Recognizing psoriatic arthritis in the dermatology clinic

CONTINUING

MEDICAL EDUCATION

Recognizing psoriatic arthritis in the dermatology clinic Amit Garg, MD,a and Dafna Gladman, MDb Boston, Massachusetts, and Toronto, Ontario, Canada Dermatologists care for patients with psoriasis in whom there exists an inherent risk of psoriatic arthritis, a condition with potential for causing joint damage and subsequent disability. Most patients have psoriasis for years before the development of psoriatic arthritis, and there may be a significant proportion of psoriasis patients with joint involvement that are cared for by the dermatologist. With the absence of a diagnostic measure, the criterion standard for recognizing or monitoring psoriatic arthritis remains the clinical assessment. Recognition of psoriatic arthritis in the psoriasis patient—and the dermatologist’s ability to differentiate it from other types of arthritis—provide an opportunity to improve patient outcomes through early recognition and facilitation of intervention in collaboration with a rheumatologist. ( J Am Acad Dermatol 2010;63:733-48.) Learning objectives: After completing this learning activity, participants should be able to recognize the presence of psoriatic arthritis among patients with psoriasis; distinguish psoriatic arthritis from reactive arthritis, osteoarthritis, gout, rheumatoid arthritis, and ankylosing spondylitis; and use appropriate laboratory and imaging tests in the evaluation of patients with psoriasis and musculoskeletal complaints. Key words: dermatologist; psoriatic arthritis; screening.

D

ermatologists care for patients with psoriasis in whom there exists an inherent risk of coupled morbidity, the most common and well described of which is psoriatic arthritis (PsA). PsA may be defined as an inflammatory arthritis which is seronegative for rheumatoid factor (RF) and enthesitis that is associated with psoriasis.1 It has been classified among the four main spondyloarthropathies which, in addition to inflammatory arthritis, share a spectrum of components including enthesitis and dactylitis, axial involvement, RF

From the Department of Dermatology,a Rheumatic Skin Disease Center, Boston University School of Medicine, and the Centre for Prognosis Studies in the Rheumatic Diseases,b Toronto Western Hospital. Funding sources: None. Conflicts of interest: Dr Garg has been a consultant for Abbott, has received honoraria from Abbott and Genentech, and has received grants from Centocor and RegeneRx. Dr Gladman has been a consultant for and received honoraria from Abbott, Amgen, BMS, Centocor, Schering, and Wyeth, and has received grants from Abbott, Amgen, Schering, Pfizer, and Wyeth. The editors, planners, and peer reviewers have no relevant financial relationships. Reprint requests: Amit Garg, MD, Department of Dermatology, 609 Albany St, J207, Boston, MA 02118. E-mail: [email protected]. 0190-9622/$36.00 ª 2010 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2010.02.061

seronegativity, presence of the human leukocyte antigen (HLA)*B27 allele and extraarticular features.2 Once described as a disease with a more mild prognosis,3,4 PsA is now understood to have potential for joint damage with disability outcomes similar to patients with rheumatoid arthritis (RA).5-8 Up to 57% of PsA patients have erosive arthropathy,5,9 and functional disability occurs in 11% to 19% of patients.5,9-11 PsA patients also have increased mortality relative to the general population.12 Most patients have psoriasis either for several years before the development of arthritis or simultaneously with it.5 As such, a significant proportion of psoriasis patients have joint involvement without a diagnosis of PsA,13 and it is likely that many of these patients are under the care of dermatologists. Accordingly, the recognition of PsA in the psoriasis patient by the dermatologist provides an opportunity to improve outcomes through early recognition and facilitation of intervention in collaboration with a rheumatologist. The unpredictable, heterogeneous, and often insidious involvement of joints or juxtaarticular tendons and ligaments can make clinical recognition of PsA and distinction from other types of arthritis a challenge. Types of arthritis such as osteoarthritis (OA) and gout often coexist with psoriasis and mimic presentations of PsA. Alternatively, patients with psoriasis-like eruptions (ie, seborrhea) and concomitant inflammatory arthritis, such as RA or ankylosing 733

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d There are no laboratory tests that specify a spondylitis (AS), may be misdiagnosed with PsA. With diagnosis of PsA the absence of a diagnostic measure for PsA, the d The presence of marginal and central erosions, criterion standard for diagnosis or monitoring reperiostitis, and bulky syndesmophytes on mains the clinical assessment. With basic training, it is plain radiographic film distinguish PsA from possible for the dermatologist to recognize the presother forms of arthritis ence of PsA by appreciating disease demographics and clinical features, asking the appropriate questions, performing simple tarEpidemiology geted physical assessments, CAPSULE SUMMARY PsA has a worldwide prevand using the appropriate alence among psoriasis palaboratory and imaging studDermatologists care for psoriasis patients tients ranging from 6% to ies. For a comprehensive in whom there exists an inherent risk for 42%.15-23 Population heterogeneral overview of the diagcoupled morbidity, most commonly geneity and varying methods nostic and treatment chalpsoriatic arthritis (PsA). of disease classification and lenges of PsA as they relate Different types of arthritis coexist with data acquisition contribute to to pathogenesis and burden psoriasis and mimic presentations of PsA; the difficulty in establishing its of disease, the reader is rein addition, patients with psoriasis-like true prevalence. Although the ferred to the January 2005 eruptions and concomitant incidence of PsA among pacontinuing medical educainflammatory arthritis may be tients with psoriasis varies tion article published in the misdiagnosed with PsA. among epidemiologic studJournal.14 The aim of this ies, it is apparent that it is a review is to provide the derThe dermatologist may recognize the common disorder.15-20 As a matologist with a practical presence of PsA by appreciating disease rough estimate, if one-third framework for recognizing demographics and clinical features, of the 1% to 3% of the US the clinical features of PsA asking the appropriate questions, population with psoriasis has and distinguishing these feaperforming simple targeted physical PsA, then PsA may occur in tures from other common assessments, and using the most 0.3% to 1.0% of this group, a forms of arthritis, thereby faappropriate laboratory and imaging prevalence similar to that cilitating more specific and studies. seen in RA. In 70% of PsA timely referral to rheumatolThe recognition of PsA in psoriasis patients, psoriasis precedes ogy. PsA is contrasted with patients by the dermatologist provides the onset of arthritis by about reactive arthritis (ReA), OA, an opportunity to improve outcomes 10 years,5 and the likelihood gout, RA, and AS. through early recognition and facilitation of developing PsA may also of intervention in collaboration with a correlate with duration and rheumatologist. severity of psoriasis.16 The siPSORIATIC ARTHRITIS multaneous onset of psoriasis Key points d Psoriatic arthritis (PsA) and arthritis is noted in approximately 10% to 15% of cases,5 and arthritis may precede psoriasis by as many is a common condition in which psoriasis as 10 to 15 years in the remaining 15% of cases. In precedes arthritis by years in most patients d As an inflammatory arthritis, PsA is characchildren, however, arthritis may precede psoriasis in as many as 50% of cases.24-26 PsA affects men and terized by joint discomfort, swelling, and women equally, with a peak age of onset between 35 prolonged morning stiffness d Patterns of joint involvement in PsA are and 45 years of age. In children, PsA has a mean age of onset of 9 to 10 years, and may have a female variable, and relying on patterns of involvepredominance. ment alone to distinguish PsA from other With these epidemiologic considerations in mind, forms of arthritis may be a pitfall d Most common sites of entheseal involvement one may begin to classify patients among the various types of arthritis. For example, a 30-year-old man in PsA include the attachment of the Achilles with psoriasis and pain of the distal interphalangeal tendon or the plantar fascia to the calcaneus d A visual inspection and targeted examina(DIP) joint is more likely to have PsA than OA (see the section on osteoarthritis). Similarly, a 35-year-old tion of the joints and entheses may facilitate man with psoriasis and diffuse swelling of the big toe recognition of PsA with greater sensitivity is more likely to have PsA than gout (see the section than through patient-reported symptoms on gout). alone d

