Psoriatic Arthritis 

Updated: Oct 25, 2019
Author: Anwar Al Hammadi, MD, FRCPC; Chief Editor: Herbert S Diamond, MD 

Overview

Practice Essentials

Psoriatic arthritis is most commonly a seronegative oligoarthritis found in patients with psoriasis, with less common, but characteristic, differentiating features of distal joint involvement and arthritis mutilans.[1]  One in five patients with psoriasis has psoriatic arthritis (see the image below).[2]

Swelling and deformity of the metacarpophalangeal Swelling and deformity of the metacarpophalangeal and distal interphalangeal joints in a patient with psoriatic arthritis.

See Psoriasis: Manifestations, Management Options, and Mimics, a Critical Images slideshow, to help recognize the major psoriasis subtypes and distinguish them from other skin lesions.

Signs and symptoms

Onset of psoriasis and arthritis are as follows:

  • Psoriasis appears to precede the onset of psoriatic arthritis in 60-80% of patients (occasionally by as many as 20 years, but usually by less than 10 years)

  • In as many as 15-20% of patients, arthritis appears before the psoriasis

  • Occasionally, arthritis and psoriasis appear simultaneously

In some cases, patients may experience only stiffness and pain, with few objective findings. In most patients, the musculoskeletal symptoms are insidious in onset, but an acute onset has been reported in one third of all patients.

Findings on physical examination are as follows:

  • Enthesopathy or enthesitis, reflecting inflammation at tendon or ligament insertions into bone, is observed more often at the attachment of the Achilles tendon and the plantar fascia to the calcaneus with the development of insertional spurs

  • Dactylitis with sausage digits is seen in as many as 35% of patients

  • Skin lesions include scaly, erythematous plaques; guttate lesions; lakes of pus; and erythroderma

  • Psoriasis may occur in hidden sites, such as the scalp (where psoriasis frequently is mistaken for dandruff), perineum, intergluteal cleft, and umbilicus

Psoriatic nail changes, which may be a solitary finding in patients with psoriatic arthritis, may include the following:

  • Beau lines
  • Leukonychia
  • Onycholysis
  • Oil spots
  • Subungual hyperkeratosis
  • Splinter hemorrhages
  • Spotted lunulae
  • Transverse ridging
  • Cracking of the free edge of the nail
  • Uniform nail pitting

Extra-articular features are observed less frequently in patients with psoriatic arthritis than in those with rheumatoid arthritis (RA) but may include the following:

  • Synovitis affecting flexor tendon sheaths, with sparing of the extensor tendon sheath
  • Subcutaneous nodules are rare
  • Ocular involvement may occur in 30% of patients, including conjunctivitis in 20% and acute anterior uveitis in 7%; in patients with uveitis, 43% have sacroiliitis

Patterns of arthritic involvement

The patterns of psoriatic arthritis involvement are as follows:

  • Asymmetrical oligoarticular arthritis
  • Symmetrical polyarthritis
  • Distal interphalangeal arthropathy
  • Arthritis mutilans
  • Spondylitis with or without sacroiliitis

See Presentation for more detail.

Diagnosis

Classification of psoriatic arthritis

The Classification Criteria for Psoriatic Arthritis (CASPAR)[3] consist of established inflammatory articular disease with at least 3 points from the following features:

  • Current psoriasis (assigned a score of 2)
  • A history of psoriasis (in the absence of current psoriasis; assigned a score of 1)
  • A family history of psoriasis (in the absence of current psoriasis and history of psoriasis; assigned a score of 1)
  • Dactylitis (assigned a score of 1)
  • Juxta-articular new-bone formation (assigned a score of 1)
  • RF negativity (assigned a score of 1)
  • Nail dystrophy (assigned a score of 1)

Laboratory findings

No specific diagnostic tests are available for psoriatic arthritis.[4] The most characteristic laboratory abnormalities in patients with the condition are as follows:

  • Elevations of the erythrocyte sedimentation rate (ESR) and C-reactive protein level
  • Negative rheumatoid factor in 91-95% of patients
  • In 10-20% of patients with generalized skin disease, the serum uric acid concentration may be increased
  • Low levels of circulating immune complexes have been detected in 56% of patients
  • Serum immunoglobulin A levels are increased in two thirds of patients
  • Synovial fluid is inflammatory, with cell counts ranging from 5000-15,000/µL and with more than 50% of cells being polymorphonuclear leukocytes; complement levels are either within reference ranges or increased, and glucose levels are within reference ranges

Radiographic studies

Radiologic features have helped to distinguish psoriatic arthritis from other causes of polyarthritis. In general, the common subtypes of psoriatic arthritis, such as asymmetrical oligoarthritis and symmetrical polyarthritis, tend to result in only mild erosive disease. Early bony erosions occur at the cartilaginous edge, and cartilage is initially preserved, with maintenance of a normal joint space.

The following radiographic abnormalities are suggestive of psoriatic arthritis:

  • Pencil-in-cup deformity (seen in the image below)

    Arthritis mutilans (ie, "pencil-in-cup" deformitie Arthritis mutilans (ie, "pencil-in-cup" deformities).
  • Joint-space narrowing in the interphalangeal joints, possibly with ankylosis
  • Increased joint space in the interphalangeal joints as a result of destruction
  • Fluffy periostitis
  • Bilateral, asymmetrical, fusiform soft-tissue swelling
  • Unilateral or symmetrical sacroiliitis
  • Large, nonmarginal, unilateral, asymmetrical syndesmophytes (intervertebral bony bridges, seen in the image below) in the cervical, thoracic, and lumbar spine, often sparing some of the segments
  • Lateral radiograph of the cervical spine shows syn Lateral radiograph of the cervical spine shows syndesmophytes at the C2-3 and C6-7 levels, with zygapophyseal joint fusion. Courtesy of Bruce M. Rothschild, MD.

Magnetic resonance imaging studies

  • Particularly sensitive for detecting sacroiliitic synovitis, enthesitis, and erosions; can also be used with gadolinium to increase sensitivity

  • May show inflammation in the small joints of the hands, involving the collateral ligaments and soft tissues around the joint capsule, a finding not seen in persons with RA

See Workup for more detail.

Management

Medical treatment regimens include the use of nonsteroidal anti-inflammatory drugs (NSAIDs), Janus kinase (JAK) inhibitors, and disease-modifying antirheumatic drugs (DMARDs). DMARDs include the following[5] :

  • Methotrexate
  • Sulfasalazine
  • Cyclosporine
  • Leflunomide
  • Biologic agents (eg, TNF, PDE4, or interleukin inhibitors; CD80 binders)

In patients with severe skin inflammation, medications such as methotrexate, retinoic-acid derivatives, and psoralen plus ultraviolet (UV) light should be considered. These agents have been shown to work on skin and joint manifestations. Intra-articular injection of entheses or single inflamed joints with corticosteroids may be particularly effective in some patients. Use DMARDs in individuals whose arthritis is persistent.

Surgical care

  • Arthroscopic synovectomy has been effective in treating severe, chronic, monoarticular synovitis

  • Joint replacement and forms of reconstructive therapy are occasionally necessary

  • Patients in severe pain or with significant contractures may be referred for possible surgical intervention; however, high rates of recurrence of joint contractures have been noted after surgical release, especially in the hand

  • Hip and knee joint replacements have been successful

  • Arthrodesis and arthroplasty have also been used on joints, such as the proximal interphalangeal joint of the thumb

  • The wrist often spontaneously fuses, and this may relieve the patient's pain without surgical intervention

  • For arthritis mutilans, surgical intervention is usually directed toward salvage of the hand; combinations of arthrodesis, arthroplasty, and bone grafts to lengthen the digits may be used

Physical therapy

The rehabilitation treatment program for patients with psoriatic arthritis should be individualized and should be started early in the disease process. Such a program should consider the use of the following:

  • Rest: Local and systemic
  • Exercise: Passive, active, stretching, strengthening, and endurance
  • Modalities: Heat, cold
  • Orthotics: Upper and lower extremities, spinal
  • Assistive devices for gait and adaptive devices for self-care tasks: Including possible modifications to homes and automobiles
  • Education about the disease, energy conservation techniques, and joint protection
  • Possible vocational readjustments

See Treatment and Medication for more detail.

Background

Psoriatic arthritis is a chronic inflammatory arthritis that develops in at least 5% of patients with psoriasis. The association between psoriasis and arthritis was first made in the mid-19th century, but psoriatic arthritis was not clinically distinguished from rheumatoid arthritis (RA) until the 1960s. (An example of flexion deformity in psoriatic arthritis is shown below.) (See Presentation and Workup.)

Severe fixed flexion deformity of the interphalang Severe fixed flexion deformity of the interphalangeal joint.

Because of a lack of specific biologic tests, precisely defining psoriatic arthritis remains difficult. The disorder most commonly exists as a seronegative oligoarthritis found in patients with psoriasis. Distal joint involvement and arthritis mutilans are less common, but characteristic, differentiating features. (The first image below compares sites of involvement for psoriatic arthritis with those for RA. The second and third images show distal joint pathology in psoriatic arthritis.)

Comparison between sites of involvements in both h Comparison between sites of involvements in both hands and feet in psoriatic arthritis and rheumatoid arthritis.
Psoriatic arthritis involving the distal phalangea Psoriatic arthritis involving the distal phalangeal joint.
Psoriatic arthritis involving the distal phalangea Psoriatic arthritis involving the distal phalangeal joint.

Because 50% of patients with psoriatic arthritis have evidence of spondyloarthropathy, often human leukocyte antigen (HLA)-B27 associated, psoriatic arthritis has also been classified among the seronegative spondyloarthropathies. (See Pathophysiology and Etiology.)[6, 7, 8, 9, 10]

Peripheral joint disease occurs in 95% of patients with psoriatic arthritis, while in the other 5%, axial spine involvement occurs exclusively. (See Presentation and Workup.)

Evidence from one study indicated that psoriatic arthritis is more frequent in patients with severe psoriasis than in those with milder cases. While this is true, no evidence indicates that the severity of the psoriasis relates to the pattern of joint involvement. In another study, pustular psoriasis was associated with more severe psoriatic arthritis. (See Prognosis.)

Psoriatic arthritis occurring in patients over age 60 years (elderly onset psoriatic arthritis) has a more severe onset and more a destructive outcome than does psoriatic arthritis in younger patients.

The course of psoriatic arthritis is usually characterized by flares and remissions. The patterns of psoriatic arthritis involvement are as follows:

  • Asymmetrical oligoarticular arthritis

  • Symmetrical polyarthritis

  • Distal interphalangeal arthropathy

  • Arthritis mutilans

  • Spondylitis with or without sacroiliitis

Asymmetrical oligoarticular arthritis

This was previously thought to be the most common type of psoriatic arthritis. The digits of the hands and feet are usually affected first, with inflammation of the flexor tendon and synovium occurring simultaneously, leading to the typical "sausage" appearance (dactylitis) of the fingers and toes. A large joint, such as the knee, is also commonly involved. Usually, fewer than 5 joints are affected at any one time. An asymmetrical arthritis pattern is shown below.

Asymmetrical arthritis pattern of psoriatic arthri Asymmetrical arthritis pattern of psoriatic arthritis (fixed flexion deformity).

Symmetrical polyarthritis

This rheumatoidlike pattern has been recognized as one of the most common types of psoriatic arthritis. The hands, wrists, ankles, and feet may be involved.

