Before the breakthrough studies of Wright (1959) and Baker (1963), inflammatory arthritis occurring in the presence of skin psoriasis was found to represent rheumatoid arthritis coincident with psoriasis(1). Wright revealed that distal interphalangeal (DIP) joints are frequently involved, with the presence of erosions and resorption of the terminal phalanges, with concomitance of sacroiliitis, interphalangeal (IP) joints of the great toes involvement and a ravaging arthritis with bone loss occurring mainly in the digits(2). In 1964, The American Rheumatism Association (ARA) included psoriatic arthritis (PsA) in a classification of rheumatic diseases, stating it a distinct clinical entity(1).
In the early 1970's a term “seronegative spondyloarthropathies” was introduced, i.e. “a group of chronic inflammatory diseases which differ from rheumatoid arthritis for the typical absence of rheumatoid factor in serum, the positivity for class I human histocompatibility leukocyte antigen (HLA-B27) and have common several epidemiological, pathological, clinical and radiological features”(3).
In 2005 a 5-subgroup division of spondyloarthritis (SpA) was introduced as follows: ankylosing spondylitis, psoriatic spondyloarthritis, reactive spondyloarthritis, enteropathic spondyloarthritis, i.e. spondyloarthritis associated with inflammatory bowel diseases and undifferentiated spondyloarthritis(3). Each entity may present with sacroiliitis or inflammatory changes of lumbar and/or distal thoracic spine, all leading to inflammatory back pain, and peripheral arthritis, which often takes form of asymmetric oligoarthritis, enthesitis and extra-skeletal symptoms, such as uveitis(3).
Depending on the investigated population the incidence of SpA varies from 0,2 to 1,9%(3). PsA typically commences between 30 and 50 years of age, equally in men and women, yet the subtype involving the spine occurs 3 times more frequently in men(3, 4). According to Moll and Wright's definition (1973), PsA “is a chronic inflammatory arthritis that occurs in patients with psoriasis”(4).
There are various reports on the prevalence of PsA in patients with psoriasis, ranging from 5 to 42%(4). Skin involvement develop usually (70% of cases) several years before musculoskeletal manifestations. In 15%, arthritis precedes skin changes for about 2 years. In the remaining 15% of patients, PsA symptoms and skin changes evolve simultaneously(5).
The incidence of joint involvement depends on the clinical subset of psoriasis, which can be divided as follows: I type with early manifestations before the age of 40 (85% of patients, the highest incidence between the ages of 18 and 22, more severe, frequently complicated with arthritis), and II type with late symptoms, after the age of 40 (15%, the highest incidence between the ages of 57 and 60, with a mild course and infrequent arthritis)(6).
The etiology of PsA remains undiscovered. Environmental factors (i.e. injury, infection) are taken into consideration in genetically predisposed population. In patients with the spine and sacroiliac joints involvement HLA-B27 antigen is more frequently detected, whereas in erosive subset – HLA-DR4 and in DIP joints involvement – HLA-DR7. Synovitis is characterized, like in rheumatoid arthritis (RA), by lymphocyte infiltrates and neoangiogenesis, synoviocyte activation, release of proinflammatory cytokines, especially tumor necrosis factor α (TNF-α).
Differences between synovitis in RA and PsA were stated histopathologically: in PsA hypertrophy of synovial lining was reported to be smaller, edema of the sublining greater, more blood vessels and those of curved course (more linear in RA), thus greater hyperemia in PsA than in RA was detected(6, 7).
In the etiopathogenesis of PsA (like in the remaining SpA), the role of enthesitis within the spine and the peripheral joints is indicated, including that of an initial process triggering synovitis and osteitis, according to Tan and McGonagle(8, 9).
PsA is a disease of clinical heterogenicity, which may affect peripheral joints (peripheral disease) or the sacroiliac joints, and the spine (axial disease), where beyond synovitis inflammatory changes are observed in other tissues, in the form of enthesitis and dactylitis, which are regarded as hallmarks of this entity(10).
In the clinical course of PsA, chronic inflammatory spinal pain, bi- or unilateral sacroiliac joint pain, as well as at entheses, clinically diagnosed as enthesitis, peripheral arthritis, dactylitis, skin and nail psoriasis are encountered.
