1
D. Gladman
PSORIATIC ARTHRITIS
Dafna D. Gladman, MD, FRCPC
Professor of Medicine
University of Toronto
Director, Psoriatic Arthritis Program
Deputy Director, Centre for Prognosis Studies in The Rheumatic Diseases
Toronto Western Hospital, University Health Network
Rheumatologist, University Health Network, Mount Sinai Hospital, Consultant
Rheumatologist, Sunnybrook Women's College Health Sciences Centre, Toronto,
Ontario, Canada
Toronto Western Hospital, 399 Bathurst Street MP 1-318, Toronto, Ontario, M5T
2S8.
INTRODUCTION
Psoriatic arthritis is an inflammatory arthritis, associated with psoriasis
(Wright and Moll 1976). Its original definition as seronegative for rheumatoid
factor, has been replaced by "usually seronegative" since as many as 15 per cent of
the general population, particularly over age 60, may have a positive rheumatoid
factor, and rheumatoid factor may be present in more than 10 per cent of patients
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with psoriasis who do not have arthritis (Gladman et al 1986). The majority of
patients with psoriatic arthritis run a benign course. However, in about a fifth of the
patients a chronic, progressive, deforming arthritis may develop, resulting in
significant joint destruction and limitation of daily activities.
EPIDEMIOLOGY
Psoriasis is a chronic skin condition which affects 1-3 per cent of the
population (Greaves and Weinstein 1995). The association between psoriasis and
arthritis might be fortuitous. Since psoriasis is a common condition, and arthritis,
particularly osteoarthritis, is quite prevalent, it is conceivable that psoriasis and
some unrelated form of arthritis may occur in the same patient. Indeed, some
patients with psoriasis do present with a coincidental rheumatoid arthritis, or
osteoarthritis. Cats (1990) has argued that psoriasis is just a measure of disease
expression in certain patients with peripheral arthritis and spondyloarthropathy.
However, epidemiologic evidence described below supports the notion the psoriatic
arthritis is a distinct form of arthritis associated with psoriasis.
Although the first description of arthritis associated with psoriasis was
provided by Aliberti (Eccles and Wright, 1985, O'Neill and Silman, 1994),
psoriatic arthritis was considered to be a variant of rheumatoid arthritis until the
middle of the 20th Century. Epidemiological studies have confirmed the association
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between psoriasis and arthritis. These studies have shown an increased frequency of
arthritis among patients with psoriasis and an increased prevalence of psoriasis
among patients with arthritis. Thus, 6 to 42 per cent of patients with psoriasis may
have psoriatic arthritis (Table 1), while the prevalence of arthritis in the general
population is about 3 per cent. Likewise, the prevalence of psoriasis among patients
with seronegative arthritis is reported to be 20 per cent, while arthritis occurs in only
2 to 3 per cent of the general population (Eccles and Wright, 1985, O'Neill and
Silman, 1994).
Estimates of the prevalence of psoriatic arthritis range from 0.04% in the
Faroe Islands (Lomholt, 1963) to 1.2% in a Swedish study (Helgren, 1969).
Lawrence et al (1989) estimated the prevalence of psoriatic arthritis in the US to be
0.67 per cent. A recent report from Olmstead County (Mayo Clinic) suggests a
frequency of 0.1% (Shbeeb, et al 2000). This variation may be due to the fact that
there are no validated diagnostic or classification criteria for PsA (Gladman,
1995).
The discovery of the rheumatoid factor and its association with rheumatoid
arthritis helped separate psoriatic arthritis as a distinct entity, since patients with
arthritis and psoriasis tended to be seronegative. Radiologic features in psoriatic
arthritis were found to be different from those of rheumatoid arthritis (Avila et al
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1960). A female preponderance was found in rheumatoid arthritis, whereas the
gender ratio among patients with psoriatic arthritis was almost equal (Wright and
Moll 1976, Eccles and Wright, 1985, O'Neill and Silman, 1994). Unlike patients
with rheumatoid arthritis, patients with psoriatic arthritis may present with a
spondyloarthropathy. Psoriatic arthritis is therefore classified with the seronegative
spondyloarthropathies.
The frequency of psoriatic arthritis has been reported in 6 to 42 per cent of
patients with psoriasis (Leczinsky 1948, Little et al 1975, Leonard et al 1978,
Green et al 1981, Scarpa et al 1984, Stern 1985, Zanelli et al 1992, Falk and
Vandbakk 1993, Barišic-Druško et al 1994, Salvarani et al 1995, Baek et al
2000). Since psoriasis may affect 1 to 3 per cent of the population, and as many of
30 per cent of psoriatic patients may develop psoriatic arthritis, almost 1 per cent of
the population may suffer from psoriatic arthritis, which is the expected prevalence
of rheumatoid arthritis, and close to the estimated prevalence of 0.67 per cent
reported for psoriatic arthritis in the United States (Lawrence et al 1989).
Little et al. (1975) and Leonard et al. (1978) suggested that psoriatic
arthritis was more common in patients with severe psoriasis. However, psoriatic
arthritis may precede the diagnosis of psoriasis in about 15 per cent of the patients
(Wright and Moll 1976, Kammer et al 1979, Gladman et al 1987, Jones et al
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1994) (Table 2), and the highest prevalence of psoriatic arthritis was recorded
among patients attending an outpatient dermatology clinic in Cape Town (Green et
al. 1981). Patients with active psoriatic arthritis included in a multicentre drug trial
had mild psoriasis and severity of skin and joint disease did not correlate strongly
among these 225 patients (Cohen et al, 1999). A cross sectional study of 70 patients
with psoriatic arthritis suggested a correlation between the extent of skin and joint
severity only among patients with simultaneous onset of skin and joint
manifestations (Elkayam et al 2000).
CLINICAL FEATURES
Psoriatic arthritis affects women and men almost equally, usually in their
third or fourth decade (Wright 1956, Kammer et al. 1979, Green et al. 1981,
Scarpa et al. 1984, Gladman et al 1987). Nail lesions proved to be the only
clinical feature which may identify patients with psoriasis destined to develop
arthritis (Gladman et al. 1986). These lesions occur in close to 90 per cent of
patients with psoriatic arthritis (Little et al. 1975; Wright and Moll 1976;
Kammer et al. 1979; Green et al. 1981; Gladman et al. 1987) and in 46 per cent
of patients with psoriasis uncomplicated by arthritis (Gladman et al. 1986).
Psoriatic arthritis is inflammatory in nature. It may affect any peripheral
joint, as well as the axial skeleton and the sacroiliac joints. Patients usually present
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with pain, associated with stiffness, which is more marked in the morning, and
improves with activity. Morning stiffness of more than 30- min duration is
documented in more than half the patients (Gladman et al. 1987). Evidence of
inflammation may be detected clinically by the presence of stress pain or joint line
tenderness, as well as effusions (Gladman et al. 1990a), although these signs may
not be as easily detectable as they are in rheumatoid arthritis, since patients with
psoriatic arthritis are less tender than patients with rheumatoid arthritis (Buskila et
al. 1992). The inflamed joints in patients with psoriatic arthritis may have a
purplish-red discoloration, a feature which is not often seen in rheumatoid arthritis.
