1. Psoriasis is a chronic, systemic, immune-mediated disease of multifactorial origin with a dominant role of genetic factors. It is characterized by hyperproliferation and impaired differentiation of epidermal cells, as well as an imbalance between proinflammatory and anti-inflammatory cytokines [1]. Psoriasis affects 2-3% of the population, with prevalence varying by region. Residents of the Caucasus and Scandinavia are most susceptible to the disease [2].

   The vast majority (85-90%) of psoriasis cases manifest clinically as plaque psoriasis, which presents as erythematous, asymmetric plaques with thick scales, most commonly found on the extensor surfaces, trunk, and scalp. While plaque psoriasis is the most common subtype, other subtypes include erythrodermic, pustular, guttate, inverse, and palmoplantar psoriasis [3]. Psoriatic lesions, especially on sun-exposed areas, can be accompanied by pruritus and have a major impact on the quality of life, often leading to social withdrawal and psychological issues such as feelings of inferiority, depression, and anxiety.

   The concept of psoriasis as a systemic disease caused by a cascade of inflammatory reactions necessitates systemic treatment [4]. However, current treatments for moderate to severe psoriasis can have many side effects when used over long periods .

   The severity of psoriasis is determined not only by the extent of body surface area affected (Body Surface Area, BSA; with BSA <5% considered mild, BSA = 5-10% moderate, and BSA ≥10% severe) but also by the localization of the pathological process. Localizations of concern, such as involvement of exposed skin areas, extensive scalp involvement, and damage to the genitals, palms, soles, and nail plates, can significantly impact the patient’s quality of life [5].

   Palmoplantar psoriasis, often diagnosed in individuals aged 30 to 50 years engaged in physical labor, primarily affects the plantar surfaces of the feet and the palms [6]. This form of psoriasis is frequently resistant to therapy and can present in several subtypes:

   1. Barber's Pustular Psoriasis: This subtype is limited to lesions on the palms and soles. Its development can be triggered by infections, stress, use of antimalarial drugs, β-blockers, lithium, phenylbutazone, antibiotics, hormonal imbalances, abrupt discontinuation of corticosteroids, and inappropriate external therapy. Staphylococcal infection, impaired T-cell immunity, and liver dysfunction may also contribute. Hormonal imbalance is a significant factor, as evidenced by cases of generalized pustular psoriasis following corticosteroid treatment or withdrawal, large doses of progesterone, or diabetes mellitus. Generalized pustular psoriasis commonly develops between ages 40-60, typically 1-2 years after the onset of common psoriasis, although it can appear 7-10 years later depending on the intensity and duration of adverse factors [7].
   2. Vulgar Psoriasis: This type features isolated lesions on the palms and soles, presenting with various elements. Some cases show small, rounded plaques with a vivid red color, either depressed or elevated, and covered with dense, yellow, difficult-to-remove scales. Other cases display diffuse rashes with peripheral growth, resulting in a bumpy surface with extensive "calloused" deposits and painful cracks of a dirty gray color [8]. Although palmoplantar psoriasis usually covers less than 5% of BSA, it causes significant discomfort and decreased quality of life, warranting systemic therapy. Methotrexate, cyclosporine, and systemic retinoids are effective treatments in most cases [9].

   In accordance with the pathogenetic processes of psoriasis, therapy should focus on reducing inflammation, suppressing epithelial cell proliferation, and normalizing their differentiation. Numerous drugs and methods for treating psoriasis have been developed to date. When prescribing treatment, it is essential to consider factors such as the extent of skin lesions, disease stage, patient age, gender, concomitant diseases, and any contraindications to specific treatments or medications [10].

   For psoriasis predominantly affecting the palms and soles, topical treatments are commonly employed, including corticosteroids, synthetic analogues of vitamin D3 metabolites, and retinoids. Systemic retinoids, particularly acitretin, are used, and in some cases, especially when accompanied by psoriatic arthritis, immunosuppressive agents such as cyclosporine A and methotrexate may be utilized [11]. However, external therapies often prove insufficient, and systemic treatments can lead to side effects and limitations, particularly in patients with concomitant conditions. Consequently, the search for and development of new, effective, and safe therapeutic methods for psoriasis affecting the palms and soles remain pertinent [12].

