HPV-47-Induced and Tattoo-associated Verrucae Planae: Report of a Case and Review of the Literature.

The human papillomavirus (HPV), of which more than 200 different types have so far been identified, is an infectious disease impacting skin and mucous membranes. Several genera exist with distinct clinical impact. However, with ornamental tattoos increasing in popularity, a number of mostly cutaneous side effects have also been reported, such as infections, allergic reactions, or even a rise of malignant tumours within the tattoo. We report the first case of a β1-HPV-type infection in cutaneous lesions in terms of verrucae vulgares near a tattoo in an immunocompetent adult without pre-existing conditions, and discuss possible relationships and etiologic concerns of this association.

Introduction

The human papillomavirus (HPV), of which more than 200 different types have so far been identified, is an infectious disease impacting skin and mucous membranes. It is classified into five genera: α, β, γ, μ, ν [2, 3], the alpha genus being the most important for medical practice. These are also known as genital or mucosal types which are divided into high-risk and low-risk types. Persistent infections with mucosal high-risk, and therefore oncogenic, HPV types (such as HPV 16 and 18) are associated with ano-genital and head-neck (mainly HPV 16) neoplasia. Low-risk genital types are, for instance, responsible for condylomata acuminata (HPV 6 and 11) [5, 6]. The beta genus includes cutaneous types of HPV. Those of the species β1 have recently been associated with the pathogenesis of non-melonama skin cancer. β-HPV types, such as the rare β1-HPV-type 47 identified in our patient, were primarily isolated from lesions of patients diagnosed with epidermodysplasia verruciformis (EV), an extremely rare autosomal disorder [3-12]. The β1-HPV type 47 is among others responsible for pityriasis-like plaques in the case of EV; however, it has also been detected in squamous cell carcinomas of EV patients [9]. In our case, the clinical presentation showed itself analogous to hypopigmented lesions of a pityriasis versicolor (Fig. 1). The role of β-HPV types in terms of skin carcinogenesis in the normal population is as yet unknown [5, 7–10, 13].

Fig. 1

Hypopigmented, shiny maculae within a tattoo on the left upper forearm

Case Presentation

We present the case of a 48-year-old male patient with the diagnosis of plane verrucae vulgares with intralesional proof of β1-HPV type 47 on the edge areas of his tattoos on both forearms (Fig. 1). The tattooing took place 20 years ago, whereas the first cutaneous lesions had been noticed by the patient only 8 years ago. Histologically, a granular hyperparakeratosis and hypergranulosis were observed in addition to multiple clusters of keratinocytes with vacuolar cytoplasm (Fig. 2a, b). Altogether, it appeared as a viral lesion even though there was no akanthopapillomatosis. An immunohistochemical analysis in order to detect HPV by use of the monoclonal murin anti-HPV antibody (Clone K1H8) was initiated (M3528, dilution of 1:50; Agilent Technologies/Dako). This αHPV-antibody is specifically immunoreactive on formalin-fixed paraffin-embedded HPV-infected tissue when HPV subtypes 1, 6, 11, 16, 18, 31, 33, 42, 51, 52, 56 and 58 are present [1]. This stain distinguished nearly all of the corneocytes in the stratum corneum in a nuclear pattern, while a few nuclei showed reactivity in the stratum granulosum (Fig. 3). In the subsequently realised virus PCR and consecutive DNA sequencing, we could prove the presence of cutaneous β1-HPV type 47 DNA. This led to the diagnosis of tattoo-associated verrucae planae, beta1-HPV type 47-induced.

Fig. 2

HE stain of lesional skin. a Original magnification ×200. Granular hyperkeratosis and hyperparakeratosis with cluster of keratinocytes with vacuolar cytoplasm, b original magnification ×400

Fig. 3

Anti-HPV stain (Clone K1H8; M3528, dilution 1:50, original magnification ×400). Corneocytes of stratum corneum display positive nuclear stain for human papilloma virus

Informed consent was obtained from the patient for being included in this publication.

