Verruga plantar

Verrucae plantaris, usualmente conocida como verruga plantar, es una lesión cutánea de la zona plantar causada por la infección de los queranocitos por el agente HPV (virus del papiloma humano).
Asintomático en su mayoría afecta, sin embargo, a niños, adolescentes y personas inmunodeprimidas, pudiendo generar dolor y malestar así como lesiones extensas y visualmente repulsivas.
Una vez establecido, el HPV se excreta a través de las células epiteliales descamadas y, de esta forma, las partículas pueden infectar a otros huéspedes y contaminar los lugares, viéndose facilitada la transmisión viral, en gran medida, por las estrategias terapéuticas que se utilizan, que se basan en tratamientos sintomatológicos o que pretenden evitar el contacto (lo que es aún menos sensato dado su presencia ubicua).
Las estrategias actuales de tratamiento tienen bajas tasas de éxito en la eliminación de las lesiones, que son notablemente resistentes y recurrentes[i], puesto que éstas no se centran, en su mayoría, en la infección viral[ii] en sí, sino en la señal visible de esta.
Dada la alta propensión a la resistencia al tratamiento de la verruga plantar y al hecho de que no existe una facilidad y/o un método de prevención eficaz, resulta fundamental encontrar nuevas formas para luchar contra este proceso infeccioso que elimine el agente sin una acción nociva sobre los tejidos para que sea posible controlar las lesiones y su transmisibilidad.

Los aceites ozonizados – ¿una opción?

Los aceites ozonizados son altamente eficaces contra este virus, ya que los trioxolanos, los lipoperóxidos y los aldehídos presentes en este son citotóxicos para los microorganismos.
Los aceites ozonizados, a través de la oxidación de los fosfolípidos y las lipoproteínas, dañan la cápside viral creando una disrupción en el ciclo reproductivo, impidiendo el contacto virus-célula e induciendo a la perioxidación. Las células con paredes celulares de débil componente enzimática son más vulnerables a los ataques virales pero también más susceptibles a la oxidación, siendo eliminadas posteriormente del organismo y sustituidas por células sanas.
Los aceites producen, ante el contacto con la piel, ozónidos que fomentan el aumento de la producción de interferón, factor de necrosis tumoral e interleucina-2, activando la señalización celular en cascada sobre diversas reacciones inmunitarias que influyen en la invasión y la respuesta inmunitaria específica.
Los datos de una publicación de abril de 2021[iii] indican su utilidad en la lucha específica contra el HPV mientras que ya se había mencionado en otra publicación de 2012.
Su utilización en las verrugas HPV ginecológicas también se menciona con éxito en junio de 2021[iv].

[i] Sanclemente G, Gill DK. Human papillomavirus molecular biology and pathogenesis. J Eur Acad Dermatol Venereol. 2002 May;16(3):231-40. doi: 10.1046/j.1473-2165.2002.00419.x. PMID: 12195562.

[ii] Doorbar J, Egawa N, Griffin H, Kranjec C, Murakami I. Human papillomavirus molecular biology and disease association. Rev Med Virol. 2015 Mar;25 Suppl 1(Suppl Suppl 1):2-23. doi: 10.1002/rmv.1822. PMID: 25752814; PMCID: PMC5024016.

[iii] Radzimierska-Kaźmierczak M, Śmigielski K, Sikora M, Nowak A, Plucińska A, Kunicka-Styczyńska A, Czarnecka-Chrebelska KH. Olive Oil with Ozone-Modified Properties and Its Application. Molecules. 2021 May 21;26(11):3074. doi: 10.3390/molecules26113074. PMID: 34063952; PMCID: PMC8196576.

[iv] Scientific rational for the medical application of ozonized oils, an up-date. Ozone Therapy Global Journal; Vol 11, No 1 (2021): Ozone Therapy Global Journal

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Verruga plantar

(Versión Completa en Inglés)

Etiology

The cause of plantar wart is not a single virus but a group of non-enveloped viruses that are categorised into more than 150 types according to their similarities in DNA sequencing, being subsequently classified into species of 1 to 5 genera: α, β, γ, µ, and ν[i].
HPV species already isolated in plantar warts include HPV-1, -2, -3, -4, -27, -29, -57, -60, -63, -65, -66, and -69, of which 88 % are associated with types 1, 2, 27 and 57, with type 1 being the most distinct in terms of clinical profile[ii].
Transmission takes place through direct contact with viral particles.

Epidemiology and Risk Factors

It is estimated that about 40% of the population is infected with HPV but only 7 to 12% will develop plantar wart[iii].
This exhibits an annual incidence of about 14% and the most commonly identified risk factors are:

Prolonged exposure to HPV
Tissue damage/weakness of the epidermal barrier
Impaired/diminished immune response

The incidence varies according to gender, age, race and health status, but is also influenced by geographic location, seasonality, behavior and socio-economic factors, although its higher incidence is clearly during the cold and humid winter months.

