International Journal of Rheumatic Diseases 2012

ORIGINAL ARTICLE

Frequency of iridocyclitis in patients with early psoriatic

arthritis: a prospective, follow up study
Laura NICCOLI,1 Carlotta NANNINI,1 Emanuele CASSARA,1 Olga KALOUDI,1
Massimo SUSINI,2 Ivo LENZETTI2 and Fabrizio CANTINI1
1
Second Division of Medicine, Rheumatology Unit, and 2Division of Ophthalmology, Hospital of Prato, Prato, Italy

Abstract
Objective: The occurrence of iridocyclitis (IC) in early psoriatic arthritis (PsA) has been rarely assessed. The pri-
mary end-point of this study was to evaluate the frequency of IC at onset in patients with early PsA.
Methods: We evaluated the frequency of IC in a clinical series of consecutive, new outpatients with early PsA
observed between January 2000 and December 2009. All patients met the Classification Criteria for Psoriatic
Arthritis (CASPAR) criteria for PsA and had a disease duration  12 months. The following clinical patterns
were considered: peripheral PsA (oligoarthritis  4 and polyarthritis  5 involved joints), axial PsA and mixed.
IC diagnosis was made by the ophthalmologist. Follow-up visits were scheduled at baseline and every 4 months
with interval shortening in the case of urgent clinical problems.
Results: Two hundred and forty-two patients, 137 (57%) women and 105 (43%) men (mean age
50.33 11.7 years; mean symptom duration 9.38 3.1 months) were studied. One hundred and thirty-two
(51%) patients had peripheral PsA, 41 (17%) axial and 69 (28%) mixed. Twenty-six episodes of IC were
recorded at diagnosis in 22 (9%) patients, 17 (77.3%) female and five (22.7%) male; 11 (50%) patients had
peripheral PsA, two (9.1%) axial, and nine (40.9%) mixed; 5/22 (22.7%) patients were B27-positive. IC recurred
in 2/22 (9%) patients over the follow-up period. Mean follow-up duration was 51 23.2 months. Dactylitis
was significantly more frequent in patients with IC compared to those without this feature (P = 0.032).
Conclusion: IC occurred in 9% of 242 patients with early PsA with no association with the clinical pattern and
B27 positivity. This frequency is higher than previously reported.
Key words: anterior uveitis, anti-TNF, DMARDs., iridocyclitis, psoriatic arthritis, spondyloarthropathy.

ized by an acute onset over 12 days, eye pain, redness,

INTRODUCTION
Iridocyclitis (IC) represents the most frequent extra-
articular manifestation of psoriatic arthritis (PsA) with
an estimated frequency ranging between 1.5% and 25%
of cases (Table 1).114 This feature may occur at onset
or complicate the clinical course of PsA, and it has been
more commonly reported in axial PsA patients and in
B27+ ones in some studies.8 Clinically, IC is character-
Correspondence: Dr Fabrizio Cantini, Unita Reumatologica, 2
Divisione di Medicina, Ospedale di Prato, Piazza Ospedale,
159100, Prato, Italy. Email: fbrzcantini@gmail.com
miosis, photophobia and blurred vision. Ophthalmo-
logic examination shows the presence of inflammation
of the anterior chamber with presence of keratic precipi-
tates. The acute-phase usually resolves with topical ther-
apy in most cases, otherwise a short-term course of
corticosteroids (CS) is required in resistant ones.15
Iridocyclitis more commonly affects one eye but tends
to recur, often affecting both eyes in an alternate fash-
ion. The occurrence of IC in early PsA has rarely been
assessed.9
The primary end-point of this study was to evaluate
the frequency of IC at onset in a large cohort of patients

2012 The Authors

International Journal of Rheumatic Diseases
2012 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd
L. Niccoli et al.

Table 1 Reported frequency of iridocyclitis in psoriatic arthritis clinical series

Author/year/reference Patient no. Disease duration (years) Iridocyclitis no. (/%)
Roberts et al., 1976 1
168 >10 37 (22)
Lambert and Wright, 19762 112 12.5 8 (7.1)
Kammer et al., 19793 100 >10 25 (25)
Leonard et al., 19784 30 NA 1 (3.3)
Gladman et al., 19875 220 9 15 (6.8)
Torre-Alonso et al., 19916 180 NA 5 (2.8)
Jones et al., 19947 100 12.1 5 (5)
Queiro et al., 20028 70 >10 13 (18.6)
Kane et al., 20039 129 <1 2 (1.5)
Queiro-Silva et al., 200410 120 18 17 (14)
Taylor et al., 200611 588 12.5 62 (10.5)
Sampaio-Barros et al.,12 63 >10 5 (7.9)
Collantes et al., 200713 290 4 4 (1.4)
Cantini et al., 200814* 236 1 18 (7.6)
*Patients with axial PsA were not included in this series.