It is differentiated from RA by the presence of distal interphalangeal (DIP) joint involvement, relative asymmetry, an absence of subcutaneous nodules, and a negative test result for rheumatoid factor (RF). This condition is also generally milder than RA, with less deformity.

Distal interphalangeal arthropathy

Although DIP joint involvement is considered to be a classic and unique symptom of psoriatic arthritis, it occurs in only 5-10% of patients, primarily men.

Involvement of the nail with significant inflammation of the paronychia and swelling of the digital tuft may be prominent, occasionally making appreciation of the arthropathy more difficult.

Arthritis mutilans

This is a rare form of psoriatic arthritis, being found in only 1-5% of patients (although some reports suggest that arthritis mutilans may occur in as many as 16% of patients and may be as severe as RA).

In arthritis mutilans, resorption of bone (osteolysis), with dissolution of the joint, is observed as the "pencil-in-cup" radiographic finding and leads to redundant, overlying skin with a telescoping motion of the digit. (The effects of arthritis mutilans appear in the images below.)

Arthritis mutilans, a typically psoriatic pattern Arthritis mutilans, a typically psoriatic pattern of arthritis, which is associated with a characteristic "pencil-in-cup" radiographic appearance of digits.
Severe psoriatic arthritis showing involvement of Severe psoriatic arthritis showing involvement of the distal interphalangeal joints, distal flexion deformity, and telescoping of the left third, fourth, and fifth digits due to destruction of joint tissue.
Arthritis mutilans (ie, "pencil-in-cup" deformitie Arthritis mutilans (ie, "pencil-in-cup" deformities).

This "opera-glass hand" is more common in men than in women and is more frequent in early-onset disease.

Spondylitis with or without sacroiliitis

This occurs in approximately 5% of patients with psoriatic arthritis and has a male predominance.

Clinical evidence of spondylitis and/or sacroiliitis can occur in conjunction with other subgroups of psoriatic arthritis.

Spondylitis may occur without radiologic evidence of sacroiliitis, which frequently tends to be asymmetrical, or sacroiliitis may appear radiologically without the classic symptoms of morning stiffness in the lower back. Thus, the correlation between the symptoms and radiologic signs of sacroiliitis can be poor.

Vertebral involvement differs from that observed in ankylosing spondylitis. Vertebrae are affected asymmetrically, and the atlantoaxial joint may be involved with erosion of the odontoid and subluxation (with attendant neurologic complications). Therapy may limit subluxation-associated disability.

Unusual radiologic features may be present, such as nonmarginal asymmetrical syndesmophytes (characteristic), paravertebral ossification, and, less commonly, vertebral fusion with disk calcification.

SAPHO syndrome

First described by Chamot et al in 1987, synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is characterized by variable bone changes (hyperostosis, arthritis, aseptic osteomyelitis) of the chest wall, sacroiliac joints, and long bones. Dermatologic manifestations include the following:

  • Palmoplantar pustulosis

  • Hidradenitis suppurativa

  • Pustular psoriasis

  • Dissecting cellulitis of the scalp

  • Sweet syndrome

  • Sneddon-Wilkinson disease

Skin and osseous involvement may occur simultaneously or may be separated by as long as 20 years.[11, 12]

Juvenile psoriatic arthritis

Juvenile psoriatic arthritis accounts for 8-20% of childhood arthritis and is monoarticular at onset.

The median age of onset is 4.5 years in girls and 10 years in boys, and there is a female predominance. The disease is usually mild, although occasionally it may be severe and destructive, with the condition progressing into adulthood.

In 50% of children, the arthritis is monoarticular; DIP joint involvement occurs at a similar rate. Tenosynovitis is present in 30% of children, and nail involvement is present in 71%, with pitting being the most common, but least specific, finding.

In 47% of children, disordered bone growth with resultant shortening may result from involvement of the unfused epiphyseal growth plate in the inflammatory process.

Sacroiliitis occurs in 28% of children and is usually associated with HLA-B27 positivity. Although the presence of HLA-B8 may be a marker of more severe disease, HLA-B17 is usually associated with a mild form of psoriatic arthritis.

Children have a higher frequency of simultaneous onset of psoriasis and arthritis than adults do, with arthritis preceding psoriasis in 52% of children.

Classification of psoriatic arthritis

The simple and highly specific Classification Criteria for Psoriatic Arthritis (CASPAR), developed by a large international study group, has a sensitivity and specificity of 98.7% and 91.4%, respectively.[3] The criteria consist of established inflammatory articular disease with at least 3 points from the following features:

  • Current psoriasis (assigned a score of 2)

  • A history of psoriasis (in the absence of current psoriasis; assigned a score of 1)

  • A family history of psoriasis (in the absence of current psoriasis and a history of psoriasis; assigned a score of 1)

  • Dactylitis (assigned a score of 1)

  • Juxta-articular new-bone formation (assigned a score of 1)

  • RF negativity (assigned a score of 1)

  • Nail dystrophy (assigned a score of 1)

Pathophysiology and Etiology

The etiology of psoriatic arthritis remains unknown, but much information has been gathered. In addition to genetic influences, environmental and immunologic factors are thought to be prominent in the development and perpetuation of the disease. The de novo development or exacerbation of psoriasis and psoriatic arthritis in patients with human immunodeficiency virus (HIV) infection and CD4 deficiency remains controversial.

Psoriasis may remit following allogeneic bone marrow transplantation and may exacerbate with interferon-alfa treatment for hepatitis C.

Slight differences exist in the vascular patterns of joints in psoriatic arthritis, compared with those of RA, suggesting the possibility of different etiologic mechanisms in these diseases.[13]

Genetics

Genetic factors play an important role in susceptibility to psoriasis and psoriatic arthritis[14] ; approximately 40% of patients with either of these conditions have a family history of them in first-degree relatives.[15, 16]

The recurrence risk ratio for psoriatic arthritis, an estimate of the heritability of the disease, is estimated at 30-55 in first-degree relatives of patients with this condition, while that for psoriasis is 8-10.[17] Diseases with higher heritability have a higher likelihood of having genetic factors underlying disease susceptibility.[18, 19, 20, 21, 22]

The following important genetic susceptibility loci have been found (although the exact mechanism of the association between HLA and psoriatic arthritis is not yet clear)[17, 23, 24, 25, 26, 27, 28, 29] :

  • Early-onset psoriasis: HLA-Cw6, HLA-B57, HLA-DR7, and HLA-B17, with HLA-Cw*0602 variant found to be highly associated

  • Psoriasis: HLA-Cw6 (or psoriasis susceptibility 1 [PSOR1] on chromosome 6) and 6 other psoriasis susceptibility loci (PSOR2, PSOR3, PSOR4, PSOR5, PSOR6, PSOR7), transcription factor RUNX1

  • Psoriatic arthritis: HLA-B7, HLA-B27, HLA-DR4, HLA-38, and HLA-DR7

  • Psoriasis and psoriatic arthritis: HLA-Cw6, HLA-B13, HLA-B17, HLA-B57, and HLA-B39

  • Predictors of disease progression: HLA-B39; HLA-B27 in the presence of HLA-DR7; HLA-DQ3 in the absence of HLA-DR7

  • Protective: HLA-B22

Comparing psoriasis with psoriatic arthritis, it has been found that in psoriatic arthritis there is a stronger association with HLA-B alleles than with HLA-C alleles, while psoriasis (particularly early onset psoriasis) is associated with HLA-C.[30, 31]

The following associated gene polymorphisms are also thought to be associated with psoriasis and psoriatic arthritis[17, 23, 26, 32] :

  • Tumor necrosis factor (TNF)-alpha promoter[33]

  • Major histocompatibility complex (MHC) class I chain-related gene A (MICA): Independent of HLA, MICA*016 influences the risk of developing psoriasis without arthritis, while homozygosity for MICA*00801 increases the risk of developing psoriatic arthritis in patients with psoriasis[34, 35]

  • Caspase-activating recruitment domain (CARD) 15

  • Interleukin (IL)-12/IL-23p40 and IL-23 receptor: Studies indicate that HLA-C and IL23R are more strongly associated with psoriasis alone, while IL12B is more strongly associated with psoriatic arthritis[18, 19, 20, 36]

Additional loci that demonstrate an association with psoriatic arthritis include microsatellite polymorphisms in the TNF promoter.

In psoriasis, linkages with loci on 17q, 4q, and 6p have been reported in whole genome scans, with the strongest evidence for linkage on 6p.

It has also been suggested that certain immunoglobulin genes are associated with psoriatic arthritis. Serum levels of immunoglobulin A (IgA) and IgG are higher in psoriatic arthritis patients, whereas IgM levels may be normal or diminished.

Identifying susceptibility genes is likely to aid understanding of disease etiopathogenesis and identify potential therapeutic targets. Although loci identified to date explain only a fraction of the heritability estimates, a model of important pathways in psoriasis pathogenesis is emerging that combines skin barrier function (LCE3B, LCE3C); the TH17 pathway (IL12B, IL23A, IL23R, TRAF3IP2, TYK2); innate immunity involving NFκB and IFN signaling (TNFAIP3, TNIP1, NFKBIA, REL, TYK2, IFIH1, IL23RA), beta-defensin, and TH2 (IL4, IL13), as well as adaptive immunity involving CD8 T cells (ERAP1).[18, 19, 20, 21, 22, 37]

A gene-gene interaction between ERAP1 and HLA-C suggesting that ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele further implicates immune dysregulation in psoriasis pathogenesis.[37]

Immunologic factors

Autoantibodies against nuclear antigens, cytokeratins, epidermal keratins, and heat-shock proteins have been reported in persons with psoriatic arthritis, indicating that the disease has a humoral immune component.

The pathologic process of skin and joint lesions in psoriatic arthritis is an inflammatory reaction, and evidence also indicates the presence of autoimmunity, perhaps mediated by complement activation. The inflammatory nature of the skin and joint lesions in psoriatic arthritis is demonstrated by synovial-lining cell hyperplasia and mononuclear infiltration, resembling the histopathologic changes of RA. However, synovial-lining hyperplasia is less, macrophages are fewer, and vascularity is greater in psoriatic arthritis than in RA synovium.

The cytokine profile for psoriatic arthritis reflects a complex interplay between T cells and monocyte macrophages. Type 1 helper T-cell cytokines (eg, TNF-alpha, IL-1 beta, IL-10) are more prevalent in psoriatic arthritis than in RA, suggesting that these 2 disorders may result from a different underlying mechanism.

Several studies have shown a significant reduction in the number and percentage of CD4+ T cells in the peripheral blood, whereas they are found throughout the skin lesions and synovium.

Dendritic cells have been found in the synovial fluid of patients with psoriatic arthritis and are reactive in the mixed leukocyte reaction; the inference is that the dendritic cells present an unknown antigen to CD4+ cells within the joints and skin of patients with psoriatic arthritis, leading to T-cell activation.[27]

Fibroblasts from the skin and synovia of patients with psoriatic arthritis have an increased proliferative activity and the capability to secrete increased amounts of IL-1, IL-6, and platelet-derived growth factors. Several studies suggest that cytokines secreted from activated T cells and other mononuclear proinflammatory cells induce proliferation and activation of synovial and epidermal fibroblasts.

Psoriatic plaques in skin have increased levels of leukotriene B4. Injections of leukotriene B4 cause intraepidermal microabscesses, suggesting a role for this compound in the development of psoriasis.

