Papilloma Viral Skin Diseases

Introduction

Papilloma vital skin diseases are diseases caused by Human papilloma viruses (HPV) and Poxviruses. Clinically, they manifest as warts, genital warts or Condylomata and molluscs.

 

Definition

Warts – verrucae are benign infectious epitheliums, which appear on the skin and less commonly on the mucous membrane. They are caused by Human papilloma viruses – HPV. Children, young adults and people with a compromised immunity most often suffer from warts. There are 3 types of warts: 1. Vulgar warts verrucae vulgares with three sub-types (plantar warts – verrucae plantares, thread-like warts – verrucae filliformes and finger-like warts – verrucae digitatae), 2. Flat warts verrucae planae and 3.Genital warts condylomata accuminata.

Molluscum contagiosum (Lat. molluscus= soft, Lat. contingere = touch) is a relatively common skin disease that primarily affects children, especially boys. It preferentially appears around the ano-genital and in areas of eczema in patients with eczema. Taxonomically, the agent, so the molluscum contagiosum virus (MCV), is part of the Poxviridae family and the Chordopoxvirinae sub-family. It is the only representative of the newly originated Molluscipoxvirus genus. After the eradication of smallpox (variola virus), MCV is the only representative of the Poxviridae family, which causes a disease in humans. Since 1980, it has become an increasingly important opportunistic disease in HIV-infected patients.

History

Warts were known to physicians as early as during Hippocrates (460- 377BC). Historically, genital warts were referred to as condylomata (condylos = protrusion), as thyme (it got its name because the surface of warts is similar to a wild-growing thyme leaf) or as a fig or mulberry (again because of how similar the fruit is to the efflorescence of warts). Apart from other terms, condyloma is still used today. Accuminatum (Lat.acuminatus = pointy) was added to it at the end of the 19th century. Nowadays, Condylomata accuminata is the commonly used term for genital warts. Genital warts is the term used in English.

Warts have always been associated with something dirty, forbidden and exotic. In Ancient Rome, they were considered the consequence of promiscuity and unnatural (anal) sex. In the Middle Ages, the majority opinion was that all genital diseases are caused by an infection by a single agent. In this regard, there was talk about the existence of some type of venomous poison. In 1793, Benjamin Bell defined syphilitic papillary lesions, gonorrhoea and genital warts as various diseases. Currently, genital warts are the most common viral sexually transmitted diseases (STD) worldwide.

The striking resemblance of genital and skin warts has long been the cause of so-called unified theories saying that all warts are evoked infections of the same agents. However, in 1979, an article was published about the huge frequency of Human Papilloma Viruses (HPV) types. Only five had been known up until then.

The discovery that primarily initiated an increase in research on HPV was the isolation of HPV from cervical cancer in 1983. In 1842, Italian physician, D. Rigoni-Stern observed higher incidence of uterine cancer (probably cervical cancer) in married women and widows than in women with no sexual experience. Further observations imply that this disease is caused by a sexually transmitted agent. The Type 2 Human Herpes Virus (HSV-2) was a hot candidate. Professor Vonka’s group in Prague conducted extensive studies, which provided clear evidence that HSV-2 is not the triggering factor (Vonka and coll. 1984; Krčmář and coll., 1986). HPV research over the past 20 years has shown that these viruses also play an etiological role in other malignant diseases, like cancer of the vulva, vagina, penis, anus and some head and neck tumours.

Origin

The human papilloma virus (HPV) is spread throughout the human population worldwide. It causes a wide range of diseases on the skin and mucous membrane. It also plays an important role in oncology origin. Nowadays, there are 86 types of HPV that have been fully characterized and there are over 130 potentially new warts. Warts are caused by HPV types 1, 2, 3 and 4, condylomata HPV types 6, 11 and 42. Aetiology pathogenesis cervical carcinoma reports HPV types 6, 11, 16, 18 and 45. So, an individual with untreated condylomata is a high risk sexual partner.

Molluscum contagiosum virus (MCV) is a Poxvirus and is found all over the world. Molecular-biological methods have identified 4 sub-types of MCV I, II, III and IV. Individual sub-types are very similar on the nucleotide level but their restriction maps are very different.

