Method for treatment of actinic keratosis

Abstract

FIELD: dermatology; oncology.SUBSTANCE: used to treat actinic keratosis. A 4-stage laser photothermal treatment is performed using ablative and non-ablative lasers in a planar and fractional technique. In this case, photothermal exposure is carried out depending on the degree of epidermal dysplasia. At KIN I 10 min: Nd:YAG 1064 nm, 9 mm, short pulse 0.6-1.6 ms, fluence 10-20 J / cm², 6 Hz, 6 passes; 5 min: Er:YAG 2940 nm, 7 mm, MSP 100 μs, 1.0 J / cm², 20 Hz, stratum corneum ablation; 5 min: Er:YAG fractional SMOOTH, 16 J, 3.3 Hz, 1 pass; 15 min: Nd:YAG PIANO, 9 mm, 4 s, 180-200 J, 4 passes. At KIN II 10 min: Nd:YAG 1064 nm, short pulse 1.0-1.6 ms, 15-25 J / cm², 5 Hz, 6 passes; 5 min: Er:YAG MSP 100 μs, 1.5 J / cm², 20 Hz; 5 min: Er:YAG SMOOTH, 20 J, 3.3 Hz; 15 min: Nd:YAG PIANO, 300 J. At KIN III 10 min: Nd:YAG short pulse 1.0-1.6 ms, 25-30 J / cm², 3 Hz, 6 passes; 5 min: Er:YAG SP 300 μs, 2.4 J / cm² (75% ablation, 25% heating); 5 min: Er:YAG SMOOTH, 24 J; 15 min: Nd:YAG PIANO, 5 s, 350 J.EFFECT: pronounced result after the first procedure, reduction in rehabilitation time and prolongation of the remission stage of the disease, due to the combined use of laser photothermal exposure with ablative and non-ablative lasers in a planar and fractional technique, with the most optimal modes that ensure selective photodestruction of atypical keratinocytes, preventive ablation of dysplastic foci, stimulation of neocollagenesis and re-epithelialization of the epidermis.1 cl, 3 dwg, 3 ex

Description

[0001] The invention relates to medicine, namely to dermatology, oncology and can be used to treat actinic keratosis (AK).

[0002] In recent decades, there has been a rapid increase in the incidence of actinic keratosis and non-melanoma skin cancer. According to statistical studies, the average incidence rates in patients over 40 years of age (mean age 72 years) are 49% (46-52%) for men and 28% (26-31%) for women.

[0003] Actinic keratosis is a dysplastic proliferation of keratinocytes with the potential for malignant transformation. It typically occurs on sun-exposed skin and is characterized by focal intraepidermal dysplasia of varying severity (see Schmitt JW, Miot HA. Actinic keratosis: a clinical and epidemiological review. An Bras Dermatol. 2012;87:425-434. doi: 10.1590 / s0365-05962012000300012; see Berman B, Cockerell KJ. Pathobiology of actinic keratosis: ultraviolet-dependent keratinocyte proliferation. J Am Acad Dermatol. 2013;68:S10-S19. doi: 10.1016 / j.jaad.2012.09.053; see Riegel DS, Stein Gold LF. Importance of early diagnosis and treatment of actinic keratosis. J Am Acad Dermatol. 2013;68:S20-S27. doi: 10.1016 / j.jaad.2012.10.001). Currently, the fact of possible transformation of AK into squamous cell carcinoma in the absence of treatment and continued active insolation is generally recognized (see Alam M. / / Adv. Stud. Med. - 2006. - Vol. 6, No. 8 A.- P. 785-790). Several risk factors contribute to the progression of AK. The most significant constitutional risk factors for AK include older age, male gender, fair skin, immunosuppression, and a history of AK. In addition, chronic sun exposure is the most significant environmental factor contributing to the development of AK. Molecular mechanisms are involved in the development of squamous cell carcinoma, including genomic instability caused by mutations in TP53 and other genes that are provoked by ultraviolet radiation. The molecular genetic basis for the development of malignant skin neoplasms involves multiple intracellular signaling pathways. Tumor initiation and progression, leading to the proliferation of abnormal cells, are influenced by genetics, environmental factors, acute and chronic exposures, nutritional characteristics, trauma, and many other factors. Angiogenesis and metastasis depend on factors such as age and immunological status.New data confirm the role of chronic inflammation in skin carcinogenesis, mediated by changes in the expression and mutations in the NF-κB, STAT3 and HIF-1α genes (see Genetic and epigenetic abnormalities in malignant neoplasms of the skin: basal cell and squamous cell carcinoma. Sustretov V.A., Kutilin D.S., Maksimov A.Yu., Shatova Yu.S., Kasyanenko V.N. https: / / science-education.ru / article / view?id=31793).