Infections

The temporal relationship between certain viral and bacterial infections and the development or exacerbation of psoriasis and psoriatic arthritis suggests a possible pathogenetic role for viruses and bacteria.

Pustular psoriasis is a well-described sequela of streptococcal infections. However, the response to streptococcal antigens by cells from patients with psoriatic arthritis is not different from that of cells from patients with RA, making the role of Streptococcus species in psoriatic arthritis doubtful.

Psoriasis and psoriatic arthritis have been reported to be associated with HIV infection and to be prevalent in some HIV-endemic areas. Although the prevalence of psoriasis in patients infected with HIV is similar to that in the general population, patients with HIV infection usually have more extensive erythrodermic psoriasis, and patients with psoriasis may present with exacerbation of their skin disease after being infected with HIV.

Trauma

A few studies have reported the occurrence of arthritis and acro-osteolysis after physical trauma in patients with psoriasis.

Environmental factors

The theory of environmental factors playing a role in the etiology of psoriatic arthritis involves a process of superantigens reacting with autoantigens.

Epidemiology

Occurrence in the United States

Psoriasis affects 2.5% of the white population of North America but is less prevalent in the African American and Native American populations.

Psoriatic arthritis is thought to occur in up to 1% of the general population, with survey results indicating that approximately 1 million US adults have the disease. This figure is significantly higher than researchers had previously believed and suggests that many people with psoriasis may not be aware that they have psoriatic arthritis. (This is according to a study conducted by the National Psoriasis Foundation.) 

However, prevalence rates vary widely among studies. A random telephone survey of 27,220 US residents found a 0.25% prevalence rate for psoriatic arthritis in the general population and an 11% prevalence rate in patients with psoriasis. However, the exact frequency of the disorder in patients with psoriasis remains uncertain, with the estimated rate ranging from 5-30%.[27, 38]

Moreover, since the late 20th century, the incidence of psoriatic arthritis appears to have been rising in men and women. Reasons for the increase are unknown; it may be related to a true change in incidence or to a greater overall awareness of the diagnosis by physicians.[39]

International occurrence

Depending on the population studied, the prevalence of psoriatic arthritis internationally ranges widely. A 2013 German study found the rate of psoriatic arthritis in patients with psoriasis to be 30.2%.[40]  A systematic review and meta-analysis of 266 studies concluded that worldwide, approximately one in five persons with psoriasis has psoriatic arthritis.[2]  

A systematic review and meta-analysis of 28 studies estimated that the global average prevalence of psoriatic arthritis is 133 per 100,000 population (95% confidence index [CI], 107–164 per 100,000), and the incidence is 83 per 100,000 persons per year (95% CI, 41–167 per 100,000).[41]

In a prospective cohort study from Canada that involved psoriasis patients without arthritis at study entry, 51 of 464 patients developed psoriatic arthritis over the course of 8 years of followup. The annual incidence rate was 2.7 cases of psoriatic arthritis per 100 psoriasis patients.[42] Baseline variables associated with the development of psoriatic arthritis in multivariate analysis included the following:

  • Severe psoriasis (relative risk [RR] 5.4, p=0.006)
  • Low level of education (college/university vs. high school incomplete, RR 4.5, p=0.005; high school education vs. high school incomplete, RR 3.3, p=0.049)
  • Use of retinoid medications (RR 3.4, p=0.02)

There is a high prevalence of previously undiagnosed active psoriatic arthritis among patients with psoriasis who are seen by dermatologists. In a 2009 prospective German study, of 1511 patients with plaque-type psoriasis, 20.6% were found to have psoriatic arthritis, with 85% of the cases having been previously undiagnosed.[6]

The number of diagnosed cases of psoriasis and psoriatic arthritis has risen dramatically in sub-Saharan Africa in association with the area’s escalating epidemic of HIV infection. Although HIV is not known to affect the incidence of psoriasis, it may significantly exacerbate otherwise limited disease. The evolution of mild psoriasis to erythroderma in the setting of a flare-up of psoriatic arthritis may be a sign of HIV infection.

Race- and age-related related demographics

Race predilection in psoriatic arthritis has not been well studied. However, whites are known to be affected more commonly than are persons of other racial groups.

Psoriatic arthritis characteristically develops in persons aged 35-55 years, but it can occur at almost any age. In the juvenile form, the age of onset is 9-11 years.

Sex-related demographics

The male-to-female ratio for psoriatic arthritis is 1:1, with the exception of some subsets of patients. Females, however, are more commonly affected with symmetrical polyarthritis resembling RA and the juvenile form.

In contrast, the spondylitic form of psoriatic arthritis, which affects the axial spine, has a male-to-female ratio of 3:1.

In a cross-sectional analysis of a large population of patients with psoriatic arthritis, male patients were found to be more likely to exhibit axial involvement and radiographic joint damage, and female patients were more likely to experience impaired quality of life and severe limitations in function.[43]

Prognosis

Although psoriatic arthritis was originally thought to be relatively mild, as many as 40% of patients may develop erosive and deforming arthritis. Of patients observed in a large outpatient psoriatic arthritis clinic, 7% required musculoskeletal surgery.

Although a cohort study from the United Kingdom showed no increase in mortality among 453 patients with psoriatic arthritis compared with the general population, the results of another study suggested that psoriatic arthritis is associated with a significantly greater risk of hypertension, obesity, hyperlipidemia, type 2 diabetes mellitus, and cardiovascular events than is psoriasis without arthritis.[44, 45, 46]

Psoriatic arthritis was also associated with infections not treated with antibiotics, neurologic conditions, gastrointestinal disorders, and liver disease.[45]

In another study, by Labitigan et al, the prevalence of obesity, type 2 diabetes, and hypertriglyceridemia was determined to be higher in psoriatic arthritis than in RA. Using data from the Consortium of Rheumatology Researchers of North America (CORRONA) registry, the investigators found type 2 diabetes rates in psoriatic arthritis and RA to be 15% and 11%, respectively, and hypertriglyceridemia rates to be 38% and 28%, respectively.[47]

A pooled analysis of 2 large interventional lipid-lowering trials indicated that lipid-lowering therapy is effective in inflammatory joint disease, including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Furthermore, patients with and without inflammatory joint disease in the study had a 20% reduced risk of cardiovascular disease.[48]

A Norwegian study of 108 pregnancies in 103 women with psoriatic arthritis found that disease activity decreased in pregnancy and increased within 6 months postpartum. Women who used tumor necrosis factor inhibitors during in pregnancy had significantly lower disease activity than women who did not use those drugs[49]

 

Patient Education

Education is an important component of the patient's treatment plan, because he or she must be able to manage the symptoms of psoriatic arthritis and be comfortable with self-treatment strategies. Physical therapists provide education and an exercise program developed individually for each patient. Completing the wrong kind of exercise or overexertion can be harmful to patients with psoriatic arthritis.

Instructing patients with psoriatic arthritis in methods of joint protection is necessary and becomes part of the therapy process. Patients need to pace themselves and take adequate rest breaks from activity. Other examples of joint protection include wearing splints on the affected joints, using proper body mechanics and lifting techniques, and incorporating assistive devices or adaptive equipment into the patient's activities of daily living.

For patient education information, see the Psoriatic Arthritis Health Center

 

Presentation

History

Psoriasis appears to precede the onset of psoriatic arthritis in 60-80% of patients (occasionally by as many as 20 y, but usually by less than 10 y). However, in as many as 15-20% of patients, arthritis appears before the psoriasis, in which case a family history of psoriasis may reveal a hereditary pattern. Occasionally, arthritis and psoriasis appear simultaneously.

In some cases, patients may experience only stiffness and pain, with few objective findings. In a patient who presents with musculoskeletal symptoms without a history of psoriasis, the diagnosis can be suspected based on a family history of psoriasis and the pattern of arthritis.

In most patients, the musculoskeletal symptoms are insidious in onset, but an acute onset has been reported in one third of all patients.

Factors that increase the risk of a patient with psoriasis developing arthritis in his or her lifetime include the presence of nail lesions, as well as more extensive skin involvement.

One third of patients may develop inflammatory ocular symptoms reminiscent of reactive arthritis (previously termed Reiter disease).

Eder et al reported that psoriatic arthritis has a preclinical phase that presages diagnosis of the disease.[50, 51] During this phase, patients have nonspecific musculoskeletal symptoms, including joint pain, fatigue, and stiffness. In their prospective cohort study of 410 patients with psoriasis, 57 of whom developed psoriatic arthritis, the following symptoms predicted the development of psoriatic arthritis:

  • Arthralgia in women (hazard ratio [HR] 2.59, P = 0.02)
  • Heel pain (HR 4.18, P = 0.02)
  • High fatigue score (HR 2.36, P = 0.007)
  • High stiffness score (HR 2.03, P = 0.045)
  • Increase from baseline in fatigue score (HR 1.27, P = 0.001), pain score (HR 1.34, P <  0.001), and stiffness score (HR 1.21, P = 0.03)
  • Worsening in physical function score (HR 0.96, P = 0.04)

Physical Examination

Psoriatic arthritis may be present with or without obvious skin lesions, with minimal skin involvement (eg, scalp, umbilicus, intergluteal cleft), or with only nail malformations. Less joint tenderness possibly occurs with psoriatic arthritis than with RA.

Recognition of the patterns of joint involvement, as follow, is essential to the diagnosis of psoriatic arthritis:

  • Asymmetrical oligoarticular arthritis
  • Symmetrical polyarthritis
  • Distal interphalangeal arthropathy
  • Arthritis mutilans
  • Spondylitis with or without sacroiliitis

As in other spondyloarthropathies, the condition termed enthesopathy or enthesitis, reflecting inflammation at tendon or ligament insertions into bone, may be seen in psoriatic arthritis. Enthesopathy is observed more often at the attachment of the Achilles tendon and the plantar fascia to the calcaneus with the development of insertional spurs.

Dactylitis with sausage digits (seen in the image below) occurs in as many as 35% of patients. Diagnosis is also suggested by asymmetrical joint involvement, dactylitis, the absence of RF, and DIP involvement in the absence of osteoarthritis. When localized to the foot or toe, the symptoms of psoriatic arthritis may be mistaken for gout.

Psoriatic arthritis showing nail changes, distal i Psoriatic arthritis showing nail changes, distal interphalangeal joint swelling, and sausage digits.

Skin involvement

The following skin lesions may be seen in the context of psoriatic arthritis:

In one study, as previously mentioned, arthritis was noted more frequently in patients with severe skin disease.

In patients presenting with an undefined seronegative polyarthritis, looking for psoriasis in hidden sites, such as the scalp (where psoriasis frequently is mistaken for dandruff), perineum, intergluteal cleft, and umbilicus is extremely important.

Nail involvement

Nails are involved in 80% of patients with psoriatic arthritis but in only 20% of patients with uncomplicated psoriasis, with nail involvement frequently seen at the onset when skin and joint disease begin simultaneously. The following changes in the nails support the diagnosis of psoriatic arthritis[52] :

  • Beau lines
  • Leukonychia
  • Onycholysis
  • Oil spots
  • Subungual hyperkeratosis
  • Splinter hemorrhages
  • Spotted lunulae
  • Transverse ridging
  • Cracking of the free edge of the nail
  • Uniform nail pitting: A direct correlation exists between the number of pits and their diagnostic significance (see the image below)
  • Left, typical appearance of psoriasis, with silver Left, typical appearance of psoriasis, with silvery scaling on a sharply marginated and reddened area of skin overlying the shin. Right, thimblelike pitting of the nail plate in a 56-year-old woman who had suffered from psoriasis for the previous 23 years. Nail pitting, transverse depressions, and subungual hyperkeratosis often occur in association with psoriatic disease of the distal interphalangeal joint. Courtesy of Ali Nawaz Khan, MBBS.

