Psoriatic Arthritis

Petros Efthimiou

Joseph A. Markenson

KEY POINTS

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy of the peripheral joints and axial skeleton, occurring in a subset of patients with psoriasis.
Arthritis might precede skin psoriatic lesion in 13% to 17% of cases.
The extent of skin disease does not generally parallel the arthritic activity.
Radiographic findings considered “classic” for PsA include asymmetric distal interphalangeal (DIP) joint erosion and ankylosis, “pencil-in-cup” deformity and resorption of the phalangeal tufts, and “fluffy” periostitis.
PsA follows a moderate course, affecting few joints. However, in 20% of cases it evolves into a destructive debilitating arthritis.
The modern treatment paradigm is early aggressive treatment with disease-modifying antirheumatic drugs (DMARDs), aiming at a status of no evidence of disease, to avoid joint damage.

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy of the peripheral joints and axial skeleton, occurring in 7% to 42% of patients with psoriasis. Psoriasis affects 1% to 3% of the general population.

Psoriasis usually appears in the second to third decades, but the onset of associated arthritis is usually delayed by two decades. However, 13% to 17% of patients with PsA will present with joint symptoms before the appearance of skin lesions, making diagnosis difficult. Although skin disease is a useful diagnostic marker for PsA, its extent does not parallel the activity of arthritis.
Enthesopathy or inflammation at the sites where tendons and ligaments attach to the bone is a hallmark feature of PsA. The enthesis, composed of fibrocartilage and collagen type II, is a highly vascular structure aimed to absorb and dissipate mechanical stress and appears to be the primary target in PsA.

ETIOPATHOGENESIS

The pathogenesis of PsA remains unknown. There is evidence of distinct immunologic processes causing persistent skin and synovial inflammation that are not shared with the pathogenesis of rheumatoid arthritis (RA). A predominance of clonally expanded CD8+ T lymphocytes in both skin and synovial tissue suggests the presence of a triggering antigen.
- The pattern of proinflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, and IL-8], expressed in PsA synovial fluid and surgical explants, is similar to RA, with cytokines expressed at even higher levels. Elevated levels of TNF-α are found in psoriasis in the psoriatic plaques and the uninvolved skin alike.
- Angiogenesis is believed to play a pivotal role in the pathophysiology of PsA synovitis and is controlled by growth factors such as vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and Ang-2, which in turn may be controlled by cytokines such as TNF-α
- Osteoclast precursors are found in large amounts in the blood of patients with PsA and their participation in the development of joint damage is likely. Furthermore, marked upregulation of the osteoclastogenesis enhancer receptor activator of NF-γB ligand (RANKL) and low expression of its natural antagonist osteoprotegerin (OPG) were detected in psoriatic synovial tissues.
GENETIC FACTORS PLAY AN IMPORTANT ROLE. First-degree relatives of patients with PsA have a 40% to 50% risk of developing the disease. Concordance between monozygotic twins is high (70%) when compared to RA (30%). Human leukocyte antigen (HLA)-B27 has clearly been associated with axial disease, and HLA-DR4 with peripheral polyarticular involvement in PsA. CARD 15 is the first non-MHC gene that has been recently associated with PsA.
Infectious agents have long been suspected to act as disease triggers.
Psoriasis and PsA tend to take a more aggressive form in patients infected with human immunodeficiency virus (HIV), although the incidence of psoriasis in these patients is not greater than in the general population. HLA-associated genes (HLA-BW38, BW39, and CW6) are found in patients with PsA who are HIV infected in a frequency similar to that seen in patients with PsA who are not HIV infected. This is in contrast to HIV-associated reactive arthritis (ReA), where frequency of HLA-B27 can be higher than 75%.
A history of trauma often precedes the diagnosis of PsA, suggesting the presence of a possible “internal” Köbner’s phenomenon (the appearance of psoriasis at sites of traumatic cutaneous injury).

PREVALENCE

Recent community-based epidemiologic studies have suggested a rate of incidence of approximately 6/100,000/annum and a prevalence of 1/1,000. The male to female ratio is 1:1, and the peak incidence occurs between the ages of 45 and 54 years.

CLINICAL MANIFESTATIONS

Typically, patients present with pain and stiffness of the affected joints, which tend to be less tender than the affected joints in patients with RA. Morning stiffness lasting for over 30 minutes is seen in more than 50% of patients.
Five distinct patterns of PsA are recognized and are listed as follows:
- Oligoarticular (four or fewer inflamed joints) disease that constitutes 70% of all cases of PsA is characteristically asymmetric and affects a few scattered distal interphalangeal (DIP), proximal interphalangeal (PIP), and metacarpophalangeal (MCP) joints, knees, ankles, and feet. These are often in association with dactylitis, manifested by diffuse swelling of one or more fingers and toes in a sausage digit configuration. This diffuse swelling is due to the intense and diffuse inflammatory changes that occur both in the joints and soft tissues, and is not present in RA.
- Asymmetric involvement of DIP joints of the hands and feet is sometimes referred to as “classic” psoriatic arthropathy, but this pattern appears in as few as 10% of cases. Digits affected often have characteristic psoriatic nail changes.
- Arthritis mutilans is a particularly disabling form occurring in approximately 5% of all cases of PsA. The deformity, most striking in the fingers and toes, is caused by osteolysis of the affected joints.
- Symmetric polyarthritis (resembling RA) is usually rheumatoid factor-negative, and constitutes approximately 15% of all cases of PsA. Constitutional symptoms such as morning stiffness and fatigue are common and tend to parallel the activity of joint disease.
- Psoriatic spondyloarthritis occurs in up to 5% of patients with PsA and presents with clinical and radiographic features of axial and sacroiliac inflammation. These may be indistinguishable from those of ReA, and their involvement tends to be
  asymmetric as opposed to the symmetric spinal and sacroiliac disease of ankylosing spondylitis. The histocompatibility antigen HLA-B27 is found in 40% of this group.
Enthesopathy, although unusual in RA, is a primary feature of PsA. Common clinical manifestations of enthesopathy in PsA include plantar fasciitis, epicondylitis, Achilles tendinitis, and enthesitis of the ligamentous insertions around the pelvic bones.
EXTRA-ARTICULAR MANIFESTATIONS. Conjunctivitis and uveitis occur in up to one-third of patients with PsA. Aortic insufficiency may rarely complicate PsA.
SAPHO syndrome [synovitis, acne, palmoplantar pustulosis (50% to 60% have this or another form of psoriasis), hyperostosis, and osteitis] is often considered a variant of PsA. Features in common with PsA include asymmetric synovitis, pustulosis, enthesopathy (e.g., anterior chest pain), and involvement of the sacroiliac joint. However, the characteristic constellation of symptoms and the absence of HLA-B27–associated sacroiliitis help differentiate this syndrome.