Psoriasis: Clinical Guidelines

List of Abbreviations

IL – interleukin

PUVA therapy is ultraviolet irradiation with a wavelength of 320–400 nm using photosensitizing drugs; the combined use of furocoumarin photosensitizers and long-wave ultraviolet radiation of 320–400 nm

UVA is long-wave ultraviolet radiation of 350–400 nm

UVB is medium-wave ultraviolet radiation of 280–320 nm (selective phototherapy)

UVB-311 therapy is narrow-band medium-wave ultraviolet therapy with a wavelength of 311 nm (or narrow-band (311 nm) medium-wave therapy)

TNF is tumor necrosis factor

cAMP – Cyclic adenosine monophosphate

PASI is Psoriasis Area and Severity Index.

Terms and Definitions

Psoriasis is a chronic immuno-associated disease of a multifactorial nature with a dominant role of genetic factors in its development, characterized by accelerated proliferation of keratinocytes and impaired differentiation, an imbalance between pro-inflammatory and anti-inflammatory cytokines, and frequent pathological changes in the musculoskeletal system.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Psoriasis is a chronic disease of a multifactorial nature with a dominant role of genetic factors in its development, characterized by accelerated proliferation of keratinocytes and impaired differentiation, an imbalance between pro-inflammatory and anti-inflammatory cytokines, and frequent pathological changes in the musculoskeletal system.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The development of psoriasis is influenced by hereditary predisposition, dysfunction of the immune, endocrine, and nervous systems, and adverse environmental factors. A number of genes (PSORS) have been described whose presence predisposes to the development of the disease. In particular, patients with psoriasis are more likely to express HLA-Cw6 and HLA-DR7 antigens.

Precipitating factors include psychoemotional stress, chronic infections (most commonly streptococcal), alcohol abuse, administration of

chloroquine/hydroxychloroquine**, oral contraceptives, interferons, other immunostimulants, etc.).

In psoriasis, the pathological process is triggered through antigen presentation by dendritic antigen-presenting cells followed by the stimulation of interleukin-(IL)-12 and IL-23 release by T cells, resulting in the proliferation and differentiation of T lymphocytes into Th-1 and Th-17. These T-lymphocyte subpopulations express genes responsible for the synthesis and subsequent release of a large number of various inflammatory mediators into the tissues. Specifically, Th-1 predominantly stimulates immune responses through the excessive release of IL-2, IFN-γ, and TNF-α. In turn, Th-17 is responsible in the body both for defense against various pathogenic agents (this effect is mediated via the production of IL-21 and IL-22) and for tissue inflammation (respectively, via IL-17A). Stimulation of tissue inflammation processes leads to IL-17A-induced activation and hyperproliferation of keratinocytes. Acting through a feedback loop, the latter themselves contribute to the further production of pro-inflammatory cytokines and chemokines in the skin, leading to acanthosis and impaired differentiation of epidermal keratinocytes.

1.3 Epidemiology of the Disease or Condition

Psoriasis is one of the most common skin diseases and, according to literature data, occurs in 1–2% of the population worldwide. According to official state statistics in the Russian Federation, the prevalence of psoriasis in 2021 was 243.7 cases per 100,000 population; the incidence was 59.3 per 100,000 population.

1.4 Features of Coding the Disease or Condition

L40.0 – Psoriasis vulgaris

L40.1 – Generalized pustular psoriasis

L40.2 – Acrodermatitis continua suppurativa [Allopo]

L40.3 – Palmar and plantar pustulosis

L40.4 – Guttate psoriasis

L40.8 – Other psoriasis

L40.9 – Psoriasis, unspecified

1.5 Classification of the disease or condition

Currently, it is customary to distinguish several clinical forms of psoriasis: psoriasis vulgaris (plaque psoriasis), seborrheic, guttate, pustular (generalized of von Zumbusch; of palms and soles of Barber; acrodermatitis continua suppurativa of Allopo), inverse, psoriatic erythroderma, and psoriatic arthritis (arthropathic psoriasis).

1.6 Clinical presentation of the disease or condition

Psoriasis in the progressive stage is characterized by the peripheral growth of skin rash elements, fusion of papules into plaques, and the appearance of fresh elements at the site of trauma (Köbner phenomenon). The efflorescences are bright pink, covered with silvery-white scales, and surrounded by a peripheral rim of erythema ("growth") free from scaling. Psoriatic phenomena are positive.

Psoriasis in the stationary stage is distinguished by the absence of fresh rash elements; the plaques are dull red, moderately infiltrated, and exhibit mild scaling, with scales completely covering the eruptions. The psoriatic triad is doubtful. Pruritus is practically absent.

Psoriasis in the regressive stage is characterized by the absence of scaling, a significant decrease in infiltration, resolution of plaques in the center, and the formation of a peripheral pseudoatrophic Woronoff ring. Subjective sensations are absent.

Psoriasis vulgaris (plaque psoriasis) is characterized by the appearance of pinkish-red papular elements on the skin with clear boundaries, tending to coalesce and form plaques of various shapes and sizes, covered with silvery-white scales. The plaques are predominantly located on the scalp, the extensor surfaces of the elbow and knee joints, and the lumbar and sacral regions, but can be localized on any other areas of the skin.

Exudative psoriasis manifests in patients with obesity, diabetes mellitus, or thyroid dysfunction; increased exudation is observed in the lesions, accompanied by the appearance of grayish-yellow crust-scales that tightly adhere to the surface of the plaques, making the psoriatic triad difficult to detect.

Seborrheic psoriasis is characterized by the localization of rashes exclusively on seborrheic skin areas (scalp, nasolabial and retroauricular folds, chest, and interscapular region). In seborrheic psoriasis, the scales usually have a yellowish hue, while scaling on the head can be very pronounced, and the eruptions may extend from the scalp onto the forehead, forming the so-called "psoriatic crown."

Guttate psoriasis is an acute form of the disease characterized by the appearance of numerous drop-like bright red papules on the skin with slight scaling and infiltration. It often occurs in childhood or adolescence and develops following streptococcal infections. Guttate psoriasis may transform into psoriasis vulgaris.

Pustular psoriasis occurs against the background of infections, stressful situations, hormonal disorders (including those caused by oral contraceptives), rapid withdrawal of corticosteroids or other immunosuppressive drugs, or irrational topical therapy. Pustular psoriasis manifests as generalized or localized eruptions, most commonly located in the palms and soles, represented by superficial pustular elements.

Generalized von Zumbusch psoriasis is characterized by the paroxysmal appearance of small, superficial, sterile pustules against a background of bright erythema, accompanied by burning and pain, located both in the area of typical psoriatic plaques and on previously unchanged skin. Erythematous patches with pustulation rapidly increase in size, coalesce, and involve extensive skin areas, making individual psoriatic plaques indistinguishable. The coalesced pustules detach the epidermis, forming "lakes of pus." Generalized von Zumbusch psoriasis is severe, accompanied by fever and malaise; patients complain of burning and stinging sensations in the affected areas. Dystrophic nail changes, joint involvement, and sometimes kidney involvement are frequently noted. Blood tests reveal leukocytosis and an elevated ESR. After the formation of pustules ceases, the patient's condition improves, and the temperature decreases; however, a new attack typically develops suddenly.

Palmar and plantar pustular psoriasis of Barber is more common than generalized von Zumbusch psoriasis. The eruptions are located predominantly in the thenar and hypothenar eminences, as well as the instep of the feet. It is characterized by sharply demarcated erythematosquamous plaques with multiple pustular eruptions on their surface. Pustules may form both within the plaques and on other areas of the skin.

Acrodermatitis continua suppurativa of Allopo manifests as erythematosquamous and vesiculopustular eruptions on the distal phalanges of the fingers and toes. The affected areas of the digits exhibit bright erythema, edema, and multiple pustules merging into "lakes of pus." The distal phalanges are thickened, and the nail plates are dystrophically altered.

Psoriatic erythroderma most commonly occurs as a result of an exacerbation of preexisting plaque psoriasis under the influence of irritating factors or inappropriate treatment (taking baths in the progressive stage, excessive sun exposure or ultraviolet ray overdose, using high concentrations of resolving ointments during an exacerbation). Erythroderma may also develop primarily in a healthy person through the coalescence of rashes in rapidly progressive psoriasis. The process spreads to the entire skin surface, involving more than 90% of the integument. The skin becomes brightly red, edematous, infiltrated, lichenified in places, hot to the touch, and covered with a large number of large and small dry white scales that easily fall off when removing clothing. Patients are bothered by itching, sometimes severe, burning and a sensation of skin tightness, and pain. The patient's general condition is impaired: weakness, malaise, loss of appetite appear, body temperature rises to 38–39°C, lymph nodes enlarge (primarily inguinal and femoral), and sweating decreases. With the prolonged persistence of such a condition, hair loss and nail involvement may occur.

Inverse psoriasis manifests with rashes typical of vulgaris psoriasis; its specific feature is the predominant localization on the flexor surfaces of the extremities.