with early PsA. Secondary end-points were to evaluate
the association of IC occurrence, if any, with the demo-
graphic, clinical and laboratory variables of PsA
patients, and the frequency of IC flares over the follow-
up period.
PATIENTS AND METHODS
We evaluated the frequency of IC in a clinical series of
consecutive, new outpatients with early PsA observed
between January 2000 and December 2009.
Setting
The Rheumatology Unit of the Hospital of Prato, Prato,
Italy, is a secondary referral center which serves around
300 000 people living in the Prato province and the
surrounding industrial areas. About 75% of patients are
sent by their general practitioners, and the remainder
are self-referred. Since January 2000, data of all new
outpatients presenting with rheumatic manifestations
were recorded in a computed individual chart, compre-
hensive of all demographic, clinical history, complete
physical examinations, laboratory findings, diagnosis,
treatment, outcome measures and follow-up visits.
Data extraction
The clinical records of all new, consecutive outpatients
presenting with PsA of <12 months duration and meet-
ing the Classification Criteria for Psoriatic Arthritis
(CASPAR) criteria for PsA11 between January 2000 and
December 2009 were reviewed. At baseline patients had
a standardized diagnostic procedure, including the
following steps: history, demographic data recording,
symptom duration, complete physical examination,
articular and extra-articular features evaluation, routine
blood examinations, including blood cell count with
differential count, kidney and liver function tests, eryth-
rocyte sedimentation rate (ESR), C-reactive protein
(CRP), calcemia, uric acid level, rheumatoid factor,
human leukocyte antigen (HLA) typing, affected joint
radiological examination and pelvis X-rays or magnetic
resonance imaging (MRI) to investigate sacroiliitis. The
following clinical patterns were considered: peripheral
PsA (oligoarthritis  4 and polyarthritis  5 involved
joints), axial PsA (Calins criteria for inflammatory
spinal pain,16 radiographic or MRI evidence of sacroili-
itis) and mixed PsA (concomitant axial and peripheral
features). Involved joints were counted separately with-
out grouping hand and foot small joints.
Iridocyclitis diagnosis was accepted if certified by the
ophthalmologist in the presence of typical ocular signs/
symptoms and ophthalmology examination. Ophthal-
mologic evaluation included complete ocular examina-
tion, best-corrected visual acuity measurement (Snellen
chart of 0.11.0 at a distance of 5 m), slit-lamp biomi-
croscopy, tonometry and ophthalmoscopy. Ophthal-
mologic follow-up visits were performed by the same
ophthalmologist.
Therapy for peripheral PsA was standardized as pre-
viously reported.14 PsA patients presenting with
mono-oligoarthritis were initially treated with nonste-
roidal anti-inflammatory drugs (NSAIDs), and local
corticosteroid (CS) infiltrative therapy when indicated.
Short-term, low-dose CSs were added in resistant