[0004] Histologically, AK is characterized by foci of hyperkeratosis and parakeratosis, under which dysplastic changes in the epidermis are observed in the form of disorganization of cellular layers, nuclear polymorphism, and proliferation of atypical keratinocytes. Keratinocyte dysplasia has varying degrees of severity and prevalence. In some cases, it is expressed only in the basal and parabasal layers, while in others, it occurs throughout the entire epidermis, mimicking Bowen's disease. In this regard, three degrees of epidermal dysplasia in AK are distinguished: mild - KIN I, moderate - KIN II, and severe (KIN III) (see Cockerell C.J., Wharton JR / / J. Drugs Dermatol. - 2005. - Vol. 4. - P. 462-467). The progression of AC towards squamous cell carcinoma is a stepwise process, and in most cases (over 30%) the precursor to squamous cell carcinoma was stage III AC (KIN III).

[0005] There are several main types of AK: hypertrophic, lichenoid, atrophic, acantholytic, pigmented, bowenoid and proliferative, between which there may be transitions and combinations (see Cockerell C.J., Wharton J.R. / / J. Drugs Dermatol. - 2005. - Vol. 4. - P. 462-467. Lever's Histopathology of the Skin. - 9th Ed. - Philadelphia: Lippincott Williams and Wilkins; 2005). Atypical pathomorphological variants of AK include bullous and pagetoid types (see Landry D., Stinson WA, Perkins DG et al. / / Histopathology. - 2002. - Vol. 41. - P. 331-336. Sarma DP, Sharma P. / / Inter. J. Dermatol. - 2006. - Vol. 4, N 1. http: / / www.scribd.com / doc / 22920860 / Dermatopathology).

[0006] Diagnosis of lesions is based on clinical and dermatoscopic examination, but in some cases, histopathological analysis may be required. Unlike melanoma, there are currently no uniform diagnostic algorithms for AK. Symptoms characteristic of AK, squamous cell carcinoma, and Bowen's disease are based solely on clinical case series.

[0007] Additional diagnostic methods include:

[0008] 1. Immunohistochemical examination. Not used in routine diagnosis of AK, but can be helpful in difficult cases, such as when differential diagnosis is necessary.

[0009] 4. Optical coherence tomography. This is a new, non-invasive technique that allows for real-time assessment of structures located at a depth of 1-2 mm.

[0010] 5. Confocal microscopy. A non-invasive in vivo diagnostic method that improves the accuracy of skin neoplasm identification. It operates using a specialized optical system that captures light in the infrared spectrum. This creates conditions for visualizing the structures of the epidermis and upper dermis.

[0011] A well-known article (see Dianzani, Caterina & Conforti, Claudio & Giuffrida, Roberta & Corneli, Paola & di Meo, Nicola & Farinazzo, Eleonora & Moret, Anna & Rizzi, Giovanni & Zalaudek, Iris. (2020). Current therapies for actinic keratosis. International Journal of Dermatology. 59. 10.1111 / ijd. 14767. https: / / www.researchgate.net / publication / 339013846_Current_therapies_for_actinic_keratosis) provides an overview of the known treatments for actinic keratosis such as cryotherapy, laser therapy, surgery, curettage, field-directed therapy. Available laser therapies include lasers (Co2 and erbium:yttrium aluminum garnet), which remove the superficial layers of skin, removing the epidermis and superficial dermis, or non-ablative fractional laser systems (erbium:glass lasers), which vaporize or coagulate tiny columns of skin, leaving the surrounding skin intact.The treatment response rate is approximately 90%, while the lesion recurrence rate after 6 months is approximately 10-15%. Potential side effects include pain, inflammation, pigmentation changes, and delayed skin healing. Both ablative and fractional lasers can be combined with other treatments, such as topical agents, to enhance treatment efficacy. A randomized trial comparing cryotherapy and CO2 laser ablation for the treatment of isolated actinic keratoses of the face and scalp shows that at 3 months, complete response rates are similar for both treatment methods (71.6% for cryotherapy versus 65.3% for laser ablation). A higher proportion of patients remain stable for a year with cryotherapy treatment (66.8% for cryotherapy versus 37% for laser ablation).

[0012] Because actinic keratosis is potentially associated with malignant transformation and because it is impossible to predict which lesions will undergo it, all lesions should be treated (see Schmitt JW, Miot HA. Actinic keratosis: a clinical and epidemiological review. An Bras Dermatol. 2012;87:425-434. doi: 10.1590 / s0365-05962012000300012; see Riegel DS, Stein Gold LF. Importance of early diagnosis and treatment of actinic keratosis. J Am Acad Dermatol. 2013;68:S20-S27. doi: 10.1016 / j.jaad.2012.10.001; see Cohen JL. Treatment of actinic keratosis as a key component of preventive strategies for non-melanoma skin cancer. J Clin Aesthet Dermatol. 2010;3:39-44; see Ianez M, Fleury LFF, Miot HA, Bagatin E. Retinoids for the prevention and treatment of actinic keratosis. An Bras Dermatol. 2013;88:585-593. doi: 10.1590 / abd1806-4841.20131803).When treating patients with actinic keratosis, it is necessary to regularly examine the skin of the entire body, assess the presence and treatment of foci of malignancy, conduct targeted ablative treatments for hyperkeratotic lesions and similar diseases, inform patients about the chronic course of actinic keratosis, the need for photoprotection and frequent procedures, and also regularly self-examine the patient's skin.