   Phototherapy has become a widely adopted treatment modality for this condition. Commonly used methods include PUVA (psoralen and ultraviolet A) therapy, narrow-band UVB therapy (311 nm), and UVA1 (ultraviolet A1) therapy (340400 nm). Narrow-band UVB therapy, introduced in the 1980s, was developed following research by J.A. Parrish, who identified that the optimal radiation range for psoriasis is 296–313 nm, with 310–313 nm offering the best safety profile. Narrow-band UVB (311 nm) is noted for its immunoregulatory effects [13], reducing proinflammatory cytokines such as IL-2, IL-6, and IL-23. IL-6 and IL-23 activate STAT3, which increases the expression of transcription factors RORγt and RORγ, subsequently enhancing the expression of key Th-17 cytokines (IL-17A, IL-17F, IL-21, and IL-22) [14].

   UVB 311 nm radiation can induce apoptosis, likely by reducing the expression of survivin, a protein that inhibits apoptosis by suppressing the activation of caspase-3. This method also inhibits keratinocyte proliferation by increasing the epidermal expression of GATA3 (GATA Binding Protein 3). In the skin, GATA3 is essential for the proper formation of the epidermal barrier and regulation of epidermal differentiation through the activation of kallikrein-1 [15].

   A pressing issue is childhood psoriasis, which is showing a marked increase in incidence. Palmar-plantar psoriasis in children occurs in about 25% of all clinical forms, causing significant discomfort and reduced quality of life. This form of psoriasis often presents with a persistent course and resistance to conventional treatments [16].

   Scientific studies indicate that UVB 311 nm wavelengths offer the maximum therapeutic effect with minimal erythema and reduced carcinogenic risk compared to other types of UV therapy. Fewer treatments are needed to achieve results, leading to longer remissions and fewer side effects. Additionally, UVB therapy can be combined with other treatments and helps restore immunological reactivity, enhance the body's adaptive and compensatory capabilities, and improve blood circulation and metabolism in the skin. These benefits make UVB phototherapy a preferred option, particularly in pediatric practice.

   Local application of UVB 311 nm therapy combined with topical calcipotriol is highly effective for treating children with palmoplantar psoriasis. This approach achieves clinical remission and significant improvement in the majority of patients (96%). Additionally, using pulsed UVB 311 nm therapy after the primary treatment allows for disease management and monitoring in 83.3% of patients for up to one year [17].

   An excimer lamp emitting at 308 nm is also recommended for treating both palmoplantar and generalized forms of psoriasis, either as monotherapy or as part of a comprehensive treatment regimen. The duration of exposure should be individualized based on the patient's skin sensitivity to radiation [18].

   In 2017, research focused on the use of photodynamic therapy (PDT) for patients with psoriasis, particularly those with significant comorbidities. Notably, PDT has shown remarkable efficacy in treating palmoplantar psoriasis, which often has a persistent course and limited response to methotrexate, significantly affecting patients' quality of life and psychological well-being. The outcomes of PDT are comparable to those of 10-15 sessions of PUVA (psoralen and ultraviolet A) therapy or 4 rounds of methotrexate. For patients who cannot tolerate these therapies, PDT offers a valuable alternative as part of the core treatment strategy [19].

   The study results indicate that incorporating photodynamic therapy (PDT) into the standard treatment regimen provides high clinical efficacy for psoriasis. PDT procedures are associated with minimal contraindications and are suitable for treating psoriasis in patients with significant comorbidities as well as those with palmoplantar psoriasis [20].

   New-generation biologic drugs, which target key mediators in the inflammatory pathway of psoriasis, offer effective and relatively safe treatment options [21]. In the Russia, tumor necrosis factor (TNF) blockers, such as etanercept and adalimumab, and an interleukin (IL) 12 and 23 blocker, ustekinumab, are approved for treating psoriasis in children. Research has demonstrated the high clinical efficacy of ustekinumab, with a relatively low incidence of adverse events [22].