Psoriatic arthritis (arthropathic psoriasis) may develop simultaneously with psoriatic skin rashes or precede them. Subsequently, synchronicity in the development of exacerbations of skin and joint lesions may be observed. The articular process is accompanied by skin redness over the affected joints, edema, pain, restricted mobility, and morning stiffness. Joint deformations, ankylosis, enthesitis (inflammation of tendons at their attachment sites to bones), dactylitis, and spondylitis may occur. The clinical and anatomical variant of joint involvement is determined by the predominance of a particular symptom complex in the clinical picture of the disease.

Nail involvement is very common in psoriasis, with the most frequent surface changes being pinpoint pits resembling the surface of a thimble ("thimble" sign). Quite often, small, several millimeters in diameter, reddish and yellowish-brown spots can be seen under the nail plate near the nail folds or lunula ("oil drop" sign). Subungual hyperkeratosis with the development of onychogryphosis is sometimes encountered. Nail plate involvement may precede the onset of psoriatic arthritis.

Patients with psoriasis have an increased risk of comorbid conditions: coronary artery disease, Crohn's disease, type 2 diabetes mellitus, and depression. Additionally, among patients with moderate and severe psoriasis, there is an increased prevalence of metabolic syndrome, which combines visceral obesity, insulin resistance, dyslipidemia, and arterial hypertension. Specialists should consider the potential presence of comorbidities when managing patients with psoriasis.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the diagnosis/condition: the diagnosis of psoriasis is established based on the clinical manifestations of the disease.

2.1 Complaints and Anamnesis

Patients complain of the presence of rashes and a sensation of skin tightness. Patients with psoriasis may be bothered by itching of varying degrees of intensity.

When taking the anamnesis, attention should be paid to the presence of psoriasis in relatives.

2.2 Physical Examination

For establishing a diagnosis, the primary method is a visual examination of the patient's skin.

Rashes are characterized by the presence of the psoriatic triad, which consists of phenomena sequentially occurring upon scraping of papular rashes: the stearin spot phenomenon (light scraping of the papule leads to increased scaling, giving the papule surface a resemblance to a crushed drop of stearin); the terminal film phenomenon (the appearance of a moist, thin, shiny, translucent surface of the elements after complete removal of the scales); and the auspitz sign / pinpoint bleeding (the appearance of pinpoint, non-coalescing droplets of blood after careful scraping of the terminal film) [1, 2].

During the progression of psoriasis, the Koebner phenomenon or isomorphic response can be observed—the appearance of new rashes at sites of skin trauma, such as friction or pressure.

2.3 Laboratory Diagnostics

Comments: During systemic therapy with methotrexate**, systemic retinoids for psoriasis, cyclosporine**, targeted synthetic and biological immunosuppressants, tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors, adverse events such as anemia, neutropenia, lymphocytopenia, and thrombocytopenia may develop.

Comments: During systemic therapy with methotrexate**, systemic retinoids for psoriasis, cyclosporine**, targeted synthetic and biological immunosuppressants, tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors, adverse events may develop, including liver and kidney dysfunction, and metabolic disorders.

Comments: During systemic therapy with tofacitinib**, tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors, activation of chronic infections is possible, which necessitates the determination of antibodies to the hepatitis B surface antigen (HBsAg) in the blood of patients prescribed therapy with these medicinal products

Comments: During systemic therapy with tofacitinib**, tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors, activation of chronic infections is possible, which necessitates the determination of antibodies to hepatitis C virus (Hepatitis C virus) in the blood of patients prescribed therapy with these medicinal products

Comments: During systemic therapy with tofacitinib**, tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors, activation of chronic infections is possible, which necessitates the determination of classes M and G antibodies (IgM, IgG) to human immunodeficiency virus HIV-1 (Human immunodeficiency virus HIV 1) in the blood of patients prescribed therapy with these medicinal products.

Comments: During systemic therapy with tofacitinib**, tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors, activation of chronic infections is possible, which necessitates testing for antibodies of classes M, G (IgM, IgG) to human immunodeficiency virus HIV-2 (Human immunodeficiency virus HIV 2) in the blood of patients prescribed therapy with these medicinal products.

Comments: Selective immunosuppressants (phosphodiesterase 4 inhibitors, Janus kinase blockers), tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors should not be used during pregnancy (with the exception of certolizumab pegol**). Therefore, women of childbearing potential must obtain a negative pregnancy test result prior to initiating therapy, and must use reliable methods of contraception during treatment and for at least 6 months after its completion.

2.4 Instrumental Diagnostics

Radiography of the feet in one projection [12–15]

GRC CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Pelvic radiography [12–15]

GRC CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Radiography of the thoracic and lumbar spine [12–15]

GRC CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: To evaluate the status of a patient with psoriasis presenting with back pain, radiography of the junctional spine (lower thoracic including the lumbar spine in a lateral projection) is necessary due to the possible development of psoriatic arthritis [12–15]. Pelvic radiography should be performed in the anteroposterior projection. Foot radiography should be performed in the anteroposterior projection. Radiographic imaging of other joints and spinal segments (cervical) involved in the pathological process should be performed as clinically indicated.

Comments: If signs of involvement of other joints are identified, radiography of the corresponding joints should be performed. These studies are conducted no more frequently than once a year. Characteristic radiographic changes in psoriatic arthritis include: joint space narrowing; bone remodeling (resorption of terminal phalanges, large eccentric erosions, osteolysis – "pencil-in-cup" deformity) and proliferation (marginal bone proliferations, periostitis, enthesophytes, and bony ankylosis), asymmetric bilateral/unilateral sacroiliitis, paravertebral ossification, and marginal syndesmophytes [16, 17]

Comment: Magnetic resonance imaging of the spine in patients with psoriasis to detect signs of psoriatic arthritis should be performed in T1, T2, and STIR sequences. MRI-active sacroiliitis is defined by the presence of bone marrow edema (osteitis), which manifests as areas of high signal intensity on STIR sequences. There must be at least two signals on a single slice or one signal (one inflammatory zone) on two consecutive slices. MRI-active spondylitis also manifests as high-intensity signal areas on STIR sequences at the corners of the vertebral bodies (anterior spondylitis) and in the posterior elements of the spine (facet joints, ligaments, etc.) [19–22].

2.5 Other Procedures

Comments: Morphological changes in psoriasis are characterized by marked epidermal acanthosis with characteristic club-shaped downward elongation of epidermal rete ridges and thinning of the epidermis over the tips of elongated dermal papillae, impaired keratinization processes in the form of parakeratosis and disappearance of the granular layer. During the progressive stage of the disease, accumulations of neutrophilic leukocytes (Munro microabscesses) are found in the stratum corneum and the parakeratotic zone. Inflammatory infiltrates of varying intensity consisting of lymphocytes, histiocytes, and occasional neutrophilic leukocytes are detected around the convoluted, engorged capillaries of the papillary dermis.

• In the presence of signs of joint involvement, continuously relapsing and progressive arthritis, or therapy-refractory arthritis, consultation with a rheumatologist is recommended to exclude concomitant pathology [1, 2, 23].

GRL CLEL 4Guideline Recommendation Level C (Level of Evidence – 4)

• When prescribing genetically engineered biologic therapies to patients and during the course of treatment, consultations with a phthisiatrician are recommended in order to rule out contraindications to genetically engineered biologic therapy [24].

GRL CLEL 5Guideline Recommendation Level C (Level of Evidence – 5)

Comments: During therapy with genetically engineered biologic drugs—tumor necrosis factor alpha (TNF-alpha) inhibitors or interleukin inhibitors—reactivation of mycobacterial infection with the development of pulmonary tuberculosis and other organ involvement is possible. The risk of mycobacterial infection activation is higher with the use of TNF-α inhibitors.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 Conservative Treatment

Patients with psoriasis may be prescribed topical corticosteroids for dermatological use, salicylic acid, and other topical antipsoriatic agents (calcipotriol) for external therapy. The prescription of other dermatological agents is also possible. If the disease is of moderate or severe degree, systemic therapy with methotrexate**, retinoids for the treatment of psoriasis, the immunosuppressant cyclosporine**, or ultraviolet irradiation of the skin is administered.

If systemic psoriasis treatments are insufficiently effective, the patient must be switched to immunosuppressive therapy. Selective immunosuppressants (phosphodiesterase-4 inhibitors, Janus kinase blockers), tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors are used, regardless of the pharmacokinetics of systemic therapy. If adverse events occur that lead to the discontinuation of methotrexate**, cyclosporine**, or retinoids for psoriasis treatment, a washout period must be provided until impaired functions and/or laboratory parameters normalize, which should precede the induction phase of targeted biologic therapy. When switching a patient from methotrexate** or cyclosporine** therapy, it is advisable to gradually reduce the dose of the aforementioned drugs while initiating the induction phase using standard regimens and doses of selective immunosuppressants (phosphodiesterase-4 inhibitors, Janus kinase blockers), tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors as recommended in the prescribing information (within 12–16 weeks for methotrexate**; no more than 2–8 weeks for cyclosporine**).

