List of Abbreviations
HIV – human immunodeficiency virus
HPV – human papillomavirus
DNA – deoxyribonucleic acid
ICD – International Classification of Diseases
Terms and Definitions
Viral warts (verrucae) are a benign proliferative skin disease caused by human papillomaviruses (HPV) and characterized by the appearance of epidermal nodules with reactive changes in the dermis.
Human papillomavirus (HPV) is a group of DNA-containing viruses of the family Papavaviridae. It has been established that certain HPV types can infect specific topographic regions of the skin, causing stereotyped skin lesions.
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Viral warts (verrucae) are a benign proliferative skin disease associated with human papillomaviruses (HPV) and characterized by the appearance of epidermal nodules with reactive changes in the dermis.
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
The causative agent of the disease is human papillomaviruses (HPV), a group of DNA-containing viruses of the Papavaviridae family. It has been established that certain types of HPV can infect specific topographic areas of the skin, causing stereotyped skin lesions. Some types of HPV are associated with the risk of developing epithelial malignancies; depending on their carcinogenic potential, they are divided into low- and high-oncogenic-risk types. Clinical and histological features of HPV infection vary depending on individual susceptibility (e.g., in immunocompromised patients), the site of the lesion, and the HPV type. The histological features of HPV infection are very easily identified in sections stained with hematoxylin and eosin. The most frequent cause of viral warts is HPV types 1, 2, 3, and 4. Less commonly, HPV 7, 10, and HPV types 26-29 are detected [1,2].
Transmission of the virus can occur via contact and household routes, through auto- or heteroinoculation at sites of epithelial damage. The risk of HPV infection depends on a number of factors, such as the location of the lesions, quantitative HPV indicators (viral load), the degree and nature of contact with the infection, and the state of general and local immune status. Infection is promoted by the presence of microtrauma and inflammatory processes of the skin and mucous membranes.
In the cells of the basal layer, the virus can persist for a long time in a latent state. In the presence of favorable factors, the process of HPV replication in the epithelium begins, which leads to impaired cell differentiation and the formation of morphologically altered tissues.
Human papillomaviruses exhibit tissue specificity, which is the ability of certain HPV types to affect topographically specific areas. Typically, HPV types 1, 2, and 4 are detected in plantar warts; HPV type 60 in cystic variants of warts. HPV types 1, 2, 4, and more rarely HPV types 26-29 are found in common warts, whereas HPV types 75-77 are detected in immunosuppressed patients; HPV types 3 and 10 are found in flat warts [3].
1.3 Epidemiology of the Disease or Condition
Viral warts are one of the most widespread infectious skin pathologies, tending toward a prolonged, recurrent course. Clinical manifestations of cutaneous papillomavirus infection are observed in 3-9% of children and adolescents and in 28-30% of adults. No reliable correlation has been observed between the incidence of this pathology and race or gender. Approximately 38-42% of people are carriers of HPV on visibly healthy skin [3].
1.4 Features of Coding the Disease or Condition
B07 – Viral warts.
1.5 Classification of the disease or condition
According to the 2018 WHO Classification of Skin Tumors [2], the following are distinguished:
Common warts.
- Filiform warts
Plantar (palmoplantar) warts.
- Cystic warts
Flat warts.
1.6 Clinical presentation of the disease or condition
Common warts: multiple painless papillomatous papules 0.2-0.8 cm in diameter, with surface hyperkeratosis, localized predominantly on the skin of the hands. Filiform warts are a variant of common warts localized on the facial skin in the perioral and periorbital areas, and the nasal vestibule, characterized by thin horny growths.
Palmoplantar warts: dense, often painful rounded papules localized on the skin of the soles of the feet and/or the palmar surface of the hands, projecting slightly above the level of the surrounding skin, with a granular surface covered by hyperkeratotic layers; black-brown dots—thrombosed capillaries of hypertrorophied dermal papillae—are frequently observed in the center. Warts show a tendency toward peripheral growth and coalescence, with wart size varying from 2-4 mm to 1-3 cm. Cystic warts: formations in the form of a soft node with hyperkeratosis and fissures on the surface, upon opening of which a white-yellow cheesy content is released; localized in areas of greatest pressure from the bony structures of the foot.