[0013] In 1953, Slaughter proposed the theory of cancerization fields. He was the first to suggest that "cancer does not arise as an isolated cellular phenomenon, but is an anaplastic tendency involving many cells at once..." (see Slaughter D., Southwick H., Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin / / Cancer. - 1953; 6: 963-8). In the case of multiple foci of actinic keratosis within a single anatomical area, one can speak of the presence of a "cancerization field", when genetically similarly altered cells exist in the surrounding visually uninvolved tissues, which can give rise to the growth of other similar neoplasms (see https: / / justdemia.ru / actinic-keratosis). As a rule, clinically manifest foci of AK are associated with a peripheral zone of subclinical manifestations of the disease, the “cancerization field,” which requires treatment of the entire anatomical area, and not just obvious symptoms.

[0014] Currently, the treatment of actinic keratosis includes several approaches. These include ablative or surgical methods and topical therapy. The use of these methods, either simultaneously or sequentially, is common in the management of these patients (see De Berker D, MacGregor JM, Mohd Mustapa MF, Exton LS, Hughes BR. British Association of Dermatologists guidelines for the treatment of patients with actinic keratosis 2017. Br J Dermatol. 2017;176:20-43. doi: 10.1111 / bjd.15107). The choice of treatment depends on the clinical presentation, location, number and extent of lesions. Therefore, treatment of AK should be individualized according to the needs of each patient.

[0015] A method for choosing a treatment strategy for actinic keratosis is known from patent sources (see patent for invention RU 2495628 C1, published 20.10.2013, Bulletin No. 29). The method involves identifying foci of the disease, followed by a U3 examination and dermal analysis. If a hypoechoic zone is present in the dermis, occupying 5% to 30% of the total dermal thickness, liquid nitrogen applications with a textile tip are performed. If a hypoechoic zone is detected occupying 30% to 70% of the total dermal thickness, liquid nitrogen applications with a copper tip or photodynamic therapy with topical application of a photosensitizer are performed. When a hypoechoic zone is detected, occupying from 70% to the entire thickness of the dermis, photodynamic therapy is performed with topical application of a photosensitizer.This method allows for the most accurate treatment strategy for this condition based not only on the clinical manifestations of the disease but also by taking into account the proliferative capacity of cells, eliminating the need for tissue biopsies. However, cryodestruction cannot control the depth of tissue damage. Consequently, excessive exposure to the cold element can cause a burn leading to scarring, while insufficient exposure can lead to relapse. Furthermore, the recovery period is longer compared to other methods.

[0016] A treatment strategy for actinic keratosis is known to involve a clinical examination. If isolated, small lesions are detected, electrocoagulation or cryodestruction is recommended. For multiple lesions, 5% fluorouracil ointment applications twice daily for 3-4 weeks are recommended. For solar keratosis accompanied by peeling and hyperemia, 0.05-0.1% tretinoin cream is used once a day for 2-4 months, sometimes in combination with cryotherapy or applications of 5% fluorouracil cream (see Molochkov V.A., Shabalin V.N., Kryazheva S.S., Romanenko G.F. Handbook of Gerontological Dermatology, MONIKI, Moscow 2004, pp. 71-72).However, despite the simplicity of the technology (treatment with topical agents requires no physician training, is low-cost, and lacks sophisticated equipment), the recurrence rate is higher than other methods, and in the short term. Electroexcision, while effective in removing solitary lesions, leaves the entire cancerized area intact, which inevitably leads to recurrence in areas of skin adjacent to those treated with the coagulator. Recurrences, in turn, require repeat procedures, leading to multiple scarring.

[0017] The invention "Methods for treating and / or preventing actinic keratosis" discloses methods for treating actinic keratosis, comprising administering a therapeutically effective amount of KX-01 at a dose of about 0.025 mg / cm 2 up to approximately 0.1 mg / cm 2 or at a dose of approximately 0.1 mg / cm 2 up to approximately 10 mg / cm 2, where the term "approximately" refers to a dose of ±5%. The invention allows for the effective treatment of actinic keratosis (see patent RU 2805929 C2, published October 24, 2023, Bulletin No. 30). However, the effectiveness of this treatment was evaluated in patients with mild forms of actinic keratosis. Specifically, patients with clinically atypical and / or rapidly changing AK lesions in the treatment area, such as hypertrophic, hyperkeratotic, or cutaneous horn, were excluded from the study. This may be due to the drug's insufficient penetration into thick lesions containing a large number of horny scales, which limits the method's applicability.