   Additionally, retinoid medications have shown efficacy in treating palmoplantar psoriasis in children [23]. Clinical diagnostic studies highlight the effectiveness of netakimab as a monotherapy for severe forms of psoriasis. Netakimab is well-tolerated, with no adverse reactions or side effects typically associated with biologic drugs, such as upper respiratory infections or cardiovascular complications. Treatment with netakimab resulted in reductions in PASI (Psoriasis Area Severity Index), DAS28 (Disease Activity Score-28), and BASDAI (Bath Ankylosing Spondylitis Disease Activity Index). Consequently, netakimab effectively controls the disease, significantly improves patients' quality of life, and is suitable for monotherapy in severe psoriasis cases [24].

   Another immunosuppressive treatment for psoriasis involves the use of sodium salt of the synthetic dipeptide gammaD-glutamyl D-tryptophan. This compound selectively suppresses the functional activity of immunocompetent cells and inhibits autoimmune processes, while sparing cells of other organs and tissues, and it is associated with virtually no side effects [25].

   Therapy with gamma-glutamyl-tryptophan has demonstrated a pronounced clinical effect, significantly delaying the onset of relapses and substantially extending the duration of clinical remission compared to other antipsoriatic therapies.

   Secukinumab, approved in Russia in 2016, is indicated for the treatment of moderate to severe psoriasis in adult patients who are candidates for systemic therapy or phototherapy. Secukinumab is a fully human monoclonal antibody targeting interleukin-17A (IL-17A), a key cytokine in the inflammatory process of psoriasis [26].

   Extensive clinical research, including numerous large-scale direct comparative trials (Phase II and Phase III), has been conducted to evaluate the safety, efficacy, and impact of secukinumab on the quality of life in patients with psoriasis. These studies, involving over 4,500 patients, have assessed its effectiveness in cases resistant to standard treatments or with challenging localizations, such as palmoplantar psoriasis, scalp psoriasis, psoriatic onychodystrophy, and psoriatic arthritis [27].   

   IL-17 inhibitors, especially brodalumab and ixekizumab, are known for their rapid onset of efficacy. Both IL-17 and IL-23 inhibitors, including brodalumab, ixekizumab, and risankizumab, have demonstrated high long-term efficacy and acceptable safety records in clinical studies [28]. However, some safety concerns have been identified. TNF-α inhibitors are associated with a slightly increased risk of serious infections, tuberculosis, paradoxical reactions, lupus, and infusion reactions (specifically with infliximab). IL-17 inhibitors are linked to candidiasis, neutropenia, and inflammatory bowel disease, whereas no specific adverse events have been reported for IL-23 inhibitors thus far [29]. General safety concerns for biologics include the risk of hepatitis B virus reactivation and interstitial pneumonia, particularly with TNF-α inhibitors. There is insufficient evidence regarding the long-term safety of newer agents like IL-17 and IL-23 inhibitors [30].

   Systemic corticosteroids, although not part of current psoriasis treatment protocols, are still used in clinical practice [31]. However, they are not suitable for long-term use due to their serious side effects. Methotrexate (MTX) acts by inhibiting keratinocyte proliferation. After oral administration, peak blood concentrations are reached within 1-2 hours, with bioavailability ranging from 25% to 70%. When administered subcutaneously or intramuscularly, peak concentrations are achieved within 30-60 minutes. MTX is minimally metabolized by the liver and is excreted unchanged by the kidneys. In low doses, MTX has a noticeable immunosuppressive effect without pronounced hemolytic activity, making it suitable for long-term treatment of chronic diseases such as psoriasis, rheumatoid arthritis, and Crohn's disease.

   In cases of psoriasis exacerbation, topical therapy should commence with stronger corticosteroids and then transition to medium-strength drugs. Clobetasol and mometasone are suitable for this approach. IL-12/23, IL-17 antagonists, and new IL-23p19 antagonists represent a revolutionary breakthrough in psoriasis treatment. Several studies have summarized data on the efficacy and safety of IL-17 and IL-23 drugs [32]. The choice of therapeutic measures for psoriasis primarily depends on the severity of the condition. Patients with moderate to severe disease require systemic immunosuppressive therapy. Methotrexate, synthetic retinoids, and cyclosporine are commonly used but can be associated with organ toxicity and side effects, necessitating clinical and laboratory monitoring throughout treatment.