Flat warts: small multiple papules 2-4 mm in diameter, hyperpigmented or skin-colored, flat in shape, localized predominantly on the skin of the face, backs of the hands, and forearms.
2. Diagnostics, medical indications and contraindications for diagnostic methods
Criteria for establishing the diagnosis/condition:
1) Anamnestic data
2) Physical examination data and, in some cases, dermatoscopic examination data
3) Results of vital morphological examination of biopsy material when differential diagnosis with other skin diseases and/or skin neoplasms is necessary.
It is recommended to collect complaints and anamnesis in all patients in order to identify risk factors and factors that may influence the choice of treatment tactics and secondary prevention [2].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
2.1 Complaints and Anamnesis
The duration of the disease can vary from several weeks to years. The nature of complaints depends on the affected area, the size of the formations, and their localization. Patients may complain of:
the presence of single or multiple skin neoplasms;
pain upon compression in the area of the warts.
2.2 Physical Examination
Physical examination data are described in the "Clinical Presentation" section.
2.3 Laboratory Diagnostics
It is recommended to perform a morphological examination of biopsy (surgical) material when differential diagnosis with other skin and/or mucous membrane diseases is necessary [2].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
2.4 Instrumental Diagnostics
It is recommended for adults and children to perform skin examination under magnification (dermatoscopy) when differential diagnosis is necessary [4, 5].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: dermatoscopic examination of warts reveals papillary lines, a mosaic pattern, a nodular pattern; a vascular pattern and its combinations (glomerular, hairpin, dotted) [5].
2.5 Other Procedures
It is recommended in cases of recurrent and/or progressive course (dissemination): to test for the levels of class M and G antibodies (IgM, IgG) to human immunodeficiency virus HIV-1/2 and p24 antigen (Human immunodeficiency virus HIV 1/2 + Agp24) in the blood [6].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: chronic and recurrent viral skin infections are an indication for HIV testing [6].
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
3.1 Conservative Treatment
It is recommended to use physical methods of destruction that do not cause toxic and local adverse reactions for the treatment of children and adults [7, 8].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: The leading approach in the treatment of viral warts is destructive therapy. This technique is a priority despite the fact that its efficacy is 50-80%, and the probability of recurrence after tissue regeneration remains quite high. A high risk of recurrence is noted in widespread warts (with an area of more than 2 cm2), long-standing warts, and a progressive course of the disease—the appearance of new elements and growth of existing ones. When choosing a therapy method, the localization and area of the affected lesions must be taken into account.
It is recommended for the treatment of children and adults to achieve reduction of clinical manifestations of viral warts as a result of the treatment performed [7, 8].
For adults, Grade of Recommendation B (Level of Evidence – 3)
For children, Grade of Recommendation C (Level of Evidence – 5)
It is recommended for the treatment of children and adults to perform electrocoagulation of viral warts with the aim of reducing clinical manifestations [7, 8].
For adults, Grade of Recommendation B (Level of Evidence – 3)
For children, Grade of Recommendation C (Level of Evidence – 5)
Comments: Viral warts are removed layer by layer using the electrocoagulation method. Electrosurgical devices registered in the Russian Federation and approved for medical use are used. Destruction is carried out under local infiltration anesthesia. Hyperkeratotic layers and the wart stroma are subject to destruction, including the epidermal part and reactively altered deep layers of the dermis. Tissue detritus/scab is removed with a gauze swab moistened with an aqueous solution of chlorhexidine**. Areas of lateral hypercoagulation of tissues are excised with scissors. The patient treats the wound surface with solutions belonging to the drug group "Antiseptics and disinfectants" D08A; trauma to the wound, contact with water, and independent removal of the scab/crust until the healing process is complete should be avoided.
It is recommended for the treatment of adults and children to perform laser destruction of skin tissue with the aim of reducing clinical manifestations of warts [7, 8].