[0018] Also, in the open literature, there is a publication in which the authors aimed to determine the optimal laser parameters for the treatment of various skin diseases. The Erbium:YAG laser is of particular interest in dermatology and cosmetic surgery, as it enables ablative tissue treatment and dissection with surgical precision while minimizing thermal damage due to the Er:YAG wavelength (2940 nm), which is well absorbed by liquid water in tissue. Sixty-four patients were treated for benign skin diseases: seborrheic warts, flat warts, milia, xanthelasma of the eyelids, hidradenoma, chloasma, age spots, epidermal nevi, actinic keratosis, fibroepithelial papillomas, and scars. The affected areas were irradiated with single laser pulses of 100-1000 mJ energy, a repetition rate of 2-10 Hz, and a spot diameter of 2-8 mm. The epidermis was effectively removed layer by layer.Ablation required energy densities greater than 2.5 J / cm. 2 When bleeding occurred, the hemostatic effect was achieved by irradiating the bleeding surface with several pulses of an Er:YAG laser with a lower power density (0.5-1.5 J / cm 2). Healing was successful, without visible scars. It was found that the Er:YAG laser with properly selected parameters is a tool for tissue ablation and / or coagulation. It was found that the Er:YAG laser is an ideal option for the effective treatment of benign skin diseases (see Use of Er:YAG laser for benign skin disorders. Dmovsek-Olup B, Vedlin B. Lasers Surg Med. 1997;21(l):13-9. doi: 10.1002 / (sici)1096-9101(1997)21:1<13::aid-lsm3>3.0.co;2-0.PMID: 9228635). However, despite its high ability to destroy dysplastic tissue, this method had no effect on factors involved in the development of actinic keratosis, such as chronic inflammation in the dermis and elastosis, or on vascular congestion in the papillary and reticular dermis. It also had no stimulating effect on the renewal of fibroblast cells in the underlying tissue.

[0019] The task set before the authors is to achieve a pronounced clinical effect of the treatment of actinic keratosis in one procedure, including four successive stages, to reduce the rehabilitation period, and to increase the relapse-free period.

[0020] The technical result is the development of a method that allows, depending on the degree of epidermal dysplasia of actinic keratosis, to improve its treatment.

[0021] The technical result is achieved by the fact that, depending on the degree of epidermal dysplasia, a 4-stage photothermal effect is carried out with an ablative and non-ablative laser in a planar and fractional technique as follows: with KIN I, at the first stage, for 10 minutes, telangiectatically altered vessels are treated, dermal matrix remodeling is carried out using the following setup: Nd: YAG laser 1064 nm, 9 mm spot, microsecond pulse duration mode short pulse 0.6 - 1.0 - 1.6 ms, fluence 10 J per cm 2for 0.6 ms, 15 J / cm 2 for 1.0 ms, 20 J / cm 2 for 1.6 ms, pulse frequency of 6 Hz, 6 passes are carried out - 2 passes at one pulse duration, blowing 6 units, after which the second stage is immediately carried out for 5 minutes, in which excess stratum corneum and pathologically altered epidermocytes are removed, using the installation: Er: YAG laser 2940 nm, 7 mm spot, MSP mode 100 μs - 100% of the energy is spent on ablation, Fluence 1.0 J per cm 2, frequency 20 Hz, after which the third stage is immediately carried out for 5 minutes using the following installation: Er: YAG 2940 nm laser, SMOOTH fractional mode - a packaged pulse consisting of 6 sub-pulses of 750 microseconds each, 16 J, 3.3 Hz, 1 pass, which reduces the area of ​​the dermal flap, activates the stem cells of the dermis and hypodermis, after which the fourth stage is immediately carried out for 15 minutes, during which deep heating is carried out to the hypodermis, using the following installation: Nd: YAG 1064 nm laser, PIANO mode, 9 mm, 4 sec, 180-200 J, 4 passes; In KIN II, the first stage involves treating telangiectatically altered vessels and remodeling the dermal matrix for 10 minutes using the following setup: Nd: YAG laser 1064 nm, 9 mm spot, short pulse mode 1.0 - 1.6 ms, fluence 15 J / cm 2 for 1.0 ms, frequency Hz, and 25 J per cm 2for 1.6 ms, frequency 5 Hz, 6 passes are carried out - 3 passes at one pulse duration, blowing 7 units, after which the second stage is immediately carried out for 5 minutes, in which excess stratum corneum and pathologically altered epidermocytes are removed, using the installation: Er: YAG laser 2940 nm, 7 mm spot, MSP mode 100 μs, Fluence 1.5 J per cm 2, frequency 20 Hz, after which the third stage is immediately carried out for 5 minutes using the following device: Er: YAG laser 2940 nm, fractional SMOOTH mode, 20 J, 3.3 Hz, 1 pass to reduce the area of ​​the dermal flap, activate the stem cells of the dermis and hypodermis, after which the fourth stage is immediately carried out for 15 minutes, during which deep heating is carried out to the hypodermis, using the following device: Nd: YAG laser 1064 nm, PIANO mode, 9 mm, 4 sec, 300 J, 4 passes; with KIN III, at the first stage, telangiectatic vessels are treated for 10 minutes, dermal matrix remodeling is carried out using the following device: Nd: YAG laser 1064 nm, 9 mm spot, short pulse mode 1.0 - 1.6 ms, fluence 25 J per cm 2 for 1.0 ms, and 30 J per cm 2for 1.6 ms, frequency 3 Hz, 6 passes are carried out - 3 passes at one pulse duration, blowing 8 units, after which the second stage is immediately carried out for 5 minutes, in which excess stratum corneum and pathologically altered epidermocytes are removed, using the installation: Er: YAG laser 2940 nm, 7 mm spot, SP mode 300 μs: energy distribution 75% for ablation and 25% for heating, Fluence 2.4 J per cm 2 , frequency 20 Hz, after which the third stage is immediately carried out for 5 minutes using the following device: Er: YAG laser 2940 nm, fractional SMOOTH mode 24 J, 3.3 Hz, 1 pass, reducing the area of ​​the dermal flap, activating the stem cells of the dermis and hypodermis, after which the fourth stage is immediately carried out for 15 minutes, during which deep heating is carried out to the hypodermis, using the following device: Nd: YAG laser 1064 nm, PIANO mode. 9 mm, 5 sec, 350 J, 4 passes.