   In recent years, genetically engineered drugs—monoclonal antibodies (MABs)—have been widely used to treat psoriasis. MABs are highly effective due to their anticytokine activity, targeting specific pathways in the pathological process, which significantly improves patients' quality of life and achieves prolonged remission. Vitamin A analogues are primarily prescribed for severe and rare forms of psoriasis. These drugs have anti-inflammatory properties that reduce skin cell proliferation, but their use is associated with severe adverse effects, including liver damage and teratogenicity [33].

   A topical combination drug containing calcipotriol and betamethasone is the preferred choice for external treatment of various clinical forms of psoriasis. Studies have confirmed that both the ointment and gel forms of this drug are effective, promoting rapid resolution of clinical manifestations and improving the quality of life. The combination of calcipotriol and betamethasone can be used to manage exacerbations and maintain long-term control over the disease. The drug's favorable organoleptic properties, combined with its high efficacy and good tolerability, ensure high patient compliance [34].

   Studies have also indicated the high efficacy of various combination therapies, particularly when combined with ultraviolet therapy. These methods work through mutual potentiation and summation of each component's effects. Developing combined pharmaco-physiotherapeutic methods, including the use of ultraviolet radiation and low doses of immunosuppressive drugs, holds promise for treating certain dermatoses. In psoriasis, methotrexate, a first-line treatment for moderate psoriasis, is promising; however, increased photosensitivity limits its use with ultraviolet therapy, especially in patients with comorbidities. Combined ultraviolet therapy with emission at 311 nm and 320-400 nm (UVB/UVA) is theoretically suitable for psoriasis.

   The combined method of treating psoriasis has a high safety profile, as evidenced by the absence of clinically significant adverse events, such as thrombocytopenia and leukopenia, and stable liver transaminases and creatinine levels. This enhances patient compliance. The high therapeutic and prophylactic efficacy and safety of the combined method make it a recommended approach for widespread use in dermatovenerology practice.

   New biological agents such as risankizumab, guselkumab, ixekizumab, and brodalumab have demonstrated high efficacy in patients with moderate to severe psoriasis [35]. The physiological features of the skin in the palmar-plantar zone, particularly the thickness of the stratum corneum, allow the use of medium and strong topical corticosteroids. Mometasone furoate 0.1% ointment, and mometasone furoate 0.1% with salicylic acid 5%, are preferred due to their high therapeutic activity combined with safety (low resorption coefficient). The treatment regimen for palmar-plantar psoriasis is determined by its clinical form. Re-PUVA therapy (psoralen and ultraviolet A) is recommended for palmar-plantar pustular psoriasis, with acitretin taken orally in parallel with long-wave ultraviolet irradiation (PUVA therapy, PUVA baths). PUVA therapy, whether as monotherapy or combined with systemic retinoids, is effective but slow to show results. PUVA baths, PUVA therapy with photosensitizers on an oil or gel basis, and local SPT (spectral phototherapy) also have favorable effects [36].

   Other methods in the treatment of psoriasis involve non-drug therapies, including stress reduction, spa treatments, a healthy lifestyle, and diet. While psoriasis can be well-managed to control its course and relieve symptoms, its multifactorial genesis prevents a complete cure. Patients can temporarily achieve clear skin, but since psoriasis is recurrent, plaques can reappear, especially under stress [37].

   Recent data on the pathogenesis of psoriasis have led to its classification as a long-term chronic disease characterized by systemic inflammation. Patients with moderate to severe psoriasis require screening for concomitant pathologies and systemic therapy. For mild to moderate psoriasis, local therapy is generally sufficient to alleviate the primary symptoms of the disease.