Severe, deforming arthritis of the hands and feet is frequently associated with extensive nail involvement.

Involvement of DIP joints correlates moderately well with psoriasis in adjacent nails, although this is not an invariable association. In fact, psoriatic nail changes may be a solitary finding in patients with psoriatic arthritis.

Fungal infection of the nails is the main consideration in the differential diagnosis in a patient with a seronegative polyarthritis.

Extra-articular features

Extra-articular features are observed less frequently in patients with psoriatic arthritis than in those with RA. In patients with psoriatic arthritis, synovitis has a predilection for the flexor tendon sheath, with sparing of the extensor tendon sheath; both tendon sheaths are commonly involved in persons with RA.

Subcutaneous nodules are rare in patients with psoriatic arthritis. If nodules are present in a patient who has psoriasis and arthritis, particularly if the RF titer is positive, they suggest the coincidental occurrence of psoriasis and RA.

Ocular involvement may occur in 30% of patients with psoriatic arthritis, including conjunctivitis in 20% of patients and acute anterior uveitis in 7% of them. In patients with uveitis, 43% have sacroiliitis and 40% are HLA-B27–positive. Scleritis and keratoconjunctivitis sicca are rare. Possible ocular findings also include iritis.

Inflammation of the aortic valve root, which may lead to insufficiency, has been described in 6 patients with psoriatic arthritis and is similar to that observed more frequently in persons with ankylosing spondylitis or reactive arthritis. Occasionally, patients with psoriatic arthritis may develop secondary amyloidosis.

 

DDx

Diagnostic Considerations

Psoriasiform skin lesions may be observed in association with reactive arthritis, inflammatory bowel disease, and the syndrome of inappropriate secretion of diuretic hormone.

The differential diagnosis also includes rheumatoid arthritis of the hands and spine. Enteropathic arthritis (arthritis of inflammatory bowel disease) should also be considered, and spotted bone disease has been reported in a patient with psoriatic arthritis.[53]

Lupus erythematosus can produce a rash similar to a psoriatic rash. Usually, however, lupus-associated arthritis is not as deforming as psoriatic arthritis.

Secondary syphilis can also cause a rash similar to a psoriatic rash. However, although an arthropathy can be associated with syphilis, it occurs years after the skin lesions have cleared in an untreated patient.

Ankylosing spondylitis can produce back pain similar to that associated with psoriatic arthritis but without the associated peripheral arthropathy or skin lesions.

Differential Diagnoses

 

Workup

Approach Considerations

No specific diagnostic tests are available for psoriatic arthritis.[4] Diagnosis of the disease is instead based on clinical and radiologic criteria in a patient with psoriasis. Radiologic features can, for example, help to distinguish psoriatic arthritis from other causes of polyarthritis, such as RA.

The most characteristic laboratory abnormalities in patients with psoriatic arthritis are elevations of the erythrocyte sedimentation rate (ESR) and C-reactive protein level. The results from these laboratory tests help to track the activity of the disease by measuring inflammation.

Laboratory Studies

Erythrocyte sedimentation rate

An elevated ESR is found in approximately 40% of patients with psoriatic arthritis. An ESR of greater than 15 mm/h, along with medication use before the first clinical visit, evidence of radiologic damage, and absence of nail lesions, has been associated with increased mortality in patients with psoriatic arthritis.

Rheumatoid factor

Patients with psoriatic arthritis are typically seronegative for RF, although RF is detected in 5-9% of patients. RF testing is usually associated with a high false-positive rate; thus, RF-positive and RF-negative patients should undergo the same treatment.

Antinuclear antibodies

Antinuclear antibody titers in persons with psoriatic arthritis do not differ from those of age- and sex-matched controls. In 10-20% of patients with generalized skin disease, the serum uric acid concentration may be increased and, on occasion, may predispose patients to acute gouty arthritis. Low levels of circulating immune complexes have been detected in 56% of patients with psoriatic arthritis but do not appear to parallel disease activity.

Immunoglobulin

Serum IgA levels are increased in two thirds of patients with psoriatic arthritis and in one third of patients with psoriasis.

Synovial fluid

Synovial fluid is inflammatory in psoriatic arthritis, with white blood cell (WBC) counts ranging from 5000-15,000/µL and with more than 50% of cells being polymorphonuclear leukocytes. Within the synovium, the infiltrate consists predominantly of T lymphocytes. Glucose levels are within reference ranges, and synovial fluid complement levels are either within reference ranges or increased.

Psoriatic versus rheumatoid arthritis

The table below compares laboratory values in psoriatic arthritis with those in RA.

Table. Comparison of Expected Laboratory Values in Psoriatic Arthritis and Rheumatoid Arthritis (Open Table in a new window)

Laboratory Studies

Psoriatic Arthritis

Rheumatoid Arthritis

Erythrocyte sedimentation rate

Elevated (< 100)

Elevated (< 100)

Rheumatoid factor

Negative

Positive (85% of patients)

Antinuclear antibody

Negative

Positive (30% of patients)

C-reactive protein

Elevated

Elevated

Synovium

WBC count 5000-15,000/µL, >50% polymorphonuclear leukocytes

WBC count 2000/µL

Histologic findings

The histopathology of psoriatic synovitis is similar to that observed in other inflammatory arthritides, with a notable lack of intrasynovial immunoglobulin and RF production and a greater propensity for fibrous ankylosis, osseous resorption, and heterotopic bone formation.

Imaging Studies

Radiologic features have helped to distinguish psoriatic arthritis from other causes of polyarthritis. For full discussion, see Psoriatic Arthritis Imaging. In general, the common subtypes of psoriatic arthritis, such as asymmetrical oligoarthritis and symmetrical polyarthritis, tend to result in only mild erosive disease. Early bony erosions occur at the cartilaginous edge, and cartilage initially is preserved, with maintenance of a normal joint space.

Juxta-articular osteopenia, which is a hallmark of RA, is minimal in persons with psoriatic arthritis. Asymmetrical erosive changes in the small joints of the hands and feet are typical of psoriatic arthritis and have a predilection (in decreasing order) for the DIP, proximal interphalangeal, metatarsophalangeal, and metacarpophalangeal joints. (See the images below.)

Swelling and deformity of the metacarpophalangeal Swelling and deformity of the metacarpophalangeal and distal interphalangeal joints in a patient with psoriatic arthritis.
Psoriatic arthritis involving the distal phalangea Psoriatic arthritis involving the distal phalangeal joint.
Psoriatic arthritis involving the distal phalangea Psoriatic arthritis involving the distal phalangeal joint.
Psoriatic arthritis involving the distal phalangea Psoriatic arthritis involving the distal phalangeal joint.

Erosive disease frequently occurs in patients with either DIP involvement or progressive deforming arthritis and may lead to subluxation and, less commonly, to bony ankylosis of the joint.

Erosion of the tuft of the distal phalanx, and even of the metacarpals or metatarsals, can progress to complete dissolution of the bone. Although this form of acro-osteolysis is not diagnostic, it is highly suggestive of psoriatic arthritis.

The pencil-in-cup deformity observed in the hands and feet of patients with severe joint disease usually affects the DIP joints but also may involve the proximal interphalangeal joints.

Radiography

Traditional methods of monitoring patients with rheumatic conditions include, along with clinical assessment for joint inflammation or damage, radiographic evaluations.

Radiography shows a combination of erosion (unlike in ankylosing spondylosis) and bone growth (unlike in RA) in affected joints.[54] The following radiographic abnormalities are suggestive of psoriatic arthritis:

  • Pencil-in-cup deformity (seen in the image below)

    Arthritis mutilans (ie, "pencil-in-cup" deformitie Arthritis mutilans (ie, "pencil-in-cup" deformities).
  • Joint-space narrowing in the interphalangeal joints, possibly with ankylosis

  • Increased joint space in the interphalangeal joints as a result of destruction

  • Fluffy periostitis

  • Bilateral, asymmetrical, fusiform soft-tissue swelling

  • Unilateral or symmetrical sacroiliitis

  • Large, nonmarginal, unilateral, asymmetrical syndesmophytes (intervertebral bony bridges, seen in the image below) in the cervical, thoracic, and lumbar spine, often sparing some of the segments

    Lateral radiograph of the cervical spine shows syn Lateral radiograph of the cervical spine shows syndesmophytes at the C2-3 and C6-7 levels, with zygapophyseal joint fusion. Courtesy of Bruce M. Rothschild, MD.

A study validated the use of radiologic scoring methods—ie, the original Steinbrocker method, a modified Steinbrocker method, and the Larsen method—for the assessment of peripheral joint radiographs in patients with psoriatic arthritis. The latter 2 methods can now be used to assess the disease's progression.

CT scanning and MRI

Computed tomography (CT) scanning and MRI may be useful for detecting early signs of joint synovitis.

MRI is particularly sensitive for detecting sacroiliitic synovitis, enthesitis, and erosions; it can also be used with gadolinium to increase sensitivity. MRI may show inflammation in the small joints of the hands, involving the collateral ligaments and soft tissues around the joint capsule, a finding not found in persons with RA.

Ultrasonography

Ultrasonography has an emerging role in the diagnosis and management of psoriatic arthritis. Its uses include predicting progression to psoriatic arthritis in patients with psoriasis by detecting subclinical signs of synovitis and enthesitis, diagnosing psoriatic arthritis, providing accurate and objective monitoring of disease activity, and predicting clinical and structural outcome.[55]

 

Treatment

Approach Considerations

The treatment of psoriatic arthritis is directed at controlling the inflammatory process. Although no clear correlation exists between joint inflammation and the skin in every patient, the skin and joint aspects of the disease often must be treated simultaneously.

 Although traditional therapy has consisted of nonsteroidal anti-inflammatory drugs (NSAIDs) and local corticosteroid injections, with disease-modifying antirheunatic drugs (DMARDs) being reserved for NSAID-resistant cases, the finding that 40% of patients may develop erosive and deforming arthritis has led to recommendations of early treatment with DMARDs in patients with active disease (see Guidelines). In addition to older DMARDs, several biologic agents and targeted synthetic agents have become available for use in psoriatic arthritis.[56]

Physical therapy should be started early in the disease process, with the regimen individualized. Different approaches are appropriate, depending on the disease phase.

Currently, no prospective studies are addressing surgical intervention in patients with psoriatic arthritis. Patients in severe pain or with significant contractures may be referred for possible surgical intervention (eg, synovectomy, joint replacement). Treatment should be aimed at pain relief or increasing the patient's function.

