Arthroropathic psoriasis. Psoriatic arthritis: clinical guidelines

List of Abbreviations

AST – aspartate aminotransferase

ALT – alanine aminotransferase

HIV – human immunodeficiency virus

GGT – gamma-glutamyl transferase

IL – interleukin

ESR – erythrocyte sedimentation rate

CRP – C-reactive protein

PDE4 – phosphodiesterase 4

TNF – tumor necrosis factor

cAMP – Cyclic adenosine monophosphate

MRI – magnetic resonance imaging

Terms and Definitions

Arthritis is inflammation of joint tissues with mandatory involvement of its synovial membrane (synovitis).

Dactylitis is inflammation of a digit resulting from a combination of arthritis and tenosynovitis.

Remission of psoriatic arthritis is the absence of any clinical signs of inflammation in the osteoarticular structures (arthritis, dactylitis, enthesitis, tenosynovitis, spondylitis)

Sacroiliitis is inflammation of the iliosacral (syn. sacroiliac) joints of the pelvis.

Spondylitis is inflammation of the axial skeleton structures.

Tendinitis is inflammation of tendons in various locations, most commonly flexors and/or extensors of the fingers and toes.

Tenosynovitis is inflammation of tendon sheaths in various locations, most commonly flexors and/or extensors of the fingers and toes.

Tendinitis/tenosynovitis is inflammation of the structures of the musculotendinous and ligamentous apparatus

Enthesitis is inflammation at the site of tendon attachment to bone (enthesis).

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

These clinical guidelines are dedicated to the diagnosis and treatment of musculoskeletal involvement in psoriasis (L40.0). According to the ICD-10 classification, these manifestations can be coded as L40.5 – psoriatic arthropathy, and M07.0–M07.3 Psoriatic and enteropathic arthropathies. For the convenience of presentation and reading, the guideline developers use the umbrella term "psoriatic arthritis".

Psoriatic arthritis (arthropathic psoriasis) is a chronic inflammatory disease of the joints, spine, and entheses that can occur in patients with psoriasis. Psoriatic arthritis is primarily characterized by inflammation of peripheral joints (arthritis), fingers and toes (dactylitis), entheses (enthesitis), as well as potential inflammation of axial structures – vertebral bodies (spondylitis) and sacroiliac joints (sacroiliitis) [1].

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

The etiology of psoriatic arthritis is unknown. There is evidence of a hereditary predisposition to the development of psoriasis and psoriatic arthritis: more than 40% of patients with psoriatic arthritis have first-degree relatives suffering from these diseases. Psoriasis and psoriatic arthritis are considered T-cell-mediated diseases characterized by the activation of cellular immunity in the skin and synovium, followed by hyperproduction and imbalance of key pro- and anti-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukins (IL)-12, IL-23, IL-17, IL-1, IL-1β, IL-6, and chemokines [2].

1.3 Epidemiology of the Disease or Condition

Psoriatic arthritis is detected in 19.7% of patients with psoriasis and in 24.6% of those with moderate-to-severe psoriasis [3].

Psoriatic arthritis can develop at any age, frequently affecting the working-age population.

Psoriatic arthritis can develop at any age. In 70% of patients, psoriasis appears before musculoskeletal involvement, in 20% simultaneously, and in 15–20% of patients, psoriatic arthritis arises before the first clinical manifestations of psoriasis [4]. There is no correlation between the severity of psoriasis and psoriatic arthritis; however, cohort observations have noted a high frequency of psoriatic arthritis cases in patients with widespread psoriasis [5]. In psoriatic arthritis, the inflammatory process affects not only musculoskeletal structures (joints, spine, entheses), but also the skin, nails (psoriasis), gastrointestinal tract (inflammatory bowel disease), and eyes (uveitis, iridocyclitis). In addition, patients with psoriatic arthritis have a higher risk of developing obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, arterial hypertension, dyslipidemia, cardiovascular disease, a number of neuropsychiatric disorders, and fibromyalgia compared to the general population [6].

1.4 Features of Coding the Disease or Condition

All variants of the disease can be coded as L40.5 Psoriatic arthropathy. At the same time, codes in category M07* Psoriatic and enteropathic arthropathies specify the forms of the disease:

M07.0 – Distal interphalangeal psoriatic arthropathy;

M07.1 – Mutilating arthritis;

M07.2 – Psoriatic spondylitis;

M07.3 – Other psoriatic arthropathies.

1.5 Classification of the disease or condition

Currently, 5 clinical forms of psoriatic arthritis are distinguished:

predominant involvement of the distal interphalangeal joints of the hands and feet, distal form (L40.5, M07.0);

mutilating arthritis (L40.5, M07.1);

psoriatic spondylitis (L40.5, M07.2);

asymmetric mono-oligoarthritis (L40.5, M07.3);

symmetric polyarthritis, rheumatoid-like form (L40.5, M07.3)

1.6 Clinical presentation of the disease or condition

The clinical symptoms of psoriatic arthritis with predominant involvement of the distal interphalangeal joints of the hands and feet (distal form) are characterized by classic isolated involvement of the distal interphalangeal joints of the hands and/or feet. This form is observed in 5% of patients with psoriatic arthritis. Involvement of the distal interphalangeal joints of the hands and feet along with other joints is frequently observed in other clinical variants of psoriatic arthritis. Asymmetric mono-oligoarthritis occurs in the majority of patients with psoriatic arthritis (up to 70%). Typically, the knee, wrist, ankle, elbow, and interphalangeal joints of the hands and feet are involved, while the total number of inflamed joints does not exceed 4.

Symmetric polyarthritis (rheumatoid-like form) is observed in approximately 15–20% of patients with psoriatic arthritis. It is characterized by the involvement of paired joint areas similar to rheumatoid arthritis. Asymmetric polyarthritis of five or more joints is frequently observed.

Psoriatic spondylitis is characterized by inflammatory involvement of the spine similar to ankylosing spondylitis, frequently (in approximately 50% of cases) combined with peripheral arthritis, and rarely (2–4%) observed as isolated spondylitis.

Mutilating arthritis is a rare clinical form of psoriatic arthritis. It is observed in 5% of patients with psoriatic arthritis and is characterized by widespread resorption of joint surfaces (osteolysis) with shortening of the fingers and/or toes, formation of "telescopic deformity", shortening, and multidirectional subluxations of the digits of the limbs. At the same time, local (limited) osteolysis of joint surfaces can develop in all clinical variants of psoriatic arthritis.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the diagnosis/condition:

The diagnosis of psoriatic arthritis is established in accordance with the CASPAR criteria (ClASsification criteria for Psoriatic ARthritis, 2006) [31]. According to the CASPAR criteria, patients must have evidence of inflammatory articular disease (arthritis, spondylitis, tenosynovitis, or enthesitis) and score 3 or more points out of 5 categories (Table 1).

Table 1. CASPAR criteria for psoriatic arthritis

Assessment of the nature of spinal pain is carried out in accordance with the ASAS (Assessment of SpondyloArthritis international Society) criteria (2009) [32]:

1. Age of onset <40 years

2. Insidious onset

3. Improvement with exercise

4. No improvement with rest

5. Pain at night (with improvement upon getting up)

Back pain is considered inflammatory in the presence of at least 4 out of 5 features.

The diagnosis of spondylitis in psoriatic arthritis is established based on the presence of two of the four features presented below [33]:

1. Presence of inflammatory back pain according to the criteria (ASAS, 2009).

2. Limitation of mobility of the cervical, thoracic, or lumbar spine in the sagittal and frontal planes.

3. Signs of bilateral sacroiliitis of stage 2 or higher, or unilateral sacroiliitis of stage 3 or higher (according to Kellgren) on plain pelvic radiography, OR syndesmophytes in the spine.

4. Detection of MRI-active sacroiliitis (osteitis/bone marrow edema in the sacroiliac joint region on STIR fat-suppressed sequences).

Assessment of clinical activity in psoriatic arthritis is performed according to the criteria presented in Table 2 [34]:

Table 2. Grades of clinical activity of psoriatic arthritis

Poor prognostic factors –

1. Polyarthritis (≥ 5 tender joints/swollen joints).

2. Presence of erosions on radiographic examination.

3. Elevated erythrocyte sedimentation rate / blood C-reactive protein levels.

4. Dactylitis.

5. Psoriatic nail dystrophy.

6. Functional impairment.

Disease activity indices taking into account clinical heterogeneity are presented in Appendices G1–G4 [112–121].

2.1 Complaints and Anamnesis

Patients complain of pain and swelling in the joints of the hands and feet, knees, ankles, and less commonly shoulders, elbows, and hips, or uniform swelling of an entire finger or toe. Concurrently, patients may experience heel pain when walking, at the insertion of the Achilles tendons, as well as pain in any part of the spine, predominantly in the cervical or lumbosacral region, which occurs at night, decreases after physical exercise or the use of nonsteroidal anti-inflammatory and antirheumatic drugs, and chest pain upon breathing.