Plantar Wart – Physiopathology

HPV can survive on surfaces for many months^[iv]. The host infection process occurs either through direct contact with the plantar wart or through indirect contact via fomites (passive vectors), such as the floor, socks, towels, sports equipment, etc.
In this type of contagion, HPV does not have a viraemic phase or systemic dissemination, and therefore contact with body fluids (except for those emanating from the lesion itself) does not transmit the virus^[v].
The existence of a continuity solution in the skin (a wound or microtrauma) allows the entry of the virus^[vi] which, when in contact with the host, penetrates the basal epithelial layer where the stem cells are in division^[vii]. It is in this environment that the virus binds to cell receptors and enters cells, which become infected^[viii].
After an incubation period of 1 to 20 months, the viral DNA establishes itself within the host cell, usually without integration into its genome, and the infection is installed^[ix].

Once the infection occurs, one of 3 situations is expected:

Clearance of infection – immunity to this particular type of HPV
Latent infection
Clinical manifestation – plantar wart^[x]

If the infectious process occurs without clearance, the basal keratinocyte is stimulated to divide and replicate the viral DNA via HPV E1 and E2 proteins, a process that produces several stem cells, each of which contains between 20 and 100 copies of the viral DNA^[xi].
The cells themselves contain low levels of viral protein which allows the agent to evade the immune response.
As basal cells differentiate into keratinocytes, they progress towards the epithelial surface at the same time as the viral genome promoter is activated, increasing the production of viral proteins that potentiate HPV genomic amplification between each of the cell differentiation phases. It is possible that the E5 membrane protein produced via viral DNA serves to potentiate growth factor signaling, which, in turn, enables cellular DNA replication.
Once the viral DNA copies are sufficient, the viral capsular proteins L1 and L2 are expressed on the surface of the keratinocytes^[xii].
E2 proteins recruit copies of viral DNA to the nucleus, where it is wrapped in capsids composed of L1 and L2 proteins, and these particles can be released in large quantities through the keratinocyte desquamation, thus potentiating the infection of other hosts^[xiii].
The induction of cell replication through the viral genome amplification process leads to a hyperkeratinized papule characteristic of plantar warts, which tend to develop in areas where the foot is under greater pressure, such as the metatarsal heads and heel. It is these pressure points that potentiate the microtrauma of the epidermal barrier, which increases the possibility of invasion by HPV.
It is also due to the action of this pressure that the lesion tends to progress toward the interior of the skin (the so-called «icebergeffect») instead of forming only an external papule, which is one of the main reasons for resistance to treatment^[xiv].
As a result of the normal shedding of the epithelium, viral particles are released and can be transmitted to surfaces, where the virus will remain until it is picked up by a new host or spread to adjacent sites (autoinoculation). Thus, once a plantar wart develops, the host is susceptible to developing additional warts^[xv].
Sixty-five to 78% of cutaneous warts regress within 2 years^[xvi] however, in individuals older than 12 years, the spontaneous regression ratio decreases significantly^[xvii].

Wart regression depends on the development of an effective cellular immune response^[xviii]. However, the ability to evade the host’s immune system means that even healthy individuals can be infected^[xix].
In most healthy people, HPV infection is controlled through an immune response that is initiated upon contact with viral particles. The viral antigen is verified by Langerhans cells, which migrate to the lymphatic system and later reach a lymph node where they present the antigen to a T lymphocyte, which is activated and induces a specific response in the area of viral contact. Antigen-presenting cells activate keratinocytes to release inflammatory cytokines and promote the migration of neutrophils and monocytes, as well as the activation and migration of Th lymphocytes, the maturation of B cells, and natural-killer (NK) cell activity.
Keratinocytes release tumour necrosis factor α, which enhances the recognition of infected keratinocytes by T lymphocytes, which destroy the infected keratinocytes. This is the response that causes the eradication of the infection and prevents the appearance of the lesion/wart and/or its regression, forming B cells that produce specific antibodies, responsible for the humoral response. It is when this process fails that the wart develops.

[i] King CM, Johnston JS, Ofili K, Tam M, Palefsky J, Da Costa M, Mathur Y, Barbosa P. Human papillomavirus types 2, 27, and 57 Identified in plantar verrucae from HIV-positive and HIV-negative individuals. J Am Podiatr Med Assoc. 2014 Mar;104(2):141-6. doi: 10.7547/0003-0538-104.2.141. PMID: 24725033.

[ii] Bruggink SC, de Koning MN, Gussekloo J, Egberts PF, Ter Schegget J, Feltkamp MC, Bavinck JN, Quint WG, Assendelft WJ, Eekhof JA. Cutaneous wart-associated HPV types: prevalence and relation with patient characteristics. J Clin Virol. 2012 Nov;55(3):250-5. doi: 10.1016/j.jcv.2012.07.014. Epub 2012 Aug 11. PMID: 22884670.