The effusions in psoriatic arthritis joints tend to be tense, and are often difficult to
detect. There is no predilection to particular joints, with the exception of the distal
interphalangeal joints. Features which appear to differentiate psoriatic arthritis from
rheumatoid arthritis clinically are shown in Table 3.
The spondyloarthropathy may present with an inflammatory type of back
pain, associated with stiffness and improves with activity. Clinical evidence of
sacroiliitis may be obtained by specific tests, including the Gaenslen's manoeuvre,
the FABER (Flexion, Abduction, External Rotation of the hip) test and direct
pressure over the sacroiliac joints (Gladman et al. 1987; Hanly et al. 1988). Some
patients have restricted range of back movements documented by a reduction of
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flexion-extension as well as lateral flexion and rotation (Gladman et al. 1987;
Hanly et al. 1988). Unlike ankylosing spondylitis, many of the patients with
psoriatic spondyloarthropathy are asymptomatic, and demonstrate full range of back
movement (Gladman et al. 1987; Hanly et al. 1988; Gladman et al. 1992b;
Gladman et al. 1993).
Clinical Spectrum of psoriatic arthritis
In their seminal work Wright and Moll (1976) presented five clinical
patterns of psoriatic arthritis: distal arthritis, involving the distal interphalangeal
joints (Fig. 1); an asymmetric oligoarthritis involving small or medium sized joints
in an asymmetric distribution (Fig. 2); a symmetric polyarthritis, indistinguishable
from rheumatoid arthritis; arthritis mutilans, which is a deforming, destructive and
disabling form of arthritis (Figs 3 and 4); and a spondyloarthropathy (Figs 5 and 6).
Similar descriptions have been reported by others (Kammer et al. 1979; Scarpa et
al. 1984; Gladman et al. 1987; Helliwell et al. 1991; Jones et al. 1994; TorreAlonso et al. 1991; Veale et al. 1994b). The frequency of the various patterns has
varied in the literature (Table 2). Although initially the most common pattern was
thought to be asymmetric oligoarthritis (Wright and Moll 1976), polyarthritis has
emerged as the most frequent clinical subset of psoriatic arthritis. In comparison
with rheumatoid arthritis, psoriatic arthritis tends to be characterised as an
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asymmetric form of arthritis. Helliwell et al. (1991) suggested a method for defining
symmetrical involvement in patients with psoriatic arthritis, such that for each level
of joints if the ratio of the number of matched pairs to the total number of joints was
more than 0.5 then the distribution was considered symmetrical. Jones et al. (1994)
showed that using this method more patients were found to have a symmetrical
arthritis, and Helliwell et al. (2000) found no difference in symmetry between
patients with rheumatoid arthritis and psoriatic arthritis. They confirmed that
symmetry was a function of the total number of joints involved. Although the distal
pattern has been described as typical for psoriatic arthritis, its frequency has varied
widely, and some investigators have not been able to identify patients with isolated
distal joint involvement. It has also been recognised that the patterns may change
with time in individual patients (Gladman 1992). A patient may present initially
with an oligoarthritis which later becomes polyarticular, or develop an initial
polyarthritis, which persists in only a few joints. Indeed, Jones et al. (1994)
documented these changes in pattern over time in over 60 per cent of their patients
with psoriatic arthritis. A Spanish study suggested that only two clinical associations
could be defined, namely axial arthritis and peripheral arthritis, in a cross-sectional
study of psoriatic arthritis (Marsal et al, 1999). Unless radiographs are performed
on all patients, joints which had been previously involved may not be identified, and
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the spondyloarthropathy may be missed (Little et al. 1975; Gladman et al. 1987;
Hanly et al. 1988, Battistone et al. 1999).
A typical feature of psoriatic arthritis is the development of dactylitis, which
presents as a swelling of a whole digit, with inflammation involving distal and
proximal interphalangeal, and occasionally the metacarpophalangeal joints (Fig. 7).
Dactylitis occurs in over a third of the patients (Gladman et al. 1987), and appears
to result from extensive inflammation and effusion in the joints of a particular digit,
with an associated tenosynovitis. Ultrasonography demonstrated the presence of
both synovitis and tenosynovitis in digits affected by dactylitis (Kane et al, 1999).
Tenosynovitis is also a feature of psoriatic arthritis. As in the other
spondyloarthropathies, such as Reiter's syndrome and ankylosing spondylitis,
Achilles tendinitis, heel pain, and plantar fascitis are common among patients with
psoriatic arthritis.
Enthesitis, or inflammation at sites of tendon insertion, is
frequent, particularly at the Achilles tendon, the insertion of the plantar fascia, and
ligamentous insertions around the pelvic bones. These are commonly diagnosed
radiologically as spurs (Fig. 8). Recent studies support a role for ultrasonography in
identifying involvement of the tendons and entheses in patients with psoriatic
arthritis.(Lehtinene et al. 1994; Galluzzo et al 2000). Isolated enthesitis and
dactylitis may constitute a specific subset of psoriatic arthritis, even in the absence
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of peripheral joint involvement (Salvarani et al 1997). McConagle et al (1999)
proposed that psoriatic arthritis be considered an enthesopathic disease.
The Spondyloarthropathy of psoriatic arthritis
The frequency of spinal involvement in psoriatic arthritis has varied from 2
per cent, as isolated back disease, to as high as 78 per cent, when associated with
peripheral arthritis (Wright and Moll 1976; Lambert and Wright 1977; Kammer
et al. 1979; Scarpa et al. 1984; Gladman et al. 1986; Gladman et al. 1987;
Hanly et al. 1988; Moll 1994; Battistone et al. 1999, Baek et al, 2000).
Lambert and Wright (1977), found that 40 per cent of 130 patients with psoriatic
arthritis had back involvement, based on back pain and reduced spinal mobility.
Gladman et al. (1987), documented spinal involvement, based on both clinical and
radiological evidence, in 35 per cent of their patients at their first visit to the
psoriatic arthritis clinic.
This number increased to 51 per cent at follow-up
(Gladman et al. 1992b). In both studies patients with spinal involvement tended to
be male and older than patients without back involvement. Among patients
participating in a multicentre trial who underwent sacroiliac radiography, 78% were
found to have at least grade 2 sacroiliitis (Battistone et al. 1999). Among Korean
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patients with psoriatic arthritis spondyloarthropathy was detected in 50%, and it
may even be higher if the patients with psoriasis who had radiographic changes of
sacroiliitis were included among the psoriatic arthritis group (Baek et al, 2000).
The spondyloarthropathy of patients with psoriatic arthritis is less severe
than that seen in ankylosing spondylitis (Hanly et al. 1988; Scarpa et al. 1988;
Scarpa 2000). This is evidenced by the lower frequency of symptomatic neck and
back disease, as well as less limitation of movement and grade 4 sacroiliitis in
patients with psoriatic arthritis compared to those with ankylosing spondylitis
(Gladman
et
al.
1993).
Moreover,
among
patients
with
psoriatic
spondyloarthropathy, there are gender-related differences in disease expression, with
more advanced spondyloarthropathy noted among men (Gladman et al. 1992b).