With prolonged use of selective immunosuppressants (phosphodiesterase-4 inhibitors, Janus kinase blockers), tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors in cases of effective treatment and good tolerability, therapy should be continued using standard doses and regimens. Discontinuation of selective immunosuppressants (phosphodiesterase-4 inhibitors, Janus kinase blockers), tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors should be avoided in such cases, as patients with moderate-to-severe psoriasis have a high risk of relapse upon cessation of this therapy. When resuming treatment with targeted biologic agents, previous efficacy may be difficult to achieve, as intermittent treatment increases the risk of neutralizing antibody formation. The efficacy of combining tumor necrosis factor alpha (TNF-alpha) inhibitors with methotrexate** to prevent autoantibody formation has been proven (currently, no randomized clinical trial results have been published demonstrating the benefits of combining interleukin inhibitors with methotrexate** to reduce the immunogenicity of these drugs and prevent loss of efficacy) [25]. Repeated switching between drugs from the tumor necrosis factor alpha (TNF-alpha) inhibitor and interleukin inhibitor groups may be accompanied by a decrease in therapeutic efficacy and the inability to achieve clear or almost clear skin in the patient.

During therapy with selective immunosuppressants (phosphodiesterase-4 inhibitors, Janus kinase blockers), tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors, in accordance with the instructions for medical use, monitoring of adverse events and laboratory parameters should be carried out.

• For the treatment of localized rashes, topical therapy is recommended for patients [1, 2, 26].

GCR CLEL 5Grade of Recommendations C (Level of Evidence – 5)

• For the treatment of localized rashes, corticosteroids used in dermatology are recommended for patients [1, 2, 26]:

hydrocortisone** 0.1% ointment, 0.1% cream, 1% ointment for topical use; apply to skin lesions 2 times a day for 3–4 weeks [27–33].

GCR CLEL 5Grade of Recommendations C (Level of Evidence – 5)

Comments: Hydrocortisone** 0.1% cream and ointment may be used from the age of 6 months. A contraindication for the prescription of hydrocortisone** 1% ointment is age under 2 years.

or

alclometasone 0.05% cream, 0.05% ointment; apply an even layer to affected skin areas 2–3 times a day for 3–4 weeks. In children and during the maintenance phase, the drug may be used 1 time a day. To prevent relapses during the maintenance treatment of chronic conditions, therapy should be continued for some time after all symptoms disappear [34, 35].

GRC BLEL 2Guideline Recommendation Level B (Level of Evidence – 2)

Comments: Contraindications for prescribing alclometasone cream and ointment include age under 6 months. The maximum duration of treatment in children (from 6 months of age) is 3 weeks.

or

triamcinolone 0.1% ointment for topical use; apply to affected skin areas 2 times a day for 3–4 weeks [36].

GRC BLEL 3Guideline Recommendation Level B (Level of Evidence – 3)

Comments: A contraindication for prescribing triamcinolone is age under 2 years. The duration of treatment with triamcinolone ointment in children over 2 years of age should not exceed 5 days.

or

mometasone** 0.1% cream, 0.1% ointment; apply a thin layer to affected skin areas 1 time a day for 3–4 weeks [36–38].

GRC BLEL 2Guideline Recommendation Level B (Level of Evidence – 2)

Comments: A contraindication for prescribing mometasone** is age under 2 years.

or

methylprednisolone aceponate 0.1% ointment for topical use; apply a thin layer to affected skin areas 1 time a day for 3–4 weeks [39–42].

GRC CLEL 4Guideline Recommendation Level C (Level of Evidence 4)

Comments: An age under 4 months is a contraindication for prescribing #methylprednisolone aceponate ointment.

or

#methylprednisolone aceponate cream 0.1%, emulsion 0.1% for external use; apply a thin layer to the affected skin areas 1 time per day for 3–4 weeks [39–42]

LoR CLoE 4Level of Recommendation C (Level of Evidence – 4)

Comments: An age under 4 months is a contraindication for prescribing #methylprednisolone aceponate cream and emulsion.

or

betamethasone** cream 0.05%, 0.1%, ointment 0.05%, 0.1%; apply to the affected skin areas 2 times per day for 3–4 weeks [43–48].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: An age under 1 year is a contraindication for prescribing betamethasone** cream 0.05% and ointment 0.05%. An age under 6 months is a contraindication for prescribing betamethasone** cream 1%.

or

betamethasone spray 0.05%; apply to the affected skin areas 2 times per day for 3–4 weeks [45, 49–51]

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: An age under 2 years is a contraindication for prescribing betamethasone spray 0.05%.

or

fluocinolone acetonide ointment for external use 0.025%; apply to the affected skin areas 2–4 times per day, duration of treatment is up to 25 days [52]

GCR CLEL 4Grade of Recommendations C (Level of Evidence – 4)

Comments: An age under 2 years is a contraindication for the use of fluocinolone acetonide ointment.

or

fluocinolone acetonide cream for external use 0.025%, gel for external use 0.025%; apply to the affected skin areas 2–4 times per day for up to 4 weeks [53, 54]

(Grade of Recommendations C (Level of Evidence – 5)

Comments: An age under 2 years is a contraindication for the use of fluocinolone acetonide cream and gel.

or

#fluticasone ointment 0.005% for external use, cream 0.05% for external use; apply to the affected skin areas 2 times per day for 3–4 weeks [45, 55]

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: An age under 10 years is a contraindication for prescribing fluticasone ointment and cream.

or

clobetasol ointment, cream for external use 0.05%; apply a very thin layer to the affected skin areas 1 time per day for 3–4 weeks [33, 56–58].

GCR CLEL 2Grade of Recommendations C (Level of Evidence – 2)

Comments: Depending on the nature and localization of psoriatic eruptions, dermatological corticosteroids (for local treatment of skin diseases) are used in various dosage forms—ointments, creams, sprays, or lotions. As symptoms subside, the frequency of application can be reduced or other topical therapies can be prescribed. In pediatric practice, treatment should be initiated with weak or moderately active topical glucocorticoids. Glucocorticoids used in dermatology should not be applied to the skin of the face, neck, and natural skin folds in infants and toddlers. An age under 1 year is a contraindication for prescribing clobetasol.

• In case of pronounced desquamation in skin lesions, patients with psoriasis are recommended topical agents containing salicylic acid to reduce the intensity of desquamation:

salicylic acid** 2–5% ointment applied to skin lesions with pronounced desquamation [1, 2, 26, 59–61]

GGR BLEL 3Grade of Recommendation B (Level of Evidence – 3)

or

Glucocorticosteroids in combination with antiseptics:

Betamethasone + salicylic acid ointment, topical solution applied to affected skin areas 2 times a day [59, 62–65]

GGR CLEL 2Grade of Recommendation C (Level of Evidence – 2)

Comments: For most dosage forms of the drug Betamethasone + salicylic acid, children under 2 years of age is a contraindication for prescribing.

or

mometasone + salicylic acid ointment applied in a thin layer to affected skin areas 2 times a day [36, 66].

GGR BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comments: In the progressive stage of psoriasis, it is indicated to use topical agents containing salicylic acid in a low concentration of 2%. In the stationary and regressive stages, it is possible to prescribe agents with a higher concentration of salicylic acid – 3% and 5%. Children under 12 years of age is a contraindication for prescribing mometasone + salicylic acid ointment.

• Patients are recommended other topical preparations for the treatment of psoriasis

calcipotriol 0.005% topical ointment applied 2 times a day to affected skin areas for 6–8 weeks [67–70].

GGR ALEL 2Grade of Recommendation A (Level of Evidence – 2)

Comments: During long-term treatment, the daily dose should not exceed 15 g, and the weekly dose should not exceed 100 g of cream or ointment. The drug should not be applied to extensive skin areas exceeding 30% of the body surface area. Repeated courses of treatment are possible during subsequent exacerbations. The use of calcipotriol can serve as a method of choice for the treatment of plaque psoriasis; however, the drug should not be prescribed before UV irradiation, as this leads to inactivation of calcipotriol. Children under 6 years of age is a contraindication for prescribing calcipotriol 0.005% topical ointment.

or

betamethasone + calcipotriol ointment 1 time a day for adults for a period of not more than 4 weeks [71–75].

GGR BLEL 2Grade of Recommendation B (Level of Evidence – 2)

or

betamethasone + calcipotriol gel 1 time a day for adults for 4 weeks on the scalp and 8 weeks on non-lesional/smooth skin [76].

GGR BLEL 3Grade of Recommendation B (Level of Evidence – 3)

Comments: The application area of the combined drug betamethasone + calcipotriol should not exceed 30% of the body surface area. The maximum daily dose is no more than 15 g, the maximum weekly dose is 100 g. The drug should remain on the skin during the night or day to achieve an optimal therapeutic effect. Repeated use of the drug is possible under medical supervision. The use of the combined drug betamethasone + calcipotriol accelerates the achievement of a clinical effect. Simultaneous topical application of salicylic acid leads to the inactivation of calcipotriol.