In many cases symptoms of PsA correspond to those of RA: stiffness, pain, swelling, joint and neighboring soft tissue tenderness, range of motion limitation, morning stiffness and fatigue.
Both in PsA and RA, radiographic manifestations of early disease are often unclear and remain so until the disease is established, when more distinctive features may be seen. On the contrary to RA, patients with PsA usually occur to be seronegative for rheumatoid factor (RF). Moreover, joint involvement in PsA is often asymmetric and may be oligoarticular, whereas in RA is usually symmetric and polyarticular(4).
For years PsA was believed to be a mild disease, yet recent studies have shown that it can lead to significant deformations and severe joint damage; in approximately 40% of patients erosive joint disease has been reported(4).
Classification criteria for PsA
The original criteria from 1973 according to Moll and Wright(1, 11) are the most straightforward and has most frequently been used prior to 2006. They include:
Inflammatory arthritis (peripheral arthritis and/or sacroiliitis or spondylitis)
The presence of psoriasis
The (usual) negative serological test for RF.
In 2006 The Classification of Psoriatic Arthritis (CASPAR) Study Group criteria were introduced as a new classification criteria for PsA(1, 12, 13). On the contrary to Moll and Wright's criteria, Caspar Study Group criteria provide a diagnosis of PsA in patients without skin psoriasis. In order to increase their sensitivity, additional features such as dactylitis, nail psoriasis and positive family history were included (Tab. 1). These are of the most frequent clinical use.
CASPAR – classification criteria for psoriatic arthritis
|Psoriatic arthritis can be diagnosed in a patient presenting with inflammatory articular disease (peripheral arthritis, spondylitis and sacroiliitis, or enthesitis) with ≥ 3 points from the following:|
|1.||Evidence of current psoriasis (psoriatic skin changes judged by a rheumatologist or dermatologist), a personal or family history of psoriasis (in a first- or second-degree relative) – score of 1 evidence of current psoriasis – 2 points|
|2.||Typical psoriatic nail dystrophy (onycholysis, pitting and hyperkerato-sis) observed on current physical examination – 1 point|
|3.||A negative test result for the presence of rheumatoid factor by any method (except latex), preferably by enzyme-linked immunosorbent assay (ELISA) or nephelometry – 1 point|
|4.||Dactylitis, defined as swelling of an entire digit (i.e. sausage finger) either current or in a history recorded by a rheumatologist – 1 point|
|5.||Radiographic evidence of juxtaarticular new bone formation, appearing as ill-defined ossification near joint margins (but excluding osteo-phyte formation) on plain radiographs of the hand or foot – 1 point|
Several new classifications of PsA have been suggested, for example Marsal et al. distinguished axial and peripheral disease, Helliwell's, who divided PsA into three groups, including SAPHO, the Assessment of SpondyloArthritis (ASAS) group that in 2009 established peripheral and axial arthritis (Tab. 2), and also McGonagle's, who proposed an unification of pathologic classification basing on the study results showing that enthesitis in PsA is common in all sites of inflammation(4).
ASAS classification criteria for peripheral spondyloarthritis
|Peripheral arthritis (usually asymmetric inflammation of joints within lower extremities, enthesitis, dactylitis (sausage fingers) plus:|
|≥ 1 SpA feature:|
Crohn's Disease or Ulcerative Colitis
sacroiliitis on plain radiography
|≥ 2 other SpA features:|
dactylitis/sausage-like toe or digit
inflammatory back pain
family history of SpA
According to ASAS classification criteria(14, 15), axial disease can be diagnosed upon radiologic criteria, based on unilateral sacroiliitis on plain radiography or active inflammatory changes on magnetic resonance imaging (MRI), also starting with unilateral manifestation (see next part of the paper: Magnetic Resonance Imaging). Diagnosis of peripheral arthritis is based on the involvement of peripheral joints and entheses (Tab. 2).
Despite that whole scope of proposed classification criteria, the Moll and Wright system is still widely used and approved. It considers the fact that PsA can adopt different clinical patterns, thus the classification of 5 subtypes of the disease has been implemented(16) (Tab. 3).