Pharmacotherapy

Medical treatment regimens include the use of NSAIDs, Janus kinase (JAK) inhibitors, and disease-modifying antirheumatic drugs (DMARDs). DMARDs include methotrexate, sulfasalazine, cyclosporine, and leflunomide, as well as biologic agents (eg, anti–TNF-alpha medications, interleukin-12 [IL-12], IL-17, or IL-23 monoclonal antibodies).[5, 57, 58]

A randomized, 6-month study by Scarpa et al showed that the early use of methotrexate in patients with early psoriatic arthritis markedly improved tender and swollen joints and/or entheses. However, no significant difference was found after 3 months of treatment with NSAIDs or methotrexate.[59] These results suggest that other therapeutic approaches capable of modifying the early course of the disease should be used.[60]

Patients receiving long-term methotrexate therapy with high cumulative doses can be monitored using serial liver function tests (LFTs). Liver biopsy should be considered if LFT values are persistently elevated. Pro-collagen 3 N-terminal peptide (PIIINP) is an alternate test, although Lindsay et al reported that PIIINP frequently showed elevated values despite normal liver biopsy results.[61]

The U.S. Food and Drug Administration (FDA) and the European Union approved ustekinumab, an IL-12/23 inhibitor, for the treatment of active psoriatic arthritis in adults who have not responded adequately to previous treatment with nonbiologic DMARDs.[62] The drug was already approved in Europe and the United States for treatment of moderate to severe psoriatic plaques in adults.

Approval was based on 2 randomized, double-blind, placebo-controlled trials in 927 patients with active psoriatic arthritis who had at least 5 tender and 5 swollen joints and C-reactive protein levels of 0.3 mg/dL or higher despite previous conventional therapy.[62] At week 24, 42% of patients receiving ustekinumab 45 mg and 50% of those receiving 90 mg achieved at least 20% improvement; at 52 weeks, this response was found to have been sustained. Treatment with ustekinumab also improved dactylitis, enthesitis, and skin component.[62]

The TNF inhibitor certolizumab pegol (Cimzia) was also approved by the FDA for the treatment of active psoriatic arthritis in adults.[63] Approval was based on an ongoing, randomized, double-blind, placebo-controlled trial in 409 patients with active and progressive adult-onset psoriatic arthritis (RAPID-PsA) in which certolizumab-treated patients were significantly more likely to meet American College of Rheumatology 20%, 50%, and 70% response criteria by week 12 than placebo-treated patients. Certolizumab reduced radiographic progression and improved skin manifestations.[63]  Further analysis of the RAPID-PsA  showed that improvement occurred with certolizumab pegol used as monotherapy or given with concomitant DMARDs.[64]

Apremilast (Otezla), was approved by the FDA for treatment of active psoriatic arthritis. It is a phosphodiesterase-4 (PDE4) inhibitor that is specific for cyclic adenosine monophosphate (cAMP), resulting in increased intracellular cAMP levels. In studies involving nearly 1500 patients with psoriatic arthritis, improvement was observed in 32-41% of patients at week 6, a statistically significant difference compared with placebo (p < 0.05). Patients received apremilast 30 mg orally twice daily plus concomitant therapy with at least 1 DMARD, methotrexate, leflunomide, oral corticosteroids, or NSAIDs.[65, 66, 59, 60]

Secukinumab (Cosentyx) is a human IgG1 monoclonal antibody that selectively binds to and neutralizes IL-17A, which is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Secukinumab was approved by the FDA for adults with active psoriatic arthritis in January 2016.

Approval of secukinumab was based on the FUTURE 1 and 2 phase 3 trials. In the FUTURE 1 trial (n=606), the American College of Rheumatology 20 (ACR20) response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg (50.0%) and 75 mg (50.5%) than in those receiving placebo (17.3%) (P< 0.001 for both comparisons with placebo).[57] In FUTURE 2, a significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab doses of 300 mg (54%; P< 0.0001) and 150 mg (51%; P< 0.0001) compared with placebo (15%).[58]

Like certolizumab, golimumab (Simponi Aria) is a fully human anti-TNF-alpha monoclonal antibody. Golimumab received FDA approval for psoriatic arthritis in October 2017. It was initially approved in 2013 for the treatment of moderately to severely active rheumatoid arthritis. 

The approval was based on data from the GO-VIBRANT trial. In this phase 3, multicenter, randomized, double-blind, placebo-controlled trial, patients were randomized to either IV or golimumab 2 mg/kg at weeks 0, 4, 12, and 20 with crossover to golimumab at week 24. At week 14, 75.1% in the golimumab group achieved ACR criteria (ACR20) vs. 21.8% in the placebo group. Greater proportions of golimumab-treated patients had ACR50 (43.6% vs 6.3%), ACR70 (24.5% vs 2.1%), and PASI75 (59.2% vs 13.6%) at week 14. The golimumab group had greater mean changes at week 14 in Health Assessment Questionnaire-Disability Index (HAQ-DI) compared with placebo (-0.60 vs -0.12;). At week 24, the mean change in van der Heijde-Sharp (vdH-S) score was -0.4 in the golimumab group and 2.0 in the placebo.[67]

Abatacept (Orencia) was approved by the FDA for adults with active psoriatic arthritis in June 2017. Approval was based on a randomized, placebo-controlled phase 3 clinical trial in which abatacept significantly increased ACR20 response compared with placebo at week 24 (39.4% vs 22.3%; p< 0.001). The study was continued with open-labeled SC abatacept and efficacy was maintained or improved up to week 52.[68]

Ixekizumab (Taltz) was approved for active psoriatic arthritis in December 2017. Ixekizumab is a humanized monoclonal IgG4 antibody that targets IL-17A, resulting in neutralization of IL-17A’s proinflammatory effects.

Approval of ixekizumab was based on 2 randomized, double-blind, placebo-controlled phase 3 studies (SPIRIT-P1 and SPIRIT-P2), which included more than 670 adults. Results from both studies demonstrated that patients treated with ixekizumab achieved significant improvement in joint symptoms, as measured by ACR20, compared with placebo.

SPIRIT-P1 evaluated the safety and efficacy of ixekizumab compared with placebo in patients who had never been treated with a biologic DMARD. SPIRIT-P2 evaluated safety and efficacy compared with placebo in patients in whom treatment with 1 or 2 TNF inhibitors had failed. At 24 weeks, patients who received ixekizumab had an ACR20 response superior to placebo (58% vs 30%, respectively, in SPIRIT-P1; 53% vs 20% in SPIRIT-P2) .[69, 70]

In December 2017, tofacitinib was approved by the FDA as the first-in-class Janus kinase (JAK) inhibitor for active psoriatic arthritis in patients who inadequately respond or are intolerant to methotrexate or other DMARDS.  Approval was based on data from the Phase 3 Oral Psoriatic Arthritis Trial (OPAL) clinical development program, OPAL Broaden and OPAL Beyond, and available data from the ongoing long-term extension trial, OPAL Balance.

In the OPAL Broaden study, 50% of patients who received tofacitinib 5 mg PO BID in combination with a nonbiologic DMARD achieved an American College of Rheumatology 20 (ACR20) response at 3 months, compared with 33% of those treated with placebo.[71]

In the OPAL Beyond study, 50% of patients achieved an ACR20 response with tofacitinib 5 mg PO BID at 3 months, when compared with 24% taking placebo. In both studies, significant improvements in ACR20 response was also seen with tofacitinib 5 mg PO BID when compared with placebo at week 2, which was a secondary endpoint and the first post-baseline assessment (OPAL Broaden: 22% vs. 6%; OPAL Beyond: 27% vs. 13%).[72]

In patients with severe skin inflammation, medications such as methotrexate, retinoic acid derivatives, and psoralen plus ultraviolet (UV) light should be considered. These agents have been shown to work on skin and joint manifestations.

Intolerance to methotrexate was observed in 14.3% of patients with psoriatic arthritis in a cross-sectional study (n=291), as measured with the Methotrexate Intolerance Severity Score (MISS). GI symptoms, including nausea, abdominal pain, and vomiting, occurred during methotrexate treatment in 123 patients (42.3%); behavioral symptoms, including restlessness and irritability, were also common. Methotrexate intolerance was more common with parenteral (20.6%) than oral (6.2%) administration.[61, 73]

Intra-articular injection of entheses or single inflamed joints with corticosteroids may be particularly effective in some patients. Use disease-modifying drugs in individuals whose arthritis is persistent. If the skin disease is well controlled with topical medication, the joint disease can be treated with a variety of second-line or cytotoxic drugs. Intramuscular administration of gold has been used in the past but has been supplanted by newer DMARDs.

In a study completed by the Psoriatic Arthritis Study Group, patients with psoriasis and psoriatic arthritis who were receiving stable doses of methotrexate were found to benefit from the addition of 1 or more courses of intramuscular alefacept, a T-cell inhibitor via a human lymphocyte function–associated antigen 3 (LFA-3) Fc fusion protein that blocks the interaction between CD2 on T cells and LFA-3 on antigen-presenting cells. Further benefit in psoriatic arthritis was apparent after a second course of alefacept, and no additional toxicity was observed.[4]

Sulfasalazine and cyclosporine are second-line DMARDs that have received particular attention in the management of psoriatic arthritis. Although these drugs may control the acute inflammation in persons with psoriatic arthritis, they have not been helpful in arresting the progression of clinical and radiologic damage. Thus, the disease must be treated earlier or better drugs are necessary, to prevent the damage that may ensue as a result of psoriatic arthritis.

Cyclosporine appears to be an effective agent for the treatment of psoriasis and psoriatic arthritis. The major concern with this drug is its toxicity, especially its nephrotoxicity, and hypertension.

Combination therapy (eg, methotrexate/sulfasalazine, methotrexate/cyclosporine) may be more efficacious in some patients.[74]

Other agents that have been tried in psoriatic arthritis but whose efficacy remains unproven include the following:

  • Vitamin D-3
  • Bromocriptine
  • Peptide T
  • Fish oils

The Medical Board of the National Psoriasis Foundation weakly recommends vitamin D supplementation in patients with psoriatic arthritis, as well as dietary weight reduction with a hypocaloric diet in overweight and obese patients. The Board recommends that dietary interventions should always be used in conjunction with standard medical therapies.[75]

Antimalarials, particularly hydroxychloroquine, are usually avoided in patients with psoriasis for fear of precipitating exfoliative dermatitis or exacerbating psoriasis. However, 2 studies showed that these reactions did not occur in patients who were treated with hydroxychloroquine; therefore, this drug is occasionally used to treat psoriatic arthritis.

Systemic corticosteroids are usually avoided because of possible rebound of the skin disease upon withdrawal.

Physical Therapy

The rehabilitation treatment program for patients with psoriatic arthritis should be individualized and should be started early in the disease process. Such a program should consider the use of the following:

  • Rest: Local and systemic

  • Exercise: Passive, active, stretching, strengthening, and endurance

  • Modalities: Heat and cold treatments can temporarily relieve pain and reduce joint swelling; such treatments include soaking in a warm tub or placing a warm compress or cold pack on the painful joint

  • Orthotics: Upper and lower extremities, spinal

  • Assistive devices for gait and adaptive devices for self-care tasks: Including possible modifications to homes and automobiles

  • Education about the disease, energy conservation techniques, and joint protection

  • Possible vocational readjustments

With regard to the first item above, prolonged rest should be avoided to prevent the deleterious effects of immobility. In a very few people, psoriatic arthritis may cause extreme fatigue.

Acute phase

Encourage rest as indicated. Splints may be used for rest and pain relief, especially for the hands, wrists, knees, or ankles. Cold modalities should be used to decrease inflammation and assist with pain relief. Joints should not be moved beyond the limit of pain; passive movements should be limited at this time. Education should be completed during this phase, with topics including the disease itself, the importance of rest, the exercise program, joint protection, energy conservation, and weight loss, if appropriate.