The cervical spine in psoriatic arthritis received special attention in two
recent studies. Salvarani et al. (1992a) studied 57 patients with psoriatic arthritis,
of whom 70 per cent had radiological evidence of cervical spine disease. They
identified a high prevalence (23 per cent) of atlanto-axial subluxation. Jenkinson et
al. (1994) detected cervical spine disease in 57 per cent of their patients with
psoriatic arthritis, of whom only 3 had atlanto-axial subluxation. The majority of
their patients had spondylitic type changes with apophysial joint narrowing or fusion
and syndesmophytes.
In both these studies neck involvement was related to
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prolonged disease duration. Jeannou et al (1999) found the frequency of neck pain
much higher among 30 patients with psoriatic arthritis (73%) than in 30 controls of
the same age but who had “common low back pain” (26%). Moreover, among the
psoriatic arthritis patients the neck pain was inflammatory in nature in 63.6%
compared with only 12.5% of the controls. However, on radiographs none of their
subjects had syndesmophytes while 3 patients had atlanto-axial subluxation.
EXTRA-ARTICULAR FEATURES
Skin psoriasis
Skin psoriasis consists of an erythematous scaly area that varies from a
localized plaque on the elbows and knees to an incapacitating, generalized skin
involvement with significant effect on the cardiovascular and heat regulating
mechanism (Goodfield 1994). The skin lesions are classified as: typical psoriasis
vulgaris, with major involvement of the extensor surfaces; inverse psoriasis,
affecting the flexural areas; pustular psoriasis, which may be localized to the palms
and soles, or may be of the more generalized serious form called Von Zambush, and
which may pose a threat to life; and the erythrodermic generalized group. The
majority of patients with psoriatic arthritis demonstrate the classic psoriasis vulgaris
pattern (Wright et al. 1979; Gladman et al. 1986; Gladman et al. 1987). All areas
of the skin may be affected, including the mucosa and the nails. Nail lesions include
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pitting, ridging and onycholysis (Wright and Moll 1976). Two or all of these
features in the same patient are in favour of a psoriatic origin for the nail dystrophy
(Eastmond and Wright 1979). As already mentioned, nail lesions are particularly
common among patients with psoriatic arthritis (Gladman et al 1986). Nail lesions
were associated with DIP joint disease in one study (Cohen et al 1999).
Other extra-articular features
The extra-dermal extra-articular features of psoriatic arthritis are similar to
the features described in other seronegative spondyloarthropathies and include iritis,
which may occur in 7 per cent of the patients (Gladman et al. 1987). Uveitis
associated with psoriatic arthritis was more insidious in onset, posterior, persistent,
and more likely to be bilateral than when associated with other spondyloarthropathy
(Paiva et al, 2000). Mouth ulcers, urethritis, colitis, and aortic valve disease may
also complicate psoriatic arthritis (Wright and Moll 1976). A case of a patient
with psoriatic arthritis with pyoderma gangrenosum was described (Smith and
White 1994), and we have seen a case in our psoriatic arthritis clinic.
The
development of lymphoedema of the upper limb in patients with psoriatic arthritis
has also been described (Mulherin et al. 1993). Cantini et al. (2001) identified
distal extremity swelling with pitting edema in 39/183 (21%) PsA patients and in
18/366 (4.9%) rheumatology clinic controls which excluded spondyloarthropathy
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(p < 0.0001). They concluded that Upper or lower distal extremity swelling with
pitting edema due to tenosynovitis, usually unilateral, is a common feature in PsA
patients and may represent the first, isolated manifestation of the disease
LABORATORY INVESTIGATIONS IN PSORIATIC ARTHRITIS
There are no specific laboratory tests diagnostic for psoriatic arthritis.
Anaemia occurred in 14 per cent of the patients presenting to the psoriatic arthritis
clinic (Gladman et al. 1987), and at a higher level at follow-up (Gladman et al.
1990b), and was thought to represent the untoward effect of these drugs. Elevated
white- cell counts and other acute phase reactants, may also be present (Gladman et
al. 1987). Elevated sedimentation rates may be seen in more than 40 per cent of
patients with psoriatic arthritis, and likely reflect both joint and skin inflammation
(Gladman et al. 1986; Gladman et al. 1987). Hyperuricemia occurred at least
once in 20.7% of a cohort of 265 patients with PsA followed prospectively over a
6-year period (Bruce et al, 2000). Although it has been thought to result from the
high turnover of skin cells there was no correlation between skin severity and uric
acid levels. Since both psoriasis and gout may occur in young males, one must rule
out the possibility that the arthritis is crystal induced, before making the diagnosis of
psoriatic arthritis in a patient with psoriasis. On the other hand, the presence of an
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acute monoarthritis, even in the first metatarsophalangeal joint in the presence of
psoriasis does not mean the patient has gout. In both these situations a careful
search for negatively birefringent, uric acid crystal should be carried out on the fluid
obtained by joint aspiration.
Patients with psoriatic arthritis are usually seronegative for rheumatoid
factor. However, in each series of patients with psoriatic arthritis there are about 10
to 15 per cent of the patients who have a positive rheumatoid factor, albeit in a low
titre. In addition, patients with psoriasis uncomplicated by arthritis demonstrate the
same frequency of positive rheumatoid factor, despite the fact that they are younger
on average than the patients with psoriatic arthritis (Gladman et al. 1986).
Antinuclear factor has also been demonstrated in the sera of patients with
uncomplicated psoriasis and patients with psoriatic arthritis, in the same frequency
(Gladman et al. 1986). Whether this antinuclear antibody reflects the presence of
antibodies to stratum corneum antigens is unclear (Gladman 1985).
RADIOLOGIC FEATURES OF PSORIATIC ARTHRITIS
Radiologic abnormalities may be seen in both peripheral joints and the axial
skeleton in patients with psoriatic arthritis (Resnick and Niwayama 1981). The
features commonly associated with psoriatic arthritis and which help differentiate it
from rheumatoid arthritis include: absence of juxta-articular osteoporosis; the
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predilection for distal interaphlangeal joints; "whittling" (lysis) of terminal
phalanges (Fig. 9); lack of symmetry; gross destruction of isolated joint; "pencil-incup" appearance (Fig. 10); ankylosis (Fig. 10); fluffy periostitis (Fig. 11); both
classical and atypical spondylitis (Wright and Moll 1971; Resnick and Niwayama
1981; Fig 5, 6 and 7). However, a direct comparison of radiographs of patients with
rheumatoid arthritis and patients with psoriatic arthritis matched for age and disease
duration, the differences were not obvious (Rahman et al, 2001).
DIAGNOSIS OF PSORIATIC ARTHRITIS
There are no available diagnostic criteria for psoriatic arthritis (Gladman
1995). The European Spondyloarthropathy Study Group preliminary criteria for
the classification of the spondyloarthropathies were only 65% sensitive for
psoriatic arthritis (Salvarani et al 1995). A new classification based on a
comparison of clinical and laboratory features of 100 patients with psoriatic
arthritis, 80 patients with ankylosing spondylitis and 80 patients with rheumatoid
arthritis identified 9 criteria which were 95% sensitive and 98% specific for
psoriatic arthritis in the study population (Fournie et al, 1998). These criteria
include the presence of psoriasis either in the patient or a relative, distal joint
arthritis, inflammatory spinal involvement, asymmetric oligoarthritis, enthesitis,
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the presence of one of 5 radiological digit criteria, the presence of a relevant HLA
antigen and a negative rheumatoid factor. The proposed criteria would be difficult
to achieve at the bedside as they require both laboratory and radiological evidence.