The majority of patients presenting with these complaints have skin and/or nail psoriasis at the time of examination or a family history of psoriasis. In some patients, the listed complaints arose spontaneously, and in about a third, following trauma, significant physical, or emotional stress. It should be noted that spinal pain in most patients may go unnoticed for a long time.

2.2 Physical Examination

Physical examination focuses on the following signs:

in peripheral arthritis – pain, swelling, limited joint mobility, arthritis of the distal interphalangeal joints of the hands/feet and "pencil-in-cup" deformity, axial arthritis (simultaneous involvement of three joints of a single digit), dactylitis, and "sausage-like" deformity of the fingers and toes.

in dactylitis (syn. inflammation of a digit) – pain, uniform swelling of the entire digit with bluish-purple skin discoloration, dense edema of the entire digit, painful limitation of flexion, and the "sausage-like" digit deformity characteristic of psoriatic arthritis.

in enthesitis – pain, sometimes with swelling at enthesis sites: upper pole of the patella, iliac crests, greater trochanters, insertion of the Achilles tendon and plantar aponeurosis into the calcaneus, lateral epicondyle of the humerus, medial femoral condyle.

in spondylitis – active detection of inflammatory back pain followed by the assessment of spinal mobility (measurement of spinal mobility) using the tests listed below. To detect limitation of movement in the lumbar spine in the sagittal plane, the modified Schober test is used. It is performed with the patient standing straight: a point is marked on the midline of the back at the imaginary line connecting the posterior superior iliac spines. A second point is then marked 10 cm above the first point. The patient is then asked to bend forward as far as possible without bending the knees, and in this position, the distance between the two points is measured using a tape measure. Normally, this distance increases to more than 15 cm. The measurement is taken twice. The result of the best attempt is recorded;

- To assess mobility in the lumbar spine in the frontal plane, lateral flexion in this region is measured. With the patient standing against a wall with heels, buttocks, and shoulder blades pressed against it, a tape measure is first used to determine the distance between the tip of the middle finger and the floor; the patient then bends sideways, and this distance is measured again. The difference between the initial distance and the post-flexion distance is evaluated. Normally, this difference should be at least 10 cm. The measurement is taken twice for each side. The result of the best attempt is recorded;

- To assess the severity of cervical kyphosis, the tragus-to-wall and occiput-to-wall distances are used: the patient stands with their back to the wall and is asked to press their shoulder blades, buttocks, and heels against it. The chin is maintained at its usual level. The patient tries to bring the head (occiput) as close to the wall as possible without tilting the head backward. The distance from the occiput to the wall and from the tragus to the wall is measured using a tape measure. The measurement is taken twice for the occiput-to-wall distance and for each side when measuring the tragus-to-wall distance. The result of the best attempt is recorded;

- To assess the degree of cervical spine mobility, cervical rotation is measured using a goniometer, and normally the rotation angle should be at least 70 degrees;

- To assess mobility impairment in the hip joints, the maximum distance between the medial malleoli (in cm) is measured. For this, lying on their back, the patient is asked to spread their legs as far apart as possible, and the distance between the medial malleoli is measured. A distance of 100 cm or more is considered normal. The measurement is taken twice. The result of the best attempt is recorded;

- Chest expansion is determined as the difference between its circumference at deep inspiration and full expiration at the level of the 4th intercostal space. Normally, it should be at least 5 cm. The measurement is taken twice. The result of the best attempt is recorded [7].

2.3 Laboratory Diagnostics

Comments: The erythrocyte sedimentation rate is an indicator reflecting the activity of psoriatic arthritis. Therefore, determining the erythrocyte sedimentation rate is necessary to assess psoriatic arthritis activity; an increase in this rate indicates disease activity and is a poor prognostic factor. The erythrocyte sedimentation rate is not a sensitive and/or specific diagnostic method for psoriatic arthritis, as it is elevated in 50% of patients despite high disease activity.

Comments: The serum C-reactive protein level is an indicator reflecting the activity of psoriatic arthritis. Therefore, measuring the serum C-reactive protein level is necessary to assess psoriatic arthritis activity; an increase in this level indicates disease activity and is a poor prognostic factor. Measuring the serum C-reactive protein level is not a sensitive and/or specific diagnostic method, as it is elevated in 50% of patients despite high disease activity. The C-reactive protein test is performed using a high-sensitivity method.

Comments: Psoriatic arthritis belongs to the group of spondyloarthritides, predominantly peripheral ones, which are characterized by the absence of rheumatoid factor in the blood, asymmetric joint involvement predominantly of the lower extremities, the development of dactylitis, as well as involvement of the spine, entheses, and in some cases extra-articular/extra-axial manifestations (uveitis and inflammatory bowel disease). In most cases, patients with psoriatic arthritis have psoriasis. Establishing a diagnosis of psoriatic arthritis requires the presence of at least one clinical sign of bone and joint inflammation (arthritis, enthesitis, tenosynovitis, or spondylitis) and the evaluation of all criteria included in the CASPAR classification. Determination of IgM rheumatoid factor in the blood of patients with psoriatic arthritis should be performed using the nephelometric method.

Comments: In psoriatic arthritis, rheumatoid factor and anti-cyclic citrullinated peptide antibodies (anti-CCP) can be detected in low titers in 15–18.9% and 0.9–2.9% of patients, respectively. If they are detected in high titers, as well as upon detection of other immunological abnormalities uncharacteristic of psoriatic arthritis (e.g., antinuclear factor, anti-DNA, anti-RNP, Scl-70, lupus anticoagulant, antibodies to beta-2 glycoprotein, etc.), a differential diagnostic workup should be performed to rule out rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, etc.

Comments: The preferred method is to determine the HLA-B27 antigen using polymerase chain reaction with blood as the substrate. The HLA-B27 antigen is detected in 40–50% of patients with psoriatic arthritis. The test is performed once throughout the entire course of the disease. The absence of the HLA-B27 antigen does not rule out the diagnosis of psoriatic arthritis.

Comment: Patients with severe psoriasis or psoriatic arthritis may exhibit secondary hyperuricemia not accompanied by acute gout attacks. The decision regarding the nature of hyperuricemia and/or the presence of gouty arthritis is made by a rheumatologist based on the clinical situation [15, 16].

Comments: Diagnostic and therapeutic joint puncture allows for the retrieval and analysis of synovial fluid for the presence of uric acid crystals. It is performed to establish the diagnosis of psoriatic arthritis and for differential diagnosis with gout.

2.4 Instrumental Diagnostics

radiography of the hands [19–22]

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

radiography of the feet (single-projection foot radiograph) [19–22]

Level of Evidence 5Strength of Recommendation C (level of evidence – 5)

pelvic radiography [19–22]

Level of Evidence 5Strength of Recommendation C (level of evidence – 5)

spinal radiography:

cervical spine

lumbar spine

thoracic and lumbar spine [19–22]

Level of Evidence 5Strength of Recommendation C (level of evidence – 5)

Comments: Pelvic radiography should be performed in the anteroposterior (AP) projection. Spinal radiography (cervical, lumbar, junctional) should be performed in the lateral projection. Frequency of examination: once every 2 years.

Radiography of the hands and feet should be performed in the anteroposterior projection.

If the patient complains of pain or if visual changes are observed in other joint areas, X-ray imaging of these joints should be performed.

Comments: Radiography of the hands and feet is performed no more than once a year. Characteristic radiographic changes in the hands and feet in psoriatic arthritis include: joint space narrowing; cystic radiolucencies of bone tissue; marginal erosions; marginal osteolysis; resorption of terminal phalanges and mutilating changes resulting in a "pencil-in-cup" deformity; bone proliferations (marginal outgrowths distinct from osteophytes); periosteal reactions; enthesophytes at enthesis insertion sites (calcaneal regions); bony ankylosis. Characteristic radiographic changes in the sacroiliac joints include sacroiliitis of various stages (grades 1 to 4 according to Kellgren); in the spine, marginal syndesmophytes, including "bridging" ones; gross paraspinal ossification; involvement of the facet joints (joint space narrowing, erosions, bony ankylosis); rarely, anterior subluxation of the 1st cervical vertebra [23, 24]

Comment: Magnetic resonance imaging of the sacroiliac joints and spine in patients with psoriatic arthritis should be performed using T1, T2, and STIR sequences. Spondylitis is observed in 60% of patients with psoriatic arthritis. MRI-active sacroiliitis is defined by the presence of bone marrow edema (osteitis), manifested as areas of high signal intensity on STIR sequences. At least two high-signal foci on a single slice or a single high-signal focus (inflammatory zone) on two consecutive slices are required. MRI-active spondylitis is also manifested as areas of high-signal intensity on STIR sequences at the corners of vertebral bodies (anterior spondylitis) and in posterior spinal structures (facet joints, ligaments, etc.). To detect chronic changes in the sacroiliac joints, T1-weighted images are evaluated for subchondral bone marrow fatty degeneration, subchondral osteosclerosis, erosions of articular surfaces, and bony ankylosis. To detect chronic changes in the spine, T1-weighted images are evaluated for foci of bone marrow fatty degeneration in the anterior and posterior corners of vertebral bodies [26–29].