For adults, Grade of Recommendation B (Level of Evidence – 3)
For children, Grade of Recommendation C (Level of Evidence – 5)
Comments: Semiconductor (diode), carbon dioxide, and erbium lasers are used. Warts are removed layer by layer. Laser destruction should be performed in a pulsed quantum radiation generation mode (to prevent deep coagulation necrosis). Laser devices registered in the Russian Federation and approved for medical use are used. Destruction is carried out under local infiltration anesthesia. Hyperkeratotic layers and the wart stroma are subject to destruction, including the epidermal part and reactively altered deep layers of the dermis. Depending on the type of laser device, treatment is performed in a contact/non-contact manner with scanning movements. Tissue detritus/scab is removed with a gauze swab moistened with an aqueous solution of chlorhexidine**. Areas of lateral hypercoagulation of tissues are excised with scissors [7, 10, 11]. The patient treats the wound surface with solutions belonging to the drug group "Antiseptics and disinfectants" D08A; trauma to the wound, contact with water, and independent removal of the scab/crust until the healing process is complete should be avoided.
It is recommended for the treatment of adults and children to perform high-frequency radiowave destruction of viral warts with the aim of reducing clinical manifestations [12, 13].
Level of Evidence AGrade of Evidence 2Level of Recommendations A (Grade of Evidence – 2)
Comments: High-frequency radiowave surgery devices registered in the Russian Federation and approved for medical use are used. Destruction is performed under local infiltration anesthesia. Hyperkeratotic layers and the wart stroma are subject to destruction, including the epidermal part and reactive-altered deep layers of the dermis. The procedure is performed using a contact method. Tissue detritus/eschar is removed with a gauze swab moistened with an aqueous chlorhexidine** solution. Areas of lateral hypercoagulation of tissues are excised with scissors. The patient treats the wound surface with solutions belonging to the drug group "Antiseptics and disinfectants" D08A; trauma to the wound, contact with water, and independent removal of the eschar/crust should be avoided until the healing process is complete [12-13].
It is not recommended to use laser devices implementing the principle of selective photothermolysis (neodymium laser device, pulsed dye laser) for the destruction of viral warts [14-19].
For adult patients, Level of recommendation B (reliability level of evidence – 2)
For children, Level of recommendation C (reliability level of evidence – 4)
Comments: The pulsed dye laser selectively destroys dilated capillaries of the dermal papillae. In randomized clinical trials of 37 patients, no significant differences were found between treatment with the pulsed dye laser and placebo at 14 weeks of treatment.
It is recommended to perform cryodestruction of viral warts in order to reduce clinical manifestations [20-24].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
Comments: Freezing of the pathological formation is carried out using liquid nitrogen. Instrumental and manual cryodestruction (the "cotton bud" method – a cotton swab on a wooden applicator) are used. Superficial hyperkeratotic layers must be removed beforehand, especially when treating plantar warts. The cooled cryoprobe is placed perpendicular to the skin surface and pressed firmly against it. The exposure time is 1-5 min, until a 1-2 mm cryo-rim appears. For the destruction of plane and common warts, a single-cycle method is used; for plantar warts, the "Olympic rings" method and a double-cycle method are used. Repeated cryotherapy is performed in 7-14 days; the total duration of treatment should not exceed 4 months [20].
Recommended for adults for the removal of viral warts and prevention of recurrence (both as monotherapy and in combination with destructive methods):
#imiquimod, 5% cream for external use on the lesion site in a thin layer [30, 31, 32].
GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)
Comments: The cream is applied in a thin layer to viral warts (including common, plantar, flat, and periungual warts) once daily before bedtime (for 6–10 hours) 3 times a week (every other day). In the morning, the cream is washed off with warm water and soap. The affected area in adults is pre-treated with a keratolytic agent. The use of an excessive amount or a longer contact of the medicinal product with the skin may cause a pronounced local reaction in the form of redness, irritation, induration, erosions, vesicles, or hypopigmentation [33, 34].