[0022] The novelty of this method is that it utilizes a four-stage photothermal treatment with ablative and non-ablative lasers, using both planar and fractional techniques, depending on the degree of epidermal dysplasia. This treatment targets not only dysplastic keratinocytes but also structures within the dermis that are pathogenetically involved in the development of the precancerous process.

[0023] For a more precise understanding of the method, we provide figures.

[0024] Fig. 1 shows an example of a 4-stage laser resurfacing of patient M., 74 years old. Patient No. 1. A - Actinic keratosis of the fronto-parietal region. 4-stage resurfacing. B - Result after 3 months. Pronounced

[0025] Figure 2 shows a case of successful treatment of actinic keratosis in patient K., KIN II. A, B - photos before treatment. B, D - photos 4 months after the first treatment. There was no recurrence. In addition to the therapeutic effect, the rejuvenating effect of the procedure is clearly visible: wrinkle reduction, even skin tone and texture, and soft tissue lifting.

[0026] Figure 3 shows an example of successful treatment of actinic keratosis in patient B. Diagnosis: Actinic keratosis L 57.0, KIN III. Additionally, multiple sebocystomas of the lower third of the face. A, B - photos before the procedure, B, D - photos 5 months after treatment. The sebocystomas were also removed during the treatment. A significant reduction in the manifestations of actinic keratosis and a rejuvenating effect with a soft tissue lift are noted.

[0027] The method is as follows.

[0028] When patients with suspected actinic keratosis seek treatment, a histological examination is performed to determine the degree of epidermal dysplasia - KIN I, KIN II, KIN III. Depending on the degree of dysplasia, a 4-stage photothermal exposure is prescribed with an ablative and non-ablative laser in a planar and fractional technique according to the following scheme: with KIN I, at the first stage, telangiectatic vessels are treated for 10 minutes, dermal matrix remodeling is carried out using the following setup: Nd: YAG laser 1064 nm, 9 mm spot, short pulse microsecond duration mode 0.6 - 1.0 - 1.6 ms, fluence 10 J / cm 2 for 0.6 ms, 15 J / cm 2 for 1.0 ms, 20 J / cm 2for 1.6 ms. The pulse frequency is 6 Hz, 6 passes are performed - 2 passes at one pulse duration, blowing 6 units, after which the second stage is immediately carried out for 5 minutes, during which excess stratum corneum and pathologically altered epidermocytes are removed, using the following setup: Er: YAG laser 2940 nm, 7 mm spot, MSP mode 100 μs - 100% of the energy is spent on ablation, Fluence 1.0 J per cm 2 , frequency 20 Hz, after which the third stage is immediately carried out for 5 minutes using the following device: Er: YAG laser 2940 nm, fractional SMOOTH mode - a packaged pulse consisting of 6 sub-pulses of 750 microseconds each, 16 J, 3.3 Hz, 1 pass, which reduces the area of ​​the dermal flap, activates the stem cells of the dermis and hypodermis, after which the fourth stage is immediately carried out for 15 minutes, during which deep heating is carried out to the hypodermis, using the following device: Nd: YAG laser 1064 nm, PIANO mode, 9 mm, 4 sec, 180-200 J, 4 passes.