Comments: In case of irreversible damage and impaired function of the knee joints, surgical treatment for their replacement (orthopedic knee arthroplasty) or knee arthrodesis is indicated. Indications for surgical treatment are determined by an orthopedic traumatologist [30].

2.5 Other Procedures

dermatovenerologist consultation (examination, inspection)

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

or

urologist consultation (examination, inspection) [35]

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

or

infectious disease specialist consultation (examination, inspection) [35]

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

or

gastroenterologist consultation (examination, inspection) [35]

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

Comments: For the differential diagnosis of psoriatic arthritis from infection-associated arthritides, laboratory tests to detect Chlamydia, Salmonella, Yersinia, Shigella, and Campylobacter are required, performed in specialized medical institutions in accordance with current clinical guidelines for these diseases [35].

cardiologist – for the diagnosis of cardiovascular diseases if the patient has cardiovascular symptoms, and for prescribing or adjusting ongoing cardioprotective therapy [36–40];

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

endocrinologist – for the diagnosis of endocrine system disorders, primarily diabetes mellitus [36–40];

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

ophthalmologist – for the diagnosis of conjunctivitis, iritis, iridocyclitis, and uveitis [36–40];

GDR CLE 5Grade of recommendation C (level of evidence – 5)

gastroenterologist – only if ulcerative colitis or Crohn's disease is suspected [36–40];

GDR CLE 5Grade of recommendation C (level of evidence – 5)

phthisiatrician – before initiating therapy with tumor necrosis factor alpha (TNF-alpha) inhibitors or interleukin inhibitors, and then every 6 months during treatment [36–40]

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: Indications for surgical treatment in patients with psoriatic arthritis are determined by an orthopedic traumatologist [30].

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

3.1 Conservative Treatment

The goal of psoriatic arthritis therapy is to achieve remission or reduce the manifestations of the main clinical symptoms of the disease to a minimum, slow down or prevent radiographic progression, and increase the life expectancy and quality of life of patients [41–43].

For the treatment of patients with psoriatic arthritis, nonsteroidal anti-inflammatory and antirheumatic drugs, systemic corticoids (administered intra-articularly), antimetabolites (#methotrexate**), immunosuppressants (#sulfasalazine**, leflunomide**), selective immunosuppressants (apremilast**, tofacitinib**, upadacitinib**), tumor necrosis factor alpha (TNF-alpha) inhibitors – infliximab**, adalimumab**, golimumab**, certolizumab pegol**, etanercept** – and interleukin (IL) inhibitors: IL-12/23 – ustekinumab**; IL-17A – secukinumab**, ixekizumab**, netakimab**; IL-23 – risankizumab**, guselkumab** [2].

Before starting therapy with nonsteroidal anti-inflammatory and antirheumatic drugs, the benefit-risk ratio for the patient regarding the cardiovascular system, eyes, and gastrointestinal tract should be evaluated. Nonsteroidal anti-inflammatory drugs and antirheumatic drugs are used for a short period (4 weeks) to reduce musculoskeletal inflammatory symptoms. In patients with a very high risk, the use of any nonsteroidal anti-inflammatory and antirheumatic drugs should be avoided, especially at doses exceeding the established daily limits. Nonsteroidal anti-inflammatory drugs and antirheumatic drugs are used either as monotherapy or in combination with intra-articular glucocorticoids for systemic use, as well as with antirheumatic drugs such as antimetabolites, immunosuppressants, selective immunosuppressants, tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors. In patients with mono-oligoarthritis without poor prognostic factors (dactylitis, joint erosions, nail psoriasis, elevated erythrocyte sedimentation rate (ESR) / C-reactive protein (CRP) in blood), the duration of nonsteroidal anti-inflammatory and antirheumatic drug intake, including in combination with intra-articular corticosteroids, should not exceed 4 weeks; if activity persists, a combination with antimetabolites (#methotrexate**) and immunosuppressants (leflunomide**, #sulfasalazine**) is necessary. In patients with predominant enthesitis and/or spondylitis, the response to nonsteroidal anti-inflammatory and antirheumatic drugs is evaluated after 4 weeks. If there is a response to therapy, nonsteroidal anti-inflammatory and antirheumatic drug intake is continued; if there is no response, other drugs (selective immunosuppressants, tumor necrosis factor alpha (TNF-alpha) inhibitors, or interleukin inhibitors) are used in accordance with the guidelines. Long-term continuous use of nonsteroidal anti-inflammatory and antirheumatic drugs provides better control of disease symptoms than "on-demand" dosing. Topical medications for joint and muscle pain may be used in combination with nonsteroidal anti-inflammatory and antirheumatic drugs or alone.

For patients with psoriatic arthritis in case of insufficient efficacy of previously administered therapy with antimetabolites (#methotrexate**) or immunosuppressants (leflunomide**, #sulfasalazine**), including those with peripheral arthritis (polyarthritis or mono/oligoarthritis with poor prognostic factors such as erosions, dactylitis, elevated erythrocyte sedimentation rate / C-reactive protein in the blood, combined with functional impairment); acute multiple dactylitis (involving 3 or more digits) with functional impairment who have not achieved remission or minimal disease activity despite treatment with #methotrexate** or immunosuppressants, intra-articular glucocorticoid injections for ≥ 3–6 months; multiple enthesitis with functional impairment in the absence of a response to nonsteroidal anti-inflammatory and antirheumatic drugs combined with intra-articular systemic corticosteroid injections for 4–12 weeks; active spondylitis with functional impairment in the absence of a response to nonsteroidal anti-inflammatory and antirheumatic drugs for 4–12 weeks, therapy with selective immunosuppressants (apremilast**, tofacitinib**, upadacitinib**) or tumor necrosis factor alpha (TNF-alpha) inhibitors (infliximab**, adalimumab**, etanercept**, golimumab**, certolizumab pegol**) or interleukin inhibitors (ustekinumab**, secukinumab**, ixekizumab**, netakimab**, guselkumab**, risankizumab**) is indicated.

Before initiating therapy with selective immunosuppressants, tumor necrosis factor alpha (TNF-alpha) inhibitors, or interleukin inhibitors, the following tests are required:

1. complete blood count (CBC), including differential leukocyte count and platelet count;

2. general general-medical blood biochemistry, including blood creatinine, blood urea, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase;

3. urinalysis (routine);

4. ultrasound examination of the abdominal organs (comprehensive);

5. comprehensive pelvic ultrasound (transvaginal and transabdominal);

6. esophagogastroduodenoscopy;

7. targeted chest X-ray (in 2 projections) or chest computed tomography, tuberculin skin test, and phthisiatrician consultation to rule out active and latent tuberculosis infection;

8. screening for HIV infection (determination of antibodies of classes M and G (IgM, IgG) to human immunodeficiency virus HIV-1 in blood, determination of antibodies of classes M and G (IgM, IgG) to human immunodeficiency virus HIV-2 in blood);

9. screening for viral hepatitis B and C (determination of antibodies to hepatitis B surface antigen (HBsAg) in blood, determination of antibodies to hepatitis C virus in blood);

10. pregnancy test (urine human chorionic gonadotropin test).

Against the background of therapy with tumor necrosis factor alpha (TNF-alpha) inhibitors and interleukin inhibitors, there is a risk of reactivation of any infection [123–125]. Risankizumab**, guselkumab**, which inhibit IL-23; secukinumab**, netakimab** and ixekizumab**, which inhibit IL-17A; and ustekinumab**, which inhibits IL-12/23, carry a lower risk. During the registration trials of risankizumab** and guselkumab**, not a single case of tuberculosis was registered, including in patients with positive tests for latent tuberculosis [134–139, 147–150]. The results of targeted chest X-ray (in 2 projections) or computed tomography of the thoracic cavity organs, and the Mantoux tuberculin skin test are evaluated by a phthisiologist, who provides a conclusion on the possibility of initiating therapy with tumor necrosis factor alpha (TNF-alpha) inhibitors and interleukin inhibitors or, if tuberculosis infection is detected, on the need for specific antituberculosis therapy. The nature of this therapy and its duration are also determined by the phthisiologist. If viral hepatitis is detected, the decision to prescribe therapy with tumor necrosis factor alpha (TNF-alpha) inhibitors or interleukin inhibitors is made by an infectious disease specialist depending on the activity of the disease.

Tumor necrosis factor alpha (TNF-alpha) inhibitors, interleukin inhibitors, and selective immunosuppressants (apremilast**, tofacitinib**, upadacitinib**) can be prescribed either as monotherapy or in combination with #methotrexate** [44–46]. Data on the effect of tumor necrosis factor alpha (TNF-alpha) inhibitors on spondylitis in psoriatic arthritis are extrapolated from randomized clinical trials in ankylosing spondylitis and axial spondyloarthritis.

Clinical studies of upadacitinib** have demonstrated its efficacy regarding the axial manifestations of psoriatic arthritis. Data on the efficacy of tofacitinib** are extrapolated from registration studies for ankylosing spondylitis. The efficacy of apremilast** in spondylitis is low, with data obtained from a subanalysis of relevant registration trials in psoriatic arthritis.