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Fig 1. Synovial fluid in psoriatic arthritis. Synovial fluid from a patient with psoriatic arthritis, an inflammatory arthritis, contains a white blood cell count greater than 2000, of which at least 75% are polymorphonuclear cells. This composition imparts a cloudy or opaque appearance to the aspirate (right). Synovial fluid from a patient with noninflammatory arthritis has a white cell count of less than 2000 and is transparent in appearance (left).

Clinical features. PsA is an inflammatory arthritis (Fig 1) in which initial musculoskeletal symptoms are more often insidious in onset, rather than acute. Joint discomfort, more often than pain, characterizes PsA. However, asymptomatic disease, even with evidence of radiographic damage of the involved joint, is not uncommon. While 100% of patients with RA and AS, for example, complain of morning stiffness, only about half of PsA patients give the same complaint. Prolonged morning stiffness lasting longer than 60 minutes results from inflammatory involvement of entheses, the point at which tendons or ligaments insert to bone. The stiffness in PsA continues to improve throughout the day with activity, and it becomes more prominent with periods of rest, such as overnight sleep. Patterns of joint involvement The patterns of joint involvement in PsA are variable, and the natural course of disease and treatment bear further influence on dynamic patterns of involvement over the course of disease. What begins as oligoarthritis (4 or fewer joints) may convert to polyarticular (more than 4 joints) disease over years, and may revert once again to oligoarthritis with treatment. Axial involvement may occur at onset, may develop later in the disease course, or may be absent altogether. As such, relying on patterns of involvement alone to distinguish among different forms of arthritis may be a pitfall. Among the recognized patterns of PsA initially described by Moll and Wright,1 the DIP predominant pattern may be the most readily recognized because it is unique to PsA. However, this pattern occurs in

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only 5% to 10% of patients, and primarily in men.27 An asymmetric oligoarthritis pattern occurs in about 30% of patients. In this pattern, there is typically involvement of a large joint, such as the knee, and a few small joints of the hands or feet, often in association with dactylitis. However, several series suggest the polyarthritis pattern to be at least as common as the oligoarticular pattern in PsA, especially among women.5,6,9,28,29 Polyarticular disease involves the fingers, wrists, toes, and ankles. While bearing similarity to the pattern observed in RA (see the section on rheumatoid arthritis), the polyarthritis pattern in PsA may be distinguished further by involvement of DIP joints and the relative asymmetry among involved joints. Moreover, whereas PsA is more likely to affect all of the joints in any one digit (RAY distribution) while others remain free of arthritis, RA affects the same joints in all of the digits. Occurring in about 5% of PsA patients, arthritis mutilans of the hands and feet is not nearly as common as it is in RA. Axial disease alone, in the form of spondylitis (inflammation of apophyseal joints of the spine) and/or sacroiliitis (inflammation of the sacroiliac joint in the pelvis) occurs in 5% of patients with PsA and most often in males. More often though, axial disease occurs in conjunction with peripheral arthritis, and so in total, up to 40% of PsA patients have some form of axial involvement. Spondylitis in PsA involves the cervical spine with relative sparing of the thoracolumbar spine. The atlantoaxial joint is at risk for subluxation with severe cervical disease. Vertebrae of the spine are affected dysynchronously with skipping in PsA. Notably, there may be discordant involvement of the spine without sacroiliac disease, unlike axial disease in AS (see the section on ankylosing spondylitis). When present, sacroiliitis in PsA is usually asymmetric, also in contrast to AS. Enthesitis and dactylitis. Whereas synovitis is the primary lesion in RA, synovitis along with enthesitis characterizes PsA. Ensthesitis, or inflammation at the site of tendon or ligament insertion into bone, is present in up to 42% of patients.30 There are many entheseal structures that serve to absorb and dissipate mechanical stress around joint structures, and inflammation of these structures results in clinically apparent tightness around joints, most notable after periods of rest. Enthesitis may affect both peripheral and axial sites independently from inflammatory involvement of the joint. The most common sites of entheseal involvement in PsA include the attachment of the Achilles tendon or the plantar fascia to the calcaneus (heel), as well as the ligaments around the rib cage, pelvis, vertebral bodies, posterior tibial tendon, quadriceps muscle, patellar tendon, and the elbow.