• To accelerate the regression of rashes, patients are recommended other drugs for the treatment of skin diseases:

zinc pyrithione 0.2% topical aerosol is sprayed from a distance of 15 cm onto affected skin areas 2–3 times a day. To achieve a sustained effect, it is recommended to continue using the drug for 1 week after the disappearance of clinical symptoms [77, 78].

LoR CLoE 4Level of Recommendation C (Level of Evidence – 4)

Comments: Zinc pyrithione aerosol is contraindicated in children under 1 year of age.

or

apply zinc pyrithione 0.2% topical cream in a thin layer to the affected skin 2 times a day for 1–1.5 months [79].

GGR BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comments: Zinc pyrithione cream is contraindicated in children under 1 year of age.

In the stationary stage, patients with dense infiltrated plaques are recommended:

#ichtammol 5% (extemporaneously compounded) or 10% ointment applied to the lesions 1–2 times a day [1, 2, 26; 80]

GRC CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Extemporaneously compounded medicinal products are used in dermatology, and 5% ichtammol ointment may also be compounded and used.

or

naphthalan oil 5% or 10% ointment (extemporaneously compounded) applied to the lesions 1–2 times a day [1, 2, 26; 80]

GRC CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Extemporaneously compounded medicinal products are used in dermatology, including 5% or 10% naphthalan oil-containing ointment, which may be compounded and used.

or

birch tar liquid for external use applied to skin lesions initially for 15 minutes once daily, gradually increasing the application time up to 30 minutes. The product is removed with a cotton or gauze swab moistened with vegetable oil or liquid paraffin. The duration of the treatment course is up to 4 weeks, with intervals of 1–2 months between courses [26; 80]

GRC CLEL 5Grade of Recommendation C (Level of Evidence – 5)

clobetasol 0.05% shampoo applied daily by adult patients to dry scalp (exposure time 15 minutes), followed by rinsing [81–83].

GGR BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comments: Long-term therapy with this shampoo for up to six months, administered twice a week, prevents the recurrence of scalp dermatosis. Clobetasol 0.05% shampoo is contraindicated in children under 18 years of age.

or

Betamethasone + Salicylic acid topical solution applied to the lesions 2 times a day [63]

GCR CLEL 2Grade of Recommendations C (Level of Evidence – 2)

Comments: Betamethasone + Salicylic acid topical solution is contraindicated in children under 2 years of age. The drug should be used with caution in children under 12 years of age.

or

betamethasone + calcipotriol topical gel once daily for adults for 4 weeks [76].

GGR BLEL 3Grade of Recommendation B (Level of Evidence – 3)

Comments: Betamethasone + calcipotriol topical gel is contraindicated in children under 18 years of age.

or

zinc pyrithione 1% shampoo applied to wet hair followed by scalp massage, then rinse the hair, reapply and leave the shampoo on the head for 5 minutes, then rinse thoroughly with plenty of water. Use 2–3 times a week; treatment course is 5 weeks [78].

GRC CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: During remission, the shampoo can be used 1–2 times a week as a relapse prevention measure.

methotrexate** subcutaneously, intramuscularly, or orally 10–15–20 mg, if necessary up to 25–30 mg, once a week [84–89].

LoR AGoE 2Level of Recommendation A (Grade of Evidence – 2)

Comments:Methotrexate** is a highly effective drug for the treatment of vulgaris psoriasis, psoriatic erythroderma, pustular, and arthropathic psoriasis, but it is associated with potentially serious side effects. The patient's condition must be monitored before prescribing methotrexate** and during methotrexate** therapy. In order to timely detect adverse events, it is necessary to monitor the peripheral blood counts; for this purpose, a complete blood count (CBC) with leukocyte and platelet counts should be performed once a week. It is necessary to monitor liver transaminase activity, renal function, and perform targeted chest X-rays as needed. Methotrexate** therapy should be discontinued if the leukocyte count in the blood is less than 1.5x109/L, the neutrophil count – is less than 0.2x109/L, and the platelet count is less than 75x109/L. An increase in blood creatinine by 50% or more compared to baseline requires re-measurement of the creatinine level. An increase in blood bilirubin levels requires intensive detoxification therapy. In the event of diarrhea and ulcerative stomatitis, methotrexate** therapy must be interrupted. If signs of pulmonary toxicity appear (especially a dry cough without sputum), treatment with methotrexate** should be discontinued. The appearance of signs of bone marrow depression, unusual bleeding or bruising, black tarry stools, blood in the urine or stool, or pinpoint red spots on the skin requires immediate medical consultation. Men and women of reproductive potential should use reliable methods of contraception during methotrexate** treatment and for at least 3 months thereafter to avoid conception. Patients receiving methotrexate** must avoid immunization (unless approved by a physician) for an interval ranging from 3 months to 1 year after taking the drug.

To reduce the likelihood of adverse events, treatment with methotrexate** should be accompanied by oral #folic acid** therapy at 5 mg once a week, 24 hours after taking methotrexate** [90, 91]. A contraindication for prescribing #folic acid is pediatric age under 18 years.

After achieving a therapeutic effect, maintenance therapy at the minimum effective dose (not exceeding 22.5 mg per week) is possible.

Methotrexate** is contraindicated in children under 3 years of age.

or

Retinoids for the treatment of psoriasis, according to the instructions for use, are prescribed at an initial daily dose of 25 mg (i.e., 1 capsule of 25 mg) or 30 mg per day (i.e., 3 capsules of 10 mg); the drug is taken once daily with meals or with milk; the duration of administration is 2–4 weeks. The maintenance dose depends on the clinical efficacy and tolerability of the drug. As a rule, the optimal therapeutic effect is achieved at a daily dose of 25–50 mg, taken for an additional 6–8 weeks. The maximum dose is 75 mg/day (i.e., 3 capsules of 25 mg) [92–95].

GGR BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comments: The drug from the retinoids group for the treatment of psoriasis is taken with meals or with milk. Before prescribing and during therapy with retinoids for the treatment of psoriasis, the patient's condition must be monitored. Liver function should be monitored before starting treatment with retinoids for the treatment of psoriasis, every 1–2 weeks during the first month after starting treatment, and then every 3 months. If test results indicate pathology, monitoring should be performed weekly. If liver function does not normalize or worsens, the drug should be discontinued. In this case, it is advisable to continue monitoring liver function for at least 3 months.

It is necessary to monitor fasting serum cholesterol and triglyceride levels.

In patients with diabetes mellitus, retinoids for the treatment of psoriasis may impair glucose tolerance, so blood glucose concentrations should be checked more frequently than usual during the early stages of treatment.

Due to the possibility of impaired night vision, careful monitoring of visual disturbances is required.

Due to the high teratogenicity of retinoids for the treatment of psoriasis, a negative pregnancy test result must be obtained 2 weeks before starting treatment. During treatment, it is advisable to perform additional pregnancy tests at least once a month. It is absolutely essential that every woman of childbearing potential uses effective hormonal oral contraceptives (birth control pills) without interruption for 4 weeks before starting treatment, during treatment, and for two years after completing therapy with retinoids for the treatment of psoriasis. Retinoids for the treatment of psoriasis must not be prescribed to nursing mothers. In children, retinoids for the treatment of psoriasis are prescribed only when all other treatment methods are ineffective.

or

Cyclosporine** in adult patients at an initial dose of 2.5 mg/kg of body weight per day in 2 divided doses (morning and evening). If no improvement is observed after 4 weeks of treatment, the dose can be increased to 5 mg/kg of body weight per day in the absence of clinically significant laboratory abnormalities [85, 96–100].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: Before prescribing cyclosporine** and during cyclosporine** treatment, the patient's condition should be monitored to prevent the development of side effects. Regular monitoring of plasma creatinine concentration is necessary—an increase may indicate a nephrotoxic effect and require a dose reduction: by 25% if the creatinine level increases by more than 30% from baseline, and by 50% if it doubles. If reducing the dose over 4 weeks does not lead to a decrease in creatinine levels, cyclosporine** is discontinued. Monitoring of blood pressure, blood potassium, uric acid, bilirubin, determination of aspartate aminotransferase and alanine aminotransferase activity in the blood, and a biochemical blood test for lipid metabolism disorders are indicated [4, 6, 101]. In severe cases of the disease, to rapidly achieve an effect, the initial dose may be 5 mg/kg. Upon achieving a satisfactory clinical result, cyclosporine** is discontinued, and upon subsequent relapse, it is prescribed at the previous effective dose. The drug should be withdrawn gradually, reducing its dose by 1 mg/kg per week for 4 weeks or by 0.5–1 mg/kg every 2 weeks. The use of the drug must be discontinued if a satisfactory response is not achieved after 6 weeks of treatment at a dose of 5 mg/kg per day. Treatment with cyclosporine** increases the risk of lymphoproliferative disorders and other malignant neoplasms, especially of the skin [102, 103]. The use of live attenuated vaccines during cyclosporine** treatment is not indicated. Patients using cyclosporine** should not simultaneously receive PUVA therapy or medium-wave UV therapy. Simultaneous use of cyclosporine** and phototherapy methods (PUVA therapy; UVB-311 therapy) is contraindicated due to an increased risk of non-melanoma skin cancer. A contraindication for prescribing cyclosporine** to patients with psoriasis is pediatric age under 18 years.

or

Phototherapy [104–127]

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: Before prescribing phototherapy, to identify contraindications, a clinical examination of the patient and a set of laboratory tests are advisable, including a complete blood count (CBC), general urinalysis, general clinical biochemical blood test (including the determination of liver and kidney function parameters), a consultation with a general practitioner, endocrinologist, obstetrician-gynecologist (for women), and ophthalmologist (when prescribing ultraviolet skin irradiation, photochemotherapy with internal photosensitizers (PUVA)). Examinations by other specialists are performed according to indications. Narrowband ultraviolet B therapy with a wavelength of 311 nm can be used in children from 7 years of age for severe forms and a torpid course of the disease. Selective phototherapy (SPT) is used in children from 7 years of age. PUVA therapy is used from 18 years of age.

