SARS-CoV-2 spike protein positivity in pityriasis rosea-like and urticaria-like rashes of COVID-19.

dear editor, The spike protein of SARS‐CoV‐2 is responsible for receptor recognition and cell membrane fusion. Positive immunohistochemistry (IHC) for SARS‐CoV/SARS‐CoV‐2 spike protein has been found in lungs, tracheal mucosa and renal tubular epithelial cells, and recently in chilblain‐like and erythema multiforme‐like lesions of patients with COVID‐19. Herein we report on two patients, one with a pityriasis rosea‐like rash and one with an urticarial rash, with positive IHC for SARS‐CoV/SARS‐CoV‐2 spike protein.

Our first case is a 49‐year‐old man who presented to the dermatology clinic with a 7‐day disseminated pruriginous dermatosis. Two weeks earlier he presented cough, malaise, dysgeusia, myalgias, arthralgias and headache. Nasopharyngeal swab test for SARS‐CoV‐2 was negative. Systemic symptoms resolved after 10 days. Physical examination showed oval, erythematous plaques with collarette scale, and scarce erythematous papules on the arms, legs and trunk (Figure 1a). Histopathological analysis of an upper‐extremity lesion revealed a psoriasiform dermatitis with mounds of parakeratosis and mild spongiosis (Figure 1b). IHC with SARS‐CoV/SARS‐CoV‐2 spike protein was positive on endothelial cells and perivascular lymphocytes (Figure 1d) [SARS‐CoV/SARS‐CoV‐2 (COVID‐19) spike antibody (1A9), dilution 1 : 100, lot no. 43943, GTX632604; GeneTex Inc., Irvine, CA, USA]. Serum antibody testing for SARS‐CoV‐2 IgM and IgG was positive 3 weeks after the rash began. Topical corticosteroids were prescribed, and the rash resolved partially after 1 month.

Figure 1

(a) Pityriasis rosea‐like rash on the upper extremity of a patient with COVID‐19 infection. (b) Skin biopsy revealed a psoriasiform dermatitis with mounds of parakeratosis, mild spongiosis and a perivascular superficial lymphocytic infiltrate (haematoxylin and eosin, original magnification × 10). (c) Positive control showing chorionic villi with nuclear and cytoplasmic SARS‐CoV/SARS‐CoV‐2 spike protein positive immunohistochemistry in cytotrophoblast cells (× 100). (d) Positive immunohistochemistry for SARS‐CoV/SARS‐CoV‐2 spike protein. Black arrow: positive endothelial cells; orange arrow: positive lymphocytes (× 100).

Our second patient is a 53‐year‐old man who was evaluated due to a recurrent urticarial rash. Six weeks earlier he presented COVID‐19 infection (confirmed with SARS‐CoV‐2 reverse‐transcriptase polymerase chain reaction); his symptoms included malaise, dysgeusia, anosmia and an urticarial rash. Skin lesions did not improve with antihistamines; however, the administration of systemic steroids resulted in complete response. After 1·5 months the rash relapsed. Physical examination showed a disseminated dermatosis in the arms, legs and trunk consisting of erythematous papules and urticarial plaques, some with arciform appearance. Serum antibody testing was positive for SARS‐CoV‐2 IgM and IgG. Skin biopsy revealed a perivascular lymphocytic infiltrate with dermal oedema and eosinophilia. IHC stain with SARS‐CoV/SARS‐CoV‐2 spike protein was positive in the endothelium of the dermal blood vessels. Positive control on placental tissue of postpartum women with SARS‐CoV‐2 infection (Figure 1c) and negative controls (on normal and inflamed skin) were performed in both cases.

During the COVID‐19 pandemic, the diagnosis of pityriasis rosea has become more common. It remains unknown whether this is secondary to direct invasion of SARS‐CoV‐2, due to reactivation of human herpesvirus (HHV)‐6 or ‐7, or due to other factors. Reactivation of HHV‐6 and Epstein–Barr virus (EBV) was demonstrated in the serum of a patient with pityriasis rosea and COVID‐19. However, an IHC study for the local presence of viruses was not conducted.

Infection with COVID‐19 has been associated with urticaria, angio‐oedema and urticarial vasculitis. Similarly, urticaria has been linked with viral agents including herpesvirus and EBV. Our case was positive for SARS‐CoV‐2 viral particles 6 weeks after the initial diagnosis. To our knowledge, these are the first pityriasis rosea‐like dermatosis and urticarial rash with confirmed SARS‐CoV‐2 viral particles in the skin. Our findings suggest that viral infection of lymphocytes or endothelial cells by SARS‐CoV‐2 may cause these manifestations. IHC analysis of skin biopsies may represent a useful tool in selected patients with suspected COVID‐19 diagnosis. Larger case series and electron microscopy evaluation are needed to confirm our findings.

Author Contribution

Esperanza C. Welsh: Conceptualization (lead); Formal analysis (equal); Investigation (equal); Methodology (equal); Project administration (equal); Supervision (equal); Writing‐original draft (equal); Writing‐review & editing (equal). Jesus Alberto Cardenas‐de la Garza: Conceptualization (equal); Formal analysis (equal); Investigation (lead); Methodology (equal); Supervision (equal); Writing‐original draft (lead); Writing‐review & editing (lead). Adrian Cuellar‐Barboza: Formal analysis (equal); Investigation (equal); Methodology (equal); Project administration (equal); Validation (equal); Writing‐original draft (equal); Writing‐review & editing (equal). Rodolfo Franco‐Marquez: Conceptualization (equal); Formal analysis (equal); Investigation (equal); Methodology (equal); Validation (equal); Writing‐review & editing (equal). Rosa Icela Arvizu‐Rivera: Conceptualization (equal); Investigation (equal); Methodology (equal); Writing‐original draft (supporting); Writing‐review & editing (equal).