Discussion:
EV is a rare inherited genodermatosis characterized by an increased susceptibility to specific genotypes of human papillomaviruses (HPV).2 HPV 5 and 8 are reported to be the major causative agents. Causal genetic mutations have been identified in the EVER genes.3 The etiopathogenesis is multifactorial, involving viral, genetic and environmental factors. Over time, affected subjects have an increased risk of squamous cell carcinoma on sun-exposed areas. In 1983, Lutzner and colleagues had detected, in a renal-allograft recipient, HPV 5 DNA, in both Squamous cell carcinomas and benign skin lesions that resemble clinically and histologically to the lesions of inherited EV. They suggested a synergistic action between HPV infection, immunosuppression and sunlight exposure in the occurrence of skin carcinoma in renal-transplant recipient.4Acquired EV is a term coined in 2009 by Rogers and colleagues to describe acquired phenotypes of EV discovered in HIV patients.5 Other conditions of suppressed cellular immunity have been associated with acquired EV such as systemic lupus erythematosus,6 GVH disease,7 atopic dermatitis 8 and solid organ transplantation such as renal transplantation.9 The description of acquired EV in immunocompromised hosts suggests the potential role of a specific immune deficiency. A novel classification for the different types of EV subdivides the disease into genetic EV (classic and non-classic according to the mutations) and acquired EV.10Although an underlying genetic susceptibility to HPV infection in immunocompromised patients with acquired EV has been hypothesized, it has not yet been identified.
Clinically, acquired EV manifests usually with the same features as genetic EV, namely a tinea versicolor-like eruption of the trunk, face and extremities and verruca-like lesions on the distal extremities.2 Published data about acquired EV related to renal transplantation is scarce with mainly single case reports. Table 1 shows all reported clinical cases of acquired EV in renal- transplant recipients. Most cases have a typical presentation.9,11,12 In other papers, the presentation was atypical with lesions limited to the perineum 13and the inguinal folds.14 A case of acquired EV mimicking a periungual malignant melanoma was reported in a patient diagnosed with a cutaneous T cell lymphoma.15 In our case, the diagnosis was discovered fortuitously on a biopsy for a drug reaction suspicion.
As for cancer susceptibility, the progression to non-melanoma skin cancers in acquired EV has not been well established.2,5 In organ-transplant recipients, the use of immunosuppressive medications to prevent organ rejection is responsible for increasing the susceptibility for viral infections, particularly HPV, that may explain the occurrence of the acquired EV phenotypes. In his report, Mendes highlights the role of post-transplantation immunosuppressive medications in increasing both the susceptibility for viral infections and the rate of malignancies. This effect is caused by most of the molecules used.9In the cases of the literature, all renal-transplant recipients were undergoing maintenance immunosuppressive therapy.7,9-14 These immunosuppressant molecules are known to increase the risk of malignancy.16 Similarly to genetic EV, acquired EV may be associated with a higher rate of cutaneous cancers. The cumulative effect of these two risks in renal-transplant recipients is still unknown and an intensification of the monitoring could be an option. As a precaution, photoprotection is mandatory.
No effective curative treatment has yet been discovered for neither the genetic nor the acquired forms.2,5 Several treatment options have been proposed. However, no modality has been shown to be consistently successful. A case of an acquired EV in a renal-transplant recipient that cleared with a multimodal therapy including Gardasil vaccination has been reported.14