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Table I. Comparison of clinical features among types of arthritis that may coexist with psoriasis or that mimic psoriatic arthritis Clinical feature

Gender Age at onset (yrs) Onset Quality of joint symptoms Morning stiffness (min) Extraarticular features

PsA

M=F 35-45 Gradual Discomfort/pain less than in RA [60, better with activity Present

OA

Gout

RA

AS

MzF [50 Gradual Discomfort

M[F 20-40 Acute Pain

F[M 30-50 Acute/gradual Pain

M[[[F 20-40 Acute/gradual Pain

M[[F 20-40 Acute Pain

\20, worse with activity Absent

None

[60, better with activity Present

[60, better with activity Present

[60, better with activity Present

Absent

ReA

AS, Ankylosing spondylitis; F, female; M, male; OA, osteoarthritis; PsA, psoriatic arthritis; RA, rheumatoid arthritis; ReA, reactive arthritis.

Enthesitis has been proposed as a common denominator between psoriatic nail changes and PsA. Magnetic resonance imaging coupled with histologic findings suggest a connection between nail changes and the enthuses.31 Associated extraarticular symptoms. Inflammatory arthritis is associated with extraarticular symptoms, the frequency and extent of which depend on the type of arthritis involved. Similar to patients with other types of inflammatory arthritis, PsA patients experience constitutional symptoms, especially fatigue and sometimes anorexia, weight loss, and generalized weakness. PsA belongs to the spondyloarthritis group, which shares extraarticular features different from those seen in seropositive disease, of which RA is the prototype. For example, conjunctivitis or uveitis tends to occur in seronegative diseases, whereas scleritis and episcleritis are more likely to occur in seropositive diseases. In PsA, conjunctivitis or uveitis resulting in pain, photophobia, and lacrimation may be present in 7% to 33% of cases. Ocular involvement in PsA tends to be chronic and bilateral, and it may involve posterior chambers. Aortic insufficiency resulting in symptoms of congestive heart failure is a rare complication in PsA. Table I compares the clinical features among types of arthritis that may coexist with psoriasis or that mimic PsA. Physical examination The dermatologist is not expected to perform a joint examination on a psoriasis patient routinely. However, a functional appreciation of signs suggestive of inflammatory arthritis and enthesitis may allow the dermatologist to recognize PsA with greater sensitivity than through patient reported symptoms alone, and to refer for rheumatology consultation with better specificity and timing. If history and a review of systems alone do not suggest the presence of PsA, simple targeted physical

examination of the joints and entheses may facilitate reaching the threshold for the appropriate index of suspicion. Important information is obtained through visual inspection of joints and through straightforward examination maneuvers. In the same way the integument lends itself to visual diagnostic assessment, so may skin overlying peripheral joints and entheses. Erythema is often present overlying inflamed joints of the hands and feet in PsA (Fig 2). Swelling around joints may be appreciated through close visual inspection, although this feature may go unnoticed if overlying erythema is also subtle or absent. Contours of joints become less apparent with swelling, and this is more noticeable upon comparison to uninvolved joints (Fig 3). Larger joints, such as the knee, may have overlying erythema when inflamed, and swelling is easier to visually appreciate in these larger joints (Fig 4). In mutilating disease, hands with shortened fingers resulting from progressive osteolysis are readily apparent on visual inspection as a characteristic deformity in PsA known as ‘‘operaglass hands’’ (Fig 5). Mutilating PsA is more common in men and it is more frequent with early onset disease, making early recognition of PsA in this subset of patients essential. Ankylosis, or fusion, of small joints, which may manifest clinically with either fixed bent (contractures) or straight joints, is another common deformity (Fig 5) noted through visual inspection. Uniform swelling of a finger or toe (Fig 6), or the appearance of a ‘‘sausage digit,’’ represents dactylitis, which occurs in up to 49% of those with PsA and results from simultaneous inflammation of all three joints and tenosynovitis of the involved digit. Because the toes are more commonly involved,32 it is essential to examine the feet with shoes and socks removed when evaluating patients with psoriasis. Dactylitis of fingers is often accompanied by

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Fig 2. Erythema overlying joints in psoriatic arthritis. Dull red erythema overlying inflamed joints of the foot.

Fig 4. Swelling of the right knee in psoriatic arthritis. Swelling of larger joints such as the knee may be appreciated by visual inspection.

Fig 3. Swollen joints in psoriatic arthritis over the second and third metacarpophalangeal joints of the hands.

Fig 5. Opera glass hands in psoriatic arthritis. Mutilating psoriatic arthritis in which shortened fingers result from progressive erosive disease and osteolysis, leading to collapse of the involved joints and telescoping of digits. Anykylosis or bending of the digits is also apparent.

psoriatic nail disease, which has been identified in more than 80% of patients with PsA and less than 50% of patients with psoriasis without arthritis.33,34 In addition, superficial tendons, such as the Achilles tendon, may appear visibly swollen, especially when compared to the contralateral tendon. While there are specific measures to assess enthesitis,35 it is not expected that the dermatologist would perform such evaluations. When joint and entheseal symptoms in PsA are present without obvious visual clues, targeted examination maneuvers may facilitate the recognition of skeletal involvement. Activation of range of motion of the neck, shoulders, elbows, wrists, fingers, knees, ankles, and toes may elicit stiffness or pain. Specifically, one might stress the wrists, shoulders, elbows, finger joints, and toe joints to elicit pain. Dermatologists and rheumatologists have shown their ability to elicit joint tenderness in a reliable way.36 It may also be possible for a dermatologist to elicit tenderness at the insertion of the Achilles tendon and the plantar fascia. Axial disease in PsA is easily missed, partly because the examination of axial joints is fraught with poor

sensitivity and specificity because of the relative inaccessibility of these joints. Such maneuvers have limited roles, even in rheumatology practice. A patient occasionally presents with obvious difficulties with spinal mobility. In some, range of motion or maneuvers that stress the sacroiliac joint may elicit pain or stiffness. The loss of spinal mobility may be noted through simple attempts at anterior and lateral flexion. If axial disease is ultimately suspected, plain film or magnetic resonance imaging (MRI) with fat suppressed signal (STIR images) in anticipation of the rheumatology consultation may be considered. Table II compares the physical examination features in PsA with other types of arthritis that may coexist with psoriasis or that mimic PsA. Laboratory tests. There are no laboratory tests that specify a diagnosis of PsA. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are unreliable in detecting the presence of PsA,5 and they are more often elevated in RA, AS, and ReA. While not diagnostic for PsA, acute phase reactants are prognostic for both joint destruction and survival