Recommended for children (contraindication – infancy) and adult patients (over 18 years of age) with contraindications to and/or refusal of direct physical destruction or the impossibility of its performance, destruction with salicylic acid + lactic acid + polidocanol preparation [24].
CGR CLEL 5Level of Clinical Guidance: C (Level of Evidence: 5).
Comments: the preparation is used externally, 1 drop 1–2 times a day. The maximum daily dose for adults is 2 g (calculated as salicylic acid), which corresponds to 10 ml of the preparation; for children, it is 0.2 g (1 ml of the preparation). The course of treatment when using the preparation in maximum daily doses is no more than 1 week. When treating children, simultaneous treatment of multiple skin areas should be avoided.
Recommended for adult patients (over 18 years of age) in case of contraindications to and/or refusal of direct destruction, the use of ferezole (solution for external use) [3, 25].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: Ferezol is intended for external use only. The preparation is applied precisely to the treated area using a small, thin wooden applicator, avoiding contact with adjacent healthy skin and mucous membranes. For filiform warts, Ferezol is applied once. Small warts (2-3 mm in size) are treated with the preparation 3-4 times, allowing time for the applied liquid to dry between applications.
Before using ferezole on hands with a dense keratinized surface or plantar warts, it is necessary to remove the cornified layers from their surface. For this purpose, keratolytic preparations for the treatment of calluses and warts are applied under occlusion for several hours. Afterwards, the skin is soaked in hot water with the addition of soap and soda for 10–15 minutes, and the cornified layers are removed (cut off with manicure scissors or nippers). Ferezole is applied to the dried skin several times, taking 3–4 minute breaks for the preparation to dry. Warts on the hands and soles are treated with ferezole solution 7–10 times at intervals of 3–4 minutes. If repeated application of the preparation is necessary, to avoid burns to the surrounding skin, it is advisable to carry out the procedures in accordance with the instructions.
Recommended for widespread warts, long-term persistence of warts, progressive and recurrent course of the disease, intralesional (intradermal) administration of #interferon alfa-2b** in adult patients at high risk of viral wart recurrence [3, 26].
GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)
Comments: the prescribing information for #interferon alfa-2b** does not include an indication for the treatment of viral warts. Intralesional (intradermal) administration of #interferon alfa-2b** may be used as a standalone treatment method or as part of combination therapy for viral warts (prior to destructive therapy). Intralesional (intradermal) injections of the drug at a dose of 2,000,000 IU every other day, with a treatment course totaling 18,000,000.
Recommended in adults and children (aged 3 and older) is immunotherapy with inosine pranobex for widespread warts, prolonged wart persistence, progressive and recurrent course [27].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: For papillomavirus infection, adults are prescribed 2 tablets of 500 mg 3 times/day; children are prescribed 1/2 tablet per 5 kg of body weight/day in 3–4 divided doses for 14–28 days as monotherapy.
3.1 Other treatment
Recommended for electrosurgical, laser (diode and carbon dioxide laser devices), and radiowave destruction of viral warts: performing infiltration anesthesia, with a preliminary assessment of the allergic history, using local anesthetics: 2% lidocaine** solution; in some cases, it is acceptable to use 0.5% procaine** solution (for children over 12 years of age) [28].
GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)
Comments: for local anesthesia, techniques of bolus intradermal or subcutaneous administration of the drug are used, with retrograde or antegrade administration of the local anesthetic. The volume of the administered drug is determined by achieving the required level of pain relief and the allowable dosage of the anesthetic, in accordance with the instructions for medical use of the specific medicinal product.
Diet therapy is not used.
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Rehabilitation is not carried out.
5. Prevention and Dispensary Observation
Recommended: avoidance of contact with rashes as primary prevention of infection and development of warts [29].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: primary prevention of viral warts includes observing personal hygiene rules when visiting public places—swimming pools, fitness and sports centers; not walking barefoot; wearing footwear made of materials that can be disinfected; and ensuring that exercise equipment contact surfaces are treated with appropriate solutions.