Five subtypes of psoriatic arthritis according to Moll and Wright
|Five subtypes of psoriatic arthritis:|
|1.||Symmetrical peripheral polyarthritis resembling RA|
|2.||Asymmetrical mono- or oligoarthritis usually involving the knee and small peripheral joints|
|4.||Predominant DIP joint involvement|
|5.||Arthritis mutilans associated with destruction, osteolysis, telescoping of fingers|
The listed above subtypes can overlap or a patient may be affected by several kinds at the time. Additionally, an accurate assessment of the frequency of each pattern is complicated, as they may alter in a patient over time(4, 6, 8, 16).
Symmetric polyarthritis affects more than five joints. It is symmetric and manifests itself with changes in multiple joints of the fingers, wrists and toes and in 15%–20% of cases cannot be differentiated from RA as it can destroy joints in a similar pattern. Patients are RF-negative.
Asymmetric oligoarthritis is the most frequent form of PsA (ca. 70% of patients), which affects less than 5 peripheral joints, with asymmetric involvement of several small joints (interphalangeal and metacarpophalangeal) or large joints, especially the ankle, knee and the shoulder.
Axial spondyloarthritis affects sacroiliac joints and the spine and may result in fusion of the vertebrae. This infrequent form affects approximately 5% of patients with PsA. Concomitant peripheral arthritis is reported in about 40% of patients with spondylitis SpA.
DIP joint of the hand and feet involvement, often associated with nail dystrophy is a form distinctive for PsA with unique clinical features and changes in DIP joints (5%–12% of cases), where along erosions, proliferative changes are observed.
Arthritis mutilans involves osteolysis of the DIP and proximal interphalangeal (PIP) joints of the hand and foot and leads to severe deformations. With the prevalence between 5–16% in PsA patients, this erosive disease affects small joints in the form of dissolution or resorption of the distal parts of bones, resulting in “pencil in cup” or whittling appearance, especially in phalangeal tufts. If the disease progresses, shortening of the digits, recognized clinically as telescoping or “opera glass” of the digits occur with marked fingers deformations known as arthritis mutilans. In this case a joint may be often ankylotic and dislocated. Despite the common recognition of its phenotype, immunopathogenesis data remains ambiguous. However, bone edema, bone erosions and new bone formation are common in this form.
Early inflammatory changes in PsA affect soft tissue and bone marrow and cannot be detected with the use of plain radiography, or the image is indistinctive (for example soft tissue swelling, increased radiodensity of juxtaarticular soft tissue)(16). With the disease progression this image becomes similar to RA, i.e. joint space narrowing and erosions develop. Characteristic radiographic features of PsA occur in an advanced disease mainly within synovial joints, but also fibrocartilaginous joints, such as sacroiliac joints, and entheses of the tendons and ligaments(8, 10, 16) (Fig. 1).
Polyarticular PsA in 32 y.o. female, X-rays, A. DIP joints of the 2–4 fingers of the left hand: bony ankylosis of the DIP joint of the 4th finger; B. the left wrist region: soft tissue swelling, radiocarpal, midcarpal and carpometacarpal joint space narrowing, osteolysis (fluffy apperacance, arrow) of the first metacarpal's base, indistinct outline of the ulnar styloid; C. right forefoot, AP at the top, oblique at the bottom: MTP 5 joint space narrowing, erosions of the medial part of the great toe's proximal phalanx and lateral aspect of the 5th metatarsal's head, osteolysis and erosion in a few interphalangeal joint with concomitant ankylosis of the DIP 2 and 3 joints, degenerative changes in the 1st MCP joint; D. AP of the pelvis: ill-defined articular surface in the anterior part of the right sacroiliac joint with marked subchondral bone osteosclerosis, within the left joint partial and simultaneous widening and narrowing of the joint space (erosions and early ankylosis), image indicative of bilateral sacroiliitis, grade 2 on the right side, grade 3 on the left side
Typical inflammatory destructive lesions in hand and foot in PsA are as follows (Fig. 2 and 3):
dactylitis (so-called sausage digit) seen on radiographs as soft tissue swelling of an entire digit resulting from inflammatory changes in the DIP and PIP joints, flexor tenosynovitis, finger's joints synovitis or inflammation of subcutaneous and extrasynovial soft tissues;
marked deformity of fingers;
destructive changes, i.e. subchondral cyst and erosions, are commonly detected in DIP joints of hand and foot and IP joint of the big toe with distinctive spike-like or fluffy proliferative alterations on joint surface margins and phalangeal tuft;