Tumor necrosis factor alpha (TNF-alpha) inhibitors show no significant differences in clinical efficacy or long-term tolerability. The choice between tumor necrosis factor alpha (TNF-alpha) inhibitors and interleukin inhibitors is made on a personalized basis. The use of tumor necrosis factor alpha (TNF-alpha) inhibitors (except for etanercept**) is effective in psoriatic arthritis combined with uveitis. In patients with severe psoriasis and peripheral arthritis, it is preferable to use interleukin inhibitors (secukinumab**, ixekizumab**, netakimab**, ustekinumab**, guselkumab**, risankizumab**). When psoriatic arthritis is combined with inflammatory bowel disease, preference is given to tumor necrosis factor alpha (TNF-alpha) inhibitors, except for etanercept**, and ustekinumab**, while the use of secukinumab**, ixekizumab**, and netakimab** is not advisable. If one tumor necrosis factor alpha (TNF-alpha) inhibitor is ineffective, the patient is switched to another tumor necrosis factor alpha (TNF-alpha) inhibitor, interleukin inhibitors, or selective immunosuppressants (upadacitinib**, tofacitinib**). In cases where the prescribing of tumor necrosis factor alpha (TNF-alpha) inhibitors or interleukin inhibitors is impossible for any reason, the use of selective immunosuppressants (tofacitinib**, upadacitinib**, apremilast**) is considered as an alternative therapeutic option.

Obesity, smoking, fatty liver disease, depression, and the presence of atherosclerotic plaques in the carotid arteries (a manifestation of atherosclerosis) are predictors of insufficient therapeutic efficacy of tumor necrosis factor alpha (TNF-alpha) inhibitors and interleukin inhibitors in patients with psoriatic arthritis [47, 48]. During treatment with all tumor necrosis factor alpha (TNF-alpha) inhibitors and interleukin inhibitors, there is a varying degree of risk of neutralizing antibody formation, leading to reduced treatment efficacy. The use of #methotrexate** at a dose of at least 15 mg/week reduces the risk of neutralizing antibody formation.

When prescribing therapy to patients with psoriatic arthritis, the combination of psoriatic lesions of the joints, spine, and skin should be taken into account. In cases where patients with psoriatic arthritis also have moderate-to-severe psoriatic skin lesions, medicinal products indicated for the treatment of both psoriatic arthritis and cutaneous psoriasis are preferred for systemic therapy. Such medicinal products include #methotrexate**, apremilast**, tofacitinib**, upadacitinib**, infliximab**, adalimumab**, etanercept**, ustekinumab**, secukinumab**, ixekizumab**, netakimab**, guselkumab**, and risankizumab**. Before prescribing the selective immunosuppressants tofacitinib** and upadacitinib** in patients with severe cutaneous psoriasis and psoriatic arthritis, a risk-benefit assessment is required due to the need for higher doses of these drugs, which increases the risk of thrombosis, particularly in individuals over 60 years of age with additional risk factors.

The achievement of remission or minimal disease activity in psoriatic arthritis should be assessed every 3–6 months [49, 50]. The evaluation of ongoing therapy efficacy in psoriatic arthritis can be performed using the indices presented in Appendix G2.

Comments: Patients with psoriatic arthritis may be prescribed oral or intramuscular diclofenac** or meloxicam, or oral indomethacin, nimesulide, aceclofenac, naproxen, celecoxib, etoricoxib, and ibuprofen**. Age restrictions are taken into account when prescribing nonsteroidal anti-inflammatory and antirheumatic drugs. Pediatric age under 18 years is a contraindication for prescribing diclofenac** solution for intramuscular injection, diclofenac** prolonged-release tablets, meloxicam solution for intramuscular injection, aceclofenac tablets, and celecoxib capsules. Etoricoxib is contraindicated in children and adolescents under 16 years of age. Naproxen tablets are contraindicated in children under 15 years of age. Indomethacin tablets are contraindicated in children under 14 years of age. Nimesulide tablets are contraindicated in children under 12 years of age. Meloxicam tablets are contraindicated in children under 12 years of age. Diclofenac** gastro-resistant film-coated tablets are contraindicated in children under 6 years of age. Ibuprofen** oral suspension (for children) is intended for the treatment of children aged 3 months to 12 years and is contraindicated in children with a body weight of less than 5 kg. Ibuprofen** rectal suppositories (for children) are intended for the treatment of children aged 3 months to 2 years; the contraindication for prescribing ibuprofen** rectal suppositories (for children) is a child's body weight of less than 6 kg [51–62].

diclofenac [63, 160, 161]

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

Comments: Diclofenac 2% topical gel is applied in a thin layer over the inflammatory site 2 times a day. A contraindication for prescribing diclofenac topical gel is children under 12 years of age.

Comments: Triamcinolone – suspension for injection in 40 mg/ml ampoules, administered intra-articularly. Contraindicated in children under 12 years of age. Betamethasone suspension for injection, administer 1 ml into the joint. Contraindicated in children under 3 years of age.

There is no evidence of the efficacy of systemic corticosteroids in the treatment of patients with psoriatic arthritis based on randomized clinical trial data. In psoriatic arthritis, systemic corticosteroids are not routinely used orally, intramuscularly, or intravenously. In certain clinical situations, low-dose systemic corticosteroids may be used if there is no other way to block inflammation. Intra-articular administration of systemic corticosteroids is typically prescribed to patients with psoriatic arthritis in combination with nonsteroidal anti-inflammatory and antirheumatic drugs and/or immunosuppressants to rapidly suppress inflammatory changes in joints and entheses and achieve clinical improvement [64, 65].

Comments: In psoriatic arthritis, systemic immunosuppressive therapy reduces symptoms of peripheral arthritis and the severity of dactylitis as part of its effect on peripheral arthritis. The ability of systemic immunosuppressive therapy to affect enthesitis and spondylitis, as well as to delay the formation of joint erosions, has not been proven [69]. Treatment outcomes are evaluated every 3–6 months, at which point the feasibility of their continued use is determined; dose reduction or temporary discontinuation is possible upon achieving disease remission. In patients with severe psoriasis, #methotrexate** should be preferred [70, 71].

#methotrexate** for adult patients orally, subcutaneously or intramuscularly, 10 mg/week with a 5 mg increase every 2–4 weeks up to a maximum dose of 20–25 mg/week, depending on efficacy and tolerability [72, 73, 162, 163, 164]

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: at the start of therapy with #methotrexate** and when increasing its dose, it is necessary to monitor the safety of therapy, for which the following should be performed: blood creatinine level test, blood free and conjugated bilirubin level test, blood total bilirubin level test, blood aspartate aminotransferase activity determination, blood alanine aminotransferase activity determination, complete blood count – every 2 weeks for 2 months, and then every 3 months; clinical assessment of adverse events and/or risk factors should be performed during each patient visit. If signs of infection appear, the next dose of the drug should be skipped until they disappear completely. During treatment with #methotrexate**, #folic acid** should be prescribed at a dose of at least 5 mg, but not more than 10 mg per week, 24 hours after taking #methotrexate** [74–76].

or

#methotrexate** for pediatric patients – 10–15 mg/m² of body surface area once a week intramuscularly [77–79]

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

Comments: A contraindication for prescribing #methotrexate** solution for injection or tablets is age under 3 years.

or

leflunomide** for adult patients orally with an initial dose of 100 mg once daily for 3 days, then switching to maintenance treatment of 10–20 mg once daily [80].

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

Comments: During treatment with leflunomide**, it is necessary to assess adverse events, measure peripheral blood pressure, perform a complete blood count and general clinical blood chemistry analysis, liver function tests and blood parameters (Determination of blood alanine aminotransferase activity. Complete blood count.). The greatest effect of leflunomide** therapy occurs in 8–10 weeks. A contraindication for prescribing leflunomide** is age under 18 years.

or

#sulfasalazine** for adult patients orally, initial dose 500 mg/day, increasing by 500 mg weekly to a therapeutic dose of 2 g per day. If there is no effect, it is advisable to increase the dose of the drug to 3 g per day [81, 82].

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

Comments: The effect of #sulfasalazine** is evaluated after 6–8 weeks, with the greatest effect occurring after 12–16 weeks. Taken long-term.

or

#sulfasalazine** for pediatric patients orally 30 mg/kg per day in 2 divided doses [78]

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

apremilast** for adult patients orally 30 mg twice daily, morning and evening, with a 12-hour interval [85].

