Comment on ‘Clinical and histological characterization of vesicular COVID‐19 rashes: a prospective study in a tertiary care hospital’. Pseudoherpetic Grover disease seems to occur in patients with COVID‐19 infection

We read with great interest the article by Fernandez‐Nieto et al. showing histopathological pictures of one of the two biopsied cases from their series of 24 patients diagnosed of vesicular lesions related to COVID‐19.¹ They additionally performed a real‐time PCR assay for SARS‐CoV‐2 that was negative in four tested cases.¹ Regarding their case using histopathological pictures, we agree with their description as we can observe acantholytic cells, some of them with dyskeratotic features or grouped without a clear moulding of nucleus, but reminiscent of the multinucleated giant cells typically observed in herpetic lesions, a picture that looks to our eyes, most likely to be a rare entity named pseudoherpetic Grover disease (GD),² first described as vesicular GD by Fernandez‐Figueras et al.³

Pseudoherpetic GD is characterized clinically by asymptomatic or itchy papules, intermingled with crusts and isolated vesicles or pustules that mostly involve the trunk (Fig. 1), a picture that overlaps with the diffuse pattern of vesicular lesions related to COVID‐19, described by Fernandez‐Nieto et al.¹ Histopathologically, the main clues for the diagnosis of pseudoherpetic GD are the presence of intraepidermal vesicles, frequently filled with plasma, along with scarce groups of acantholytic cells, mostly located in the lateral parts of the vesicle. A dermal inflammatory infiltrate, which may contain neutrophils, can also be present (Fig. 2). In our series of pseudoherpetic GD, we did not find any viral inclusions, and immunostaining for herpesvirus and varicella were negative in all the cases.²

Figure 1.

(a) Papules and vesicles involving the whole trunk. Different sizes of the lesions can be observed. (b) Anterior trunk of the same patient detail showing mostly vesicles and crusted papules.

Figure 2.

(a) Intraepidermal vesicle filled with plasma. (b) Detail of dyskeratotic cells as well as groups of acantholytic cells resembling multinucleated herpetic cells.

COVID‐19 infection characteristically produces lymphopenia, and immunosuppression is a predisposing factor for both herpesvirus recurrence⁴ and development of pseudoherpetic GD.²

As many patients during hospitalizations can present flares or new onset of GD related to sweating in the context of fever, increased bed rest and immunosuppression, COVID‐19 is likely to favour GD. As we assume that tests to exclude a superimposed viral infection were performed for all the published cases by Fernandez‐Nieto et al., we would like to know if in the biopsied cases, immunostaining for herpes simplex and herpes zoster viruses were negative, as we consider these two types of immunostaining to be mandatory to confirm the diagnosis of pseudoherpetic GD, as true herpesvirus may superimpose on acantholytic diseases such as GD or others, making the diagnosis more challenging.⁵

The appearance of vesicles as a clinical presentation of GD raise the differential diagnosis of varicella or disseminated herpes zoster, and even with the vesicular lesions associated to COVID‐19, as the clinical pattern of these entities may overlap.

In conclusion, we consider that when faced with vesicular lesions even during the COVID‐19 pandemic, tests such as Tzanck smear or PCR for Herpesviridae family on vesicle fluid or skin biopsy should be performed to exclude disseminated forms of other common viral infections and also rarer entities such as pseudovesicular GD, as these two cases seem to be.