phalangeal tuft acroosteolysis;
osteolytic lesions of the phalanx, which constitutes socalled pencil in cup deformity;
coexistence of osteolysis and ankylosis in joints of the same anatomical region (hand, foot);
periostitis along metaphyses and shafts of digits of the hand and foot;
perisoteal and endosteal bone formation, which may increase bone density of an entire phalanx (ivory phalanx);
juxtaarticular and gross osteoporosis (less frequent than in RA);
X-ray of the hands of the 53 y.o. female patient with PsA and erosive osteoarthritis, on the left – AP, on the right – PIP joint of the 5th left finger and IP joint of the left thumb enlarged: soft tissue swelling of the ulnar side of the left wrist, malalignment of the DIP joint of the 2nd finger of the right and 3rd finger of the left hand, subluxation of the IP joint of the right thumb and left hand's PIP 4 joint, joint space narrowing in a few interphalangeal joints and in both wrist regions, with concomitant destructive changes and decreased distance between articular surface of the distal radius and the base of the 3rd metacarpal on the right side, gross and juxtaarticular osteoporosis, destructive changes in a few PIP and DIP joints (gull-wing appearance, erosive osteoarthritis), osteolytic and erosive lesions (fluffy appearance in the course of PsA) in PIP joint of the 5th left finger and IP joint of the left thumb, with proximal phalangeal shortening (telescoping of finger), degenerative cyst in the head of the proximal phalanx of the 4th left finger, erosion on the lateral side of the base of the proximal phalanx of the 2nd right finger
Foot radiograph of the 42 y.o. male patient with PsA, AP on the left, oblique on the right: osteoporosis, well-difined area of the decreased bone density in the medial part of the big toe's proximal phalanx, uneven outline of the big toe's distal bony phalanx with inflammatory cysts and medial erosion, increased bone density of the distal phalanx of the big toe (ivory phalanx)
Early erosive changes are quite common in PsA – they develop in 15–47% of patients within first two years of a disease(7). Early erosions, like in RA, are marginal and well-defined, but as the disease progresses they become irregular and ill-defined because of periosteal bone formation adjacent to erosions, which can make an erosion of a speculated appearance, particularly towards its margins(4, 16). A high-resolution micro-computed tomography showed that erosions in PsA are smaller and deeper, and that, unlike in RA, there is no preponderance to radial side(7). Bone repair processes are more active in PsA than in RA and in PsA they integrate destructive elements with anabolic bone responses – such a combination promotes periostitis and formation of enthesophytes or osteophytes(7). Other detectable changes are soft tissue swelling, due to dactylitis, and periostitis, which usually affects the bony shaft(16).
If the disease progresses despite treatment, the bone destruction may worsen and erosions become more irregular and indistinct, simultaneously with new bone formation. This may result in some distinctive deformities, including “pencil in cup” deformity affecting usually the DIP joint (pencil-like thinning of the head of middle phalanx due to erosion and osteolysis and cup-like erosive changes of the base of distal phalanx with new bone formation that expands and curves laterally), or can lead to gross osteolysis(4, 16). These features are a typical radiographic image of arthritis mutilans.
The DIP joints are usually affected firstly, yet asymmetric erosions may be detected radiographically in the MCP, PIP joints and the carpus. Additionally, phalangeal tufts and sites of entheses may be involved(4).
Abnormalities are much more frequently diagnosed in hands that in feet, being nearly in the ratio of 2:1. MTP and (IP) joints of feet are of common involvement, particularly the IP joint of the great toe(4, 16).
Radiodensity of an entire phalanx may be increased by periosteal and endosteal bone formation which can result in “ivory” phalanx(4). This finding, although rare, is a unique and specific radiographic manifestation of PsA.
Out of 7 radiological features seen in hand and feet joints, (i.e. interphalangeal bony ankylosis, DIP erosive changes, juxtaarticular new bone formation, joint osteolysis, radiographic involvement, tuft osteolysis, any peripheral X-ray feature) Avila(17) showed that juxtaarticular new bone formation, joint osteolysis and phalangeal periostitis were excellent markers of PsA. However, the only feature independently associated with PsA in a multivariate logistic regression analysis was juxtaarticular new bone formation. Thus, it was the one included in CASPAR criteria.