Level of Evidence AGrade of Evidence 2Level of Recommendations A (Grade of Evidence – 2)

Comments: Therapy with apremilast** should be initiated according to the following schedule: first day 10 mg in the morning, second day 10 mg in the morning and evening, third day 10 mg in the morning, 20 mg in the evening, fourth day 20 mg in the morning and evening, fifth day 20 mg in the morning, 30 mg in the evening, then 30 mg in the morning and evening. The therapeutic effect develops gradually, over a long period of time. Apremilast**, by inhibiting phosphodiesterase 4, indirectly through the blockade of signaling pathways, reduces the production of pro-inflammatory cytokines. It has moderate efficacy in patients with psoriatic arthritis and psoriasis; in practice, it is used in patients with metabolic disorders, diabetes mellitus, infectious complications, etc., when other immunosuppressants cannot be prescribed. Efficacy has been demonstrated in patients with the mono-oligoarticular form of psoriatic arthritis, especially at an early stage. It reduces symptoms of arthritis, dactylitis, and enthesitis. It has a favorable safety profile. It is used as monotherapy or in combination with an antimetabolite (#methotrexate**). The most common adverse event is diarrhea in the first 2–4 weeks of treatment in 19% of patients, which usually resolves spontaneously and in most cases does not require discontinuation of therapy. After initial dose titration, if treatment is interrupted, re-titration is not required. The prescription of apremilast** does not require mandatory constant monitoring of laboratory parameters or tuberculosis screening before and during treatment. There is a risk of developing depression, which resolves after drug discontinuation. A contraindication for prescribing apremilast** is age under 18 years.

tofacitinib** film-coated tablets for adult patients 5 mg twice daily in combination with #methotrexate** [86, 87].

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

Comments: In registration trials, tofacitinib** demonstrated efficacy regarding arthritis, enthesitis, dactylitis, and psoriasis in combination with #methotrexate**. Among serious adverse reactions of tofacitinib**, a higher incidence of infections, cases of Herpes zoster, confirmed gastrointestinal perforation in one patient, and confirmed tumors in 3 patients should be noted [86, 87]. Tofacitinib** at a dose of 20 mg/day should not be used in patients older than 65 years, with a high risk of thromboembolic complications, with risk factors for cardiovascular disease, with a history of serious cardiovascular events, heart failure, as well as in female patients using hormonal contraceptives [88]. The clinical efficacy of tofacitinib** and its safety profile are comparable to tumor necrosis factor alpha (TNF-alpha) inhibitors. Tuberculosis screening is required before starting treatment and every 6 months of therapy. A contraindication to prescribing tofacitinib** is age under 18 years.

or

upadacitinib** for adult patients 15 mg once daily in combination with #methotrexate** or as monotherapy [140-141]

Comments: Upadacitinib** demonstrated efficacy regarding arthritis, enthesitis, dactylitis, spondylitis, and psoriasis both in combination with #methotrexate** and as monotherapy [140-145]. In a comprehensive analysis of the safety profile of upadacitinib** in psoriatic arthritis at a dose of 15 mg once daily, a comparable incidence of adverse events was demonstrated with the adalimumab** 40 mg once every 2 weeks therapy group, except for a higher incidence of Herpes zoster virus reactivation and increased blood CK levels in the upadacitinib** therapy group. Most Herpes zoster cases were non-serious and involved no more than 1 dermatome [146]. The clinical efficacy of upadacitinib** and its safety profile are comparable to tumor necrosis factor alpha (TNF-alpha) inhibitors. Tuberculosis screening is required before starting treatment and every 6 months of therapy. A contraindication to prescribing upadacitinib** is age under 18 years.

Comments: The efficacy of tofacitinib** and upadacitinib** for spondylitis in patients with psoriatic arthritis has been extrapolated from registration trials for ankylosing spondylitis and from sub-analyses of relevant RCTs. When a patient has a combination of severe psoriasis and active spondylitis, it is preferable to use secukinumab** or netakimab** or ixekizumab**. RCTs have proven the effect of secukinumab** on manifestations of spondylitis in PsA. Data on the effect of tumor necrosis factor alpha (TNF-alpha) inhibitors and netakimab** and ixekizumab** on spondylitis in psoriatic arthritis have been extrapolated from randomized clinical trials in ankylosing spondylitis and axial spondyloarthritis and obtained as a result of sub-analyses of relevant RCTs. Data on the efficacy of ustekinumab** and guselkumab** were obtained as a result of sub-analyses of relevant RCTs [79, 86, 87, 97–100, 152-158]  

infliximab** lyophilized powder for solution for infusion, lyophilized powder for concentrate for solution for infusion for adult patients 5 mg/kg intravenously as an infusion at weeks 0, 2, and 6, then every 8 weeks [89].

Level of Evidence AGrade of Evidence 2Level of Recommendations A (Grade of Evidence – 2)

Comments: If there is no effect within 6 weeks, continuing treatment with infliximab** is impractical. A contraindication to prescribing infliximab** for psoriatic arthritis is age under 18 years.

or

adalimumab** solution for subcutaneous injection for adult patients 40 mg subcutaneously once every 2 weeks [90];

Level of Evidence AGrade of Evidence 2Level of Recommendations A (Grade of Evidence – 2)

or

etanercept** solution for subcutaneous injection, lyophilized powder for solution for subcutaneous injection [91–94];

GRC ALEL 2Grade of Recommendation A (Level of Evidence – 2) – for adults

Level of Recommendation CLevel of Evidence 4Level of recommendation C (level of evidence – 4) – for children

Comments: subcutaneously for adults 50 mg once a week; for adolescents over 12 years of age, the dose is determined based on 0.4 mg/kg of body weight (maximum single dose 25 mg), the drug is administered 2 times a week with an interval of 3–4 days; administration of a dose of 0.8 mg/kg of body weight once a week (maximum single dose – 50 mg) once a week is also possible. The efficacy and safety of etanercept** for the treatment of psoriatic arthritis in children under 12 years of age have not been studied. Treatment with etanercept** in adolescents over 12 years of age should be discontinued if no positive dynamics are observed after 4 months of therapy.

or

golimumab** solution for subcutaneous injection for adult patients 50 mg subcutaneously once a month on the same day of the month; in patients with a body weight of more than 100 kg, if there is no adequate response after 3–4 injections, increasing the dose of golimumab** to 100 mg monthly may be considered [95];

Level of Evidence AGrade of Evidence 2Level of Recommendations A (Grade of Evidence – 2)

Comments: If there is no effect after 12–14 weeks of therapy with golimumab** (3–4 injections) at a dose of 50 mg in patients with a body weight of no more than 100 kg, it is necessary to evaluate the feasibility of further use of the drug. In patients with a body weight of more than 100 kg, after increasing the drug dose to 100 mg and in the absence of an effect after 3–4 injections of golimumab** at 100 mg, the feasibility of further use must be re-evaluated. A contraindication to prescribing golimumab** is pediatric age under 18 years.

or

certolizumab pegol** solution for subcutaneous injection for adult patients subcutaneously initially at an induction dose of 400 mg at weeks 0, 2, and 4, then 200 mg once every 2 weeks or 400 mg once every 4 weeks [96];

Level of Evidence AGrade of Evidence 2Level of Recommendations A (Grade of Evidence – 2)

Comments: A contraindication to prescribing certolizumab pegol** is pediatric age under 18 years.

or

ustekinumab** solution for subcutaneous injection 45 mg for adult patients subcutaneously, the second administration is carried out after 4 weeks, then every 12 weeks. For patients weighing more than 100 kg – at a dose of 90 mg subcutaneously with the same frequency [97]

Level of Evidence AGrade of Evidence 2Level of Recommendations A (Grade of Evidence – 2)

Comments: Ustekinumab** is approved for use in children with active juvenile psoriatic arthritis aged 5 years and older at approved doses depending on the patient's body weight (less than 60 kg – dose is determined at 0.75 mg/kg; 60 kg and more, the dose is 45 mg)

or

ixekizumab** solution for subcutaneous injection, administered at 160 mg subcutaneously at week 0, then 80 mg every 4 weeks. The starting dose of 160 mg is administered as two separate subcutaneous injections of 80 mg each [98–100].

GOR ALEL 2Level of recommendation validity A (level of evidence reliability – 2)

Comments: In combination with moderate to severe plaque psoriasis, the dosage regimen corresponds to that for plaque psoriasis – on the first day, the drug is administered at a dose of 160 mg (two 80 mg injections), the next administration is carried out after 2 weeks at a dose of 80 mg, subsequently the drug is administered once every 2 weeks at 80 mg at 4, 6, 8, 10, and 12 weeks after the first administration, and after 12 weeks of treatment, the drug is administered once every 4 weeks. A contraindication to prescribing ixekizumab** is pediatric age under 18 years.

or

secukinumab** solution for subcutaneous injection, lyophilized powder for solution for subcutaneous injection for adult patients 150 mg subcutaneously at weeks 0, 1, 2, and 3, followed by monthly administration as a maintenance dose starting from week 4 as monotherapy or in combination with #methotrexate**. Depending on the clinical response, the dose of the drug can be increased to 300 mg [101–103].

Level of Evidence AGrade of Evidence 2Level of Recommendations A (Grade of Evidence – 2)

Comments: For patients with an inadequate response to therapy with tumor necrosis factor alpha (TNF-alpha) inhibitors or for patients with concomitant moderate-to-severe psoriasis, the recommended starting dose of the drug is 300 mg at weeks 0, 1, 2, and 3 subcutaneously, followed by monthly administration as a maintenance dose starting from week 4. A contraindication to prescribing secukinumab** for psoriatic arthritis is pediatric age under 18 years.