The initial irradiation dose is determined based on individual skin sensitivity by measuring the minimum phototoxic dose in PUVA therapy or the minimum erythemal dose in UVB therapy, or without determining minimum phototoxic/erythemal doses based on skin phototype (according to T.B. Fitzpatrick's classification). The degree of suntan, affected area, and severity of the skin inflammatory reaction should also be considered. Across all phototherapy methods, the main immediate adverse reactions are erythema and pruritus. Blisters, hyperpigmentation, or skin dryness are observed less frequently. Long-term multi-course phototherapy dose-dependently causes the development of symptoms of chronic skin photodamage. Lentigines, diffuse hyperpigmentation, and actinic elastosis develop most frequently. Reticular seborrheic keratosis, telangiectasias, and mottled skin pigmentation are less common. Since systemically administered psoralens can penetrate the lens of the eye via the bloodstream and bind to lens proteins under the influence of UVA, there is a potential risk of cataract development during PUVA therapy. Long-term multi-course PUVA therapy increases the risk of cutaneous squamous cell carcinoma. Factors increasing the carcinogenic risk of PUVA therapy include a total number of sessions exceeding 200; a cumulative UVA dose exceeding 1100 J/cm2; irradiation of the genitals in men; a high number of sessions over a short period; skin types I and II; prior skin tumor processes; ionizing and X-ray radiation therapy; arsenic compound treatment; and other carcinogenic factors (smoking, insolation, treatment with cyclosporine**, methotrexate**, etc.).

To reduce pruritus and skin dryness, patients must use emollients or moisturizers during the treatment course. In cases of persistent pruritus, systemic antihistamines, hypnotics, and sedatives are prescribed. When undergoing phototherapy, the following precautions must be observed: throughout the entire course of treatment, patients must avoid sun exposure and protect the skin of exposed body areas with clothing or sunscreen; during the phototherapy session (and throughout the entire day in the case of PUVA therapy), eyes must be protected with side-shielded protective goggles to prevent the development of keratitis, conjunctivitis, and cataracts; during procedures, the lips, auricles, nipples, and areas subject to chronic solar radiation (face, neck, dorsum of the hands) should be protected with clothing or sunscreens if no rashes are present on them; the use of other photosensitizing drugs and cosmetics must be excluded: tetracycline**, griseofulvin, sulfonamides, thiazides, antipsychotics (phenothiazine derivatives), aromatic oils, etc.

Patients with psoriasis receiving multi-course phototherapy (UVB, UVB-311, PUVA therapy, PUVA baths, 308 nm ultraviolet skin irradiation [excimer UV irradiation]) must have their total number of procedures and cumulative lifetime irradiation dose recorded, indicating the date of the treatment course, phototherapy method, number of procedures, and cumulative irradiation dose. Patients with moderate-to-severe forms of psoriasis who have previously received courses of PUVA therapy are indicated for rotation to the safer method of narrow-band UVB phototherapy.

Selective phototherapy (broadband ultraviolet therapy): the initial irradiation dose is 50–70% of the minimum erythemal dose. When dosing irradiation based on the patient's skin type and degree of suntan, irradiation is started at a dose of 0.01–0.03 J/cm2. Procedures are performed 3–5 times a week. In the absence of erythema, the single dose is increased every 2–3 procedures by 5–30%, or by 0.01–0.03 J/cm2. A course consists of 15–35 procedures [128, 129].

GCR CLEL 4Grade of Recommendations C (Level of Evidence – 4)

or

Narrow-band medium-wave ultraviolet therapy: the initial irradiation dose is 50–70% of the minimum erythemal dose. When dosing irradiation based on the patient's skin type and degree of suntan, irradiation is started at a dose of 0.1–0.3 J/cm2. Procedures are performed 3–4 times a week. In the absence of erythema, the single dose is increased every procedure or every other procedure by 5–30%, or by 0.05–0.2 J/cm2; if mild erythema appears, the dose is kept constant. A course consists of 15–35 procedures [104, 106, 108, 110, 114–116].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: Narrow-band medium-wave therapy with a wavelength of 311 nm (UVB-311) is a more effective method of UVB therapy compared to selective phototherapy. Narrow-band medium-wave therapy with a wavelength of 311 nm (UVB-311) is preferred when there is minimal infiltration in skin lesions.

or

308 nm ultraviolet skin irradiation (excimer UV irradiation). When rashes are localized on the face, neck, trunk, upper and lower extremities (except for the elbow and knee joints) and there is minimal infiltration of lesions, treatment is started with an irradiation dose equal to 1 minimum erythemal dose, and with marked infiltration of lesions – with a dose equal to 2. When rashes are localized on the skin of the elbow and knee joints and there is minimal infiltration of psoriatic plaques, the initial irradiation dose is 2 minimum erythemal doses, and in the presence of dense infiltrated plaques – 3. The single irradiation dose is increased every procedure or every 2nd procedure by 1 minimum erythemal dose, or 25% of the previous dose. Treatment is administered 2–3 times a week. A course consists of 15–35 procedures [104, 112, 118, 119].

LoR BLE 3Level of recommendation evidence B (level of data reliability – 3)

Comments: Treatment with 308 nm ultraviolet skin irradiation (excimer UV irradiation) is indicated mainly for localized forms of psoriasis with a lesion area of no more than 10% of the body surface.

or

Ultraviolet skin irradiation. Photochemotherapy with internal administration of photosensitizers (PUVA) in adult patients. Systemic psoralens are used as photosensitizers, taken at a dose of 0.6–0.8 mg per 1 kg of body weight in a single dose, 1.5–2 hours before irradiation with long-wave UV light. The initial UVA dose is 50–70% of the minimum phototoxic dose. When dosing irradiation based on the patient's skin type and degree of suntan, the initial dose is 0.25–1.0 J/cm2. Procedures are performed 2–4 times a week. In the absence of erythema, the single irradiation dose is increased every 2nd procedure by a maximum of 30%, or by 0.25–1.0 J/cm2. If mild erythema appears, the irradiation dose is kept constant. The maximum single UVA dose values are 15–18 J/cm2. A course consists of 15–35 procedures [104, 111, 123, 125–127].

GGR BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comments: PUVA therapy is preferred when there is marked infiltration in skin lesions. Before prescribing treatment to identify contraindications, a clinical examination of the patient and a set of laboratory tests are performed, including a complete blood count, urinalysis, blood chemistry (including liver and kidney function tests), and consultations with a general practitioner, ophthalmologist, endocrinologist, and obstetrician-gynecologist. According to indications, examinations by other specialists are performed. With widespread rashes, the entire skin is irradiated (general phototherapy), and with localized rashes, the affected body area is irradiated (local phototherapy). In a number of patients, lesions on the scalp and extremities regress more slowly than in other areas of the body. In such cases, general skin irradiation is combined with subsequent local irradiation of the head and/or extremities.

To reduce dyspeptic symptoms observed with oral administration of systemic psoralens, they should be taken with meals, washed down with milk, or the dose should be divided into 2 consecutive doses at a 30-minute interval. In individual cases, it is advisable to reduce the dose of the administered drug.