Transmission

The transmission of warts is possible from person to person by means of very close personal contact, indirectly by means of contaminated objects, like rough, wet surfaces (saunas, swimming pools, sports facilities) and also by autoinoculation. Transmission is also possible by animals, most frequently from cattle, horses and dogs. Genital warts, known as condylomata, are exclusively transmitted by sexual intercourse. They thrive in a warm and humid environment of the mucous membrane near and inside the genitals of both sexes. They appear exclusively in intimate areas. In homosexual men, they appear around the anus, with the possibility to penetrate deep into the anus.

The transmission of molluscs in children presumes direct contact or contact with contaminated objects and also by means of autoinoculation. In school-aged children, transmission is most common at swimming pools. Lesions preferentially occur in children suffering from atopic eczema, near the eczema. Sexual intercourse is another possible way of transferring molluscs in young adults.

Epidemiological Data

The prevalence of warts in the European Union is about five percent. People with a compromised immune system are more susceptible to this infection. In sexually active women, the HPV infection is detected in 5–30% of the cases and is comparable to the prevalence of HPV in healthy men, where it ranges from 10 to 25%. The virus enters the body through traumatized skin and the mucous membrane. The incubation period ranges from 4 weeks to 20 months.

The extreme occurrence of Moluscum contagiosum (MC) on Fiji, Papua New Guinea and in Zaire is particularly interesting. In these areas, children younger than 5 are most commonly affected and the prevalence may reach up to 25%. Research was conducted by physicians in the Netherlands, which showed a 17% molluscs incidence in children younger than 5.

Young adults are the second group most frequently affected by MCV. In these cases, MCV is newly considered a sexually transmitted disease. As the study has shown, the occurrence of genital MC has gone up in the last ten years. The worldwide incidence of genital MC is estimated to be 2 –8%. In 1995, 0.7% of STD patients in New Zealand were diagnosed with MC. Genital molluscum contagiosum may be an indication of a more serious sexually transmitted disease and the HIV infection. According to one study, up to 30% of the patients with MV lesions have other sexually transmitted diseases. MC occurs in 5 – 20% of patients suffering from AIDS and the symptomatic HIV infection. The incubation period ranges from 14 – 50 days.

The Clinical Picture

Verruca vulgaris preferentially occurs on the soles, fingers, along the nails, under the nails but also on the mucous membrane of the mouth. The initial wart is flat and gradually gets bigger, it arches upwards and is covered with many layers of keratin, which cracks, leaving the surface jagged and rough (Fig.1). The size of warts varies from the size of a pinhead to formations, which are several centimetres in diameter. The wart is initially yellow and may later turn greyish to brown. Warts are usually isolated but the autoinoculation may spread and then appear in clusters.

Verrucae filiformes (thread-like warts) have thin, thread-like protrusions on the surface. They preferentially appear on the lips, the mucous membrane of the mouth, in the moustache or on eyelids (Fig.2).

Verrucae digitatae (finger-like warts) have finger-like protrusions on the surface and most commonly occur on the mucous membrane of the mouth and the nasal mucous membrane (Fig.3).

Verrucae plantares (foot warts) have a very special position. Under the influence of body weight, they don’t protrude outwards but rather sink deep down into the rough skin. People confuse them with calluses or corns. They appear like raised bumps with a solid layer of rough, yellow-greyish skin on the surface. A crater-like depression is formed once these warts are removed. Dark, red dots, which are blood-clot capillaries or hemorrhagic spots, are often seen through the efflorescence. These spots may be problematic in differential diagnosis. If left untreated for a long time, they grow to be mosaic lesions (Fig.4). They preferentially appear in places under the metatarsophalangeal joint or in the middle of the heel. They can be very painful when walking.

Verruca plana juvenilis (young, flat warts) are round or polygonal, inconspicuous, 2-4mm small, yellowish-grey papules, sometimes pinkish with a smooth or slightly rough surface (Fig.5). They preferentially appear on the face, the backs of hands and less frequently on other parts of the body. Since they are subjectively slightly itchy, individuals scratch them and its eczema spreads and appears suddenly and quickly.