Or

netakimab**, solution for subcutaneous injection

GRC ALEL 2Grade of Recommendation A (Level of Evidence 2)

Comments: administered at a dose of 120 mg (as two subcutaneous injections of 1 ml (60 mg) of the drug each) once a week at weeks 0, 1, and 2, then once every 2 weeks up to week 10 inclusive, and starting from week 14, the drug is administered once every 4 weeks as monotherapy or in combination with #methotrexate. For patients with psoriatic arthritis presenting with spondylitis or those who have not achieved efficacy with netakimab** at a frequency of once every 4 weeks, prescribing the drug once every 2 weeks is possible

A contraindication to prescribing netakimab** is pediatric age under 18 years.

or

risankizumab** solution for subcutaneous injection, 150 mg at week 0, week 4, and every 12 weeks thereafter.

GRC ALEL 2Grade of Recommendation A (Level of Evidence 2)

Comments: A contraindication to prescribing risankizumab** is pediatric age under 18 years.

or

guselkumab** solution for subcutaneous injection

GRC ALEL 2Grade of Recommendation A (Level of Evidence 2)

Comments: 100 mg at week 0, week 4, and every 8 weeks thereafter. A contraindication to prescribing guselkumab** is pediatric age under 18 years [127–132, 147–158].

Treatment of psoriatic arthritis is carried out depending on the predominant clinical phenotype and its activity (tables 5–9).

Table 5. Treatment of peripheral arthritis

# - drugs are used only for code L 40.5

Table 7. Treatment of spondylitis

# - drugs are used only for code L 40.5

Table 8. Treatment of enthesitis

# - drugs are used only for code L 40.5

Table 9. Treatment of dactylitis

# - drugs are used only for code L 40.5

3.2 Surgical Treatment

total hip replacement

or

total knee replacement

or

replacement of small joints of the foot and hand

or

spinal arthrodesis

or

arthrodesis of the foot and ankle

or

arthroscopic ankle arthrodesis

or

knee arthrodesis

or

hip arthrodesis

or

arthrodesis of large joints

or

arthrodesis of other joints

GPP CLEL 4Grade of Recommendation C (Level of Evidence – 4).

Comments: Indications for surgical treatment in patients with psoriatic arthritis are determined by an orthopedic traumatologist [30, 104].

3.3 Other Treatment

These include non-pharmacological methods such as therapeutic exercise for joint diseases and injuries, physiotherapeutic methods including acupuncture point stimulation with other physical factors, health resort (sanatorium) treatment, and patient education regarding the necessity of a healthy lifestyle, weight normalization, and smoking cessation. Small case-control studies have demonstrated a moderate and short-term analgesic effect of acupuncture point stimulation with other physical factors, magnetotherapy (exposure to magnetic fields), laser therapy, and mineral baths (balneotherapy); an effect on disease prognosis has not been proven [105]. Isolated observational studies have shown potential reductions in disease activity and improvements in quality of life with mud baths in patients with psoriatic arthritis who have low disease activity while maintaining stable anti-inflammatory therapy [126]. One small randomized study showed that a very-low-calorie diet reduces disease activity in obese patients with psoriatic arthritis [106].

Diet therapy is not used.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Rehabilitation methods have not been developed.

5. Prevention and Dispensary Observation

Primary prevention has not been developed. Dispensary monitoring by a dermatologist and/or rheumatologist.

6. Organization of Medical Care

Medical care for patients with psoriatic arthritis is provided in the following forms:

Medical care for patients with acute lower limb ischemia is provided in the form of:

- specialized, including high-tech, medical care.

Medical care for patients with psoriatic arthritis can be provided in the following settings:

- out-patiently (in settings not requiring round-the-clock medical observation and treatment);

- in a day hospital (in settings providing medical observation and treatment during daytime hours, not requiring round-the-clock medical observation and treatment);

- inpatiently (in settings providing round-the-clock medical observation and treatment).

Primary health care includes measures for the prevention, diagnosis, and treatment of patients with psoriatic arthritis, medical rehabilitation, and the promotion of a healthy lifestyle.

Primary health care includes:

primary medical (physician-led) health care;

primary specialized health care.

Primary general medical care for patients with psoriatic arthritis is provided in medical organizations by a district general practitioner, district pediatrician, or general practitioner (family physician) in an outpatient setting upon the recommendation of a rheumatologist, general practitioner, or dermatologist.

Within the framework of primary general medical care, district general practitioners, district pediatricians, and general practitioners (family physicians), upon identifying symptoms or signs of psoriatic arthritis or its exacerbation, refer patients to a medical organization for primary specialized health care, and also provide medical care in accordance with the recommendations of a rheumatological, therapeutic, or dermatological profile medical organization when there are no medical indications for referral thereto.

Primary specialized health care for patients with psoriatic arthritis is provided by rheumatologists, general practitioners, or, in the presence of psoriatic skin rashes, dermatologists.

If outpatient medical care cannot be provided and medical indications exist, a patient with psoriatic arthritis is referred to a medical organization providing inpatient medical care.

Specialized, including high-tech, medical care for patients with psoriatic arthritis is provided by rheumatologists, general practitioners, or, in the presence of psoriatic skin rashes, dermatologists, and includes prevention, diagnosis, and treatment using special methods and complex medical technologies, as well as medical rehabilitation.

When medical indications are present, treatment of patients with psoriatic arthritis is carried out with the involvement of medical specialists in accordance with the Nomenclature of Specialties of Specialists with Higher and Postgraduate Medical and Pharmaceutical Education in the Healthcare Sector of the Russian Federation, approved by Order of the Ministry of Health of the Russian Federation dated October 7, 2015, No. 700n (registered by the Ministry of Justice of the Russian Federation on November 12, 2015, registration No. 39696), as amended by Orders of the Ministry of Health of the Russian Federation dated October 11, 2016, No. 771n (registered by the Ministry of Justice of the Russian Federation on December 26, 2016, registration No. 44926) and dated December 9, 2019, No. 996n (registered by the Ministry of Justice of the Russian Federation on December 30, 2019, registration No. 57070).

Specialized, excluding high-tech, medical care is provided to patients with psoriatic arthritis in federal state medical organizations subordinate to the Russian Ministry of Health when necessary to establish a definitive diagnosis due to atypical disease course, lack of effect from ongoing therapy and/or repeated treatment courses with potential efficacy of other treatment methods, high surgical risk due to complicated underlying disease course or comorbid conditions, necessity of supplementary diagnostic workup in diagnostically complex cases and/or comprehensive preoperative preparation in patients with complicated forms of the disease and comorbidities, and when repeated hospitalization is recommended by said federal state medical organizations in accordance with the Procedure for Referring Patients to Medical Organizations and Other Organizations Subordinate to Federal Executive Bodies for Specialized (Excluding High-Tech) Medical Care, set forth in the Appendix to the Regulation on Organizing the Provision of Specialized, Including High-Tech, Medical Care, approved by Order of the Ministry of Health of the Russian Federation dated December 2, 2014, No. 796n "On Approval of the Regulation on Organizing the Provision of Specialized, Including High-Tech, Medical Care" (registered by the Ministry of Justice of the Russian Federation on February 2, 2015, registration No. 35821), as well as in the presence of medical indications in the patient – in federal state medical organizations providing specialized medical care, in accordance with the Procedure for Referring Citizens by Executive Bodies of the Subjects of the Russian Federation in the Healthcare Sector to the Place of Treatment in the Presence of Medical Indications, approved by Order of the Ministry of Health and Social Development of the Russian Federation dated October 5, 2005, No. 617 (registered by the Ministry of Justice of the Russian Federation on October 27, 2005, registration No. 7115).

If a patient with psoriatic arthritis has medical indications for high-tech medical care, their referral to a medical organization providing high-tech medical care is carried out in accordance with the Procedure for Referring Citizens of the Russian Federation for the Provision of High-Tech Medical Care at the Expense of Budgetary Allocations Provided in the Federal Budget to the Ministry of Health and Social Development of the Russian Federation through the Application of a Specialized Information System, approved by Order of the Ministry of Health and Social Development of the Russian Federation dated December 28, 2011, No. 1689n (registered by the Ministry of Justice of the Russian Federation on February 8, 2012, registration No. 23164).

If there are indications for inpatient surgical treatment in a surgical hospital associated with persistent irreversible joint function impairment, patients with psoriatic arthritis are referred by a general practitioner, district pediatrician, family physician, or rheumatologist for a consultation with an orthopedic trauma surgeon.

Patients with psoriatic arthritis are referred to specialized medical and sanatorium-resort organizations for rehabilitation measures when there are medical indications.

Dermatovenerologists treating and monitoring patients with psoriasis may screen for psoriatic arthritis using patient questionnaires [107, 108, 122] (Appendix G5).

Indications for planned hospitalization in a rheumatology, internal medicine, or dermatovenerology department:

1) Indications for providing medical care in a day hospital setting:

- inadequate effectiveness of outpatient treatment in patients with low disease activity of psoriatic arthritis;

2) Indications for inpatient medical care;

- high-activity psoriatic arthritis;

- need for maintenance therapy with immunosuppressants;

- insufficient efficacy of ongoing outpatient treatment.