Moreover, the criteria still require confirmation in an additional, larger patient
cohort.
None the less, the diagnosis of psoriatic arthritis is generally based on the
definition of the disease: an inflammatory arthritis in the presence of psoriatic skin
lesions, usually seronegative for rheumatoid factor. In a patient with psoriasis, the
development of an inflammatory arthritis makes the diagnosis easier. The clinical
and radiologic features described above help identify the patient with psoriatic
arthritis who had not previously demonstrated skin lesions. Thus, a patient who
presents with an asymmetric oligoarthritis, or an inflammatory polyarthritis which
includes
distal
interphalangeal
joints,
or
peripheral
arthritis
with
a
spondyloarthropathy, should be investigated for the presence of psoriasis, and
psoriatic arthritis should clearly be considered in the differential diagnosis. The
presence of dactylitis is certainly helpful, as is the presence of enthesitis. The skin
lesions may be minimal, and indeed "hidden". One must therefore search for
these lesions, particularly in the umbilical area, the anal cleft, the groin, the scalp,
and the ears. Nail lesions are not always recognised by the patient, and should be
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looked for carefully. The common occurrence of distal joint involvement means
that psoriatic arthritis needs to be differentiated from osteoarthritis. The distal
interphalangeal lesions in patients with psoriatic arthritis are inflammatory in
nature, and tend to be swollen, such that for the most part they can be
differentiated clinically as softer than the hard bony enlargement of Heberden's
nodes. The presence of more proximal joint involvement, particularly the wrist
and metaacrpophalangeal joints also helps distinguish psoriatic arthritis from
osteoarthritis. However, osteoarthritis is a common condition, particularly with
advancing age, and a patient may have Heberden's nodes complicating preexisting psoriatic arthritis. Reiter's disease occasionally presents a diagnostic
difficulty. The skin lesions in pustular psoriasis may be indistinguishable both
clinically and pathologically from those of Reiter's syndrome, and the clinical
features of the arthritis and the spondyloarthropathy are similar. Psoriatic arthritis
tends to be polyarticular, which may help. Iritis and mucous membrane lesions
may be more common in Reiter's disease.
PATHOGENESIS OF PSORIATIC ARTHRITIS
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Although the exact pathogenesis of psoriatic arthritis remain to be elucidated,
factors thought to be important include environmental genetic, and immunologic
((Gladman 1992; Abu-Shakra and Gladman 1994).
Genetic factors
A family history of the skin or joint disease in first-degree family members is
obtained in more than 40 percent of patients with psoriatic arthritis (Gladman et al.
1986; Gladman et al. 1987). Moll and Wright (1973) identified the prevalence
of psoriatic arthritis among first degree relatives of 88 probands with the disease
at 5.5% compared to the calculated prevalence in the UK population of 0.1%.
Population based studies and twin studies support the genetic contribution in
psoriasis (Espinoza 1985; Eastmond 1994). Segregation studies in psoriasis
conclude that a polygenic or a multifactorial pattern is the most likely mode of
inheritance (Bhalerao and Bowcock 1998).
Population studies in psoriasis revealed an increased frequency of HLA
antigens B13, B17, B37, Cw6 and DR7 (Espinoza 1985; Gladman et al. 1986;
Eastmond 1994). In psoriatic arthritis, increased frequencies of HLA-B13, B17,
B27, B38, B39, DR4 and DR7 have been reported (Espinoza 1985; Gladman et al.
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1986; Sakkas et al. 1990). Gladman et al. (1986) compared 158 patients with
psoriatic arthritis to 101 patients with uncomplicated psoriasis. They found that the
HLA-B7 or B27 antigen were more common among patients with psoriatic arthritis,
whereas B17, Cw6 and DR7 were more common among patients with
uncomplicated psoriasis. HLA-B27 has clearly been associated with back disease in
psoriatic arthritis, thus lending further credence to its grouping with the HLA-B27associated spondyloarthropathy.
HLA-DR4 appears to be associated with the
peripheral articular pattern of psoriatic arthritis (Gladman et al. 1986). No specific
T-cell receptor genes unique to the disease were identified (Sakkas et al.1990), but
immunoglobulin heavy chain gene (IgH) on chromosome 14q32 may confer
susceptibility to arthritis in patients with psoriasis (Sakkas et al. 1991).
Several genetic loci have been identified in family investigations in
psoriasis, including loci on chromosome 17q (Tomfohrdre et al. 1994; Nair et
al. 1997), 4q (Matthews et al. 1996) and 6p (Burden et al. 1996; Trembath et
al. 1997; Leder et al. 1998; Samuelsson et al. 1999; Veal et al. 2001), and 1p
(Veal et al. 2001). The strongest association by far is with loci on chromosome
6p. An analysis of all families for whom complete data was available in the
literature suggests that HLA-B locus is in linkage disequilibrium with the
PSORS1 gene (Leder et al. 1998). However, the exact location and nature of
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PSOR1 on 6p is unclear. Similar studies are currently underway for psoriatic
arthritis.
Environmental Factors
Infection
Support for the role of bacterial antigens in the pathogenesis of psoriasis and
psoriatic arthritis comes from indirect observations of enhanced humoral and
cellular immunity to Gram-positive bacteria typically found in the psoriatic plaques
(Vasey 1985). However, psoriatic plaques often get secondarily infected, thus the
cause-effect relationship of bacteria and psoriasis is complicated. Moreover,
investigators have demonstrated that there is no specific role for streptococcal
responsive synovial T lymphocytes psoriatic arthritis (Grinlinton et al. 1993,
Thomssen et al. 2000). However, Prinz (2001) recently pointed out the possibility
that an infectious agent may have triggered the psoriatic process, and the
immunological response seen in patients with both psoriasis and psoriatic arthritis
may be the result of molecular mimcry between streptococcal antigens and
epidermal autoantigens.
The exacerbation of psoriasis and psoriatic arthritis seen in the context of
acquired immunodeficiency virus infection is intriguing (Vasey et al. 1989). The
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possibility that psoriatic arthritis might be virus induced has been proposed
(Luxembourg et al. 1987). Hepatitis C virus has been detected more commonly
among patients with psoriatic arthritis, but its role in the pathogenesis of the disease
cannot be confirmed (Taglione et al, 1999).
Trauma
In almost all accounts of psoriatic arthritis there are reports of patients whose
arthritis developed after trauma. However, the majority of the reports are anecdotal
case reports (Punzi et al., 1998). A case series was reported Scarpa et al. (1992)
who found that trauma of some type preceded the diagnosis of psoriatic arthritis in 9
per cent of the cases, whereas in rheumatoid arthritis it was found in only 1 per cent
of the patients, suggesting a role for trauma in some patients with psoriatic arthritis.
