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.