   The literature describes isolated cases of spontaneous regression of palmar-plantar psoriasis lesions. There is evidence of positive outcomes from long-term use (4 years) of calcipotriol. One case reported regression of lesions after a 9-month course of external therapy with 5-fluorouracil, with no relapses during a subsequent 4-year observation period. However, in most cases, foreign studies have found several external therapy agents to be ineffective. These include glucocorticosteroids, glucocorticosteroids combined with retinoids, calcipotriol, 10% urea, vitamin A, tacrolimus, salicylic acid, 0.05% isotretinoin, ketoconazole, imiquimod, antibiotics, and colloidal dressings [38].

   Contemprory liposomal technologies have enabled the creation of a unique base that effectively replenishes lipid deficiency and restores the protective function of the epidermis. For vulgar psoriasis of smooth skin, it is advisable to use a cream formulated for dry and sensitive skin of the face and body. For palmar-plantar psoriasis, a specialized hand cream is recommended, and for scalp lesions, a balm for dry scalp is appropriate.

   Basic external therapies for chronic squamous-hyperkeratotic conditions of the palms and soles, characterized by pronounced dryness, peeling, and skin cracking, include emollients (from the French molle – soft). In contemporary dermatological practice, emollients are recognized as highly effective and essential for managing patients with dry skin prone to hyperkeratosis and desquamation. These agents have the capability to moisturize, soften, and replenish the skin with lipid components, thereby restoring its aesthetic appearance [39]. They reduce transepidermal water loss and replenish intercorneocyte lipid layers.

   The therapeutic action of emollients is partly attributed to their ability to fill gaps between exfoliating keratinocytes. However, their primary therapeutic benefit is the enhancement of water content in the stratum corneum. Restoring hydration positively impacts not only the mechanical properties of the stratum corneum, improving skin extensibility and flexibility, but also actively supports the normalization of desquamation processes. Increased concentrations of free water molecules in the skin elevate proteolytic enzyme activity and expedite the breakdown of corneodesmosomes, resulting in more complete and uniform separation of horny scales from the skin surface [40].

   Incorporating emollients into comprehensive dermatological treatment regimens boosts the effectiveness of therapy, reduces treatment duration, prolongs remission periods, and improves the overall prognosis of the disease, thereby enhancing the patient's quality of life [41].

   In therapeutic and preventive measures, ensuring adequate provision of energy, macronutrients, and micronutrients through an optimal diet is crucial [42]. Rational dietary therapy, which involves consuming diets balanced in essential nutrients and biologically active substances, combined with lifestyle modifications, can significantly enhance the patient's quality of life, correct metabolic disorders, and improve the condition of affected organs and systems, thereby positively influencing the progression of the skin condition [43].

   Neglecting the completeness and balance of dietary nutrition, along with the patient's lifestyle, can diminish the effectiveness of therapeutic interventions. This oversight may lead to the exacerbation of alimentary-dependent pathologies, complicate existing conditions, prolong rehabilitation periods, increase the risk of complications, and heighten the frequency of adverse effects from drug therapies [44]. Despite its importance, the role of diet therapy in managing skin diseases, including psoriasis, remains underexplored. Additionally, certain lifestyle factors—such as alcohol consumption and smoking—significantly contribute to the development and progression of psoriasis, affecting its clinical course.

   Conclusion

   The treatment of palmoplantar psoriasis presents a significant challenge due to its refractory nature, which results from pronounced pathological changes in the epidermis and dermis, as well as continuous trauma and irritation of the skin on the hands and feet. The therapeutic approach involves a range of systemic and external treatments available to clinicians. Currently, various biological agents are employed in managing psoriasis, each differing in terms of onset of action, long-term effectiveness, safety profile, and effects on concomitant diseases. A thorough understanding of these attributes enables the selection of the most appropriate therapy, enhancing treatment outcomes and patient satisfaction by minimizing the disease's impact on daily life.

Aliyeva R.K. – https://orcid.org/0009-0003-3056-9129

Iztleuova G.M. – https://orcid.org/0000-0002-5695-0895

Kalakeshova A.A. – https://orcid.org/0009-0006-4774-149Х

Shaimanova A.K. – https://orcid.org/0009-0009-3507-3705

Aimagambetova A.K. – https://orcid.org/0009-0007-4116-7914

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