2 International Journal of Rheumatic Diseases 2012


patients with oligoarthritis. Non-responders were
given methotrexate (MTX) at doses of 1015 mg/week
added to NSAIDs for at least 6 months. Before the
year 2003, in the case of treatment failure, cyclosporin
A (CsA) at doses of 35 mg/kg per day was added to
MTX. Switching to CsA was done in case of intoler-
ance to MTX, and CSs were permitted in case of resis-
tance to therapy. PsA patients presenting with
polyarthritis were scheduled to start MTX and NSAIDs
at diagnosis. Non-responders were treated with the
same schedule described above.
Patients were followed by the same rheumatologist,
and follow-up visits were scheduled at baseline and
every 4 months. Control visit intervals were shortened
in the case of urgent clinical problems, and all patients
were instructed to call the centre if there was worsening
of previous arthritis, additional joint involvement,
extra-articular manifestation onset or adverse events
(AEs).
Statistical analysis
All demographic, clinical and laboratory data were
imputed and descriptive statistics and statistical differ-
ences were calculated using SPSS statistical package
version 11 for Windows (SPSS Inc., Chicago, IL, USA).
Wilcoxons matched pairs signed rank test to measure
the changes from baseline of ocular inflammation and
ocular attacks and Chi-square test to compare the clini-
cal parameters in patients with and without IC were
used.
The correlation between the initial independent vari-
ables and remission rate was made with multiple logis-
tic regression analysis. The following variables were
analyzed: age, gender, fatigue, number of involved
joints, ESR and CRP values, dactylitis, number of pain-
ful entheses, tenosynovitis, HLA typing (B27 and
CW6). With the exception of gender, absence or pres-
ence of tenosynovitis, dactylitis and extra-articular fea-
tures, all variables were categorized into three groups
according to tertiles of distribution. P-values <0.05 were
accepted as significant.
RESULTS
Early PsA was diagnosed in 242 patients, 137 (57%)
female and 105 (43%) male, with a mean age of
50.33 11.7 years and a mean duration of symptoms
of 9.38 3.1 months. Peripheral pattern was observed
132 (51%) patients, axial in 41 (17%) and mixed in 69
(28%). Mean ESR and CRP were 31 18 mm/h and
1.83 2.28 mg/dL, respectively. The demographic and
International Journal of Rheumatic Diseases 2012
Iridocyclitis in early PsA
Table 2 Demographic, clinical and laboratory features of 242
patients with early PsA
Patient number 242
Age at diagnosis, years (mean SD) 50.33 11.7
Female/male no. (%) 137 (57%)/105 (43%)
Symptom duration, months SD 9.38 3.1
Oligoarticular peripheral PsA, 106 (43.8%)
no. of patients (%)
Polyarticular peripheral PsA, 31 (12.8%)
no. of patients (%)
Axial PsA, no. of patients (%) 26 (10.7%)
Mixed PsA, no. of patients (%) 79 (32.6%)
ESR mm/h (mean SD) 33 19.36
CRP mg/dL (mean SD) 1.7 2.26
Dactylitis, no. (%) 54 (22.3%)
Enthesitis, no. (%) 21 (8.6%)
Tenosynovitis, no. (%) 54 (22.3%)
Iridocyclitis, no. (%) 22 (9%)
HLA-B27+, no. (%) 38 (15.7%)
Follow-up, months (mean SD) 51 23.2
CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; HLA,
human leukocyte antigen; PsA, psoriatic arthritis.
clinical characteristics of the 242 patients with early PsA
are summarized in Table 2.
As shown in Table 3, a total number of 26 episodes
of IC were recorded at diagnosis in 22 (9%) patients,
17 (77.3%) female and five (22.7%) male; 11 (50%)
patients had peripheral PsA, two (9.1%) axial and nine
(40.9%) mixed; 5/22 (22.7%) patients were HLA-B27-
positive. A significantly higher frequency of dactylitis
was recorded in patients with IC compared to those
without eye involvement (50% vs. 19.5%; P = 0.032).
Otherwise the two groups did not differ for any demo-
graphic and clinical parameter. Mean follow-up dura-
tion was 4.6 3.5 years. Two patients had three
episodes each with alternate involvement of one eye.
None of the patients treated with anti-TNF (tumor
necrosis factor) drugs had IC flares. Concomitantly,
with arthritis flare, IC recurred in two patients with
peripheral PsA receiving MTX after 7 and 12 months,
respectively. These patients were switched to anti-TNF
therapy with no IC recurrence over the duration of fol-
low-up. At the end of follow-up none of the patients
had residual visual acuity impairment or other IC com-
plications, including anterior and posterior synechiae,
cataracts or secondary glaucoma.
During the follow-up period, 32 episodes of IC in 25
of 220 (11.3%) patients who had not complained of
this feature in the early phase of the disease were
recorded. Of these, 5/25 (20%) patients were receiving
NSAIDs alone, 10 (40%) MTX at doses of 1015 mg/
3
L. Niccoli et al.