[0029] In KIN II, at the first stage, telangiectatic vessels are treated for 10 minutes, and the dermal matrix is ​​remodeled using the following setup: Nd: YAG laser 1064 nm, 9 mm spot, short pulse mode 1.0-1.6 ms, fluence 15 J / cm 2 for 1.0 ms, frequency Hz, and 25 J per cm 2 for 1.6 ms, frequency 5 Hz, 6 passes are carried out - 3 passes at one pulse duration, blowing 7 units (so an increase in heating energy requires increased heat removal from the epidermis in order to avoid a burn), after which the second stage is immediately carried out for 5 minutes, in which the excess stratum corneum and pathologically altered epidermocytes are removed, using the installation: Er: YAG laser 2940 nm, 7 mm spot, MSP mode 100 μs, Fluence 1.5 J per cm 2, frequency 20 Hz, after which the third stage is immediately carried out for 5 minutes using the following device: Er: YAG laser 2940 nm, fractional SMOOTH mode, 20 J, 3.3 Hz, 1 pass to reduce the area of ​​the dermal flap, activate the stem cells of the dermis and hypodermis, after which the fourth stage is immediately carried out for 15 minutes, during which deep heating is carried out to the hypodermis, using the following device: Nd: YAG laser 1064 nm, PIANO mode, 9 mm, 4 sec, 300 J, 4 passes.

[0030] At KIN III, the first stage involves treating telangiectatically altered vessels and remodeling the dermal matrix for 10 minutes using the following setup: Nd: YAG laser 1064 nm, 9 mm spot, short pulse mode 1.0-1.6 ms, fluence 25 J / cm 2 for 1.0 ms, and 30 J per cm 2for 1.6 ms, frequency 3 Hz, 6 passes are carried out - 3 passes at one pulse duration, blowing 8 units, after which the second stage is carried out immediately for 5 minutes, during which excess stratum corneum and pathologically changed epidermocytes are removed, using the installation: Er: YAG laser 2940 nm, 7 mm spot, SP mode 300 μs: energy distribution 75% for ablation and 25%) for heating, Fluence 2.4 J per cm, frequency 20 Hz, after which the third stage is carried out immediately for 5 minutes using the installation: Er: YAG laser 2940 nm, fractional mode SMOOTH 24 J, 3.3 Hz, 1 pass, reduce the area of ​​the dermal flap, activate stem cells of the dermis and hypodermis, after which the fourth stage is carried out immediately for 15 minutes, during which deep heating is carried out to the hypodermis, using the installation: laser Nd:YAG 1064 nm, PIANO mode. 9 mm, 5 sec, 350 J, 4 passes.

[0031] We provide clinical examples of the application of the method.

[0032] Example 1.

[0033] Patient M., 74, presented with complaints of scalp rashes accompanied by a feeling of tightness. He has been experiencing these symptoms for the past 3 years and is self-treating with topical moisturizing products. Objectively: the pathological process is located in the frontal-parietal region and consists of multiple, irregularly shaped, confluent, red spots with small- and medium-sized lamellar scaling and isolated, flesh-colored epidermal papules. Histologically, the specimen shows proliferation of isolated dysplastic keratinocytes, occupying up to 25% of the epidermis. Isolated foci of moderate dysplasia are scattered, with a negligible number of mitoses in the basal and suprabasal layers. The underlying layer contains elastosis and isolated chronic inflammatory cells. Actinic keratosis L 57.0, KIN 1.

[0034] Clinical diagnosis: actinic keratosis of the fronto-parietal region L 57.0, KIN I.

[0035] The patient underwent a 4-stage laser resurfacing procedure using the author's proposed technique, followed by topical antibacterial and anti-inflammatory treatment. Sunscreen with SPF 50+ was prescribed for one year, morning and afternoon.

[0036] The procedure algorithm includes four sequential stages: Stage 1. For 10 minutes: Nd: YAG laser 1064 nm, 9 mm spot, short pulse microsecond mode 0.6 - 1.0 - 1.6 ms, fluence 10 J / cm 2 for 0.6 ms, 15 J / cm 2 for 1.0 ms, 20 J / cm 2 for 1.6 ms. Pulse frequency 6 Hz, 6 passes - 2 passes per pulse duration, blowing 6 units.

[0037] Stage 2. Er:YAG laser 2940 nm, 7 mm spot, MSP mode 100 μs, Fluence 1.0 J / cm 2 , frequency 20 Hz.

[0038] Stage 3. For 5 minutes: Er: YAG laser 2940 nm, fractional SMOOTH mode - packet pulse, 16 J, 3.3 Hz, 1 pass.