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Fig 6. Dactylitis in psoriatic arthritis. Fusiform swelling of a right thumb (A) and the fourth left toe (B) as a result of inflammation of phalangeal joints along with entheses.

and thus warrant evaluation for the PsA patient. HLAB*27, present in 7% of North American whites, is also noted in 50% to 70% of patients with axial disease and less than 15% of those with peripheral disease in PsA, and its presence is independent of disease severity.23 Although also not diagnostic of PsA, HLA-B*27, particularly in the presence of HLADR*07, is prognostic for the progression of joint damage in PsA.37 Table III compares laboratory evaluations in PsA with other types of arthritis that may coexist with psoriasis or that mimic PsA. Imaging findings Just as dermatologists apply the descriptive portion of a histopathology report to the patient’s presentation for clinical pathologic correlation, the knowledgeable dermatologist may also analyze the description of the radiology report to assess if findings in psoriasis patients are consistent with PsA. On plain radiographs, type of erosion and deformity, the presence of periostitis, and the pattern of involvement assist in distinguishing PsA from other forms of arthritis. New bony proliferation, or periostitis, that is observed adjacent to erosions and at sites of

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entheseal attachments is an identifying feature unique to PsA among inflammatory arthropathies. Radiographically, it manifests as juxtaarticular fluffy whitening. Marginal surfaces of bone, which are less well protected by articular cartilage, are susceptible to erosive changes early on in PsA (Fig 7, A). Marginal erosions in PsA may progress further to involve the central articular surface, resulting in the characteristic ‘‘pencil in cup’’ finding (Fig 7, B). This type of progressive osteolysis, or bone resorption, leads to dissolution of the joint and collapse of the phalanges and metacarpal bone, resulting in an opera glass or telescoping deformity of the digit. This type of deformity is unique to PsA. Deformities in PsA are distinguished by the presence of both lysis and ankylosis, which may occur in different joints of the same digit. Occasionally, bone loss from erosive disease may be extensive enough to also cause subluxations. The correlation between symptoms and radiologic evidence of spondylitis and sacroiliitis may be poor, and symptoms of morning stiffness in the lower back or buttocks may not be further substantiated with findings on plain radiographic film. This poor sensitivity also accounts for one of the reasons that axial disease in PsA is easily missed. Erosions at the sacroiliac joint in PsA are typically asymmetric and unilateral. With time, the joint space between the sacrum and the ilium becomes obliterated because of sclerosis of the bone. With spinal disease in PsA, inflammatory granulation tissue at the junction of the disk cartilage and the margin of the vertebral body is replaced by bony structures called syndesmophytes—which ultimately bridge adjacent vertebral bodies, resulting in ankylosis of the spine. In PsA, syndesmophytes are bulky, they may involve one side of the vertebral body and not the other at any given level (asymmetric), and they may affect the spine intermittently with skip areas. This is in contrast to syndesmophytes in AS, which are thin, symmetric, and continuous (Fig 8). Other common axial radiographic findings in PsA include paravertebral ossification and, in advanced disease, vertebral fusion with disk calcification. Enthesitis may be difficult to assess with plain radiographs, especially early in the course of disease. Erosion and periostitis may be noted at the site of insertion of tendons to bone, such as at the site of insertion of the Achilles tendon to the calcaneus. MRI and ultrasound are of greater value than plain radiographic film when evaluating for the presence of enthesitis. T1-weighted MRI is useful in defining the anatomic detail of soft tissue. In this sequence, fat and bone marrow have a bright signal and appear white in color, muscle has an intermediate signal

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Table II. Physical examination in psoriatic arthritis and in types of arthritis that may coexist with psoriasis or that mimic psoriatic arthritis Physical examination

PsA

Pattern of joint Oligoarthritis, involvement polyarthritis, axial Distribution Peripheral (including DIP) and axial Symmetry Asymmetric Swelling and Present overlying erythema of joints Enthesitis Present Dactylitis 48% Synovitis Present Typical Opera glass deformity (telescoping) digit

OA

Gout

RA

AS

Monoarthritis, oligoarthritis

ReA

Monoarthritis, Polyarthritis oligoarthritis, polyarthritis Peripheral Peripheral Peripheral (including (including DIP) and axial MCP) Asymmetric Asymmetric Symmetric Absent Present Present

Axial plus large Oligoarthritis, peripheral joints, polyarthritis. asymmetric axial Axial[[Peripheral Peripheral (including DIP) and axial Symmetric Asymmetric Absent Present

Absent Absent Absent Heberden and Bouchard nodes

Present Absent Present in some Spinal ankylosis

Absent Absent Absent Tophi

Absent Absent Present Swan neck, boutonniere, zig zag

Present Occasional Present Spinal ankylosis

AS, Ankylosing spondylitis; DIP, distal interphalangeal; MCP, metacarpophalangeal; OA, osteoarthritis; PsA, psoriatic arthritis; RA, rheumatoid arthritis; ReA, reactive arthritis.