Discussion

Currently, an estimated 10% of the general population and approximately 25% of the young adult population in Germany is tattooed [14]. However, with tattoos increasing in popularity, a number of mostly cutaneous side effects have also been reported, such as infections, allergic reactions, or even the rise of malignant tumours within the tattoo. While research reports bacterial (e.g., mycobacteriosis), viral (e.g., HPV-induced) and mycotic (e.g., dermatophytosis) infections [6, 15–19], an increasing number of cases with tattoo-associated HPV-induced verrucae can be found in the literature [20-30]. Lately, HPV 27 was identified on warts on tattoos [31].

It is worth considering a possible causality between the proximity of the tattoo and the lesions. While it is possible that the infection was already present before the patient decided to get a tattoo. it might also have been caused by the tattooing. Contamination during tattooing could occur via the instruments or the colors used, even the tattooist’s saliva could be in fault [20]. An interesting theory stipulates that virus replication may be activated by mechanical impairment of the skin barrier. Indeed, there are clues that cutaneous HPV are excessively activated in people suffering from psoriasis, or in the case of patients in which reparation processes of the skin take place [32-34]. The hair follicle is regarded as the natural reservoir for the beta HPVs. It may also be possible that the virus was released from the hair follicle caused by the act of tattooing [35-37].

There seems to be a latency period between the act of tattooing and the onset of verrucae, which ranges from 2 months to more than 10 years in our case [20-31]. This delayed replication of the virus could be directly related to sun exposure, as it has been shown that UV exposure can induce a direct activation of closely related β1-HPV [38, 39], and is believed to modulate specific and unspecific responses of the immunological system. This mechanism is thus believed to impair the resistance towards infections, including those that are HPV induced [3, 13, 40–43].

As the β1-HPV type 47 has, among others, been isolated from cutaneous lesions in patients with EV, the question as to whether EV can be excluded in our patient has to be addressed. Clinically, the patient had no other lesions than those mentioned earlier. Nor was there palmar or plantar involvement, and neither were there any lesions seen on the patient’s face. As we would have expecte an earlier onset of the condition and development of carcinomas considering the patient’s age, the diagnosis of EV seems unlikely in our case [4, 7].

Different treatment options (e.g., cryotherapy, curettage, podophyllotoxin or topical imiquimod) of viral warts on tattoos have been reported with mixed results [20-31]. In our case, we started a local off-label use therapy with Veregen® 10% ointment (green tea leaf extract), having had good results in using it for treatment of genital warts. The mode of action of this therapy remains unclear, however. It is believed that it originates from the anti-oxidative effect of the sinecatechines present in the leaves of green tea, while antiproliferative and antiviral actions should also be considered [43, 44].

Conclusions

To our knowledge, this is the first documented case of a β1-HPV-type infection in cutaneous lesions in terms of verrucae vulgares near a tattoo in an immunocompetent adult without pre-existing conditions. HPV47 belongs to the β-HPV types which are associated with a higher risk of malignancy in EV patients. The histological image of plane verrucae can be inconclusive in punch biopsies as this rather simple histology may be a challenge, even for a trained dermatopathologist, without clinical observations or photo-documentation of the clinical finding. In this context, the immunohistochemical analysis may prove helpful, although not all types of viruses are caught by the earlier mentioned antibody. According to the data sheet of this antibody, HPV type 47 is not listed as reactive [1]; however, in our case, the anti-HPV-antibody was strongly positive. We were therefore able to demonstrate that the monoclonal murine anti-HPV (Clone K1H8) shows immunoreactivity not only in the presence of the above-named subtypes but also in the case of an infection by β1-HPV type 47. In this case, we recommended that the patient undergoes regular follow-ups. Without the knowledge of the histology, this would surely not have been a standard proposal in the event of an unspecific finding in a tattoo.