A contraindication for prescribing Ammi majus fruit furocoumarin tablets is childhood under the age of 18 years. Accordingly, prescribing photochemotherapy with internal administration of photosensitizers (PUVA) to children under 18 years of age is contraindicated.

or

Ultraviolet skin irradiation. Photochemotherapy with topical photosensitizers in adult patients. Topical psoralens are used as photosensitizers, which are applied to the lesions 15–60 minutes before irradiation. The initial UVA dose is 20–30% of the minimal phototoxic dose. When dosing irradiation depending on the patient's skin type and tan level, the initial dose is 0.2–0.5 J/cm2. Procedures are performed 2–4 times a week. In the absence of erythema, the single irradiation dose is increased every 2–3 procedures by a maximum of 30%, or by 0.1–0.5 J/cm2. If mild erythema appears, the dose is kept constant. The maximum single UVA dose is 5–8 J/cm2. A course consists of 20–50 procedures [110, 111, 124].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: A contraindication for prescribing 0.3% topical solution of Ammi majus fruit furocoumarins is childhood under 18 years of age. Accordingly, photochemotherapy with topical photosensitizers is contraindicated in children under 18 years of age.

or

PUVA baths in adult patients using an aqueous solution of Ammi majus fruit furocoumarins. The initial UVA irradiation dose is 20–30% of the minimal phototoxic dose, or 0.3–0.6 J/cm2. For both general and local PUVA baths, irradiation is performed 2–4 times a week. In the absence of erythema, the single dose is increased every 2nd procedure by a maximum of 30%, or by 0.2–0.5 J/cm2. In patients with skin types I–II, dosing is carried out within the dose range of 0.5–1.0–1.5–2.0–2.5–3.0 J/cm2. In patients with skin types III–VI, irradiation is carried out within the dose range of 0.6–1.2–1.8–2.4–3.0–3.6 J/cm2. If mild erythema appears, the dose is kept constant. The maximum single irradiation dose in patients with skin types I–II is 4.0 J/cm2, and in patients with skin types III–VI, it is 8.0 J/cm2. A course consists of 15–35 procedures [116, 120–123, 125, 130].

GGR BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comments: To prepare the aqueous solution of Ammi majus fruit furocoumarins, an official 0.3% alcoholic solution of the photosensitizer is used. The concentration of Ammi majus fruit furocoumarins in the bath is 1 mg/l, water temperature is 36–37 °C, and the bath duration is 15 minutes. For widespread eruptions, general baths with an aqueous solution of Ammi majus fruit furocoumarins followed by irradiation of the entire skin surface (general PUVA baths) are prescribed; for localized eruptions, local baths followed by irradiation of the affected area (local PUVA baths) are performed.

Long-wave UV irradiation is carried out immediately after the bath (the patient's skin is first wiped dry with a towel). To determine the minimal phototoxic dose, phototesting is performed by irradiating the skin with increasing doses of UVA.

A contraindication for prescribing 0.3% topical solution of Ammi majus fruit furocoumarins is childhood under 18 years of age. Accordingly, PUVA baths are contraindicated in children under 18 years of age.

phototherapy + retinoids for the treatment of psoriasis. Irradiation is started, depending on the patient's individual sensitivity, at a dose of 30–50% of the MED or MPD. Subsequently, the single dose is increased by 10–30% of the MED or MPD. If mild erythema appears, the irradiation dose is not increased, and in the case of pronounced erythema and skin tenderness, a break in treatment is required [131].

GCR CLEL 5Grade of Recommendations C (Level of Evidence – 5)

Comments: Phototherapy and retinoids for the treatment of psoriasis have a synergistic effect, so their combination can improve treatment outcomes in severe and resistant forms of psoriasis, including erythrodermic, pustular, and palmoplantar forms. Retinoids are combined with various methods of phototherapy: UVB therapy, ultraviolet skin irradiation, photochemotherapy with systemic photosensitizers (PUVA), and PUVA baths. It should be taken into account that retinoids for the treatment of psoriasis can cause increased desquamation and a decrease in the thickness of the stratum corneum of the epidermis, which in turn can lead to increased penetration of UV light through altered skin and an increased risk of erythema. Therefore, in the initial phase of combination therapy, single doses of retinoids for psoriasis and UV irradiation should be lower than those used in monotherapy, and the dose escalation regimen should be more cautious to avoid unwanted phototoxic reactions.

Before prescribing retinoids for the treatment of psoriasis to patients receiving UVB or PUVA therapy as monotherapy, it is indicated to reduce the irradiation dose by 50% [131].

or

phototherapy + methotrexate** [132–134].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: It is possible to increase the effectiveness of treatment with methotrexate** when combined with UVB or PUVA therapy. Specific side effects of such combination therapy have not been established, as long-term observation is required. An increase in phototoxicity is possible when methotrexate** is combined with PUVA therapy, which was not observed when the drug was used in combination with UVB therapy.

or

narrowband medium-wave ultraviolet therapy + apremilast** in adult patients** [135]

Level of Evidence CGrade of Recommendation 4Level of Evidence C (grade of recommendation – 4)

Comments: Apremilast** is contraindicated in patients under 18 years of age.

• In the absence of a clinical effect from other systemic therapies, including cyclosporine** and retinoids for the treatment of psoriasis (in adults), methotrexate** (in children aged 3 years and older, and adults), and PUVA therapy (in adults), or in cases of intolerance or contraindications to their use in patients with widespread eruptions (moderate to severe psoriasis), it is recommended to use selective immunosuppressants (phosphodiesterase-4 inhibitor apremilast**, Janus kinase inhibitor tofacitinib**), as well as immunosuppressants that are genetically engineered biological products by manufacturing method – tumor necrosis factor alpha (TNF-alpha) inhibitors and interleukin inhibitors. Below, the immunosuppressant drugs used in the treatment of psoriasis are listed not in order of priority, but in alphabetical order.

adalimumab** in adults and children aged 4 years and older with moderate-to-severe plaque psoriasis, subcutaneously into the thigh or abdomen at an initial dose of 80 mg, maintenance dose of 40 mg every 2 weeks, starting one week after the initial dose [136–138,209].

Level of Evidence AGrade of Recommendation 2Level of Evidence A (grade of recommendation – 2)

Comments: If the therapeutic response to adalimumab** monotherapy decreases, a combined use of adalimumab** and UVB-311 therapy can be employed

or

apremilast** in adult patients at 30 mg 2 times a day, morning and evening, approximately 12 hours apart, orally, regardless of meals. Initial dose titration is required; after the initial titration, repeat titration is not required [139–141].

GGR ALEL 2Grade of Recommendation A (Level of Evidence – 2)

Comments: The efficacy of apremilast** is noted in patients with nail psoriasis, scalp psoriasis, palmoplantar psoriasis, and psoriatic arthritis. The use of apremilast** is contraindicated during pregnancy. Pregnancy must be excluded before starting treatment. Women of childbearing potential must use an effective method of contraception during therapy. It should not be used during breastfeeding. The drug is contraindicated in children under 18 years of age and in the presence of rare hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the drug contains lactose). The combined use of apremilast** and UVB-311 therapy can be used to increase treatment efficacy. A contraindication for prescribing apremilast** is childhood under 18 years of age.

or

guselkumab** is recommended for the treatment of severe and moderate plaque psoriasis in adult patients who are candidates for systemic therapy. The recommended dose is 100 mg administered as subcutaneous injections. The second injection is given 4 weeks after the first dose, and then every 8 weeks [142–145].

Level of Evidence AGrade of Recommendation 2 Level of Evidence A (grade of recommendation – 2)

Comments: The efficacy of guselkumab** is noted in patients with nail psoriasis, scalp psoriasis, and palmoplantar psoriasis. The drug's efficacy does not depend on the patient's weight. A contraindication for prescribing guselkumab** is childhood under 18 years of age.

or

ixekizumab** for pediatric and adolescent patients aged 12 years and older with a body weight of 50 kg or more with moderate-to-severe plaque psoriasis when systemic therapy is indicated, and for adult patients with moderate-to-severe psoriasis. For adult patients, the recommended initial dose of ixekizumab** (week 0) for the treatment of adult patients is 160 mg administered as a subcutaneous injection, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, and then a maintenance dose of 80 mg every 4 weeks (regardless of body weight). The initial dose of 160 mg is administered as two separate 80 mg subcutaneous injections [146–152]. The recommended initial dose of ixekizumab** (week 0) for the treatment of pediatric and adolescent patients aged 12 years and older with a body weight of 50 kg or more is 160 mg administered as a subcutaneous injection, followed by a maintenance dose of 80 mg every 4 weeks (regardless of body weight). The initial dose of 160 mg is administered as two separate 80 mg subcutaneous injections [153].

LoR AGoE 2Level of Recommendation A (Grade of Evidence – 2)

Comments: The efficacy of ixekizumab** has been noted in patients with nail psoriasis, scalp psoriasis, palmoplantar psoriasis, and anogenital psoriasis. Ixekizumab** is contraindicated in children under 12 years of age.

or

infliximab** for adult patients with psoriasis as an intravenous infusion over at least 2 hours at a rate of no more than 2 mL/min under the supervision of medical personnel. For the treatment of psoriasis, the initial dose of infliximab** is 5 mg per kg of the patient's body weight. Following the initial dose, subsequent doses are administered at the same amount at 2 weeks, then 6 weeks later, and every 8 weeks thereafter. If there is no response within 14 weeks (after four intravenous infusions), continuing treatment is not recommended [154–158].