Subacute and long-term phase

Isometric exercises are begun, with progression to active movement. Gradual range-of-motion (ROM) exercises include passive and active exercises; areas with subluxation should not be forced passively. Heating modalities, including moist heat packs, paraffin wax, diathermy, and ultrasound, can be used to decrease pain; heat therapy should be administered just prior to the performance of ROM exercises.

Institute gait activities, with the patient bearing weight as tolerated, with or without an assistive device. Gentle stretching should be gradually introduced. If pain persists beyond 2 hours after therapies, then the intensity should be decreased. If a joint is swollen, then no resistive exercises should be performed through full ROM.

For patients with axial spine involvement, spine extension exercises help with flexibility and strength. ROM exercises should be performed, but not in patients with increased pain.

If the patient has sausage toes, extra-depth shoes with a high toe box should be considered to protect the foot. With pain in the toes, such shoes should have a rocker-bottom modification to alleviate forces during the toe-off phase in the gait cycle. The patient may also benefit from arch supports if plantar fascitis is a problem.

Synovectomy and Arthroplasty

Arthroscopic synovectomy has been effective in treating severe, chronic, monoarticular synovitis. Because of an enhanced tendency for patients to develop fibrosis in association with this therapy, anti-inflammatory and physical therapy measures aimed at improving ROM are important adjuncts to this intervention.

Joint replacement and forms of reconstructive therapy are occasionally necessary. Hip and knee joint replacements have been successful, for the most part, in patients with psoriatic arthritis. Arthrodesis and arthroplasty have also been used on joints, such as the proximal interphalangeal joint of the thumb. The wrist often spontaneously fuses, and this may relieve the patient's pain without surgical intervention.

Because of the diffuse soft-tissue involvement that is associated with psoriatic arthritis, high rates of recurrence of joint contractures have been noted after surgical release, especially in the hand.

For arthritis mutilans, surgical intervention is usually directed toward salvage of the hand. Combinations of arthrodesis, arthroplasty, and bone grafts to lengthen the digits may be used. The goal is to maintain the pinch mechanism of the thumb and the first 2 fingers.

Consultations

If the patient's physiatrist feels uncomfortable with prescribing medications for psoriatic arthritis, referral to a rheumatologist with more experience with these agents may be advisable. The physiatrist may then concentrate on functional restoration of the patient. Referral to a surgeon should be considered for appropriate patients.

Patients with juvenile psoriatic arthritis should be examined by an ophthalmologist annually to check for the several forms of eye inflammation usually associated with various forms of juvenile arthritis.

Given the complexity of DMARD therapy, patients with psoriatic arthritis should be followed simultaneously by a rheumatologist and physiatrist. In addition, consultation with an orthopedic surgeon is warranted for individuals who may benefit from joint replacement, arthrodesis, or contracture release.

Deterrence and Prevention

A number of medications can exacerbate psoriasis; therefore, avoidance of these agents may help to prevent or minimize flare-ups. Lithium and withdrawal from systemic corticosteroids are well known to cause disease flare-ups.

Other drugs that have been implicated include beta-blockers, antimalarials (although, as previously mentioned, evidence suggests that hydroxychloroquine does not exacerbate skin lesions), and NSAIDs. If skin lesions worsen with an NSAID, switch to a different family of NSAID.

Prevention includes rest and exercise. Joint protection, including splints, braces, and other supports, may be helpful. No definitive prevention exists, because this is a chronic disease that can wax and wane.

Complications

Many patients with psoriatic arthritis have comorbidities, such as the following:

  • Cardiovascular disease
  • Metabolic syndrome
  • Inflammatory bowel disease
  • Osteoporosis
  • Malignancy
  • Ophthalmic disease
  • Liver disease

Kocijan et al reported that psoriatic arthritis is associated with significantly decreased trabecular volumetric bone mineral density (BMD) and deterioration of trabecular bone microstructure. Those effects on bone correlated with the duration of skin disease.[76] A study by Simon et al found that despite longer disease duration, patients with psoriatic arthritis treated with biologic disease-modifying antirheumatic drugs (DMARDs) had higher bone mass and better bone strength than those treated with methotrexate PsA patients receiving MTX or no DMARDs.[77]

A longitudinal cohort study in 1061 Canadian patients with psoriatic arthritis identified liver abnormalities or disease in 32%. In most cases, the liver abnormalities or disease were not present when the patient was first evaluated in clinic, but instead developed after an average of 8.3 years of follow-up and at a mean age of 50.5 years. Drug-induced hepatitis (14%) and fatty liver (13%) were the most common conditions.[78] On multivariable analysis, the following factors were independently associated with liver abnormalities:

  • High body mass index (odds ratio [OR], 1.07)
  • Daily alcohol intake (OR, 4.46)
  • Damaged joint count (OR, 1.04)
  • Elevated C-reactive protein level (OR, 2.00)
  • Treatment with methotrexate or leflunomide (OR, 4.39)
  • Treatment with tumor necrosis factor inhibitors (OR, 10.56)

These authors recommend monitoring of liver function in psoriatic arthritis who are at high risk for liver abnormalities.[78]

 

Guidelines

Guidelines Summary

Guidelines on psoriatic arthritis have been published by the following organizations:

  • European League Against Rheumatism (EULAR) [79]
  • British Society of Rheumatology (BSR) [80]
  • American Academy of Dermatology (AAD) [81]
  • American College of Rheumatology/National Psoriasis Foundation [82]

EULAR recommendations

Based on evidence from systematic literature reviews and expert opinion, the EULAR developed 10 treatment recommendations, 5 overarching principles, and a research agenda for psoriatic arthritis. The recommendations are as follows[79] :

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) can be given to relieve musculoskeletal signs and symptoms

  • Treatment with disease-modifying antirheumatic drugs (DMARDs)—eg, methotrexate, sulfasalazine, and leflunomide—should be considered at an early stage for patients with active disease

  • If a patient with active psoriatic arthritis also has clinically relevant psoriasis, preference should be given to treatment with methotrexate or other DMARDs that are also effective against psoriasis

  • Adjunctive treatment with local corticosteroid injections should be considered; cautious use of systemic steroids, if administered at the lowest effective dose, can also be considered

  • If active psoriatic arthritis fails to adequately respond to 1 or more synthetic, DMARDs (eg, methotrexate), tumor necrosis factor (TNF)–inhibitor therapy should be employed

  • TNF-inhibitor therapy should also be considered if active enthesitis and/or dactylitis does not show sufficient response to NSAIDs or local steroid injections

  • TNF-inhibitor therapy should be considered if a patient has active, predominantly axial disease that does not respond sufficiently to NSAIDs

  • Exceptional use of TNF-inhibitor therapy may be considered if a very active patient is DMARD-treatment naïve

  • If a TNF inhibitor produces an inadequate response, consideration should be given to replacing it with another TNF inhibitor

  • If adjustments are made in a patient’s therapy, then comorbidities, safety concerns, and other considerations beyond the psoriatic arthritis itself should be factored into the change

British Society of Rheumatology recommendations

The BSR issued guidelines for the treatment of adult psoriatic arthritis with biologic agents (particularly anti-TNF therapy).[80, 83]  The BSR recommends considering anti-TNF treatment in patients with any of the following[80] :

  • Active peripheral arthritis refractory to at least 2 conventional DMARDs

  • Peripheral disease refractory to 1 DMARD plus the presence of adverse prognostic factors

  • Severe persistent oligoarthritis that is affecting well-being and refractory to at least 2 DMARDs and intra-articular therapy

  • Axial disease

The BSR recommendations on response assessment include the following[80] :

  • Use the psoriatic arthritis response criteria as the clinical response criteria for peripheral disease

  • Use the psoriasis area severity index score for significant skin psoriasis

Safety recommendations include the following[80] :

  • Do not start or continue anti-TNF therapy in patients with serious active infection; use caution in those at high risk of infection

  • Screen all patients for infection with mycobacteria, human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV) before starting anti-TNF therapy

  • Consider prophylactic vaccination for tuberculosis and HBV in high-risk patients before initiating anti-TNF therapy

  • In patients with HIV, HBV, or HCV, initiate anti-TNF therapy only in those with well-controlled disease and appropriate monitoring; appropriate antiviral therapy for patients with HBV is also important

  • Avoid anti-TNF treatment in patients with a current or previous history of malignancy, unless there is a high likelihood of cure or the malignancy was diagnosed and treated more than 10 years ago

  • Regularly screen for skin cancers in patients who are receiving anti-TNF therapy and who have a history of current or previous malignancy

  • Discontinue anti-TNF therapy prior to pregnancy; restart anti-TNF treatment following the end of lactation or delivery if the mother is not breastfeeding

  • Consider an alternative anti-TNF agent in patients whose condition is refractory to a first anti-TNF agent; assess the treatment response as for the first agent

American Academy of Dermatology recommendations

General recommendations on psoriatic arthritis from the AAD are as follows[81] :

  • Upon diagnosis of psoriatic arthritis, patients should be treated and/or referred to a rheumatologist.
  • Methotrexate or TNF blockade or the combination of these therapies is considered first-line treatment for patients with moderate to severely active psoriatic arthritis.  
  • Not all patients with psoriatic arthritis require treatment with methotrexate or TNF blockade. Patients with mild psoriatic arthritis can be successfully treated with NSAIDs or intraarticular injections of corticosteroids.
  • The choice of which TNF agent to utilize is an individual one, with the degree and severity of cutaneous involvement an important consideration.
  • Common safety concerns need to be considered when using TNF inhibitors to treat patients who have psoriatic arthritis.

General recommendations on the use of TNF inhibitors in psoriatic arthrits are as follows:

  • Anti-TNF agents are contraindicated in patients with active, serious infections
  • Tuberculosis testing (PPD) should be performed on all patients who will be treated with TNF inhibitors, given the risk of tuberculosis reactivation.
  • Do not use with live vaccines; biologically inactive or recombinant vaccines may be considered, although the immune response of these vaccines could be compromised
  • Because there is an association between anti-TNF therapy and demyelinating diseases (ie, multiple sclerosis [MS]), TNF inhibitors should not be used in patients with MS or other demyelinating diseases. First-degree relatives of patients with MS have an increased risk of developing MS, with a sibling relative risk of between 18 and 36, which strongly suggests that TNF inhibitors should not be used in first-degree relatives of patients with MS
  • Caution should be used when considering TNF inhibitor use in patients with chronic heart failure (CHF); patients with New York Heart Association (NYHA) class III or IV CHF should avoid all use of TNF inhibitors, and patients with NYHA class I or II CHF should undergo echocardiogram testing, and if their ejection fraction is < 50%, then TNF inhibitor treatment should potentially be avoided.
  • In the appropriate clinical setting, patients should be screened for HBV infection.