Table 3 Demographic, clinical and laboratory features in PsA DISCUSSION

patients with IC and comparison with those without eye
involvement To the best of our knowledge, the frequency of IC in
patients with early PsA has only been reported in one
Feature PsA with PsA without P-
study by Kane et al.9 on 129 patients with a disease dura-
iridocyclitis iridocyclitis value
tion  1 year, and in a report from the Spanish Registry
Patient no. (%) 22 (9%) 220 (91%) of Spondyloarthropathies by Collantes et al.13 describ-
Female no. (%) 17 (77.3%) 120 (54.6%) ns ing 290 patients with a disease duration of 4 years. In
Male no. (%) 5 (22.7%) 100 (45.4%) ns
both studies IC had a low prevalence not exceeding 1.5%
Symptom duration, 8.0 7.9 9.4 9.1 ns
of cases. Differing from these reports, we found IC in 9%
(mean SD)
Peripheral PsA, 11 (50%) 126 (57.2%) ns
of 242 PsA patients with a mean duration of articular
no. of patients (%) symptoms of 9.38 3.1 months. Patient selection
Axial PsA, 2 (9.1%) 24 (10.9%) ns based on different inclusion and classification criteria
no. of patients (%) may partly explain the higher IC frequency observed in
Mixed PsA, 9 (40.9%) 70 (31.8%) ns our clinical series compared to previously quoted stud-
no. of patients (%) ies. In Kane et al.s study9 only patients with peripheral
ESR mm/h 30.0 23.36 35.1 12.24 ns PsA were evaluated, while in the Collantes et al. study13
(mean SD) patients were selected using the European Spond-
CRP mg/dL 1.2 2.56 1.8 4.1 ns yloarthropathy Study Group (ESSG) classification crite-
(mean SD)
ria for spondyloarthropathies. In our study we recruited
HLA-B27, no. (%) 5 (22.7%) 33 (15%) ns
patients satisfying the CASPAR criteria for PsA11 that, as
Dactylitis, no. (%) 11 (50%) 43 (19.5%) 0.032
Enthesitis, no. (%) 2 (9.1%) 19 (8.6%) ns
calculated by Taylor et al.,17 have a higher sensitivity
Tenosynovitis, no. 4 (18.1%) 50 (22.7%) ns than ESSG criteria (91.4% vs. 56%) with a similar speci-
(%) ficity (98.7% vs. 97%), and include patients with axial
IC flares before 26 = involvement. Therefore, the inclusion of patients with
therapy, no. milder forms and with all clinical patterns of PsA may
Patients with 20 (91%) Not account for the different results.
unilateral eye applicable Sacroiliitis and axial involvement in PsA have been
involvement, associated with HLA-B27 positivity in some stud-
no. (%) ies,6,10,18,19 and IC has been described more frequently
Patients with multiple 2 (9%) Not
in patients with this disease pattern.8 According to Pa-
episodes (N/%) applicable
iva et al.,15 in our cohort of 26 (10.7%) patients with
Therapy
Local (CS eyedrops, 22 (100%) Not
axial PsA, 79 (32.6%) with both axial and peripheral
CS local injections) applicable involvement and 137 (56.6%) with peripheral dis-
Methorexate 2 (9%) ease, logistic regression analysis did not reveal any
Anti-TNF 20 (91%) significant association with the disease pattern, as well
Patients with IC flares 2 (9%) Not as with HLA-B27 characterization. Interestingly, the
after therapy applicable comparison between patients with and without IC
Follow-up, months 51 23.2 50 21.7 ns revealed a significantly higher frequency of dactylitis
(mean SD) in the group with anterior uvea inflammatory involve-
CRP, C-reactive protein; CS, cyclosporine; ESR, erythrocyte sedimenta- ment. To the best of our knowledge, this association
tion rate; HLA, human leukocyte antigen; IC, iridocyclitis; ns, not sig- has not been previously reported in patients with
nificant; PsA, psoriatic arthritis; TNF, tumor necrosis factor.
PsA.
week, three (12%) combined MTX plus CS, six (24%) Regarding clinical expression, IC was predominantly
leflunomide, and one (4%) etanercept 50 mg/week. unilateral (91% of cases) and multiple episodes were
Consequently, the overall prevalence of IC in the total observed in two HLA-B27-negative patients who had
follow-up cohort was 19.4% (47/242 patients). three ocular attacks each. In a recent report,12 five PsA
Multiple logistic regression analysis did not disclose patients had 13 episodes of IC, while in our series of 22
any significant association with IC for all demo- patients we observed a cumulative number of 26 epi-
graphic, clinical and laboratory variables (r2 = 0.0002; sodes before diagnosis. This low rate of IC flares in our
P = 0.9). clinical series may be explained by the selection of