Table III. Laboratory evaluations in psoriatic arthritis and in types of arthritis that may coexist with psoriasis or that mimic psoriatic arthritis Laboratory test

PsA

OA

Gout

Normal (elevated during attack) Normal Absent Absent 4-8% Inflammatory

ESR

1/

Normal

CRP RF CCP Ab HLA*B27 Synovial aspirate

1/ Usually absent Usually absent 15-70% Inflammatory

Normal Usually absent Absent 4-8% Noninflammatory

RA

AS

ReA

Elevated

1/

1/

Elevated Usually present Present 4-8% Inflammatory

1/ Usually absent Usually absent 90% Inflammatory

1/ Usually absent Usually absent 50-85% Inflammatory

AS, Ankylosing spondylitis; CCP, citrullinated-containing proteins; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; HLA, human leukocyte antigen; OA, osteoarthritis; PsA, psoriatic arthritis; RA, rheumatoid arthritis; ReA, reactive arthritis; RF, rheumatoid arthritis.

intensity and appears dark, while the tendons and ligaments appear black in color. As noted on T1weighted MRI, thickening of the plantar fascia in the context of plantar stiffness is suggestive of plantar enthesitis (Fig 9, A). T1-weighted MRI may also make apparent edema and fluid collections near sites of attachment of tendon to bone. Fat and marrow share the same signal intensity as fluid or edema. By suppressing the fat and marrow signal through a T2-weighted STIR signal, fluid and edema are isolated for improved visualization (Fig 9, B). The use of ultrasound for the detection of enthesitis has recently been proposed. Indeed, enthesitis was detected commonly among patients with psoriasis who have not been diagnosed with PsA.38,39

Table IV compares imaging findings in PsA with other types of arthritis that may coexist with psoriasis or mimic PsA.

REACTIVE ARTHRITIS Key points d

d

Reactive arthritis (ReA) is distinguished from psoriatic arthritis (PsA) by its acute onset of arthritis and enthesitis, and by the additive involvement of new joints over days While ReA and PsA share extraarticular symptoms, urethritis, cervicitis, and bowel symptoms are also features that distinguish ReA

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Fig 7. Marginal erosion and periostitis in psoriatic arthritis. Characteristic radiographic changes in psoriatic arthritis include marginal erosions at several joints of the hands and best noted at the second, third, and fourth metacarpophalangeal joints in this patient. Juxtaarticular fluffy whitening, known as periostitis, also occurs at several joints and may be best appreciated at the second, third, and fourth proximal interphalangeal joints in this patient (A). B, Pencil in cup deformity. Marginal erosions progressing centrally give rise to the ‘‘pencil in cup’’ deformity noted on the fifth metatarsophalangeal joint. (Photographs courtesy of Eugene Kissin, MD, Boston Medical Center.) d

d

Patterns of asymmetric peripheral and axial joint involvement are similar in ReA and PsA Physical examination, laboratory testing, and imaging findings may not distinguish ReA from PsA

Epidemiology ReA affects individuals 20 to 40 years of age, similar to the range in PsA. Men and women are affected equally by the foodborne enteric form of ReA, while the veneral form affects men nine times as often as women. Clinical features. Although ReA shares a number of features with PsA, it is distinguished by its relative acute onset of arthritis and enthesitis, which tends to occur within days of a triggering infection. In general, although stiffness in ReA may be indistinguishable from that in PsA, pain and limitation in movement tend to be more severe in ReA. In both PsA and ReA, swelling and overlying erythema of the involved joints are apparent. Patterns of joint involvement. ReA affects lower extremity and foot joints more commonly, whereas PsA often involves peripheral joints of the upper extremities. Both PsA and ReA involve the peripheral joints asymmetrically. Unlike PsA

however, there is additive involvement of new joints over the course of days in ReA. Sacroiliitis occurs in less than 10% of acute cases of ReA, but it is present in half of patients with chronic disease. Severe ankylosing disease of the spine occurs in only 5% of patients with ReA. Enthesitis and dactylitis. Enthesitis is a frequent occurrence in ReA. Furthermore, sites of enthesial involvement are similar in ReA and PsA, and both often develop dactylitis of toes (Fig 10) and fingers with Achilles tendonitis and plantar fasciitis. Associated extraarticular symptoms. In ReA, conjunctivitis or uveitis is typically bilateral. Urethritis or cervicitis along with bowel symptoms further characterize ReA but not PsA. Physical examination. Axial and peripheral assessments in ReA are similar to those in PsA, and distinction by physical examination alone between PsA with limited or inconspicuous psoriasis and ReA with psoriasiform dermatitis may be difficult. Laboratory tests. While HLA-B*27 is present in 50% to 85% of ReA patients, it is neither necessary nor sufficient for the diagnosis, as is the case in PsA. Imaging findings. The appearance of joint erosions and enthesitis, whether peripheral or axial, in ReA may be indistinguishable from those in PsA.

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Fig 8. Syndesmophytes in psoriatic arthritis. Syndesmophytes (arrows) are bulky, asymmetric, and affect the spine intermittently with skip areas, which is in contrast to ankylosing spondylitis, in which syndesmophytes are thin, symmetrical, and continuous.

OSTEOARTHRITIS Key points d

d

d

d

d

Osteoarthritis (OA) occurs in older individuals as compared with psoriatic arthritis (PsA) Onset, quality of discomfort, and pattern of joint involvement are similar in OA and PsA Identification of Heberden and Bouchard nodes may distinguish OA from distal phalangeal (DIP) and proximal interphalangeal (PIP) involvement, respectively, in PsA Enthesitis and extraarticular symptoms are not features of OA Osteophyte formation, joint space narrowing, and the absence of erosions distinguish OA from PsA on plain radiographic film

Epidemiology OA occurs in 30% of individuals between 45 and 65 years of age, but it affects 80% of people by their eighth decade of life. Symptomatic OA before 45 years of age and without predisposing factors such as obesity is rare. As such, OA occurs in an older population than does PsA. The disease is equally common among men and women 45 to 55 years of age, after which OA becomes more common among women. In addition to age and obesity, trauma to a joint is a risk factor for the development of OA, and this has also been postulated as a triggering factor in PsA.40,41 Clinical features. The onset of symptoms in OA is somewhat gradual, as it is in PsA. The quality of

Fig 9. Plantar thickening and edema in a patient with psoriatic arthritis. A, T1-weighted magnetic resonance imaging reveals thickened ([4 mm) plantar fascia (arrow). B, T2-weighted fat suppressed signal highlights edema (arrow) in the bone marrow of the calcaneus close to the site of attachment of the plantar fascia.

discomfort in OA, which may be similar to that in PsA, is a deep, dull pain localized to the involved joints, although hip pain in OA is often referred to inguinal area, buttocks, or the proximal thigh. Unlike in PsA, discomfort in OA becomes worse with activity, is relieved by rest, and may become persistent with nocturnal exacerbations in advanced disease. Although traditionally considered noninflammatory, OA may also cause morning stiffness, especially in older individuals. Morning stiffness in OA, unlike in PsA, is typically short lived, lasting 30 minutes or less. Patterns of joint involvement. Patterns of peripheral joint involvement in OA may be similar to PsA, making the two a challenge to distinguish in the patient with psoriasis. OA typically involves DIP and proximal interphalangeal (PIP) joints, the base