Whether this represents an internal Koebner phenomenon (the appearance of
psoriasis at sites of cutaneous injury due to trauma) is unclear. However, substance
P, a neuropeptide, and vasoactive intestinal peptide are over expressed in psoriatic
skin lesions and in psoriatic synovium (Veale et al. 1993a)
Immunological mechanisms
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The clinical and pathological features of both psoriasis and psoriatic arthritis
support the role of immunological factors in the pathogenesis of these conditions.
The inflammatory nature of the disease, the cellular infiltrates seen both in skin and
joint lesions, and the deposition of immunoglobulins in the epidermis as well as the
synovial membrane, all support an immune mechanism (Panayi 1994).
Psoriasis is characterised histologically by keratinocyte proliferation,
vascular changes and the presence of T Lymphocytes in affected skin (Gottlieb
1988). T lymphocytes, particularly CD8+ cells, are thought to play a prime role in
its pathogenesis. Activated T cells have been noted in the affected tissues (both skin
and joints) in psoriatic arthritis by most investigators (Gladman 1993; Veale et al.
1993b; Panayi 1994; Veale et al. 1994a). In an animal model, a severe combined
immunodeficient (SCID) mouse with grafted unaffected human skin, injection of
activated T cells from affected individuals causes psoriasis to develop in the grafted
and surrounding skin (Wrone-Smith and Nickoloff 1996). A predominance of
CD8+ T lymphocytes with clonal expansion was documented in the synovial fluid
from patients with psoriatic arthritis (Costello et al, 1999). Examination of T cell
antigen receptor beta chain variable (TCRßV) gene repertoires in skin and synovium
reveal common expansions in both sites, suggesting that a common antigen may act
as a trigger for disease in both tissues (Tassiulas et al. 1999). PsA synovial explants
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produced more IL-1, IL-2, IL-10, IFN- and TNF- than those of rheumatoid
arthritis or osteroartrhitis. Levels of IL-1, IFN-, IL-10 were higher in synovial
tissue than dermal plaques from patients with PsA (Ritchlin et al., 1998). Thus
cytokines secreted from activated T cells and other mononuclear proinflammatory
cells induce proliferation and activation of synovial and epidermal fibroblasts,
leading to the fibrosis reported in patients with longstanding psoriatic arthritis. This
is also consistent with the prominent ankylosis seen both clinically and
radiologically in patients with psoriatic arthritis. The effect of anti-cytokine therapy
further supports the role of cytokines in this disease. Anti-TNF agents have been
shown to work in both psoriasis (Chaudhari et al. 2001) and psoriatic arthritis
(Mease et al, 2000)
The role of metabolites of arachidonic acid, such as prostaglandins and
particularly leukotrienes, in the pathogenesis of both psoriasis and psoriatic arthritis
has been proposed. Increased levels of Leukotriene B4 in the psoriatic skin lesions
have been noted, and injections of this compound has caused intraepidermal
microabscesses. Greaves and Camp (1988) proposed an integrated approach to
inflammation of human skin, considering both the lipoxygenase system, platelet
activating factor and cytokines. However, studies in both psoriasis (Soyland et al,
25
D. Gladman
1993) and psoriatic arthritis (Veale et al. 1994c) failed to demonstrate clinical
improvement in either skin or joint manifestations in patients treated with fish oil.
TREATMENT OF PSORIATIC ARTHRITIS
The treatment modalities employed in psoriatic arthritis are in part based on the
pathogenetic mechanisms discussed above.
These are based on control of
inflammation, and an attempt to modify the immunological mechanisms thought to
be operating in this disease (Gladman and Brockbank 2000).
The treatment of psoriasis
The treatment of psoriatic arthritis includes treatment for the skin condition as well
as treatment for the joint disease.
The skin lesions are treated by topical
medications, aimed at controlling the inflammation and skin proliferation, including
tar, anthralin and corticosteroids. In refractory cases, systemic medications such as
methotrexate PUVA (psoralen and ultraviolet A light), retinoic acid derivatives and
more recently cyclosporin are used (Greaves and Weinstein 1995).
The treatment of psoriatic arthritis
Non steroidal anti-inflammatory therapy
26
D. Gladman
The initial treatment for psoriatic arthritis consists of non-steroidal antiinflammatory drugs (NSAIDs), including enteric-coated acetylsalicylic acid
(ECASA), ibuprofen, naproxen, indomethacin, tolmetin, piroxicam, diclofenac
sodium and other NSAIDs (Gladman and Brockbank 2000). In patients with
significant peripheral arthritis, medications such as ECASA, ibuprofen, naproxen or
diclofenac sodium might be preferred. However, for the spondyloarthropathy,
indomethacin or tolmetin would be more appropriate. The latter two drugs would
also be appropriate if morning stiffness is prolonged, and may be used in
conjunction with other NSAIDs. Several of the NSAIDs have been incriminated in
exacerbating the psoriasis, perhaps through the prostaglandin mechanism. It may
therefore be necessary to change medications if an exacerbation of psoriasis occurs.
The newer cycloxygenase-2 (COX-2) selective inhibitors recently released for the
treatment of rheumatoid arthritis and osteoarthritis, including celecoxib,
rofeocoxib and mobicoxib have not been adequately tested in psoriatic arthritis,
and do not appear to be any more effective that the previously available NSAIDs.
It remains to be determined whether they have an adverse effect on the skin
lesions.
Disease modifying drugs for psoriatic arthritis
27
D. Gladman
If the arthritis persists despite the use of non-steroidal anti-inflammatory
medications, disease-modifying anti-rheumatic drugs are added.
Gold
Gold has been studied in a controlled fashion in psoriatic arthritis, using either
intramuscular (Dowart et al. 1978) or oral (Carrett and Calin 1989) preparations.
Intramuscular preparation has been proven superior to the oral gold in patients with
psoriatic arthritis (Palit et al. 1990). However, although gold may control the
inflammatory process in patients with psoriatic arthritis, it has not prevented
progression of erosive disease over a 2-year period (Mader et al. 1995).
Penicillamine
Penicillamine has also been used successfully in psoriatic arthritis (Roux et al.
1979). Both gold and penicillamine are quite slow acting, however, requiring at
least 6 months for a therapeutic effect. Therefore, other medications, whose onset of
action is faster have been tried.
Antimalarials
Although physicians have been reluctant to use antimalarials because of anecdotal
reports of flares of psoriasis, and despite the lack of controlled trials, both
chloroquine phosphate and hydroxychloroquine have been used (Kammer et al.
1979). Indeed, chloroquine has been shown to reduce disease activity in patients
28
D. Gladman
with psoriatic arthritis over a period of 6 months, and the frequency of psoriatic
flares was no greater than that observed in the control group (Gladman et al.
1992a).
Methotrexate
Methotrexate, which has been found to be effective in controlling the skin psoriasis,
has been used in psoriatic arthritis since 1964, when Black et al. (1964), performed
a double-blind study of 21 patients using parenteral methotrexate. There have been
two controlled trials using low-dose weekly methotrexate in psoriatic arthritis.