American College of Rheumatology/National Psoriasis Foundation recommendations

This collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF) covers the management of active psoriatic arthritis in patients who are treatment-naive and in those who continue to have active psoriatic arthritis despite treatment.[82]

TNF inhibitors

Etanercept recommendations are as follows:

  • Monotherapy treatment option for adults with moderate-to-severe plaque psoriasis

  • Recommended starting dose of 50 mg; self-administered SC injection twice weekly for 12 consecutive weeks

  • Recommended maintenance dose of 50 mg once weekly; 50 mg twice weekly is more efficacious than once weekly and may be required for better disease control in some patients

  • Recommended as monotherapy option in adults with moderate-to-severe plaque psoriasis affecting the scalp or nails

  • Can be recommended as monotherapy option for adults with other subtypes (ie, pustular, erythrodermic) of moderate-to-severe plaque psoriasis

  • Recommended monotherapy option in adults with plaque psoriasis of any severity when associated with significant psoriatic arthritis

  • Recommended combination treatment option with topicals (eg, high-potency corticosteroids with or without a vitamin D analogue) to augment treatment of moderate-to-severe plaque psoriasis

  • Recommended combination treatment option with methotrexate for moderate-to-severe plaque psoriasis in adults

  • May be combined with acitretin, apremilast, cyclosporine, or narrowband ultraviolet phototherapy for moderate-to-severe plaque psoriasis in adults

Infliximab recommendations are as follows:

  • Monotherapy treatment option for adults with moderate-to-severe plaque psoriasis

  • Recommended starting dose is an infusion of 5 mg/kg administered at week 0, week 2, and week 6; thereafter, administered every 8 weeks

  • Recommended to be administered at more frequent intervals (less than q8wk and as frequently as q4wk during maintenance phase) and/or at a higher dose (up to 10 mg/kg) for better disease control in some adults

  • Recommended as monotherapy option for moderate-to-severe plaque psoriasis affecting the palms and soles (plaque-type palmoplantar psoriasis), nails, or scalp in adults

  • Can be recommended as monotherapy option in adults with other subtypes (ie, pustular, erythrodermic) of moderate-to-severe plaque psoriasis

  • Recommended as monotherapy option in adults with plaque psoriasis of any severity when associated with significant psoriatic arthritis; it also inhibits radiographically detected joint damage in psoriatic arthritis

  • Recommended combination treatment option with topicals (eg, high-potency corticosteroids with or without a vitamin D analogue) to augment treatment of moderate-to-severe plaque psoriasis

  • May be combined with acitretin, methotrexate, or apremilast for moderate-to-severe plaque psoriasis in adults

Adalimumab recommendations are as follows:

  • Monotherapy treatment option for adults with moderate-to-severe plaque psoriasis

  • Recommended starting dose of 80 mg taken as two self-administered SC 40-mg injections, followed by a 40-mg self-administered SC injection 1 week later, followed by 40-mg self-administered SC injections every 2 weeks thereafter

  • Maintenance dose of 40 mg/wk recommended for better disease control in some patients

  • Recommended as monotherapy option for adults with moderate-to-severe plaque psoriasis affecting the palms and soles (palmoplantar psoriasis), nails, or scalp

  • Can be recommended as monotherapy option for adults patients with other subtypes (ie, pustular, erythrodermic) of moderate-to-severe psoriasis

  • Recommended as monotherapy option in adults with plaque psoriasis of any severity when associated with psoriatic arthritis

  • Can be recommended combination treatment option with topicals (eg, high-potency corticosteroids with or without a vitamin D analogue) to augment treatment of moderate-to-severe plaque psoriasis

  • May be combined with acitretin, methotrexate, apremilast, cyclosporine, or narrowband ultraviolet phototherapy for moderate-to-severe plaque psoriasis in adults

Certolizumab has been approved by the US Food and Drug Administration (FDA) for the treatment of plaque psoriasis, psoriatic arthritis, Crohn disease, ankylosing spondylitis, and rheumatoid arthritis. Approved dosing for moderate-to-severe psoriasis is 400 mg (two 200-mg SC injections) every other week. It is likely to possess class characteristics similar to those of other TNF-alpha inhibitors.

Interleukin-12/23 Inhibitors

Ustekinumab recommendations are as follows:

  • Monotherapy treatment option for adults with moderate-to-severe plaque psoriasis

  • Recommended starting doses: (1) patients weighing 100 kg or less, 45 mg SC initially and 4 weeks later, followed by 45 mg administered SC every 12 weeks; (2) patients weighing more than 100 kg, 90 mg administered SC initially and 4 weeks later, followed by 90 mg administered SC every 12 weeks

  • Recommended alternate dosages are higher doses (90 mg instead of 45 mg in patients weighing ≥100 kg) or with greater frequency (eg, every 8 wk in maintenance phase) if response to standard dosing is inadequate

  • Can be used as monotherapy option for adults with moderate-to-severe plaque psoriasis affecting the palms and soles (plaque-type palmoplantar psoriasis), nails, or scalp

  • Can be used as monotherapy option for adults with other subtypes (ie, pustular, erythrodermic) of moderate-to-severe psoriasis; evidence is limited for use in inverse and guttate psoriasis

  • Recommended as monotherapy option in adults with plaque psoriasis of any severity when associated with psoriatic arthritis

  • Can be recommended combination treatment option with topicals (eg, high-potency corticosteroids with or without a vitamin D analogue) to augment treatment of moderate-to-severe plaque psoriasis

  • May be combined with acitretin, methotrexate, apremilast, cyclosporine, or narrowband ultraviolet phototherapy for moderate-to-severe plaque psoriasis in adults

Interleukin-17 Inhibitors

Secukinumab recommendations are as follows:

  • Monotherapy treatment option in adults with moderate-to-severe plaque psoriasis

  • Recommended starting dose of 300 mg by self-administered SC injection at week 0, week 1, week 2, week 3, and week 4, followed by 300 mg every 4 weeks

  • Recommended maintenance dose of 300 mg every 4 weeks

  • Recommended dose of 300 mg is more effective than 150 mg

  • Can be recommended as monotherapy in adults with moderate-to-severe plaque psoriasis affecting the head and neck (including the scalp) or nails

  • Recommended as monotherapy option in adults with moderate-to-severe palmoplantar plaque psoriasis

  • Can be recommended as monotherapy option in adults with moderate-to-severe palmoplantar pustulosis

  • Can be used as monotherapy in adults with erythrodermic psoriasis

  • May be used as monotherapy in adults with plaque psoriasis when associated with psoriatic arthritis

Ixekizumab recommendations are as follows:

  • Monotherapy treatment option for adults with moderate-to-severe plaque psoriasis

  • Recommended starting dose of 160 mg by self-administered SC injection, followed by 80 mg at week 2, week 4, week 6, week 8, week 10, and week 12

  • Recommended maintenance dose of 80 mg every 4 weeks

  • Can be recommended as monotherapy option in adults with moderate-to-severe plaque psoriasis affecting the scalp or nails

  • Can be recommended as monotherapy option in adults with erythrodermic psoriasis or generalized pustular psoriasis

  • Recommended as monotherapy option in adults with plaque psoriasis when associated with psoriatic arthritis

Brodalumab recommendations are as follows:

  • Recommended as monotherapy treatment option in adults with moderate-to-severe plaque psoriasis

  • Can be used as monotherapy option in adults with generalized pustular psoriasis

  • Recommended dose of 210 mg by self-administered SC injection at week 0, week 1, and week 2, followed by 210 mg every 2 weeks

Interleukin-23 Inhibitors

Guselkumab recommendations are as follows:

  • Recommended as monotherapy treatment option for adults with moderate-to-severe plaque psoriasis

  • Recommended dose of 100 mg by self-administered SC injection at week 0 and week 4, followed by every 8 weeks thereafter

  • Recommended as monotherapy option in adults with scalp, nail, or plaque-type palmoplantar psoriasis

Tildrakizumab recommendations are as follows:

  • Recommended as monotherapy treatment option in adults with moderate-to-severe plaque psoriasis

  • Recommended dose of 100 mg given in office by physician-administered SC injection at week 0 and week 4, followed by every 12 weeks thereafter

Risankizumab is not approved by the FDA, but it can be used as monotherapy in adults with moderate-to-severe plaque psoriasis. When approved, the dose will likely be 150 mg given by self-administered subcutaneous injections at week 0 and week 4, followed by every 12 weeks.

 

Medication

Medication Summary

Medical treatment regimens include the use of agents in the following classes of medication:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Immunosuppressants
  • Disease-modifying antirheumatic drugs (DMARDs).
  • Janus kinase (JAK) inhibitors

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Class Summary

Initial treatment includes NSAIDs for joint disease and topical therapies for the skin. In many patients, this approach is sufficient to control disease manifestations, although some individuals have a worsening of psoriasis with NSAIDs. In these patients, a drug belonging to a different family of NSAIDs should be used.

For people who have morning stiffness, the optimal time for taking an NSAID may be after the evening meal and again upon awakening. Taking NSAIDs with food can reduce stomach discomfort. Any NSAID can damage the mucous layer and cause ulcers and gastrointestinal bleeding when taken for long periods. Cyclooxygenase (COX)–2 selective inhibitors are associated with a lower prevalence of gastric ulcer formation.

Indomethacin (Indocin)

Indomethacin is thought to be the most effective NSAID for the treatment of ankylosing spondylitis, although no scientific evidence supports this claim. It is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of COX, which results in a decrease of prostaglandin synthesis.

Ibuprofen (Motrin IB, Advil, NeoProfen)

Ibuprofen is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of COX, which results in a decrease of prostaglandin synthesis.

Naproxen (Naprosyn, Naprelan, Aleve, Anaprox)

Naproxen is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of COX, which results in a decrease of prostaglandin synthesis.

Diclofenac (Zorvolex, Cambia)

Diclofenac inhibits prostaglandin synthesis by decreasing COX activity, which, in turn, decreases formation of prostaglandin precursors.

Immunosuppressants

Class Summary

Immunosuppressants inhibit key factors in the immune system that are responsible for inflammatory responses.

Methotrexate (Trexall, Otrexup)

Methotrexate inhibits dihydrofolic acid reductase. It inhibits purine and thymidylic acid synthesis, which in turn interferes with DNA synthesis, repair, and cellular replication; cell cycle specific for S phase of cycle. Methotrexate may inhibit rapid proliferation of epithelial cells in skin.

Cyclosporine (Neoral, Gengraf)

Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions.

5-Aminosalicylic Acid Derivatives

Class Summary

5-Aminosalicylic acid derivatives inhibit prostaglandin synthesis and reduce the inflammatory response to tissue injury.

Sulfasalazine (Azulfidine, Azulfidine EN-tabs)

Sulfasalazine has been shown to reduce the inflammatory symptoms of psoriatic arthritis.

DMARDs, TNF Inhibitors

Class Summary

The use of biologic response modifiers that target TNF and other cytokines represents an advance in the treatment of several diseases involving autoimmune mechanisms. Several such agents have been developed, in the form of either soluble fusion proteins (eg, etanercept) or monoclonal antibodies (eg, infliximab, adalimumab), that have shown considerable efficacy in the treatment of RA and other autoimmune diseases.[84]

Etanercept (Enbrel, Erelzi)

Etanercept is approved by the US Food and Drug Administration (FDA) for (1) treating adult patients (age ≥18 y) with chronic, moderate to severe plaque psoriasis; (2) reducing the symptoms and signs of moderate to severe polyarticular-course juvenile RA and ankylosing spondylitis; and (3) reducing the signs and symptoms and inhibiting the progression of structural damage associated with psoriatic arthritis. Therefore, etanercept may be an effective and safe alternative monotherapy for the treatment of psoriatic arthritis.

Infliximab (Inflectra, Remicade, Renflexis)

Infliximab is another TNF-neutralizing agent. It has been approved for the treatment of Crohn disease, ulcerative colitis, RA (in combination with methotrexate), ankylosing spondylitis, and psoriatic arthritis (and has shown success in reducing the signs and symptoms of this disease).[65]

However, the FDA has issued safety warnings for infliximab concerning worsening heart failure in patients with moderate to severe chronic heart failure, as well as risk for opportunistic infections such as tuberculosis, histoplasmosis, listeriosis, and pneumocystosis.