Condylomata accuminata (condylomata, genital warts) are initially whitish to reddish papules, which usually form on the foreskin in men and around the vagina and anal area in women and homosexuals. They gradually grow and transform into cauliflower-like formations with a wart-like surface (Fig.6). When pressure and maceration is applied, the surface becomes smoother, it erodes and remains wet. Converging condylomata can create widespread macerated and smelly surfaces. Rarely can condylomata penetrate into the corpora cavernosa, evoking a cancerous picture. We are then talking about condyloma giganteum.

Mollusca contagiosa are semi-circular papules with a smooth, pearl-like surface, hard to the touch, whitish, yellowish or even pinkish (Fig.7a). Typically, the centre of the depression is filled with tissue detritus in larger efflorescence. When pressure is applied, a white substance comes out, which contain a so-called molluscs body, which are epidermal cells filled with poxviruses. Manifestations may be infected secondarily. The size of the mollusc ranges from small formations to large efflorescence of up to 1cm, so-called moluscum giganteum (Fig.7b). In children, lesions preferentially appear on the face, chest and on the extremities. Meanwhile, in young, sexually active adults, it mainly appears on the genital areas. The occurrence of lesions has also been described on eyelids and conjunctiva. They rarely appear on the palms and soles of the feet. The lesions can also be solitary. They can multiple and cover extensive areas in children in endemic areas and in individuals with compromised immune systems. Patients don’t usually have any objective problems. In some cases, a tense feeling and itchiness may occur. In about 10% of the patients, eczema appears around the molluscs. This is known as “molluscs dermatitis”. The infection is not expected to spread throughout the bloodstream. The occurrence of many lesions on the same spot is rather explained by multiple simultaneous infections or mechanical spreading. Recurrences may occur after treatment.

Diagnosis

Determining the diagnosis is primarily based on the aspects. Molecular biological methods are the most reliable methods of detecting an HPV infection in the tissue. However, it is not commonly used in practice. Cytology can prove the formation of so-called coilocytes and dyskeratocytes. These are cells with a higher bladder-shaped hyperchromic nucleus with a perinuclear halo. Histologically, in addition to coilcytes, there is evidence that the epithelia, papillomatosis, acantosis, parakeratosis and hyperkeratosis are infected. Serological methods are not very reliable. Negative antibody titers do not rule out infection. The synthesis of virus-like particles (VLP) and its use as antigens for serological diagnostics could be promising. Direct detection methods (PCR) use a hybrid method on extracted DNA. HPV DNA is first amplified before detection. This achieves considerable sensitivity of the method. Its high sensitivity and specificity is a prerequisite.

Differential Diagnosis

Verruca seborrhoica or ageing / senile warts are included in skin benign epithelial tumours and acanthomas. It is a very common disease in almost everyone over 50. It has a wart-like surface and looks “greasy”, hence the name. It may be light brown to black (Fig. 8).

Naevus sebaceus is a defined skin formation that is created based on an embryonic disorder. It is a soft, yellow-brown, 1 to 6cm, papilloma formation on the surface. It primarily occurs on the head and gets larger over the years. The removal of this skin formation is recommended because there is a risk of tearing it when combing the hair and there is a possibility of a bacterial skin infection. Surgical excision used to be the preferred method of removal. However, nowadays, removal using an ablation laser is more common and significantly less invasive. Colloquially, this disease is incorrectly referred to as warts.

In terms of its appearance and location, the acral type of melanoma malignum may resemble plantar warts. Unfortunately, this sub-type of melanoma is commonly unrecognized, which leads to long-term unsuitable treatments. This subsequently leads to metastasis and the diagnosis is usually very unfavourable for the patient (Fig.10).

Therapy

Current medical evidence offers several options for treating different types of warts. It is important to persevere with the treatment, consult everything with your physician and follow all recommendations related to the treatment.