[0039] Stage 4. For 15 minutes: Nd: YAG laser 1064 nm, PIANO mode, 9 mm, 4 sec, 180-200 J, 4 passes.

[0040] At the end of the procedure, apply a cream with antibacterial and moisturizing properties.

[0041] Over the next 7 days, swelling was noted, followed by profuse mid-lamellar peeling. Afterward, the skin noticeably smoothed out and regained its natural color and turgor. A repeat scan was taken 3 months after the procedure. No negative changes were observed during the subsequent 6 months of observation (see Fig. 1).

[0042] Example 2. Patient K., 70 years old.

[0043] She complained of facial lesions, which she requested removal by laser excision. At the appointment, she was offered additional testing: a pathological examination of a facial skin biopsy.

[0044] Objectively: the pathological process is located on the face, predominantly in the frontal tubercles, cheekbones, cheeks, slope of the nose, and preauricular area. It presents as diffuse hyperpigmentation and lichenification, accompanied by isolated areas of hyperkeratosis with scaling, erythematous spots, and papules with small telangiectasias. Histologically, the collected material shows a proliferation of dysplastic keratinocytes, replacing up to 50% of the epidermis. Areas of moderate dysplasia alternate with unchanged epidermis, located primarily around the intraepidermal portions of hair follicles and eccrine gland sprouts, with a normal keratinization pattern. The number of mitoses in the basal and suprabasal layers is insignificant. In the underlying dermis there is pronounced elastosis, a non-specific inflammatory infiltrate with a large number of plasma cells.

[0045] Diagnosis: Actinic keratosis L 57.0, KIN II.

[0046] The patient underwent a 4-stage laser resurfacing procedure using the author's proposed technique, followed by topical antibacterial and anti-inflammatory treatment. Sunscreen with SPF 50+, morning and afternoon, was prescribed for one year.

[0047] The algorithm of the method is presented as follows:

[0048] At the first stage, for 10 minutes, Nd: YAG laser 1064 nm, 9 mm spot, short pulse mode 1.0 - 1.6 ms, fluence 15 J per cm 2 for 1.0 ms, frequency Hz, and 25 J per cm 2 for 1.6 ms, frequency 5 Hz, 6 passes - 3 passes at one pulse duration, blowing 7 units.

[0049] The second stage for 5 minutes on the Er: YAG laser 2940 nm, 7 mm spot, MSP mode 100 μs, Fluence 1.5 J / cm 2 , frequency 20 Hz, then the third stage for 5 minutes using the following installation: Er: YAG laser 2940 nm, fractional SMOOTH mode, 20 J, 3.3 Hz, 1 pass.

[0050] Then the fourth stage lasts for 15 minutes, during which deep heating is carried out to the hypodermis using a 1064 nm Nd: YAG laser, PIANO mode, 9 mm, 4 sec, 300 J, 4 passes.

[0051] Over the next 10 days, edema and localized lymphorrhea were noted in certain areas. This was followed after 2 days by serous crusting, which in turn gave way to profuse, medium-lamellar scaling. After this, the skin noticeably smoothed out, regained its natural color and turgor, and hyperkeratosis and lichenification elements decreased by 70-80%. A repeat scan was taken 3 months after the procedure. No negative dynamics of the process were noted during the subsequent 6 months of observation (see Fig. 2).

[0052] Example 3. Patient B., 86, presented for diagnosis regarding facial growths. She complained of facial growths accompanied by discomfort. She noticed these symptoms 5 years ago and self-treated with topical emollients. Objectively: facial features include signs of elastosis, deep soft tissue creases, lipoatrophy, isolated epidermal-dermal cysts 2-3 mm in size, multiple hyperpigmented spots and irregularly shaped papules confluent in nature, and isolated irregular erosions 5-10 cm in size with serous discharge.

[0053] Histological examination. Proliferation of atypical keratinocytes in all layers of the epidermis. Epithelial cells are markedly atypical with large hyperchromatic nuclei, isolated multinucleated cells, and abnormal mitoses. Irregular acanthosis, papillomatosis, and parakeratosis are present. The dermis shows a nonspecific chronic inflammatory infiltrate and dilated vessels.

[0054] Diagnosis: Actinic keratosis of the face L 57.0 KIN III.

[0055] Treatment is prescribed. Nd:YAG laser 1064 nm, 9 mm spot, short pulse mode 1.0 - 1.6 ms, fluence 25 J / cm is applied for 10 minutes. 2 for 1.0 ms, and 30 J per cm 2 for 1.6 ms, frequency 3 Hz, 6 passes are performed - 3 passes at one pulse duration, blowing 8 units, then the second stage: Er: YAG laser 2940 nm, 7 mm spot, SP mode 300 μs, Fluence 2.4 J / cm, frequency 20 Hz, after which the third stage for 5 minutes using the Er: YAG laser 2940 nm, fractional SMOOTH mode 24 J, 3.3 Hz, 1 pass, then the fourth stage for 15 minutes: Nd: YAG laser 1064 nm, PIANO mode. 9 mm, 5 sec, 350 J, 4 passes (see Fig. 3).