Golimumab (Simponi, Simponi Aria)

Golimumab is an FDA-approved human TNF-alpha antibody that is given every 4 weeks as a subcutaneous injection at doses of 50 mg and 100 mg. It has been shown to significantly improve symptoms of psoriatic arthritis.[6, 66]

Ustekinumab (Stelara)

Ustekinumab is an anti-IL-12/23 monoclonal antibody approved for treatment of active psoriatic arthritis in adult patients. It may be administered alone or in combination with methotrexate. It is approved in doses of 45 mg or 90 mg SC given at weeks 0 and 4 and then every 12 weeks. At week 24 of the PSUMMIT 1 trial, 42% of patients receiving 45 mg and 50% of patients receiving 90 mg demonstrated at least a 20% improvement in signs and symptoms as measured by the American College of Rheumatology (ACR 20). These improvements were maintained at week 52 of the study.[67]

Certolizumab pegol (Cimzia)

Other new biologic agents in clinical trials include certolizumab pegol, a PEGylated Fab' fragment of an anti–TNF-alpha monoclonal antibody. Certolizumab pegol has shown promising results in the treatment of RA and may be applicable to the treatment of psoriasis and psoriatic arthritis in the future.

Adalimumab (Amjevita, Cyltezo, Humira, Hadlima, Hyrimoz, Adalimumab-atto, Adalimumab-adbm, Adalimumab-bwwd, Adalimumab-adaz)

Recombinant human anti-TNF-alpha IgG1 monoclonal antibody. Blocks inflammatory activity of TNF-alpha, by specifically binding to TNF-alpha and blocks its interaction with p55 and p75 cell surface TNF receptors. It is indicated for reduction of signs and symptoms, inhibition of progression of structural damage, and improvement of physical function in adults with active psoriatic arthritis. FDA approved adalimumab-atto, adalimumab-adbm, adalimumab-adaz, adalimumab-bwwd as biosimilars and not as interchangeable drugs.

DMARDs, PDE4 Inhibitors

Class Summary

Agents which increase intracellular cyclic adenosine monophosphate (cAMP), such as PDE4 inhibitors, may have an antagonistic effect on proinflammatory molecule production.

Apremilast (Otezla)

Apremilast is an oral, small molecule inhibitor of phosphodiesterase-4 specific for cAMP, resulting in increased intracellular cAMP levels. The specific mechanism by which apremilast exerts it therapeutic action in psoriatic arthritis is not well defined. It is indicated for treatment of active psoriatic arthritis. It is indicated for active psoriatic arthritis.

Interleukin Inhibitors

Class Summary

Various interleukins play a role in inflammatory processes.

Secukinumab (Cosentyx)

Human IgG1 monoclonal antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin 17A (IL-17A). IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. It is indicated for adults with active psoriatic arthritis.

Ixekizumab (Taltz)

Humanized monoclonal IgG4 antibody that targets interleukin-17A (IL-17A) resulting in neutralization of IL-17A’s proinflammatory effects. It is indicated for adults with active psoriatic arthritis; may be administered alone or in combination with a conventional DMARD (eg, methotrexate).

DMARDs, Immunomodulators

Class Summary

Abatacept is a selective costimulation modulator that inhibits T-cell activation.

Abatacept (Orencia, Orencia ClickJect)

Chimeric protein which inhibits T-lymphocyte activation by binding to CD80 and CD86 located on antigen presenting cells (APC). T-cell activation is dependent on interacting with APC. Indicated for active psoriatic arthritis in adults.

Janus Kinase (JAK) Inhibitors

Class Summary

These agents modulate the signaling pathway at the point of JAKs and preventing the phosphorylation and activation of STATs. Inhibition of JAKs also prevents cytokine- or growth factor-mediated gene expression and intracellular activity of immune cells, reduces circulating CD16/56+ natural killer cells, serum IgG, IgM, IgA, and C-reactive protein, and increases B cells.

Tofacitinib (Xeljanz, Xeljanz XR)

Tofacitinib inhibits JAK enzymes, which are intracellular enzymes involved in stimulating hematopoiesis and immune cell function through a signaling pathway. In response to extracellular cytokine or growth factor signaling, JAKs activate signal transducers and activators of transcription (STATs), which regulate gene expression and intracellular activity. Inhibition of JAKs prevents cytokine- or growth factor-mediated gene expression and intracellular activity of immune cells, reduces circulating CD16/56+ natural killer cells, serum IgG, IgM, IgA, and C-reactive protein, and increases B cells. Indicated for active psoriatic arthritis (PsA) in patients who have had an inadequate response or intolerance to methotrexate or other DMARDS.

 

Questions & Answers

Overview

What is psoriatic arthritis?

What are the signs and symptoms of psoriatic arthritis?

Which physical findings are characteristic of psoriatic arthritis?

Which nail changes suggest psoriatic arthritis?

Which extra-articular features may be present in psoriatic arthritis?

What are the patterns of arthritic involvement in psoriatic arthritis?

What is the Classification Criteria for Psoriatic Arthritis (CASPAR)?

What is the role of lab testing in the diagnosis of psoriatic arthritis?

Which radiographic findings suggest psoriatic arthritis?

Which MRI findings suggest psoriatic arthritis?

How is psoriatic arthritis treated?

What is the role of surgery in the treatment of psoriatic arthritis?

What is the role of physical therapy in the treatment of psoriatic arthritis?

What is psoriatic arthritis?

What are the patterns of arthritic involvement in psoriatic arthritis?

What is the asymmetrical oligoarticular arthritis pattern of psoriatic arthritis?

What is the symmetrical polyarthritis pattern of psoriatic arthritis?

What is the distal interphalangeal arthropathy pattern of psoriatic arthritis?

What is the arthritis mutilans pattern of psoriatic arthritis?

What is the spondylitis and sacroiliitis pattern of psoriatic arthritis?

What is synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome?

What is juvenile psoriatic arthritis?

What is the Classification Criteria for Psoriatic Arthritis (CASPAR)?

What causes psoriatic arthritis?

What is the role of genetics in the pathogenesis of psoriatic arthritis?

What is the role of immunologic factors in the pathogenesis of psoriatic arthritis?

What is the role of infection in the pathogenesis of psoriatic arthritis?

What is the role of trauma in the etiology of psoriatic arthritis?

What is the role of environmental factors in the etiology of psoriatic arthritis?

What is the prevalence of psoriatic arthritis in the US?

What is the global prevalence of psoriatic arthritis?

What are baseline variables associated with the development of psoriatic arthritis in multivariate analysis?

What are the racial predilections of psoriatic arthritis?

Which age groups have the highest prevalence of psoriatic arthritis?

What are the sexual predilections of psoriatic arthritis?

What is the prognosis of psoriatic arthritis?

What should be included in patient education about psoriatic arthritis?

Presentation

Which clinical history findings are characteristic of psoriatic arthritis?

What are the symptoms of the preclinical phase of psoriatic arthritis?

Which physical findings are characteristic of psoriatic arthritis?

How are skin lesions characterized in psoriatic arthritis?

Which nail changes are characteristic of psoriatic arthritis?

What are the extra-articular signs and symptoms of psoriatic arthritis?

DDX

Which conditions should be included in the differential diagnosis of psoriatic arthritis?

What are the differential diagnoses for Psoriatic Arthritis?

Workup

What is the role of lab testing in the workup of psoriatic arthritis?

What is the role of erythrocyte sedimentation rate in the workup of psoriatic arthritis?

What is the role of rheumatoid factor testing in the workup of psoriatic arthritis?

What is the role of antinuclear antibodies testing in the workup of psoriatic arthritis?

What is the role of immunoglobulin testing in the workup of psoriatic arthritis?

What is the role of synovial fluid measurement in the workup of psoriatic arthritis?

How is psoriatic arthritis differentiated from RA based on lab findings?

Which histologic findings are characteristic of psoriatic arthritis?

What is the role of imaging studies in the workup of psoriatic arthritis?

Which radiographic findings suggest psoriatic arthritis?

What is the role of CT scanning and MRI in the workup of psoriatic arthritis?

What is the role of ultrasonography in the workup of psoriatic arthritis?

Treatment

How is psoriatic arthritis treated?

Which medications are used in the treatment of psoriatic arthritis?

What is the efficacy of methotrexate in the treatment of psoriatic arthritis?

What is the efficacy of ustekinumab in the treatment of psoriatic arthritis?

What is the efficacy of certolizumab pegol (Cimzia) in the treatment of psoriatic arthritis?

What is the efficacy of apremilast (Otezla) in the treatment of psoriatic arthritis?

What is the efficacy of secukinumab (Cosentyx) in the treatment of psoriatic arthritis?

What is the efficacy of golimumab (Simponi Aria) in the treatment of psoriatic arthritis?

What is the efficacy of abatacept (Orencia) in the treatment of psoriatic arthritis?

What is the efficacy of ixekizumab (Taltz) in the treatment of psoriatic arthritis?

What is the efficacy of tofacitinib in the treatment of psoriatic arthritis?

How is severe skin inflammation treated in psoriatic arthritis?

What are the signs and symptoms of methotrexate intolerance in the treatment of psoriatic arthritis?

What is the role of intra-articular injections in the treatment of psoriatic arthritis?

What is the role of intramuscular alefacept in the treatment of psoriatic arthritis?

What is the role of sulfasalazine and cyclosporine in the treatment of psoriatic arthritis?

Which drugs have unproven efficacy in the treatment of psoriatic arthritis?

What is the role of dietary modifications in the treatment of psoriatic arthritis?

What is the role of antimalarials in the treatment of psoriatic arthritis?

What is the role of oral corticosteroids in the treatment of psoriatic arthritis?

What is included in the rehabilitation treatment program for psoriatic arthritis?

What is the physical therapy for the acute phase of psoriatic arthritis?

What is the physical therapy for the subacute and long-term phases of psoriatic arthritis?

What is the role of surgery in the treatment of psoriatic arthritis?

Which specialist consultations are beneficial to patients with psoriatic arthritis?

How are exacerbations of psoriatic arthritis prevented?

Guidelines

Which organizations have issued guidelines on psoriatic arthritis?

What are the EULAR treatment guidelines for psoriatic arthritis?

What are BSR treatment guidelines for adult psoriatic arthritis?

What are the AAD treatment guidelines for psoriatic arthritis?

What are the AAD guidelines for the use of TNF inhibitors in the treatment of psoriatic arthritis?

Medications

Which medications are used in the treatment of psoriatic arthritis?

Which medications in the drug class Janus Kinase (JAK) Inhibitors are used in the treatment of Psoriatic Arthritis?

Which medications in the drug class DMARDs, Immunomodulators are used in the treatment of Psoriatic Arthritis?

Which medications in the drug class Interleukin Inhibitors are used in the treatment of Psoriatic Arthritis?

Which medications in the drug class DMARDs, PDE4 Inhibitors are used in the treatment of Psoriatic Arthritis?

Which medications in the drug class DMARDs, TNF Inhibitors are used in the treatment of Psoriatic Arthritis?

Which medications in the drug class 5-Aminosalicylic Acid Derivatives are used in the treatment of Psoriatic Arthritis?

Which medications in the drug class Immunosuppressants are used in the treatment of Psoriatic Arthritis?

Which medications in the drug class Nonsteroidal anti-inflammatory drugs (NSAIDs) are used in the treatment of Psoriatic Arthritis?