6. Organization of Medical Care
Treatment is carried out on an outpatient basis in a dermatovenerological medical facility.
Indications for hospitalization in a medical organization: None
7. Additional Information
Due to the lack of specific prevention methods, etiotropic treatments, and the possibility of viral persistence in epithelial cells of the skin and mucous membranes in a latent form, there is a risk of disease relapse after destructive therapy.
When performing destructive treatment methods, the viral wart is destroyed with damage to epithelial tissues, which requires maintaining antiseptic conditions during the healing period.
Non-compliance with medical prescriptions during the healing period of wounds after destructive therapy and irregular use of prescribed products can lead to wound infection with the development of an inflammatory process, an increase in healing time, and tissue scarring.
Criteria for Evaluating the Quality of Medical Care
№ | Quality criteria | Performance assessment (yes/no) |
|---|---|---|
1. | Destruction of viral warts was performed | Yes/no |
2. | Reduction of clinical manifestations of viral warts as a result of the treatment administered | Yes/no |
References
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Appendix A1. Working Group Composition
Kubanov Alexey Alekseevich – Academician of the Russian Academy of Sciences, President of the Russian Society of Dermatovenereologists and Cosmetologists (RODVK), Director of the State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health;
Dubensky Vladislav Valerievich – Candidate of Medical Sciences, Member of the Russian Society of Dermatovenereologists and Cosmetologists;
Dubensky Valeriy Viktorovich – Doctor of Medical Sciences, Member of the Russian Society of Dermatovenereologists and Cosmetologists;
Nechaeva Irina Anatolyevna – Candidate of Medical Sciences, Member of the Russian Society of Dermatovenereologists and Cosmetologists;
Stepanova Olga Viktorovna – Member of the Russian Society of Dermatovenereologists and Cosmetologists.
Conflict of interest: the authors declare no conflict of interest.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience for these clinical guidelines:
Dermatovenerologists
General practitioners
Pediatricians
General practitioners
Residents and trainees of continuing professional education programs in the specified specialties.
Table 1. Level of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)
LoE | Definition |
|---|---|
1 | Systematic reviews of studies with reference standard control or systematic reviews of randomized controlled trials with meta-analysis |
2 | Individual studies with reference standard control or individual randomized controlled trials and systematic reviews of studies of any design, except randomized controlled trials, with meta-analysis |
3 | Studies without consecutive reference standard control or studies with a reference standard not independent of the test method, or non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case report |
5 | Only justification of mechanism of action or expert opinion is available |
Table 2. Level of Evidence (LoE) grading scale for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)
LoE | Definitions |
|---|---|
1 | Systematic review of RCTs with meta-analysis |
2 | Individual RCTs and systematic reviews of studies of any design except RCTs, with meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available |
Table 3. Grade of Recommendation (GoR) scale for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)
GoR | Definition |
|---|---|
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
Procedure for updating clinical guidelines.
The clinical guidelines update mechanism provides for their systematic revision—at least once every three years, as well as upon the emergence of new evidence-based data regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.
Appendix A3. Reference Materials
Current instructions for medicinal products mentioned in these clinical guidelines can be found on the website http://grls.rosminzdrav.ru.
Appendix B. Physician Action Algorithms
Appendix C. Patient Information
Infection of the skin and mucous membranes with HPV in the presence of viral warts occurs via contact transmission, as well as through auto- and heteroinoculation.
Treatment of viral warts must be carried out under medical supervision.
Due to the lack of specific prevention methods, etiotropic treatments, and the possibility of viral persistence in epithelial cells of the skin and mucous membranes in a latent form, there is a risk of disease relapse after destructive therapy.
When performing destructive treatment methods, the viral wart is destroyed with damage to epithelial tissues, which requires maintaining antiseptic conditions during the healing period.
Non-compliance with medical prescriptions during the healing period of wounds after destructive therapy and irregular use of prescribed products can lead to wound infection with the development of an inflammatory process, an increase in healing time, and tissue scarring.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Not applicable.