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Table IV. Radiographic findings in psoriatic arthritis and in types of arthritis that may coexist with psoriasis or that mimic psoriatic arthritis Plain film finding

Periostitis Osteopenia Joint space narrowing Erosion Sacroilitis

PsA

OA

Gout

RA

AS

ReA

Present Absent Late manifestations

Absent Absent Present

Absent Absent Absent

Absent Present Present

Absent Absent Late manifestation

Absent Absent Late manifestation

Marginal and central Present

Absent Absent

C- shaped Absent

Marginal Absent

Marginal Present

Marginal Present

AS, Ankylosing spondylitis; OA, osteoarthritis; PsA, psoriatic arthritis; RA, rheumatoid arthritis; ReA, reactive arthritis.

of the thumb, and large weight-bearing joints, such as the knees or hips. As with PsA, OA may affect any part of the axial skeleton independently of peripheral joints. Enthesitis and dactylitis. Enthesitis is not a feature of OA. MRI studies assessing enthesitis were able to distinguish patients with PsA from those with OA.42 As such, patients with OA do not develop dactylitis of fingers and toes, Achilles tendonitis, or plantar fasciitis, as might patients with PsA. It should be noted, however, that patients with OA—particularly those who have diffuse idiopathic skeletal hyperostosis (DISH)—may have heel spurs. Associated extraarticular symptoms. There is an absence of extraarticular systemic features in OA. Physical examination. In OA, the DIP, PIP, and other weight-bearing joints may have tenderness localized to the involved joint. These joints, and especially the knee, may also demonstrate creptius, the sensation of bone on bone rubbing with movement. Firm bony enlargements over the DIP (Heberden nodes) and PIP (Bouchard nodes) joints (Fig 11) are often readily apparent as characteristic clinical features in OA and should be differentiated from the soft swelling resulting from effusion or proliferated synovium in inflammatory arthritis, including PsA. Laboratory tests. Laboratory analyses in OA are normal. There is no strong association with any HLA alleles. Imaging findings. Although there is bony proliferation in the form of an osteophyte (bone spur) in OA, periostitis typical of PsA is absent. Erosions are also absent in typical OA. An uncommon erosive variant of OA may be more difficult to distinguish on the basis of erosions alone. In erosive OA, ‘‘seagull’’ shaped erosions are noted on the central articular surfaces along with osteophytes, both of which help distinguish this rare variety of OA from PsA. OA of the spine may also be readily distinguished by presence of joint space narrowing and osteophytes rather than syndesmophytes.

GOUT Key points d

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Gout occurs in older individuals as compared with psoriatic arthritis (PsA) In contrast to PsA, an attack of gout is abrupt, causes severe pain, and is followed by an obligatory period of remission While monoarticular gout may be distinguished from the pattern of involvement in PsA, polyarticular gout in a patient with psoriasis bears resemblance to PsA Although a swollen toe in gout may resemble dactylitis in PsA, enthesitis is not a feature of gout The presence of tophi is the best physical clue to the diagnosis of gout Elevated serum uric acid may be noted in patients with either gout or PSA On plain radiographic film, gout is distinguished from PsA by the presence of C-shaped erosions and absence of periostitis

Epidemiology Gout affects men about twice as often as women. Men are afflicted between the ages of 30 and 50 years of age, a range that includes the peak age of onset in PsA. Because estrogenic hormones have a uricosuric effect, women do not become affected by gout until after menopause, with peak age of onset between 50 and 70 years of age—an age onset range less typical than that of PsA. Clinical features. In stark contrast to PsA, arthropathy in early gout has an abrupt onset. Gout is also distinguished from PsA by causing intense joint pain that is further aggravated by movement. Patients often cannot tolerate bed sheets over the affected area. In simple gout, painful episodes last up to 10 days, after which time there is a unique period of symptom-free ‘‘intercritical remission’’ that does not occur in PsA. Morning stiffness is not a feature of gout. Patterns of joint involvement. In gout, it is most common for a single metatarsophalangeal

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Fig 10. Dactylitis in reactive arthritis. Uniform swelling of the right fourth toe in a patient with a psoriasiform dermatitis that mimics psoriasis. This presentation bears a similarity to psoriatic arthritis.

(MTP) joint of the first toe to be involved in initial acute episodes, although other tarsal, ankle, and knee joints may be affected instead. Early on in gout, one joint is involved. With uric acid elevation and after several attacks, gout patients may develop an asymmetric polyarticular arthritis involving several joints of the fingers (Fig 12), wrists, elbows, knees, ankles, and heels, a pattern that bears similarity to polyarticular disease in PsA. The polyarticular variety of gout is more common in postmenopausal women with renal insufficiency who are taking a diuretic, and in men with hypertension and a significant alcohol intake history. Even when multiple joints are affected, gout does not tend to involve the axial skeleton, which is a rather common occurrence in PsA. By the time patients develop polyarticular gout, they often have tophi, which are deposits of uric acid crystals in the tissues. These occur in the ears, the olecranon bursa, and other extensor surfaces, or over the joints themselves. Enthesitis and dactylitis. Enthesitis is not a feature of gout. Although an entire finger or toe may be swollen in the course of a gouty attack involving the small joints of hands or feet, it is not described as dactylitis. Associated extraarticular symptoms. In gout, there is an absence of extraarticular systemic features. Physical examination. The presence of tophi, more common in patients with polyarticular disease, is the best physical clue to the diagnosis of gout. A gouty joint that is active has intense overlying red erythema and swelling, and it is warm to touch and exquisitely tender. The joint affected by PsA, by comparison, tends to be less impressive. However, the distinction between a joint chronically affected

Fig 11. Heberden and Bouchard nodes in osteoarthritis. Psoriasis patient with bony enlargements overlying the distal interphalangeal (Heberden nodes, red arrows) and proximal interphalangeal (Bouchard nodes, yellow arrows) joints suggestive of osteoarthritis and not psoriatic arthritis.

by gout and dactylitis may be difficult in the patient with psoriasis suspected to have PsA (Fig 13). Laboratory tests. Patients with gout usually have elevated serum uric acid, although the same may be apparent in patients with psoriasis. The criterion standard for diagnosis of gout and distinction from PsA involves analysis of the synovial aspirate, which shows birefringent needle-shaped monosodium urate intracellular crystals and elevated cell counts. Imaging findings. In gout, erosions have a characteristic well defined punched-out C-shape with overhanging margins (Marte sign) that appear distinct from marginal or central erosions in PsA. Soft tissue swelling and calcifications representing gouty tophi may also result in subluxation of the joint. Periostitis is absent in joints affected by gout.