Willkens et al. (1984) demonstrated improvement in grip strength, morning
stiffness and joint count in patients with psoriatic arthritis, and physician global
assessment was improved in the methotrexate group at 3 months, but only physician
global assessment was significantly higher in the methotrexate group compared with
the placebo. Zacharia and Zacharia (1987) found significant improvement in pain
and functional scores as well as a decrease in the erytherocyte sedimentation rate
during treatment with low-dose weekly methotrexate for psoriatic arthritis.
Espinoza et al. (1992), in a retrospective uncontrolled study of 40 patients with
psoriatic arthritis treated with a mean of dose of 11.2 mg/week of methotrexate
during a mean period of 34 months, found that 37 per cent of the patients had an
excellent response (no evidence of active synovitis) while 58 per cent had a good
29
D. Gladman
response (no more than 4 active joints and a decrease of at least 50 per cent in the
number of those previously involved). Only two patients had discontinued the drug
because of toxicity; one leucopenia and the other stomatitis.
Eleven patients
developed liver test abnormalities, however, cirrhosis related to methotrexate was
not noted. Abu-shakra et al. (1995) found that while methotrexate reduced the
actively inflamed joint count in patients with psoriatic arthritis, it did not prevent
disease progression in these patients over a period of 2 years of treatment. None the
less, methotrexate is used regularly for the treatment of psoriatic arthritis,
particularly in the face of severe psoriasis. Methotrexate has an advantage over gold
and penicillamine since it is effective within a few weeks. In addition, because it is
given as an intermittent dose, once a week, patients prefer to take it over
medications which are required daily, and often in repeated doses. Concerns about
severe liver disease resulting from methotrexate therapy which resulted from reports
in the late 1960s and early 1970s seem to have been alleviated since more judicious
use of intermittent dose has become commonplace. The use of either folic acid or
folinic acid has also reduced some of the side effects of methotrexate.
Sulphasalazine
Sulphasalazine has been shown in several double-blind placebo-controlled trials to
be effective in psoriatic arthritis (Farr et al 1990.; Fraser et al. 1993, Combe et al.
30
D. Gladman
1996; Clegg et al. 1998). However, the effect has been modest (Jones et al 2000).
A recent study in an outpatient clinic reported that 44% of the patients who started
on Sulphasalzine were unable to tolerate it, and that there was no long-term
advantage in terms of erosive disease (Rahman et al. 1998).
Azathioprine
Azathioprine has also been used in psoriatic arthritis (Levy et al. 1972, Lee et al.
2001), but since its effect on the psoriasis is not well recognized, it has not been as
useful as it is in rheumatoid arthritis. The use of azathioprine in patients with
psoriatic arthritis who had not responded or were unable to tolerate methotrexate
was recently described (Lee et al. 2001), with encouraging results. However,
compared to other medications used azathioprine was not found to have an
advantage in preventing damage in patients with psoriatic arthritis.
Retinoids
Retinoids have only been studied in uncontrolled fashion, since it is difficult to blind
both patients and observers to their side effects (Klinkhoff et al. 1989). While
these drugs may be effective against both skin and joint manifestations, their toxicity
appears high.
Cyclosporin A
31
D. Gladman
Cyclosporin A has been studied as a therapeutic option for both psoriasis and
psoriatic arthritis (Gupta et. al 1989, Salvarani et al. 1992b). In a comparative
study with methotrexate there was significant improvement in the skin and joints
of both groups, with no significant difference between them. However there was a
higher withdrawal rate in those patients on cyclosporin (Spadaro et al 1995).
Although it has been suggested that it is effective and safe, NSAIDs cannot be used
concomitantly. Moreover, its adverse effects, particularly on the kidney, preclude its
wide spread use.
Steroids
Oral steroids are usually avoided in psoriatic arthritis, since upon dose reduction
they can cause significant flares of the skin psoriasis (Griffith 1997). However,
intra-articular steroids may be used at any time, especially when there is a joint
which is particularly inflamed.
We tend to avoid injecting joints which are
surrounded by psoriatic plaques because of fear of causing infections.
Anti-TNF agents in psoriatic arthritis
The development of anti-TNF agents for the treatment of rheumatoid arthritis which
was based on a proposed role for TNF in the pathogenesis of the inflammatory
process opened up new avenues for the treatment of both skin and joint
manifestations of psoriatic arthritis. Etanercept is a recombinant human protein,
32
D. Gladman
consisting of two TNF receptor p75 fused with the FC domain of human IgG1.
Consequently it binds TNF and inactivates it. A double-blind controlled trial of 60
patients with psoriatic arthritis, half of whom were also on methotrexate
demonstrated an remarkable improvement in the psoriatic arthritis response
criteria (87% compared to 27% in the placebo group) which was much better than
in the study of sulfasalazine in psoriatic arthritis for which the criteria were
developed (Clegg et al 1998; Mease et al 2000). A follow-up open-label study
further demonstrated the efficacy of etanercept in patients who were randomized
to placebo in the original trial. In this group 65% responded to etanercept. A larger
multicentre randomized controlled trial of etanercept in psoriatic arthritis is
currently being completed. Etanercept is given subcutaneously at a dose of 25 mg
twice a week. Patients can self inject. It is relatively safe, with injection site
reactions being the commonest side effects. However, there is a concern about
susceptibility to infection. Infliximab is a human/mouse chimeric anti-TNF-
antibody that blocks TNF from reaching its receptor. It has also been proven
effective in rheumatoid arthritis. Infliximab is also given parentrally, however, it
is given by infusion which is more difficult for the patients since they require to
attend a medical centre at 6-8 week interval for at least 2 hours. Infliximab was
recently demonstrated to be effective in the treatment of severe psoriasis
33
D. Gladman
(Chaudhari et al. 2001). There are few case series of its use in psoriatic arthritis.
It was given to 10 patients in Germany with good response (A&R 2000). We have
had an opportunity to treat 15 patients with severe psoriatic arthritis with
infliximab. Seven of the 15 demonstrated greater than 70% reduction in the
number of actively inflamed joints. The majority demonstrated excellent response
of their skin. However, 5 patients had to discontinue the drug because of adverse
effects, which included infection, rectal bleeding, and allergic reactions.
Infliximab has been associated with allergic reactions that are thought to result
from antibody formation to the foreign protein. Recently there has been concern
about reactivation of pulmonary tuberculosis by anti-TNF agents. It is possible
that newer anti-TNF agents such as a completely human anti-TNF antibody and
TNF receptor to p55 as well as p75 will be available for the treatment of psoriatic
arthritis.
There are other biologic agents currently under study for psoriasis, including an
anti-CD11 antibody, CTLA4-Ig. They have yet to be investigated for psoriatic
arthritis.
Dietary modification
34
D. Gladman
Based on the proposed pathogenesis of both psoriasis and psoriatic arthritis, there
may be a role for fish oil preparations or specific immunomodulators in the
treatment of both psoriasis and psoriatic arthritis. However, a placebo controlled
trial of Efamol marine demonstrated no efficacy in psoriatic arthritis (Veale et al.
1994c). The use of oral vitamin D3 for the treatment of psoriatic arthritis has also
been proposed (Huckins et al. 1990).
Other medications
Psoralen and ultraviolet A light has been used in psoriatic arthritis with some
success (Perlman et al. 1979).