Indications for planned hospitalization in a surgical medical organization:

1) Indications for inpatient medical care;

- Persistent irreversible joint function impairment requiring surgical correction;

Indications for patient discharge from a medical organization:

- Partial or complete restoration of the affected joint function.

- Reduction of pain in the affected joints.

7. Additional Information

Risk factors for an unfavorable prognosis in psoriatic arthritis include polyarthritis, presence of joint erosions, elevated ESR/CRP, dactylitis, and psoriatic onychodystrophy.

An increase in the standard mortality rate of patients with psoriatic arthritis has been revealed compared to the general population, primarily due to cardiovascular diseases. All patients with psoriatic arthritis must adhere to a healthy lifestyle, which includes regular physical exercise as part of a therapeutic exercise program for joint diseases and injuries for patients with musculoskeletal disorders for at least 30 minutes 5 times a week, control of the body mass index (within 18.5–24.5), reduction of alcohol consumption, and smoking cessation.

[109–111].

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Kubanov Alexey Alekseevich – Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, President of the All-Russian Public Organization "Russian Society of Dermatovenerologists and Cosmetologists".

2. Nasonov Evgeny Lvovich – Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, President of the All-Russian Public Organization "Association of Rheumatologists of Russia".

3. Bakulev Andrey Leonidovich – Doctor of Medical Sciences, Professor, Member of the All-Russian Public Organization "Russian Society of Dermatovenerologists and Cosmetologists".

4. Znamenskaya Lyudmila Fedorovna – Doctor of Medical Sciences, Member of the All-Russian Public Organization "Russian Society of Dermatovenerologists and Cosmetologists".

5. Karamova Arfenya Eduardovna – Candidate of Medical Sciences, All-Russian Public Organization "Russian Society of Dermatovenerologists and Cosmetologists".

6. Korotaeva Tatyana Viktorovna – Doctor of Medical Sciences, Member of the All-Russian Public Organization "Association of Rheumatologists of Russia".

7. Korsakova Yulia Leonidovna – Candidate of Medical Sciences, Member of the All-Russian Public Organization "Association of Rheumatologists of Russia".

8. Loginova Elena Yurievna – Candidate of Medical Sciences, Member of the All-Russian Public Organization "Association of Rheumatologists of Russia".

9. Hobeisch Marianna Mikhailovna – Candidate of Medical Sciences, Member of the All-Russian Public Organization "Russian Society of Dermatovenerologists and Cosmetologists".

10. Chikin Vadim Viktorovich – Doctor of Medical Sciences, Member of the All-Russian Public Organization "Russian Society of Dermatovenerologists and Cosmetologists".

Conflict of interest: The authors declare no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Medical specialists: dermatovenerologists, rheumatologists

2. Residents and trainees of continuing professional development courses in the specified specialty.

Table 1. Scale for assessing levels of reliable evidence (LRE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing the levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for grading levels of recommendation certainty (LRC) 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

These clinical guidelines have been developed taking into account the following regulatory and legal documents:

1) Order of the Russian Ministry of Health No. 687n dated November 7, 2012, "On Approval of the Standard of Specialized Medical Care for Ankylosing Spondylitis, Psoriatic Arthritis, and Other Spondyloarthritides".

2) Order of the Russian Ministry of Health No. 822n dated November 9, 2012, "On Approval of the Standard of Specialized Medical Care for Ankylosing Spondylitis, Psoriatic Arthritis, and Other Spondyloarthritides (Maintenance Therapy in a Day Hospital)."

3) Order of the Russian Ministry of Health No. 900n dated November 12, 2012, "On Approval of the Procedure for Providing Medical Care to the Adult Population in the Profile 'Rheumatology'."

4) Order of the Russian Ministry of Health No. 924n dated November 15, 2012, "On Approval of the Procedure for Providing Medical Care to the Population in the Profile 'Dermatovenereology'."

5) Order of the Ministry of Health and Social Development of the Russian Federation No. 433 dated May 30, 2006, "On Approval of the Standard of Medical Care for Patients with Psoriasis."

Appendix B. Physician Action Algorithms

# - drugs are used only for code L 40.5

Appendix C. Patient Information

Psoriatic arthritis is a chronic inflammatory disease observed in patients with psoriasis. It mainly affects the joints of the fingers and toes, wrists, knees, ankles, lower back (sacroiliac joints), and neck. The prevalence of psoriasis in the population is 2–3%, while the prevalence of psoriatic arthritis among psoriasis patients ranges from 7 to 40%. Skin changes usually precede the development of joint involvement. Nail involvement occurs in approximately 80% of cases. Psoriatic arthritis most frequently begins between the ages of 20 and 50 years, affecting men and women with equal frequency. The main distinguishing symptoms are asymmetrical joint involvement, pain, stiffness, swelling of the affected joints sometimes with a purple-bluish skin discoloration over them, frequent involvement of all three joints in a single digit, "sausage-like" swelling of the fingers (dactylitis), heel pain when walking, and pain and stiffness in the neck and lower back in the second half of the night and morning, which decrease after waking up and physical warm-up.

In the absence of treatment, psoriatic arthritis can severely deform the joint and lead to disability.

Signs of internal organ involvement (eyes, myocardium, intestines) are sometimes observed.

Etiology

The exact cause of psoriatic arthritis remains unknown today. Psoriatic arthritis develops more often in the presence of pronounced skin lesions, although there is no clear correlation between the severity and course of skin and joint manifestations. Precipitating factors in the development of psoriatic arthritis often include past trauma, stress, and infectious diseases. A genetic predisposition to developing psoriasis and psoriatic arthritis has been noted.

Due to the lack of precise data on the etiology of the disease, prevention methods for psoriatic arthritis have not been developed.

As a rule, skin manifestations of psoriasis precede the development of psoriatic arthritis (often by many years); less commonly, arthritis and psoriasis develop simultaneously. In rare cases, arthritis appears before psoriasis.

Characteristic signs of psoriatic arthritis include involvement of the middle and terminal phalanges of the fingers and toes, which is often combined with nail changes. In addition, psoriatic arthritis can affect the knee and ankle joints, as well as the cervical and lumbosacral spine. Pain in the heel and Achilles tendon areas is sometimes observed due to an inflammatory process at the sites where tendons attach to the calcaneus.

Medical treatment

Currently, there is no cure for psoriasis and psoriatic arthritis, but there are many methods that can reduce painful manifestations. Modern medications make it possible to manage the disease by completely relieving its symptoms. However, this requires constant medical supervision and systematic treatment.

During periods of minimal arthritis activity or its absence, health resort treatment, pelotherapy (mud therapy), medicinal hydrogen sulfide baths, and medicinal radon baths are indicated. Before going to a health resort, be sure to inform your doctor.

Therapeutic exercises

For psoriatic arthritis, therapeutic exercise for joint diseases and injuries is prescribed, and an active lifestyle is recommended.

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

Appendix G1. BASDAI Index

Russian title: Bath Ankylosing Spondylitis Disease Activity Index

Original title (if applicable): BASDAI (Bath Ankylosing Spondylitis Disease Activity Index)

Source (official developer website, publication with validation):

1) Taylor W.J., Harrison A.A. Could the bath ankylosing spondylitis disease activity index (BASDAI) be a valid measure of disease activity in patients with psoriatic arthritis? Arthritis Rheum. 2004; 51(3): 311–315.

2) Fernandez-Sueiro J.L., Willisch A., Pertega-Diaz S. et al. Validity of the bath ankylosing spondylitis disease activity index for the evaluation of disease activity in axial psoriatic arthritis. Arthritis Care Res.2010; 62(1):78–85.

Type (underline):

- assessment scale

- score

- questionnaire

- other (specify):

Purpose: Assessment of spondylitis activity and the effect of therapy on spondylitis.

Content (template):

Assessed based on changes in the Bath Ankylosing Spondylitis Disease Activity Index BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) — a 6-question self-assessment questionnaire using a numerical rating scale from 0 ("very good") to 10 ("very bad") [104]

In the corresponding box (circle the corresponding number).

How would you rate your level of overall fatigue (tiredness) over the past week?

How would you rate your level of pain in your neck, back, or hip joints over the past week?

How would you rate your level of pain (or degree of swelling) in your joints (other than neck, back, or hips) over the past week?

How would you rate the degree of discomfort arising from touching or pressing on any tender areas (over the past week)?

How would you rate the severity of morning stiffness upon waking (over the past week)?

How long does morning stiffness upon waking last (over the past week)?

Calculation of the BASDAI index:

The sum of the values for questions 1–4 is calculated, and the mean value for questions 5 and 6 is added. The resulting result is divided by 5.

Key (interpretation):

Interpretation of scores:

<4 without functional impairment corresponds to low psoriatic spondylitis activity;

> 4 without functional impairment and BASDAI < 4 combined with functional impairment corresponds to moderate activity;

> 4 combined with functional impairment corresponds to high activity;

Note: A 50% reduction in the index indicates a response to therapy.

Appendix G2. LEI Index

Russian title: Leeds Enthesitis Index

Original title (if applicable): LEI (Leeds Enthesitis Index)

Source (official developer website, validation publication):

Healy P.J., Helliwell P.S. Measuring clinical enthesitis in psoriatic arthritis: assessment of existing measures and development of an instrument specific to psoriatic arthritis. Arthritis Rheum. 2008;59(5):686–691.