[0056] 45 patients were treated with this method.

[0057] The technical and economic efficiency of this method lies in its ability to achieve a significant treatment effect for actinic keratosis in a single procedure, with a relatively short recovery period requiring only topical treatment with emollient moisturizers. The relapse-free period lasts 6 months or more, resulting in a short period of disability (7-10 days). The procedure is performed by a single physician within 1 hour, including the preparation and processing of medical documentation. The laser device used is multifunctional and can be used in dozens of preset treatment protocols and numerous individual protocols, meaning it pays for itself economically every working day. These advantages of the method allow for more effective treatment of actinic keratosis.

Claims

A method for treating actinic keratosis, including the use of a Fotona SP Dynamis laser system with photothermal laser action, characterized in that, depending on the degree of epidermal dysplasia, a 4-stage photothermal action is carried out with an ablative and non-ablative laser in a planar and fractional technique as follows: for KIN I, at the first stage, for 10 minutes, treatment of telangiectatic vessels is carried out, remodeling of the dermal matrix, using the following setup: Nd: YAG laser 1064 nm, 9 mm spot, microsecond pulse duration mode short pulse 0.6-1.0-1.6 ms, fluence 10 J / cm 2 for 0.6 ms, 15 J / cm 2 for 1.0 ms, 20 J / cm 2for 1.6 ms, pulse frequency of 6 Hz, 6 passes are carried out - 2 passes at one pulse duration, blowing 6 units, after which the second stage is immediately carried out for 5 minutes, in which excess stratum corneum and pathologically altered epidermocytes are removed, using the installation: Er: YAG laser 2940 nm, 7 mm spot, MSP mode 100 μs - 100% of the energy is spent on ablation, fluence 1.0 J / cm 2, frequency 20 Hz, after which the third stage is carried out immediately for 5 minutes, using the following setup: Er: YAG laser 2940 nm, fractional SMOOTH mode - a packaged pulse consisting of 6 sub-pulses of 750 μs each, 16 J, 3.3 Hz, 1 pass, after which the fourth stage is carried out immediately for 15 minutes, during which heating is carried out to the hypodermis, using the following setup: Nd: YAG laser 1064 nm, PIANO mode, 9 mm, 4 s, 180-200 J, 4 passes; with KIN II, at the first stage, for 10 minutes, treatment of telangiectatic vessels is carried out, remodeling of the dermal matrix, using the following setup: Nd: YAG laser 1064 nm, 9 mm spot, short pulse mode 1.0-1.6 ms, fluence 15 J / cm 2 for 1.0 ms, frequency Hz, and 25 J / cm 2for 1.6 ms, frequency 5 Hz, 6 passes are carried out - 3 passes at one pulse duration, blowing 7 units, after which the second stage is immediately carried out for 5 minutes, in which the excess stratum corneum and pathologically altered epidermocytes are removed, using the installation: Er: YAG laser 2940 nm, 7 mm spot, MSP mode 100 μs, fluence 1.5 J / cm 2 , frequency 20 Hz, after which the third stage is immediately carried out for 5 minutes, using the following setup: Er: YAG laser 2940 nm, fractional SMOOTH mode, 20 J, 3.3 Hz, 1 pass, after which the fourth stage is immediately carried out for 15 minutes, during which heating is carried out to the hypodermis, using the following setup: Nd: YAG laser 1064 nm, PIANO mode, 9 mm, 4 s, 300 J, 4 passes; with KIN III, at the first stage, for 10 minutes, treatment of telangiectatic vessels is carried out, remodeling of the dermal matrix, using the following setup: Nd: YAG laser 1064 nm, 9 mm spot, short pulse mode 1.0-1.6 ms, fluence 25 J / cm 2 for 1.0 ms and 30 J / cm 2for 1.6 ms, frequency 3 Hz, 6 passes are carried out - 3 passes at one pulse duration, blowing 8 units, after which the second stage is immediately carried out for 5 minutes, in which excess stratum corneum and pathologically altered epidermocytes are removed, using the installation: Er: YAG laser 2940 nm, 7 mm spot, SP mode 300 μs: energy distribution 75% for ablation and 25% for heating, fluence 2.4 J / cm 2 , frequency 20 Hz, after which the third stage is immediately carried out for 5 minutes, using the following setup: Er: YAG laser 2940 nm, fractional SMOOTH mode 24 J, 3.3 Hz, 1 pass, after which the fourth stage is immediately carried out for 15 minutes, during which heating is carried out to the hypodermis, using the following setup: Nd: YAG laser 1064 nm, PIANO mode, 9 mm, 5 s, 350 J, 4 passes.

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