Herpes simplex virus mucocutaneous tumoural lesions – Systematic review
Introduction
Mucocutaneous eruptions caused by herpes simplex virus (HSV) are common worldwide. The typical lesions are painful erythematous papules, vesicles and shallow ulcers [1,2]. Among the atypical forms, the tumoural (defined, in The Oxford English Dictionary, as "pertaining to, or characteristic of a tumour") has been reported in immune-compromised patients, mainly those infected by HIV [3]. Mucocutaneous tumoural herpes simplex virus (MCT HSV) form has also been described as nodular, hypertrophic, verrucous, vegetative or exophytic. These terms aim to reflect the voluminous aspect of the lesions, and are frequently used for other inflammatory skin conditions with clinical presentation of a tumour. Recognizing this entity is of paramount importance because it can be misinterpreted as neoplasms, leading to equivocal therapeutic strategy [[4], [5], [6], [7], [8], [9], [10], [11]].
To aid in their recognition and delineation, we systematically reviewed studies on MCT HSV lesions, focusing on 1) the clinical-epidemiological profile of patients; 2) major primary morphological features and topography; 3) primary causes of immunosuppression, and 4) potential occurrence in immunocompetent individuals. We investigated the pathogenetic mechanisms attributed to the development of this atypical form of HSV infection and postulate other hypotheses.
Section snippets
Materials and methods
A literature search was undertaken through the search engine PubMed/MEDLINE, through October 30, 2018, using the following uniterms: “herpes and hypertrophic”, “herpes and tumoural”, “herpes and vegetans”, “herpes and atypical” and “herpes and verrucous”. These uniterms are used in the literature to refer to a clinical presentation that resembles a tumour, in different diseases. Each article was fully and independently scrutinized by two researchers, with a view to tumoural HSV case reports. We
Results
The patients' age ranged from 7 to 76 years (mean: 43.39; median: 42.00; n: 89); 62.73 % (69/110) were male. The lesions developed in the anogenital region, intergluteal groove and on the buttocks in 76.36 % (84/110) cases. Also the face, including mouth and oral cavity, [[12], [13], [14], [15], [16], [17], [18]] nose [19,20], ear [7,19], conjunctiva [21] and periocular region [[21], [22], [23], [24], [25]] were affected. Less common sites were reported in 7.41 % (8/108, missing 2) patients,
Discussion
HSV is a common cause of mucocutaneous infection, and, genital herpes, the most common sexually transmitted disease in the world [1,2]. There are two major antigenic and biological types of herpes virus hominis: HSV-1 which primarily affects the mouth, lips, nostrils and adjacent skin, and HSV-2 which normally causes anogenital lesions [59]. Primary infection tends to be more painful and to last longer than recurrences [45]. Atypical forms appear as asymptomatic or painful localized
Pathogenesis
The pathogenesis of MCT HSV lesions has not been elucidated, but the results of clinical, histopathological and laboratory studies have provided some hypotheses.
Inflammatory process in cutaneous infections releases interleukins (ILs) and growth factors that act in keratinocytes. These produce cytokines that stimulate dermal dendritic cells to produce IL-1, IL-6 and TNF-α, which stimulate proliferation of keratinocytes and perpetuation of the process [38,64,73,74]. HIV infection of dermal
Conclusion
The tumoural variant of herpes is strongly associated with immunosuppression, mainly because of HIV. Occurrence is most common among males with an average age of 43 years, presenting in the anogenital region, intergluteal groove/and buttocks, and usually accompanied by pain. It may include plaque or mass, be ulcerated or not, single or multiple, and the diameter is greater than 3 cm, in most cases. Physicians must have a high level of suspicion in immunosuppressed patients, especially with
CRediT authorship contribution statement
Bruna Morassi Sasso: Data curation, Formal analysis, Investigation, Methodology, Project administration, Visualization, Writing - original draft. Michelle Etienne Baptistella Florence: Conceptualization, Investigation, Validation. Renata Ferreira Magalhaes: Validation, Visualization. Paulo Eduardo Neves Ferreira Velho: Validation, Visualization. Elemir Macedo de Souza: Validation, Visualization. Maria Leticia Cintra: Conceptualization, Resources, Validation, Visualization, Writing - review &
Declaration of Competing Interest
The authors have no conflict of interest and no source of funding.
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