RHEUMATOID ARTHRITIS Key points d

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Rheumatoid arthritis (RA) is an inflammatory arthritis with features similar to psoriatic arthritis (PsA), including pain, swelling, morning stiffness, pattern of joint involvement, and extraarticular features Enthesitis is not a feature of RA Swan neck, Boutonniere, and zig-zag deformities characterize RA and may distinguish it from PsA Serologic markers in the appropriate clinical context are useful in establishing a diagnosis of RA and distinguishing it from PsA Symmetry of marginal erosions and absence of periostitis noted on plain radiographic film serve to distinguish RA from PsA

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Fig 12. Polyarticular gout. A psoriasis patient with asymmetric polyarticular gout involving several joints of the fingers, a presentation which may be mistaken for psoriatic arthritis.

Epidemiology RA affects individuals in their fourth and fifth decades of life. However, unlike PsA, RA increases in incidence with age and affects women three times more often than men. Clinical features. Although RA begins somewhat insidiously, it tends to be unremittingly progressive soon after onset. RA is distinguished by causing intense joint pain that is improved with activity and exercise and aggravated by rest. While all patients with RA complain of morning stiffness, only about half of PsA patients give the same complaint. The stiffness in RA is also more severe and prolonged than most patients with PsA. Although involved joints in RA demonstrate swelling as a result of synovitis and effusion, there is usually no erythema overlying them, as is often the case in PsA.

Patterns of joint involvement In RA, there is inflammatory polyarthritis affecting the hands, wrists, and knees that is uniformly symmetric, whereas joint involvement in PsA tends not to be. Involvement of metacarpophalangeal (MCP) and PIP joints of both hands and the MTP joints of both feet with sparing of DIP joints of the hands and feet are characteristic of RA. In PsA, DIP joints are frequently involved in oligoarticular and polyarticular disease and MCP joints are usually involved in the polyarticular form of the disease. RA tends to affect the same joint in all of the digits, whereas PsA is more likely to affect all of the joints in any one digit. This PsA pattern is referred to as the Ray distribution.

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Fig 13. Tophaceous gout in a patient with psoriasis. Psoriasis patient with gout involving the fourth toe, a presentation that may be mistaken for dactylitis in psoriatic arthritis.

Axial involvement in RA is typically limited to cervical spine disease and is related to inflammatory disease in the atlantoaxial joint with subluxation. There is usually sparing of lumbar spine and sacrum in RA, whereas in PsA, the sacrum and lumbar spine are frequently involved. Enthesitis and dactylitis. Entheseal involvement is not a feature of RA. Associated extraarticular symptoms. Ocular involvement is infrequent in both RA and PsA. Sicca symptoms (epicleritis or scleritis) rather than the uveitis that occurs with PsA is more typical in RA. Patients with RA may have a number of additional extraarticular features that are usually absent in PsA, most notably rheumatoid nodules which occur in at least 20% of RA patients. Other extraarticular features include cutaneous vasculitis, pericarditis, pleuritis, pneumonitis, and interstitial fibrosis of the lungs. Physical examination. Joints in RA are more swollen and tender than joints in PsA. Although inflamed, joints affected by RA tend not to have overlying erythema, unlike the joints in PsA. While the opera glass hand deformity is unique to PsA, the swan neck (hyperextension of PIP joint and compensatory flexion at DIP joint; Fig 14) and Boutonniere (flexion contracture at PIP joint and extension at DIP joint) deformities characterize RA. Zig-zag deformity, in which there is radial deviation of the wrist with ulnar deviation of fingers, is also characteristic in RA (Fig 15). Laboratory tests. Present in more than two thirds of RA patients, RF helps to confirm the diagnosis in an individual with clinical presentation

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Fig 14. Swan neck deformity in rheumatoid arthritis. Hyperextension of the proximal interphalangeal joint and hyperflexion of the distal interphalangeal joint results in a deformity that characterizes rheumatoid arthritis.

Fig 15. Z deformity in rheumatoid arthritis. Z deformity, with radial deviation of the wrist and ulnar deviation of the fingers, is suggestive of rheumatoid arthritis.

suggestive of RA. However, RF is also noted in 5% of healthy adults. Moreover, its frequency increases further with age, and up to 20% of individuals over 65 years of age are seropositive. The serologic presence of RF is also noted in a number of other chronic infectious and autoimmune and inflammatory conditions, including up to 5% to 10% of individuals with PsA.5,43 Antibody to citrullinatedcontaining proteins has significantly improved sensitivity and specificity over RF for establishing the diagnosis of RA. Present in less than 7% of PsA patients,43 citrullinated-containing proteins antibody is a better serologic test than RF to characterize an RA patient with inflammatory polyarthritis and a dermatitis that may mimic psoriasis (ie, seborrheic dermatitis) and to distinguish this presentation from PsA. Imaging findings. In RA, erosions appear early and involve the MCP and MTP joints almost uniformly and symmetrically. This is in contrast to polyarticular PsA, in which some but not all MCP and MTP joints are involved asymmetrically. Erosions in RA tend to stay marginal, whereas in PsA they also move away from the margin towards the center of the joint. Moreover, radiographs of hands affected by RA will feature the Z deformity, showing radial deviation of the wrist and ulnar deviation of fingers. While there is juxtaarticular new bone formation in PsA, bone loss, or osteopenia, is the rule in RA.