PsA syndesmophytes not always can be differentiated from those appearing in ankylosing spondylitis (AS) due to the presence of the “bamboo” spine in both entities. However, usually an early spine involvement in PsA manifests itself with asymmetric syndesmophytes that are roughly linear or curvilinear, thick, fluffy and parallel to the lateral surface of vertebral bodies and intersomatic spaces(3) that increase in size, defined as defined as parasyndesmophytes or non-marginal, bulky syndesmophytes (Fig. 4).
Lumbar spine AP X-ray of the 34 y.o. female patient with suspected PsA: osteoporosis, parasyndesmophytes in the thoracolumbar junction and on the left side of 4th lumbar vertebra (arrows), uneven articular surface of the sacroiliac joints as in erosions – changes indicative of bilateral sacroiliitis, grade 2
Significant size, asymmetric distribution with skipped vertebral bodies levels, or sometimes unilateral, and separation from the lateral aspect of the vertebral bodies are the main radiographic features differentiating psoriatic syndesmophytes (para-syndesmophytes) from those in AS and SpA associated with inflammatory bowel diseases. They can also tend to fuse, appearing as a massive osteophytic bone bridge that joins two or more continuous vertebrae, but usually they remain isolated and asymmetric thus rarely leading to the “bamboo” spine(3).
Squaring of vertebral bodies occurs less frequent than in AS, covers the whole spine yet initially is observed at lumbar region.
Cervical spine involvement may be typical and includes intervertebral joints erosions on vertebral surface, and syndesmophytes that form at the side of erosion or in adjacent soft tissue, calcification of ligaments along anterior aspect of vertebral bodies, dens erosions, atlantoaxial subluxation (much less frequent than in RA), apophyseal joint ankylosis, ligamentous calcification and finally vertebral bodies squaring(3, 4).
The sacroiliac joints
Asymmetric and bilateral involvement of the sacroiliac joints is typical, yet unilateral may occur as well. Both synovial and syndesmotic parts may be engaged (like in ankylosing spondylitis and remaining spondyloarthritis). The iliac side is initially involved, presumably due to mechanical factors and anatomic features(3, 10).
The 1966 New York grading system is used to evaluate sacroiliitis on radiographs(3, 18, 19). Primarily cortical bone layer is ill-defined with shallow erosions and subchondral osteosclerosis. Secondarily, with the greater amount of erosions, the bone surface gets uneven and unequal joint space widening occurs. Bony proliferations lead to bony bridges, joint space narrowing, and occasionally ankylosis(3) (Fig. 5).
AP radiograph of the sacroiliac joints: A. bilateral sacroiliitis, grade 2 on the right, grade 4 on the left, spina bifida of the last lumbar vertebra and S1; B. ill-defined articular surface of the sacroiliac joints and subchondral bone osteosclerosis, partial and simultaneous widening and narrowing of the joint space (erosions and early ankylosis), image indicative of bilateral sacroiliitis, grade 3
Entheses involvement is even regarded as the hallmark of peripheral spondyloarthritis, including PsA. Enthesopathic features include: mineralized scars and bony proliferative changes, erosions, cysts in enthesis bony part. Such changes are most frequently seen in the Achilles tendon and plantar aponeurosis entheses at the calcaneum as well as at sites of tendinous and ligamentous attachments around the pelvis(8, 16, 20–22). According to Tan and McGonagle enthesophytes in SpA are of greater size than those of mechanical origin (Fig. 6).
Oblique X-ray shows a calcaneal spur (detailed evalutation on lateral radiograph), calcification adjacent to the outline of the navicular bone, degenerative changes of the forefoot
Psoriatic arthritis, one of the spondyloarthritis, presents various clinical manifestiations. There are several classifications systems available, i.a. CASPAR or Moll and Wright criteria. Plain radiography reveals specific, yet late changes, thus in advanced stages of PsA. Early inflammatory changes are seen both in MRI and ultrasonography. The application of these two methods in diagnosis of PsA will be addressed in the second part of this paper.