keratosis, and it may play a significant role in the progression and
increase in the number of seborrheic keratoses. (10-11). It has been
shown that COVID-19 infection with lung injury can induce expression of
transforming growth factor, (12), so there is the possibility of a
similar mechanism in our patient, although severe lung findings were not
reported. However leser- trelat sign is usually associated with a
variety of immune suppression conditions such as malignancy or viral
infection ,so development of eruptive seborrheic keratosis may be due to
immunosuppression situation caused by covid-19 infection. and not
exactly due to TGF- alpha .
Immunohistochemical analysis has also revealed an increased expression
of tumor necrosis factor-alpha (TNF-alpha) in seborrheic keratosis skin
lesions (13), which is in accordance with increased inflammatory
cytokines such as TNF-alpha observed in COVID-19 patients. (14).
Although ,the development of leser –trelat sign in healthy persons does
not fully support the theories of TNF- alpha and TGF-alpha and
immunosuppression conditions .
Therefore, it is likely that viral infections like COVID-19 can be
associated with eruptive seborrheic keratosis, although the exact
pathogenesis is still not clear.