Therapy can be divided into:

  1. Conservative – most common locally (application of collodions, solutions, ointments, etc.) in severe systemic conditions (inosinum pranobexum, cidofovir – not available in the Czech Republic),
  2. Surgical – abrasion using special, sharp spoons, excision, done at the doctor’s office
  3. Physical cryo-therapy, photodynamic therapy, laser

 

  1. Conservative Therapy:

The golden standard for treating warts is still 10-60% concentration of salicylic acid (depending on the medicinal form used), which is often combined with lactic acid, monochloroacetic acid and trichloroacetic acid.

 

The above stated agents have caustic and keratolytic effects – they soften the keratin layer of the skin and destroy the wart matrix. It is applied only to the area of the wart and in the form of collodions, solutions, lacquers or adhesive patches. It is advisable to protect the area around the wart with a neutral ointment or paste to prevent damaging the healthy tissue.

It is possible to buy products with these agents over-the-counter in pharmacies (Ex. Kolodium forte) or they are prepared individually at the pharmacy. Based on our experience, it is ideal to apply this product twice a day. Salicylic acid is sometimes combined with substances, which intentionally stop the growth of HPV (Ex. fluoruracil, podophyllotoxin). However, these products can only be prescribed by a physician. Locally applied kantharidin is successful in treating warts. The mentioned products cannot be applied to inflamed areas, freckles and nevi. The duration of use depends on the type and strength of the agent used. The average length of wart treatment is 3 – 6 weeks.

When treating molluscs, kantharidin, is a very effective substance in dermatology. Kantharidin can only be applied once at the doctor’s office. This product with this substance is not available in Europe. It is produced under the name Cantharone® solution. It is available on the market in Canada and the USA. A blister forms on the application area about eight hours after applying kantharidin, which separates the pathological efflorescence. A doctor’s check-up is recommended after one week. In 90% of molluscs’ cases, a single application of kantharidin suffices. Kathradidin has an interesting history and origin. It is exclusively acquired from the Lytta vesicatoria beetle (Fig. 11). In many other countries, this beetle is known as the “Spanish Fly” and in the past, it was often used as an effective aphrodisiac. From history, it is known that the French nobleman, Marquis de Sade served it to prostitutes during orgies. In lower concentrations, Kantharidin evokes hyperaemia of the genitals and urinary organs. However, using this aphrodisiac is associated with a high risk of overdose and death.

  1. Surgical Therapy

The sharp spoon abrasion is another possible method used for removing warts and molluscs. The procedure is relatively painful. Therefore, it is a good idea to apply lidocain emulgel to the occlusion about one hour before the procedure. It is currently available in 5% and 10% magistralitre concentrations. However, the risk of recurrence is still relatively high at 20–27%.

  1. Physical Therapy

Cryo-therapy (method of freezing) is particularly used in vulgar and plantar warts. The physician uses liquid nitrogen (-196°C) every 2–3 weeks for a period of 6–12 weeks. A physically lower temperature leads to edema, cell necrosis and the subsequent destruction of the warts. It cannot be applied on bleeding warts or other skin formations. Use caution when applying cryo-therapy on children and patients with circulatory disorders. However, cryo-therapy restricts walking, tends to be painful and causes blisters and changes the pigmentation, especially on dark skin. The success rate of treatment is 79–88%. The risk of recurrence is 20–40%.

Photodynamic therapy (PDT) is a method based on the ability of affected cells to increasingly form and catch porphyrine derivatives, like 5-aminolevulic acid (ALA) and metylaminolevulate (MAL). Commercially it is known as Metvix ointment, which is unfortunately currently not available here. The ointment is applied in an occlusion with no access to light (plastic + gauze, possible tin foil) for 3–4 hours and then subject to radiation sources with emissions in the visible light band (around 630nm), resulting in the formation of a single oxygen and other free radicals that damage the affected cells, leading to their destruction. The success rate of the treatment after 1–3 sessions with 20% ALA is 96–100%. The risk of recurrence is 6.3–9.4%. It is used on children, who are more at risk of recurrence and treatment-resistant symptoms.

High-power laser is currently the most effective wart therapy option. A vascular laser (the Nd-YAG laser is the most effective type) is mostly used to remove warts. The procedure is relatively painful, so either 10% lidocain emulgel is applied into an occlusion or local anaesthesia is injected 60 minutes before the procedure. When done correctly, the success rate after 1–3 treatments is 96–100 %. The risk of recurrence is only 5%. This method is not covered by public health care, so the patient has to pay for this procedure out-of-pocket.