Type (underline):

- assessment scale

- index

- questionnaire

- other (specify):

Purpose: Assessment of the effect of therapy on enthesitis

Content (template):

The dynamics of the Leeds Enthesitis Index (LEI) are evaluated. LEI is calculated by simply summing the palpation tenderness scores at 6 paired enthesis attachment sites: Achilles tendon, lateral epicondyle of the humerus, medial femoral condyle.

Key (interpretation):

Gradations: 0 — "no pain", 1 — "pain present", maximum 6 points.

Note: The maximum number of points corresponds to widespread entheseal involvement.

Appendix G3. Disease activity scales

Russian title: Disease Activity Score

Original title (if applicable): Disease Activity Index for Psoriatic Arthritis (DAPSA)

Source (official developer website, validation publication):

Schoels M, Aletaha D, Funovits J, et al. Application of the DAREA/DAPSA score for assessment of disease activity in psoriatic arthritis. Ann Rheum Dis. 2010;69(8): 1441-1447. Doi:10.1136/ard.2009.122259.

Type (underline):

- assessment scale

- score

- questionnaire

- other (specify):

Purpose: Assessment of psoriatic arthritis activity

Content (template):

DAPSA index = TJC/68 + SJC/66 + PtGA (VAS, cm) + PtA (VAS, cm) + CRP (mg/dL)

Key (interpretation): Threshold values: DAPSA > 28 — high activity, 15–28 — moderate, 5–14 — low, 0–4 — remission.

Note: To calculate this index, 68 tender and 66 swollen joints are evaluated, while the distal interphalangeal joints of the feet are not taken into account [117, 120]. Temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, 1st–5th metacarpophalangeal, 1st interphalangeal, 2nd–5th proximal interphalangeal, 2nd–5th distal interphalangeal joints of the hands, hips (only pain on passive movement is evaluated), knees, ankles, tarsal joints, 1st–5th metatarsophalangeal, 1st interphalangeal, and 2nd–5th proximal interphalangeal joints are evaluated.

The Visual Analog Scale (VAS, cm) is used for the patient's and physician's overall assessment of psoriatic arthritis activity, as well as pain severity

Russian title: Disease Activity Score

Original title (if applicable): Disease Activity Score (DAS28)

Source (official developer website, validation publication):

Salaffi F., Ciapetti A., Carotti M. et al. Disease activity in psoriatic arthritis: Comparison of the discriminative capacity and construct validity of six composite indices in a real world. BioMed Res Int.2014, 2014: 528105.

Type (underline):

- assessment scale

- index

- questionnaire

- other (specify):

Purpose: Assessment of psoriatic arthritis activity

Content (template):

DAS28-ESR = 0.56 x (√(28 TJC)) + 0.28 x (√(28 SJC)) + 0.70 x ln(ESR) + 0.014 x (PtGA),

where TJC is the number of tender joints out of 28, SJC is the number of swollen joints out of 28, ESR is the erythrocyte sedimentation rate, PtGA is the patient's global assessment of disease activity, VAS, mm.

Key (interpretation): DAS28 threshold values: high activity — DAS28 > 5.1; moderate — 5.1 ≥ DAS28 > 3.2; low — DAS28 ≤ 3.2; DAS28 < 2.6 — remission.

Note: To calculate DAS28, the following joints are evaluated: shoulders, elbows, wrists, 1st–5th metacarpophalangeal, 1st interphalangeal, 2nd–5th proximal interphalangeal, knees. The index calculation includes the patient's assessment of psoriatic arthritis activity, for which the Visual Analog Scale (VAS, mm) is used

Appendix G4. Treatment response criteria

PsARC Criteria (Psoriatic Arthritis Response Criteria)

Russian title: Psoriatic Arthritis Response Criteria

Original title (if applicable): Psoriatic Arthritis Response Criteria (PsARC)

Source (official developer website, validation publication):

1) Mease P.J., Antoni C.E., Gladman D.D. et al. Psoriatic arthritis assessment tools in clinical trials. Ann Rheum Dis. 2005;64 Suppl. 2:ii49–54.

2) Fransen J., Antoni C., Mease P.J. et al. Performance of response criteria for assessing peripheral arthritis in patients with psoriatic arthritis: analysis of data from randomised controlled trials of two tumour necrosis factor inhibitors. Ann Rheum Dis. 2006;65:1373–1378.

Type (underline):

- assessment scale

- score

- questionnaire

- other (specify):

Purpose: Assessment of treatment efficacy response in psoriatic arthritis

Content (template):

number of tender joints (out of 68)

1. number of swollen joints (out of 66)

2. Physician's overall activity assessment on a 5-point scale: "excellent" = 1, "good" = 2, "satisfactory" = 3, "poor" = 4, "very poor" = 5

3. Patient's overall activity assessment on a 5-point Likert scale: "excellent" = 1, "good" = 2, "satisfactory" = 3, "poor" = 4, "very poor" = 5.

Key (interpretation):

Improvement:

1. reduction in the patient/physician global assessment of psoriatic arthritis activity by ≥ 1 point

2. reduction in tender joint count / swollen joint count by ≥ 30%.

Worsening:

1. increase in the patient/physician global assessment of psoriatic arthritis activity by ≥ 1 point

2. increase in tender joint count / swollen joint count by ≥ 30%.

Response to therapy:

1. improvement in two of the four specified criteria, with one of them being the tender joint count or swollen joint count.

2. no worsening of any of the parameters is allowed.

Before starting therapy and during treatment, the 68 tender joint count and 66 swollen joint count are assessed, excluding the distal interphalangeal joints of the feet [117, 120]. The temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, 1st–5th metacarpophalangeal, 1st interphalangeal, 2nd–5th proximal interphalangeal, 2nd–5th distal interphalangeal joints of the hands, hips (assessing pain on passive movement only), knees, ankles, tarsal joints, 1st–5th metatarsophalangeal, 1st interphalangeal, and 2nd–5th proximal interphalangeal joints are evaluated.

To assess psoriatic arthritis activity by the patient and physician, as well as pain severity, the Visual Analog Scale (VAS, mm) or a 5-point Likert scale is used, where: "excellent" = 0, "good" = 1, "satisfactory" = 2, "poor" = 3, "very poor" = 4.

Note: Evaluation of the efficacy of the initiated therapy in patients with psoriatic arthritis is carried out within the timeframe established individually for each medicinal product.

European Alliance of Associations for Rheumatology (EULAR) response criteria:

Russian title: Response criteria for psoriatic arthritis

Original title (if available): European Alliance of Associations for Rheumatology (EULAR) response criteria

Source (official developer website, validation publication): [121]

Fransen J., Antoni C., Mease P.J. et al. Performance of response criteria for assessing peripheral arthritis in patients with psoriatic arthritis: analysis of data from randomised controlled trials of two tumour necrosis factor inhibitors. Ann Rheum Dis. 2006;65:1373–1378. 

Type (underline):

- assessment scale

- score

- questionnaire

- other (specify):

Purpose: Assessment of treatment efficacy response in psoriatic arthritis

Content (template):

1. No response – decrease in DAS28 compared to baseline by ≤ 0.6

2. Moderate response – change in DAS28 between > 0.6 and ≤ 1.2.

3. Good response – decrease in DAS28 by > 1.2.

Assessment of activity and therapy effect on dactylitis

To evaluate treatment efficacy, the change in the number of digits with dactylitis is determined during follow-up.

Appendix G5. Screening questionnaire for psoriatic arthritis in patients with psoriasis

Russian title: PEST Questionnaire

Original title (if available): PEST (Psoriasis Epidemiology Screening Tool)

Source (official developer website, validation publication):

Ibrahim G., Buch M., Lawson C. et al. Evaluation of an existingscreening tool for psoriatic arthritis in people with psoriasis andthe development of a new instrument: the Psoriasis Epidemiology Screening Tool (PEST) questionnaire. Clin Exp Rheumatol.2009;27:469–474.

Type (underline):

- assessment scale

- score

- questionnaire

- other (specify):

Purpose: Screening for psoriatic arthritis in patients with psoriasis

Content (template):

QUESTION NO. 1. Have you ever had swelling in a joint or joints?
QUESTION NO. 2. Has a doctor ever told you that you have arthritis?
QUESTION NO. 3. Have you ever noticed any changes in your fingernails or toenails (such as pitting or roughness)?
QUESTION NO. 4. Have you ever experienced pain in the heel area?
QUESTION NO. 5. Have you ever had evenly swollen and painful fingers or toes for no apparent reason, as shown in the photo below?
QUESTION NO. 6. On the diagram below, mark the joints that have caused you discomfort (stiffness, swelling, or pain in the joint).

Key (interpretation): Each "yes" answer corresponds to 1 point. If the total score is 3 or higher, and joint complaints are present, the dermatologist suspects psoriatic arthritis.

Note: If signs of psoriatic arthritis are detected, the patient with psoriasis should be referred to a rheumatologist.