More recently, the use of extracorporeal
photochemotherapy has been proposed (de Misa et al. 1994). Buskila et al. (1991)
described a woman with psoriatic arthritis, who experienced a remarkable
improvement of her arthritis while she was taking bromocriptine for primary
infertility due to hyperprolactinemia. Others have also reported similar results.
Peptide T has also been advocated for the treatment of psoriatic arthritis, but
information is currently available only from case reports (Abu-Shakra and
Gladman 1993).
Physiotherapy and occupational therapeutic modalities should be used both
for symptomatic relief and to avoid development of deformities. Patients may
require splints, and need to be instructed as to energy conservation and joint
35
D. Gladman
protection. In patients with the spondyloarthropathy specific back exercises may be
necessary.
Surgery
Surgery is reserved for patients whose joints have become deformed and damaged.
Of 444 patients with psoriatic arthritis followed prospectively 31 (7%) had
musculoskeletal surgery at an average of 13 years after the onset of joint disease. A
high number of actively inflamed joints and advanced radiological damage at first
assessment were highly predictive of subsequent surgery (Zangger et al 1998).
Seventy-one procedures were performed in 43 patients at one centre during a 10
year period (Zangger et al. 2000). Among patients with polyarticular disease a
variety of procedures were performed including complex hand and foot surgery, hip
replacements and fusion of individual joints, whereas patients with oligoarticular
disease tended to have hip and knee replacements. Four procedures led to
complications: an infection in a hip arthroplasty which required removal of the
prosthesis, a malunion of an ankle arthrodesis which required correction, a lack of
fixation in a PIP joint which was corrected within 12 days, and a death from an
undiagnosed
hepatic
hemangioma.
An
approach
to
the
treatment
of
temporomandibular joint disease in psoriatic arthritis has been described (Peterson
36
D. Gladman
and Shepherd 1992). Hicken et al. (1994) reported their experience of 27 forefoot
and toe arthroplasty or arthrodesis procedures in 17 patients with psoriatic arthritis
collected over a 15-year period. The operations were considered successful in 89 per
cent of the cases but they did not use standardized methods for assessing functional
outcome. Complications occurred in a patient who had a local infection associated
with a local flare of psoriasis and required corrective surgery, another patient who
required an additional procedure, and a third patient who had delayed union.
THE COURSE AND PROGNOSIS OF PSORIATIC ARTHRITIS
The course of psoriatic arthritis is variable. There are patients who have few
episodes and who recover completely (Gladman et al 2001), but in many the
disease is persistent. Roberts et al. (1976) concluded in their follow-up study that
"apart from the deforming group the arthritis was not notably progressive".
However, there was time lost from work in at least 60 per cent of all patients, and
radiologic progression was recorded in about 15 per cent. Stern (1985) noted that
more than 50 per cent of the patients with psoriatic arthritis had some limitation on
their daily activities, and they were twice as likely to be unemployed as patients with
other joint disease. Hanly et al. (1988) and Gladman et al. (1990b), suggested that
the disease is progressive, based on the increased number of deformed and damaged
37
D. Gladman
joints observed in their patients, who were followed according to a standard protocol
in the University of Toronto Psoriatic Arthritis Clinic, where clinical measures of
inflammatory activity as well as damage have been validated (Gladman et al.
1990a). Coulton et al. (1989) reported on the outcome of 40 patients hospitalised
for psoriatic arthritis who were followed for a mean of 8 years. At the end of that
period, none of the patients died. However, 35 per cent of their patients were in
Steinbrocker's classes III and IV, supporting the notion that a proportion of patients
with psoriatic arthritis become disabled.
Clear evidence of progression of
deformities was demonstrable when patients were compared at presentation and at
follow-up based on duration of follow-up at the psoriatic arthritis clinic (Gladman
1994). Gladman et al. (1995) studied 305 patients who entered the psoriatic
arthritis clinic with less than ten deformed joints, and identified clinical indicators
for progression through four stages: no deformities, one to four deformities, five to
nine deformities and ten or more deformities. Patients who had five or more effused
joints at presentation to the clinic were more likely to progress, as were patients
treated with disease-modifying drugs, while patients who had a low erythrocyte
sedimentation rate were less likely to develop more deformities during follow-up.
There was no correlation with disease duration. Moreover, Gladman and Farewell
(1995) demonstrated that the HLA antigens B27 in the presence of HLA-DR7,
38
D. Gladman
HLA-B39 and HLA-DQw3 in the absence of HLA-DR7 were more important than
the clinical features in predicting such progression. The same investigators further
demonstrated that the number of actively inflamed joint at each visit is an important
predictor of subsequent clinical damage in patients with psoriatic arthritis
(Gladman and Farewell 1999).
Psoriatic arthritis may no longer be considered a mild form of arthritis.
Patients with psoriatic arthritis have an increased mortality risk compared to the
general population (Wong et al 1997). While the causes of death are similar to
those of the population at large, previously active and severe disease are predictors
for early mortality among patients with psoriatic arthritis (Gladman et al. 1998).
None the less, the arthritis specific Health Assessment Questionnaire (HAQ)
and the generic Medical Outcome Survey Short Form 36 (SF-36) in patients with
psoriatic arthritis does not give the same high scores seen in rheumatoid arthritis
(Jones et al. 1994; Blackmore et al. 1995; Husted et al 2001). This may very
well be due to the fact that the questionnaires correlate highly with pain, which is
less likely to be an issue for patients with psoriatic arthritis than for patients with
rheumatoid arthritis (Buskila et al. 1992). However, the quality of life in patients
with psoriatic arthritis was found to be lower than in patients with uncomplicated
psoriasis (Lundberg et al. 2000).
39
D. Gladman
Approach to the Management of Psoriatic Arthritis
My overall approach to a patient with psoriatic arthritis includes confirming the
diagnosis, assessing the extent of disease activity in terms of both joint and skin
disease, and assessing the degree of damage that has occurred. This involves a
careful history, physical examination, laboratory assessment and radiological
evaluation. The goal of treatment is control of inflammation which will hopefully
lead to control of symptoms, and prevention of deformities and damage, so that the
patient may continue to lead active and productive life.
Once the diagnosis has been made and the patient assessed, my approach to
management begins with patient education. I explain to the patient that he/she
suffers from an inflammatory arthritis, that the treatment is aimed at controlling
inflammation and therefore medications need to be taken regularly. The role of daily
stresses on exacerbations of both skin and joint disease is reviewed. The need to
treat both skin and joint manifestations of the disease is also discussed. These topics
often need to be repeated during follow-up.
The actual therapeutic approach is then tailored to the individual patient
(Box 1). A patient who has mild disease, with minimal skin lesions and mild
arthritis without deformities, is treated with topical ointments for the skin, and non-
40
D. Gladman
steroidal anti-inflammatory drugs for the joints. I tend to use enteric-coated
acetylsalicylicacid, ibuprofen, naproxen or diclofenac for polyarticular disease, and
those that complain of pain. In patients with oligoarticular disease, and those with
spondyloarthropathies, I tend to use indomethacin or tolmetin. While there is no
scientific proof to support this approach, it seems to be empirically correct.