[iii] Barna Z, Kádár M. The risk of contracting infectious diseases in public swimming pools. A review. Ann Ist Super Sanita. 2012;48(4):374-86. doi: 10.4415/ANN_12_04_05. PMID: 23247134.

[iv] Berry JM, Palefsky JM. A review of human papillomavirus vaccines: from basic science to clinical trials. Front Biosci. 2003 May 1;8:s333-45. doi: 10.2741/1003. PMID: 12700045.

[v] Warts and verrucas: assessment and treatment. The Pharmaceutical Journal, PJ, 20 June 2015, Vol 294, No 7867;294(7867):DOI:10.1211/PJ.2015.20068680

[vi] Longworth MS, Laimins LA. Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol Mol Biol Rev. 2004 Jun;68(2):362-72. doi: 10.1128/MMBR.68.2.362-372.2004. PMID: 15187189; PMCID: PMC419925.

[vii] Doorbar, John. ‘Papillomavirus Life Cycle Organization and Biomarker Selection’. 1 Jan. 2007 : 297 – 313.

[viii] Sterling JC, Gibbs S, Haque Hussain SS, Mohd Mustapa MF, Handfield-Jones SE. British Association of Dermatologists’ guidelines for the management of cutaneous warts 2014. Br J Dermatol. 2014 Oct;171(4):696-712. doi: 10.1111/bjd.13310. Epub 2014 Oct 1. PMID: 25273231.

[ix] Witchey, Dexter Jordan, Witchey, Nichole Brianne, Roth-Kauffman, Michele Marie and Kauffman, Mark Kevin. «Plantar Warts: Epidemiology, Pathophysiology, and Clinical Management» Journal of Osteopathic Medicine, vol. 118, no. 2, 2018, pp. 92-105. https://doi.org/10.7556/jaoa.2018.024

[x] Bruggink SC, Eekhof JA, Egberts PF, van Blijswijk SC, Assendelft WJ, Gussekloo J. Warts transmitted in families and schools: a prospective cohort. Pediatrics. 2013 May;131(5):928-34. doi: 10.1542/peds.2012-2946. Epub 2013 Apr 22. PMID: 23610204.

[xi] Longworth MS, Laimins LA. Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol Mol Biol Rev. 2004 Jun;68(2):362-72. doi: 10.1128/MMBR.68.2.362-372.2004. PMID: 15187189; PMCID: PMC419925.

[xii] Doorbar J, Egawa N, Griffin H, Kranjec C, Murakami I. Human papillomavirus molecular biology and disease association. Rev Med Virol. 2015 Mar;25 Suppl 1(Suppl Suppl 1):2-23. doi: 10.1002/rmv.1822. PMID: 25752814; PMCID: PMC5024016.

[xiii] Sanclemente G, Gill DK. Human papillomavirus molecular biology and pathogenesis. J Eur Acad Dermatol Venereol. 2002 May;16(3):231-40. doi: 10.1046/j.1473-2165.2002.00419.x. PMID: 12195562.

[xiv] King CM, Johnston JS, Ofili K, Tam M, Palefsky J, Da Costa M, Mathur Y, Barbosa P. Human papillomavirus types 2, 27, and 57 Identified in plantar verrucae from HIV-positive and HIV-negative individuals. J Am Podiatr Med Assoc. 2014 Mar;104(2):141-6. doi: 10.7547/0003-0538-104.2.141. PMID: 24725033.

[xv] Johnson LW. Communal showers and the risk of plantar warts. J Fam Pract. 1995 Feb;40(2):136-8. PMID: 7852935.

[xvi] Singh S, Chouhan K, Gupta S. Intralesional immunotherapy with killed Mycobacterium indicus pranii vaccine for the treatment of extensive cutaneous warts. Indian J Dermatol Venereol Leprol. 2014 Nov-Dec;80(6):509-14. doi: 10.4103/0378-6323.144145. PMID: 25382507.

[xvii] Bavinck JN, Eekhof JA, Bruggink SC. Treatments for common and plantar warts. BMJ. 2011 Jun 7;342:d3119. doi: 10.1136/bmj.d3119. PMID: 21652749.

[xviii] Shaheen MA, Salem SA, Fouad DA, El-Fatah AA. Intralesional tuberculin (PPD) versus measles, mumps, rubella (MMR) vaccine in treatment of multiple warts: a comparative clinical and immunological study. Dermatol Ther. 2015 Jul-Aug;28(4):194-200. doi: 10.1111/dth.12230. Epub 2015 Apr 6. PMID: 25847793.

[xix] Landini MM, Borgogna C, Peretti A, Doorbar J, Griffin H, Mignone F, Lai A, Urbinati L, Matteelli A, Gariglio M, De Andrea M. Identification of the skin virome in a boy with widespread human papillomavirus-2-positive warts that completely regressed after administration of tetravalent human papillomavirus vaccine. Br J Dermatol. 2015 Aug;173(2):597-600. doi: 10.1111/bjd.13707. Epub 2015 Jun 25. PMID: 25639663.