4 International Journal of Rheumatic Diseases 2012


patients with early disease with consequent short dura-
tion of symptoms.
Finally, over the follow-up period, IC flares were
recorded in only two (9%) patients taking MTX, with
one episode each. These patients had both axial and
peripheral active manifestations and were switched to
anti-TNF treatment with good response and no flare of
IC thereafter. The overall low frequency of IC relapses is
likely to be related to the efficacy of PsA treatment with
anti-TNF-alpha agents. As shown in Table 3, 91% of
patients received TNF-alpha blockers which have been
demonstrated as capable of significantly reducing ocu-
lar attacks in patients with spondyloarthropathies.20
CONCLUSION
In our study IC was recorded in 9% of 242 patients with
early PsA with a higher frequency than previously
reported. IC was not associated with PsA clinical pattern
and B27 positivity. The low number of IC flares before
and after diagnosis is likely due to the selection of
patients with early disease and the efficacy of anti-TNF
therapies, respectively.
ACKNOWLEDGMENTS
We declare that the research was entirely carried out at
the Prato Rheumatology Centre and no funding sup-
ported the study.
CONFLICT OF INTEREST
All Authors declare no conflict of interest with the con-
duction of this study.
REFERENCES
1 Roberts MET, Wright V, Hill AGS et al. (1976) Psoriatic
arthritis: follow-up study. Ann Rheum Dis 35, 20612.
2 Lambert JR, Wright V (1976) Eye inflammation in psoriat-
ic arthritis. Ann Rheum Dis 35, 3545.
3 Kammer GM, Soter NA, Gibson DJ et al. (1979) Psoriatic
arthritis: a clinical, immunologic and HLA study of 100
patients. Semin Arthritis Rheum 9, 7597.
4 Leonard DG, ODuffy JD, Rogers RS (1978) Prospective
analysis of psoriatic arthritis in patients hospitalized for
psoriasis. Mayo Clin Proc 53, 5118.
5 Gladman DD, Shuckett R, Russell ML et al. (1987) Psori-
atic arthritis (PsA) an analysis of 220 patients. Q J Med
62, 12741.
6 Torre Alonso JC, Rodriguez Perez A, Arribas Castrillo JM
et al. (1991) Psoriatic arthritis (PA): a clinical, immuno-
International Journal of Rheumatic Diseases 2012
Iridocyclitis in early PsA
logical and radiological study of 180 patients. Br J Rheu-
matol 30, 24550.
7 Jones SM, Armas JB, Cohen MG et al. (1994) Psoriatic
arthritis: outcome of disease subsets and relationship of
joint disease to nail and skin disease. Br J Rheumatol 33,
8349.
8 Queiro R, Sarasqueta C, Belzunegui J, Gonzalez C, Figueroa
CG, Torre-Alonso JC (2002) Psoriatic spondyloarthropathy:
a comparative study between HLA-B27 positive and HLA-
B27 negative disease. Semin Arthritis Rheum 31, 4138.
9 Kane D, Stafford L, Bresnihan B et al. (2003) A prospec-
tive, clinical and radiological study of early psoriatic
arthritis: an early synovits clinic experience. Rheumatology
(Oxford) 42, 14608.
10 Queiro-Silva R, Torre-Alonso JC, Tinture-Eguren T et al.
(2004) The effect of HLA-DR antigens on the susceptibility
to, and clinical expression of psoriatic arthritis. Scand J
Rheumatol 33, 31822.
11 Taylor WJ, Gladman D, Helliwell P et al. (2006) Classifica-
tion criteria for psoriatic arthritis. Development of new cri-
teria from a large international study. Arthritis Rheum 54,
266573.
12 Sampaio-Barros PD, Conde RA, Bonfiglioli R, Bertolo MB,
Samara AM (2006) Characterization and outcome of uve-
itis in 350 patients with spondyloarthropathies. Rheumatol
Int 26, 11436.
13 Collantes E, Zarco P, Munoz E et al. (2007) Disease pat-
tern of spondyloarthropathies in Spain: description of the
first national registry (REGISPONSER) extended report.
Rheumatology 46, 130915.
14 Cantini F, Niccoli L, Nannini C et al. (2008) Frequency
and duration of clinical remission in patients with periph-
eral arthritis requiring seond-line drugs. Rheumatology
(Oxford) 47, 8726.
15 Paiva ES, Macaluso DC, Edwards A, Rosenbaum JT (2000)
Characterisation of uveitis in patients with psoriatic arthri-
tis. Ann Rheum Dis 59, 6770.
16 Calin A, Porta J, Fries JF, Schurman DJ (1977) Clinical his-
tory as a screening test for ankylosing spondylitis. JAMA
237, 26134.
17 Taylor WJ, Marchesoni A, Arreghini M et al. (2004) A
comparison of the performance characteristics of classifi-
cation criteria for the diagnosis of psoriatic arthritis. Semin
Arthritis Rheum 34, 57584.
18 Kantor SM, Hsu SH, Bias WB, Arnett FC (1984) Clinical
and immunogenetic subsets of psoriatic arthritis. Clin Exp
Rheumatol 2, 1059.
19 Marsal S, Armandans-Gil L, Martinez M, Gallardo D,
Ribera A, Lience E (1999) Clinical, radiographic and HLA
associations as markers for different patterns of psoriatic
arthritis. Rheumatology (Oxford) 38, 3327.
20 Guignard S, Gossec L, Salliot C et al. (2006) Efficacy of
tumour necrosis factor blockers in reducing uveitis flares
in patients with spondylarthropathy: a retrospective study.
Ann Rheum Dis 65, 16314.
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