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ANKYLOSING SPONDYLITIS Key points d

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Ankylosing spondylitis (AS) has earlier onset of disease than psoriatic arthritis (PsA) AS is largely a disease of the axial skeleton with bilateral sacroiliitis and ascending continuous involvement of the spine

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AS is unremittingly progressive, with more severe pain, stiffness, and limitation in axial movement than PsA Extraarticular symptoms, including iritis, urethritis, and inflammatory bowel disease, are more common in AS than PsA Human leukocyte antigeneB*27 is present in 90% of AS patients, but the allele is also common among patients with PsA Bilateral and symmetrical erosions and sclerosis of the sacroiliac joints, as well as continuous ascending ankylosis of the spine, is noted on plain radiographic film in AS, unlike in most cases of axial PsA

Epidemiology AS, occurring in the second or third decade of life, has an earlier onset of disease than PsA. Also in contrast to PsA, AS affects men at a rate of four to 10 times that of women. Clinical features. AS begins somewhat gradually. In contrast to PsA, AS tends to be more painful and progressive soon after onset. Patients with AS more often progress to full axial ankylosis within years of diagnosis.44 While all patients with AS complain of morning stiffness, only about half of PsA patients give the same complaint. The pain and stiffness in AS tends to be more severe and prolonged, and consequently the limitation in movement is also more restricted in AS as compared with PsA. Patterns of joint involvement. AS is largely a disease of the axial skeleton. As a rule in AS, there is bilateral sacroiliitis, from which ascending involvement of the spine affects vertebrae continuously without skipping. The presence of spondylitis in the absence of sacroiliitis is highly unusual. This is in contrast to PsA, in which spondylitis may occur in the

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absence of sacroiliitis or in which spondylitis may occur before the onset of sacroiliitis. Involvement of peripheral joints in AS, although infrequent, may bear resemblance to patterns in PsA with involvement of larger lower extremity joints such as the knees. Peripheral joint involvement is unusual in primary AS. Enthesitis and dactylitis. Enthesial inflammation is most common in AS with the pelvis and spine as primary sites of involvement, as opposed to both axial and peripheral involvement in patients with PsA. Enthesitis in AS is also continuous from sacrum to cervical spine which contrasts with PsA in which the sacroiliac joint is involved asymmetrically and in which spinal enthuses may be involved discontinuously. Dactylitis is not a feature of AS. Associated extraarticular symptoms. AS is associated with extraarticular features that are typical to the spondyloarthropathies. These include iritis, urethritis, and inflammatory bowel disease. About 10% of patients with AS also have psoriasis without the additional clinical features of psoriatic arthritis. Patients with AS are also susceptible to dilatation of the base of the aorta because of aortitis, and this may also result in cardiac conduction abnormalities. Laboratory tests. HLA-B*27 is present in 90% of AS patients. While it is neither necessary nor sufficient for the diagnosis, the recently published Ankylosing Spondylitis Assessment (ASAS) group criteria for spondyloarthritis relies on the presence of HLA-B*27. CRP is elevated in half the patients with AS making it an unreliable biomarker to detect disease, similar to its application to PsA. Imaging findings. AS results in bilateral and symmetrical erosions and sclerosis of the sacroiliac joints, as well as continuous ascending ankylosis of the spine. In PsA, there may be cervical spine involvement with relative sparing of thoracolumbar spine, and even the sacroiliac joints. Because of this, axial function and mobility are more restricted in AS compared with PsA. Syndesmophytes in AS are more delicate but affect the vertebrae continuously, while syndesmophytes in PsA are bulky and affect the spine asynchronously. Peripheral joint erosions in AS, when present, are indistinguishable from erosions in PsA, although periosteal reaction is not typically noted in AS.

CONCLUSION In general, PsA may be suspected in a 30- to 40year-old man or woman with psoriasis and an

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Table V. Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for the diagnosis of psoriatic arthritis The Classification Criteria for Psoriatic Arthritis (CASPAR) criteria consist of established inflammatory articular disease* with at least 3 points from the following features: A. Current psoriasis (assigned a score of 2; all other features are assigned a score of 1) B. A personal history of psoriasis (unless current psoriasis is present) C. A family history of psoriasis (unless current psoriasis is present or there is a personal history of psoriasis) D. Current dactylitis or history of dactylitis recorded by a rheumatologist E. Juxtaarticular new bone formation F. Rheumatoid factor negativity G. Typical psoriatic nail dystrophy including onycholysis, pitting, and hyperkeratosis *Prolonged morning or immobility-induced stiffness and tender and swollen joints suggest an inflammatory joint disease.

asymmetric inflammatory peripheral and/or axial arthritis with enthesitis and dactylitis, prolonged morning stiffness, joint discomfort, erythema and swelling of the involved joints, and periostitis, marginal or central erosions, and characteristic joint deformities. PsA is a disease in which some degree of diagnostic uncertainty for difficult cases exists even among rheumatologists. Although no diagnostic criteria exist, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has developed sensitive and specific criteria, known as CASPAR (Classification Criteria for Psoriatic Arthritis43; Table V), which has been validated among rheumatologists and also in a family practice setting.45 The development and validation of classification criteria for use among dermatologists will be a focus of investigation for GRAPPA. In the interim, dermatologists should remain observant of symptoms and signs that might suggest musculoskeletal involvement, especially given the established morbidities affecting PsA patients.46 It is becoming more evident that the paradigm of managing patients with psoriasis is shifting towards a multidisciplinary approach, and it is important that dermatologists, as early caretakers of psoriasis patients, are attentively aware of signs of comorbidities, especially PsA. We thank Ms Daniella Adrien for her assistance in the preparation of this manuscript and Dr Alpa G. Garg for her expert guidance of our use of radiographic images.

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45. Chandran V, Schentag CT, Gladman DD. Sensitivity and specificity of the CASPAR criteria for psoriatic arthritis in a family medicine clinic setting. J Rheumatol 2008;35:2069-70. 46. Gladman DD, Ang M, Su L, Tom BD, Schentag CT, Farewell VT. Cardiovascular morbidity in psoriatic arthritis. Ann Rheum Dis 2009;68:1131-5.