Herpes zoster duplex following COVID-19.

Dear Editor,

Herpes zoster duplex (HZD) is a rare clinical variety of herpes zoster (HZ) in which at least two noncontiguous dermatomes, mono‐ or bilaterally, symmetrically or asymmetrically, are involved. A review of the literature revealed approximately 50 cases of HZD.

We recently observed a patient with previous coronavirus disease‐19 (COVID‐19) who developed HZD. To our knowledge, this is the first case of HZD associated with previous COVID‐19.

A 48‐year‐old Caucasian man was admitted to the hospital because of COVID‐19 in April 2020. After recovery and discharge, the patient suffered from weakness. Laboratory tests showed persistent lymphopenia (range: 1.400–1.600 lymphocytes = 9–11%). In June 2020, the patient was admitted to our Dermatology Unit because of the appearance of bilateral, asymmetric HZD (Figs. 1 and 2). The patient was in good general health and in therapy with citalopram (10 mg/day). The diagnosis of HZD was based on clinical picture (erythematous–vesicular–pustular and painful rash along two bilateral, asymmetric dermatomes) and cytological examination (the presence of multinucleated giant cells with ballooning degeneration and multiple nuclei, with different shape and size) (Fig. 3). General physical examination did not reveal anything pathological. Bacteriologic examination was negative. Laboratory examinations confirmed lymphopenia and increase in erythrocyte sedimentation rate. Positive antivaricella zoster virus (VZV) IgG and IgM were detected. PCR was not performed. Complete remission without complications was observed with valacyclovir (3 g/day for 7 days). Follow‐up (15 months) was negative.

Figure 1

HZD in a patient with previous COVID‐19

Figure 2

Erythematous–vesicular–pustular and painful rash along two bilateral, asymmetric dermatomes

Figure 3

Cytological examination of lesion, with the presence of multinucleated giant cells with ballooning degeneration and multiple nuclei, with different shape and size. Giemsa stain, magnification ×100 in oil

Herpes zoster duplex occurs mainly in Asian patients (Indians, Chinese, Koreans, and Japanese). According to a review published in 2015, 66.7% of patients with HZD were Asians. Herpes zoster duplex is more frequent in women (63.9% of them in a Chinese study). Although HZD typically occurs in adult or elderly patients, some cases in children and adolescents have been reported. Several diseases or conditions are considered as predisposing factors for HZD. They include: hepatitis C, HIV/AIDS, miliary tuberculosis, diabetes, polymyositis, systemic lupus erythematosus, ulcerative colitis, breast cancer, leukemias, multiple myeloma, and renal transplantation. Furthermore, several patients, before the appearance of HZD, were in therapy with systemic corticosteroids, cyclosporine, doxorubicin, 5‐fluorouracil, methotrexate, mycophenolate mofetil, bortezomib, and rivaroxaban. According to the previously cited Chinese study, immunosuppression caused by concomitant diseases or drugs is present in 47.2% of patients. These data mean that HZD occurs also in immunocompetent subjects.

Herpes zoster duplex can be mono‐ or bilateral, symmetric or asymmetric. The bilateral asymmetric presentation is more frequent. Herpes zoster duplex is characterized by typical features: the first lesions are erythema and edema, from pink to red in color, followed by the appearance of grouped, round, small vesicles, with a clear serous fluid. Vesicles evolve toward pustules or erosions that become yellow‐brown crusts. The latter drop off, leaving brownish macules that can persist for weeks or months. However, cases of hemorrhagic, chronic, and recurrent HZD have been described. Sometimes, a clinical diagnosis of HZD must be confirmed by cytologic, histopathologic, and PCR examinations.

As far as complications are concerned, a case of oculomotor nerve palsy was reported. The development of scars is rare and occurs in immunosuppressed patients. However, scars can also occur: a) when there is a delay in the beginning of the therapy; b) when the daily dosage of antivirals is too low; c) when the duration of the therapy is too short.

The therapy of HZD is based on the use of oral acyclovir, valacyclovir, or brivudine. As previously mentioned, in this patient we successfully used valacyclovir (3 g/day for 7 days).

To our knowledge, no cases of HZD in patients with previous COVID‐19 have been published so far. In our patient, immunosuppressive diseases or drugs cannot be considered as predisposing factors for the occurrence of HZD. However, in patients with previous COVID‐19, HZ often develops 8–10 weeks after COVID‐19 recovery: this is because of a reactivation of latent VZV infection. In our patient, the appearance of HZD can be because of chronic lymphopenia after COVID‐19 recovery. Persistent impaired cell immunity may be the mechanism underlying this association. In fact, in several cases, both chronic lymphopenia and decrease in CD4+/CD8+ ratio are observed.