LoR AGoE 2Level of Recommendation A (Grade of Evidence – 2)

Comment: During the intravenous infusion of infliximab** and for at least 1–2 hours after its completion, the patient must be under medical supervision. During the intravenous infusion of infliximab**, blood pressure, heart rate, respiratory rate, and body temperature must be measured every 30 minutes.

or

netakimab** for adult patients with moderate-to-severe psoriasis at a dose of 120 mg administered once a week at weeks 0, 1, and 2, followed by maintenance therapy at a dose of 120 mg once every 4 weeks starting from week 6. The 120 mg dose is administered as two subcutaneous injections of 1 mL (60 mg) of the drug each [159, 160].

GGR BLEL 2Grade of Recommendation B (Level of Evidence – 2)

or

risankizumab** for adult patients for the treatment of moderate-to-severe plaque psoriasis. The recommended dose is 150 mg at week 0, week 4, and every 12 weeks thereafter (administered as two 75 mg subcutaneous injections simultaneously) [161–164].

GGR ALEL 2Grade of Recommendation A (Level of Evidence – 2)

Comments: Risankizumab** is contraindicated in children under 18 years of age.

or

secukinumab** for adult patients with moderate-to-severe psoriasis subcutaneously, preferably into unaffected skin, at a starting dose of 300 mg at weeks 0, 1, 2, and 3, followed by maintenance therapy administered monthly starting from week 4. Each 300 mg dose is administered as two separate 150 mg subcutaneous injections [165–168].

GGR ALEL 2Grade of Recommendation A (Level of Evidence – 2)

Comments: the efficacy of secukinumab** has been noted in patients with nail psoriasis, scalp psoriasis, palmoplantar psoriasis, psoriatic arthritis, and generalized pustular psoriasis.

or

secukinumab** for children and adolescents aged 6 years and older for whom systemic therapy is indicated. The recommended dose of secukinumab** for children and adolescents aged 6 years and older is calculated based on body weight (see table) and administered as a subcutaneous injection as an initial dose at weeks 0, 1, 2, and 3, followed by monthly maintenance administration starting from week 4. Each 75 mg dose is administered as a single subcutaneous injection. Each 150 mg dose is administered as a single subcutaneous injection. Each 300 mg dose is administered as two separate 150 mg subcutaneous injections [169–171].

GGR ALEL 1Grade of Recommendation A (Level of Evidence – 1)

Comments: the efficacy of secukinumab** has been noted in patients with nail psoriasis, scalp psoriasis, palmoplantar psoriasis, psoriatic arthritis, and generalized pustular psoriasis.

Table: Recommended dose of secukinumab** in children and adolescents with plaque psoriasis

or

tofacitinib** 10 mg twice daily orally [172–177]

ORR AELR 1Level of recommendation validity A (level of evidence reliability – 1)

Comments:Contraindication to the administration of tofacitinib** is childhood under 18 years of age.

or

ustekinumab** in adult patients with moderate-to-severe psoriasis subcutaneously 45 mg. The second injection is given 4 weeks after the first administration, then every 12 weeks. In patients with a body weight of more than 100 kg, the drug is recommended to be used at a dose of 90 mg. In case of insufficient clinical efficacy when used every 12 weeks, the dose of the drug should be increased to 90 mg every 12 weeks. If this dosing regimen is not effective, the 90 mg dose of the drug should be administered every 8 weeks [178–182].

GGR ALEL 2Grade of Recommendation A (Level of Evidence – 2)

or

ustekinumab** in children from 6 years of age with moderate-to-severe psoriasis; in children weighing less than 60 kg, the recommended dose is 0.75 mg/kg [183, 184].

GGR ALEL 1Grade of Recommendation A (Level of Evidence – 1)

Comments: Can be combined with methotrexate** or narrowband UVB 311 nm therapy.

or

certolizumab pegol** in adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy, including patients with psoriatic arthritis, taking into account pronounced inhibition of joint destruction and high efficacy regarding dactylitis, enthesitis, and spondylitis [185].

GGR ALEL 2Grade of Recommendation A (Level of Evidence – 2)

Comments: #Certolizumab pegol** may be prescribed to female patients of reproductive age taking into account a potential pregnancy, throughout the entire pregnancy, as well as during breastfeeding [186].

or

etanercept** lyophilizate for solution for subcutaneous administration in adults with moderate or severe psoriasis 25 mg twice weekly with an interval of 3–4 days. Administration of 50 mg of the drug once a week by a single subcutaneous injection or two injections of 25 mg of the drug administered almost simultaneously is possible. Alternatively, etanercept** can be used at 50 mg twice a week for no more than 12 weeks. If continued treatment is necessary, etanercept** should be administered at a dose of 25 mg twice a week or 50 mg once a week. Therapy should be carried out until remission is achieved and, as a rule, for no more than 24 weeks. In some cases, the duration of treatment may be more than 24 weeks.

Children 6 years of age and older with severe psoriasis who have experienced intolerance or inadequate response to other systemic therapy or phototherapy, with a body weight of 62.5 kg or more, can use etanercept** in the pharmaceutical form of a lyophilizate for solution, which allows administering a dose of less than 25 mg, or a solution for subcutaneous administration in the form of single-use syringes or pre-filled pens. The dose is determined based on 0.8 mg/kg of body weight (maximum single dose 50 mg). The drug is administered once a week, the duration of therapy is no more than 24 weeks. If re-administration of etanercept** is necessary, the treatment duration specified above should be observed. The dose of the drug is 0.8 mg/kg of body weight (maximum single dose 50 mg) once a week. Combined use of etanercept** and narrowband UVB 311 nm therapy can be used when the therapeutic response to etanercept** monotherapy decreases [187, 188].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: If a dose is missed at the scheduled time, the drug must be administered as soon as remembered, provided that the next injection is due no earlier than in a day. Otherwise, the missed injection should be skipped and the regular injection given on time. Administration of etanercept** should be discontinued if no response to the ongoing therapy is observed after 12 weeks of treatment.

3.2 Surgical Treatment

Not applicable.

3.3 Other Treatment

Not applicable.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Patients with psoriasis in the regressive stage of the disease and during remission are indicated for comprehensive spa treatment (sanatorium-resort treatment), the effectiveness of which is due to the summation of the therapeutic effects of climatotherapy, balneotherapy, and peloid therapy [189–192]. In the stationary stage of psoriasis and during remission, patients are indicated for various options of balneotherapy – the external use of general mineral (hydrogen sulfide, carbon dioxide) and radon baths, as well as mud therapy (peloid therapy). Balneotherapy significantly improves metabolic and blood circulation processes in the skin, and has an anti-inflammatory and active resolving effect. Contraindications to balneotherapy and mud therapy: all diseases in the acute stage or during an exacerbation of a chronic process, infectious diseases (tuberculosis, syphilis, etc.), pregnancy, bleeding and a predisposition to it, malignant neoplasms, uterine fibroids, mastopathy, circulatory insufficiency above stage IIA, progressive angina pectoris and angina decubitus, cardiac asthma, and prognostically unfavorable heart rate and myocardial conduction disorders. The effectiveness of climatotherapy, including thalassotherapy, is indicated in the regression stage of psoriasis and in the remission phase.

Comments: Treatment with hydrogen sulfide waters is carried out in the resorts of Goryachy Klyuch, Yeysk, Pyatigorsk, Sergievskie Mineralnye Vody, Sernovodsk, Sochi, Matsesta, and Khosta.

Comments: Treatment with radon waters is carried out in the resorts of Belokurikha, Molokovka, and Pyatigorsk.

Comments: Treatment with mud baths is carried out in the resorts of Crimea.

5. Prevention and Dispensary Observation

Dispenserary observation (follow-up) of patients with psoriasis is carried out by dermatovenerologists in skin and venereal disease clinics (dispensaries) [208]

GRS CLOE 5Grade of Recommendation Strength C (Level of Evidence – 5)

6. Organization of Medical Care

As part of the provision of primary medical care, district general practitioners, district pediatricians, and general practitioners (family physicians), upon detecting skin rashes, symptoms, or signs of psoriasis in patients, shall refer the patient to a dermatovenerological medical organization to receive primary specialized medical care.

If it is impossible to provide medical care within the framework of primary specialized medical care and if there are medical indications, the patient is referred to a medical organization providing specialized medical care.

Specialized, including high-tech, medical care is provided by dermatovenerologists in inpatient settings.

To determine the criteria for indications for hospitalization, the PASI index is used:

index value from 10 to 19 – indications for hospitalization in a day hospital;

index value of 20 and above – indications for hospitalization in a 24-hour (full-time) hospital.

Additional indications for hospitalization in a medical organization:

day hospital:

- the need for maintenance therapy with selective immunosuppressants (phosphodiesterase-4 inhibitors, Janus kinase blockers), tumor necrosis factor-alpha (TNF-alpha) inhibitors, and interleukin inhibitors;

24-hour (full-time) hospital:

- ineffectiveness of previously administered treatment.

Indications for patient discharge from a medical organization:

- regression of rashes and/or reduction of clinical manifestations.