However, since patients vary both in their response to and tolerance of different
NSAIDS, this sequence is often changed. For individuals who clearly express
aversion to taking pills, I tend to choose those NSAIDS which can be given once
daily. The selective COX-2 inhibitors may provide gastroprotection, but are not
superior to the other NSAIDs in their anti-inflammatory activity.
I also use intra-articular corticosteroid injections for individual joints. I find
that in psoriatic arthritis the inflammation is intense and deformity can ensue
rapidly. My patients are educated to call immediately when a red hot joint appears,
and to present themselves for joint injections. Although some people feel that intraarticular steroids are not as effective in seronegative disease as they are in
rheumatoid arthritis, this has not been my experience. We have been able to control
severe inflammation and prevent damage in joints which we injected early (as
judged by what happened to other joints in the same individual). This applies to
both large and small joints in this disease. I use joint injections as an adjunct to
41
D. Gladman
systemic therapy as well, at any point in the disease, provided the joint is not
completely destroyed.
In a patient with active and severe arthritis, I use second line medications
early. I have used antimalarials, sulphasalazine, methotrexate, gold and azathioprine,
for this type of patient. If the patient demonstrates a spondyloarthropathy, I would
tend to choose sulphasalazine first, since it seems to control spinal disease as well as
peripheral disease, whereas the other medications have not been shown to be as
effective for spinal involvement. More recently we have been able to test the ability
of the anti-TNF agents to control psoriatic arthritis, and had these drugs been more
easily available and accessible I would prefer to use them as early as possible in
patients presenting with highly inflammatory disease.
In a patient who has severe psoriasis, even if the arthritis is not that severe, I
tend to start with methotrexate, since it has been shown to be effective for both
components of the disease. If the methotrexate is not tolerated, then I switch to
either sulphasalazine (unless there is sulpha allergy) or azathioprine. If the
methotrexate is tolerated, but not completely effective, I add either an antimalarial
or sulphasalazine. In patients with severe psoriasis and mild arthritis I have used
PUVA which works well for the skin, and has worked well for the joints.
42
D. Gladman
I reserve the use of cyclosporin A and retinoids for patients with severe
psoriasis and arthritis who either refuse to take methotrexate, or are unable to
tolerate it. These drugs are more toxic than the others and need to be used with
caution.
43
D. Gladman
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D. Gladman
67
D. Gladman
Legends for Figures
Figure 1:
Distal arthritis, involving the distal interphalangeal (DIP) joints, with
erosions and joint space narrowing.
Figure 2:
An asymmetric oligoarthritis involving the third PIP joint on the
right. Note the psoriatic lesions in the periungual areas of the left 4th
and 5th fingers.
Figure 3:
Arthritis mutilans, which is a deforming, destructive and disabling
form of arthritis, showing the inability to fully use the hands.
Figure 4:
Telescoping if the third DIP joint, seen in patients with psoriatic
arthritis, which may be part of arthritis mutilans.
Figure 5:
Thoraco-lumbar
spine
in
a
patient
with
psoriatic
spondyloarthropathy demonstrating syndesmophytes.
Figure 6:
Bilateral sacroiliitis in a patient with psoriatic spondyloarthropathy.
Figure 7:
Dactylitis, which presents as swelling of a whole digit, with
inflammation involving DIP, PIP, and occasionally the MCP joints,
involving the thumb and third finger. Note the psoriatic skin and nail
lesions.
68
Figure 8:
D. Gladman
Spur formation at the insertion of the plantar fascia, representing
enthesitis.
Figure 9:
"whittling" (lysis) of terminal phalanges of the first and second toes
bilaterally.
Figure 10:
"pencil-in-cup" appearance seen in its early phase in the second right
PIP, the fifth right DIP, and the left fifth DIP. Full developed
changes are seen in the left index DIP and the left thumb IP joints. In
addition, ankylosis is seen in the right DIP joint
Figure 11:
Fluffy periostitis in the distal end of the tibia.
69
Table 1:
D. Gladman
The prevalence of psoriatic arthritis among patients with
psoriasis
Author (year)
Centre
Number of
Percent
patients
with
studied
arthritis
Leczinsky (1948)
Sweden
534
7
Vilanova (1951)
Barcelona
214
25
Little (1975)
Toronto
100
32
Leonard (1978)
Rochester
77
39
Green (1981)
Cape Town
61
42
Scarpa (1984)
Naples
180
34
Stern (1985)
Boston
1285
20
Zanelli (1992)
Winston-Salem
459
17
Falk (1993)
Kautokeino
35
17
Barisic-Drusko (1994)
Osijek region
553
10
70
Salvarani (1995)
Reggio-Emilia
D. Gladman
205
36
71
D. Gladman
Table 2: Clinical features of PSA in
large reported series
Feature
Roberts
(1976)
Kammer
(1979)
Scarpa
(1984)
Gladman
(1987)
Helliwell
(1991)
Torre-Alonse
(1991)
Veale
(1994)
Jones
(1994)
Trobace
(1994)
168
100
62
220
50
180
100
100
58
M/F
67/101
47/53
29/33
104/116
32/18
99/81
59/41
43/57
35/33
Age of onset
36-45
33-45
40-60
37
39
39
34
37.6
42
No. of patients
53
a
16
b
54
11
14
37
54a
25a
39
19c
78
Distal (%)
17
?
7.5
12
Back (%)
5
21
21
Mutilans (%)
5
?
Sacroiliitis(%)
?
Joints before Skin(%)
16
Asymmetric
Oligo-Arthritis(%)
Symmetric
Poly-Arthritis (%)
43
e
26
50
35
33
63
40
0
0
16
1
?
2d
6
7
4
6
?
2.3
16
2
4
2
4
?
?
16
27
36
20
15
6
43
30
?
17
?
15
?
18
?
?= unspecified. a=includes patients with only distal joints involved; b=14 including symmetric oligoarthritis; c=40 including
asymmetric polyarthritis; d=33 including peripheral joint + back involvement;e=4 were symmetric,
72
D. Gladman
Table 3: comparison between psoriatic arthritis and
rheumatoid arthritis
Psoriatic
Rheumatoid
arthritis
arthritis
Female preponderance
Uncommon
Common
DIP involvement
Common
Uncommon
Symmetry
Less common
Common
Common
Uncommon
Erythema over
affected joint
Back involvement
Common
Uncommon
Enthesopathy
Common
Uncommon
Skin lesions
Common
Uncommon
Nail lesions
Common
Uncommon
Rheumatoid factor
Uncommon
Common
Osteopenia
Uncommon
Common
Osteolysis
Common
Uncommon
Ankylosis
Common
Uncommon
73
D. Gladman
Therapeutic approach to the management of psoriatic arthritis
Type of presentation
NSAIDS
2nd line
Intra-articular
mild skin
mild joint
yes
no
p.r.n.
mild skin
moderate joint
yes
sulphasalazine,
methotrexate,
antimalarials, gold,
azathioprine
p.r.n.
severe skin
mild joint
yes
methotrexate,
sulphasalazine,
cyclosporin A,
PUVA, retinoids
p.r.n.
severe skin
severe joint
yes
methotrexate,
sulphasalazine,
azathioprine,
PUVA,
cyclosporine A,
retimoids.
p.r.n