A CO2 ablation laser is most suitable for removing condylomata. Condylomata preferentially appear in the ano-genital area, which is very sensitive. The procedure is either done under surface anaesthesia using applied lidocain gel or injected anaesthesia, according to the range and size of the efflorescence. When the procedure is done carefully, it is up to 100% effective. However, the risk of recurrence is high.

  • At our dermatology facility, we have successfully been performing laser therapy on warts and condylomata for ten years now.

Prevention of Viral Skin Diseases

The most effective prevention of viral skin diseases is using sulphate-free antiseptic soaps (for example, Cutosan® Cleansing Gel). Using such soap has a double effect. Firstly, the antiseptic it contains directly eliminates the pathogens. Therefore, we recommend leaving Cutosan® on the skin for at least 1 minute before rinsing it off. Secondly, an equally important effect is that since it doesn’t contain sulphates, the skin’s protective bio-film is not destroyed. The protective layer prevents pathogens from forming colonies on the skin. Common drugstore soaps contain sulphates that destroy this protective bio-film.

Using another person’s towel, socks or shoes is not recommended. We recommend wearing rubber shoes in public areas, like showers, locker rooms and hotels.

Wearing condoms during sexual intercourse mechanically prevents condylomata. Vaccines against HPV viruses pharmaceutically prevent condylomata. These vaccines are about 90% effective.

If you already have warts, do not scratch them and avoid contact with the mouth (ex. nail biting), put a water-resistant band-aid over the wart when going to a swimming pool, start using sulphate-free antiseptic soaps and see your dermatologist as soon as possible.

Summary

Although nowadays, it is possible to buy effective over-the-counter products to treat warts, if the patient is not sure, it is safer to see a physician. Unprofessional treatment may spread warts elsewhere on the body or even to another person. It is always important to keep in mind that the disease is viral, therefore, it is infectious. Caution is especially recommended in children and genital warts. Remember that treatment may be complicated and take a long time.

Literature:

1.National Reference Laboratory for Papilloma Viruses, ÚHKT: http://papillomavirus.cz/kontakt.html.

2.Drozenová H., Warts, Internal Med., 2010, 12 (7 and 8), p. 372-373.

3.IKEM: http://www.ikem.cz/w ww?docid=1010365.

4.Braun-Falco O, Plewig G, Wolf H. Dermatology and Venerology. Osveta, Ltd., Martin 2001.

5.Ditrichová D, and coll. Repetitorium dermatovenerologie. Olomouc, 2002.

6.Štork J, et al. Dermatovenerologie. Prague Galén, 2008.

7.Sosna O, Matouš B. Papilloma Virus Infections in Gynaecology and Obstetrics, tp://www.gyne.cz /clanky/2001/201cl6.htm.

8.Dvořáková K. Differential Diagnostics and Treatment of the Most Common Sexually Transmitted Genital Infections. Urology in Practice, 2008: 9(2): 72–77, http://www.urologiepropraxi.cz/pdfs/uro/2008/02/07.pdf.

9.Poršová M., Porš J, Kolombo I, Pabišta R. Human Papilloma Virus and its Clinical Manifestations, http://www.urologiepropraxi.cz/pdfs/uro/2006/06/02.pdf.

10.Braun-Falco O, Plewig G, Wolf H. Diseases of the Penis and Prepucia Glans, Diseases of the Female Genitals. International Journal of Dermatology 1995, p. 987–1011.

11.Berger R. Therapy of Viral Warts, http://www.solen.cz/pdfs/med/2006/02/10.pdf.

12.Tachezy, R., Hamšíková, E., Roubalová, K., Suchánková, A. Viral Genital Infections.

13.Velčevský P., A News Perspective on the Treatment of Condylomates, http://zdravi.e15.cz/clanek/priloha-lekarske-listy/novy-pohled-na-lecbu-kondylomat-455347

14.Sklenář Z.,et al. Master Recipe in Dermatology

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