If there is a need to use physiotherapeutic treatment methods, patients with psoriasis are referred by the dermatovenerologist from consultative-diagnostic and inpatient departments, including day and 24-hour hospitals, for a consultation with a physical therapy doctor.

7. Additional Information

The use of systemic corticosteroids for the treatment of psoriasis is indicated only in rare cases (generalized pustular psoriasis, psoriatic erythroderma). In these cases, the administration of single injections (infusions) of systemic corticosteroids (short-acting) is justified in order to arrest the acuteness of the process. The appointment of systemic corticosteroids in long courses, as well as prolonged-action drugs of this group, can lead to the generalization of the skin process with the development of pustular psoriasis and/or erythroderma, as well as a torpid course of the disease. Treatment outcome requirements: partial or complete regression of rashes; disappearance or reduction in the severity of subjective sensations (itching, skin tightness).

Tactics in the absence of a therapeutic effect: prescription of other types of topical, photo-, and systemic therapy or their combinations.

Assessment of risk factors for adverse outcomes: worsening of the course of the disease – an increase in the severity and prevalence of the psoriatic process; development of erythroderma or generalized pustular psoriasis; resistance to ongoing therapy using agents and (or) methods with proven clinical efficacy.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

Composition of the working group on the development and revision of clinical guidelines

1. Kubanov, Alexey Alekseevich – Academician of the RAS, President of the LLC "AOCDV", Director of the State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, Moscow;

2. Karamova, Arfenya Eduardovna – PhD in Medicine, Head of the Department of Dermatology, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health; Member of the Russian Society of Dermatovenereologists and Cosmetologists, Moscow;

3. Pritulo, Olga Alexandrovna – MD, Professor, Head of the Department of Dermatovenereology and Cosmetology, Medical Academy named after S.I. Georgievsky of the V.I. Vernadsky Crimean Federal University; Member of the Russian Society of Dermatovenereologists and Cosmetologists, Simferopol;

4. Arshinsky, Mark Ivanovich – Chief Physician of the Krai Clinical Dermatovenereology Dispensary; Member of the Russian Society of Dermatovenereologists and Cosmetologists, Khabarovsk;

5. Znamenskaya, Lyudmila Fedorovna – MD, Leading Researcher at the Department of Dermatology, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health; Member of the Russian Society of Dermatovenereologists and Cosmetologists, Moscow;

6. Chikin, Vadim Viktorovich – MD, Senior Researcher at the Department of Dermatology, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health; Member of the Russian Society of Dermatovenereologists and Cosmetologists, Moscow;

7. Hobeish, Marianna Mikhailovna – PhD in Medicine, Associate Professor at the Department of Dermatovenereology with Clinic, Pavlov First Saint Petersburg State Medical University; Member of the Russian Society of Dermatovenereologists and Cosmetologists, Saint Petersburg;

8. Olisova, Olga Yuryevna – MD, Professor, Head of the Department of Skin and Veneral Diseases, Sechenov First Moscow State Medical University; Member of the Russian Society of Dermatovenereologists and Cosmetologists, Moscow;

9. Bakulev, Andrey Leonidovich – MD, Professor, Professor at the Department of Dermatovenereology and Cosmetology, Central State Medical Academy of the Presidential Administration of the Russian Federation, Member of the Russian Society of Dermatovenereologists and Cosmetologists, Saratov;

10. Zhilova, Maryana Borisovna – MD, Head of the Physiotherapy Department, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health; Member of the Russian Society of Dermatovenereologists and Cosmetologists, Moscow;

11. Konchugova, Tatyana Venediktovna – MD, Professor, Head of the Department of Physiotherapy and Reflexology, Head of the Department of Physical Therapy and Medical Rehabilitation, National Medical Research Center for Rehabilitation and Balneology of the Russian Ministry of Health, Professor at the Department of Restorative Medicine, Rehabilitation and Balneology, Sechenov University.

12. Kulchitskaya, Detelina Borisovna – MD, Professor, Chief Researcher at the Department of Physiotherapy and Reflexology, National Medical Research Center for Rehabilitation and Balneology of the Russian Ministry of Health, Member of the National Association of Experts in Spa Treatment.

Conflict of interest:

The authors declare no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Medical specialists: dermatovenereologists

2. Residents and trainees of continuing professional education programs in the specified specialty.

Table 1.Levels of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2.Levels of Evidence (LoE) grading scale for prevention, treatment and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3.Grades of Recommendation (GoR) for prevention, diagnostic, treatment and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

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

Medical care for patients with psoriasis is provided by dermatovenereologists in accordance with the Procedure for the Provision of Medical Care in the profile of "dermatovenereology", approved by Order of the Russian Ministry of Health No. 924n dated November 15, 2012 "On Approval of the Procedure for the Provision of Medical Care to the Population in the Profile of 'Dermatovenereology'."

Standard of medical care for patients with psoriasis (high-tech medical care). Approved by the Order of the Ministry of Health and Social Development of Russia No. 433 dated May 30, 2006, "On the Approval of the Standard of Medical Care for Patients with Psoriasis".

Table 1. Laboratory monitoring during methotrexate therapy**

Table 2. Laboratory monitoring during retinoid therapy for psoriasis

Table 3. Prevention of adverse reactions to retinoids for psoriasis

Table 4. Laboratory monitoring during cyclosporine therapy**

Table 5. Initial dose titration schedule for apremilast**

Table 6. Skin types according to T.B. Fitzpatrick's classification

Notes:

1Patient's report of skin reactions (sunburn and tan) upon initial sun exposure at the beginning of summer for approximately 45–60 min.

2Patients with blue or brown eyes, fair or red (sometimes dark) hair; freckles are often present on the skin.

3Patients with blue, green or brown eyes, fair, red or dark hair; freckles are often present on the skin.

4If there is a history of sunburns, the skin type of such patients should be classified into a lower category. The skin type of patients with erythrodermic psoriasis is classified as skin type I.

Table 7. Monitoring of laboratory parameters during infliximab therapy

Note: 1Hemoglobin, hematocrit, red blood cells, white blood cells, leukocyte differential, platelets.

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

1. Psoriasis is a systemic immune-mediated disease affecting 1% of the population in Russia. There is a hereditary predisposition to the development of psoriasis.

2. Psoriasis manifests as local or widespread red papules and/or plaques on the skin that rise above the skin surface and are accompanied by scaling. The underlying mechanisms of the lesions include impaired keratinization, inflammation, and excessive formation of small blood vessels in the skin. Nail plates and joints may be affected.

3. Psoriasis most commonly debuts at a young age. In some cases, the disease may progress over time.

4. To date, there are no agents and/or therapeutic methods that allow a complete cure for patients with psoriasis. However, currently used modern therapeutic agents and/or methods can significantly reduce the clinical manifestations of the disease and increase the duration of remission. These include: topical agents (e.g., ointments, gels, shampoo), phototherapy methods, as well as a number of systemic medications. The choice of the necessary therapeutic agent or method must be made by a specialist dermatologist. During periods of pronounced progression (exacerbation) of psoriasis, sick leave from work is advisable in some cases.

5. In the diet, it is recommended to limit spicy dishes, spices, alcoholic beverages, and animal fats. It is recommended to include vegetable oils in the diet, as well as foods rich in vitamins (fruits, vegetables).

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Psoriasis Severity and Extent Assessment Index

Russian name: Psoriasis Area and Severity Index

Original name: Psoriasis Area Severity Index

Source (official developer website, validation publication): Fredriksson T, Pettersson U: Severe psoriasis: Oral therapy with a new retinoid. Dermatologica 1978; 157: 238–244.

Type: index

Purpose: determination of the severity and extent of psoriasis

Content:

PASI score calculation is a composite assessment of erythema (E), induration (I), desquamation (D), and area (A) of the psoriatic plaque.

To calculate PASI, the body is conventionally divided into four regions: head (h), trunk (tr), upper extremities (u), lower extremities (l).

For each of them, the following are evaluated:

1. Area of psoriatic skin lesions – (S) (determined first in % based on: on the head 1 patient's palm corresponds to 10%, on the trunk – 3.3%, on the arms – 5%, on the legs – 2.5%, and then in scores – 0 – no psoriasis, 1 – psoriasis affects less than 10% of the area of any of the specified body parts, 2 – psoriasis affects 10 to 29%, 3 – 30 to 49%, 4 – 50 to 69%, 5 – 70 to 89%, 6 – 90 to 100%).

2. Erythema, induration, and desquamation are scored: 0 – absence of psoriasis, 1 – minimal severity, 2 – moderate, 3 – marked, 4 – maximal. Calculation formula:

PASI = [0.1 × (Eh + Ih + Dh) × Sh] + [0.2 × (Eu + Iu + Du) × Su] + [0.3 × (Etr + Itr + Dtr) × Str] + [0.4 × (El + Il + Dl) × Sl] (3).

The range of values is from 0 to 72 points.

Key (interpretation):

A PASI score up to 10 points corresponds to mild disease;

10–19 points – moderate;

20–72 – severe.