Development and initial validation of a screening questionnaire for psoriatic arthritis: the Toronto Psoriatic Arthritis Screen (ToPAS).

OBJECTIVE: To develop and validate a psoriatic arthritis (PsA) screening questionnaire: the Toronto Psoriatic Arthritis Screen (ToPAS). METHODS: The ToPAS was developed through review of items seen in patients with PsA and evaluation by patients with PsA and patients with other rheumatological conditions, and was administered to consecutive consenting patients attending five clinics: PsA, psoriasis, general dermatology, general rheumatology (excluding PsA patients) and family medicine. All patients were assessed by a rheumatologist according to a standard protocol. A three-step analysis strategy was adopted: a stepwise logistic regression to identify the questions most important in discriminating between those with and without PsA; a logistic model was fitted to three clinically relevant domains for PsA: skin, joints and nails; and a simpler weighting of each of the domains used in step 2. Receiver operating characteristic (ROC) curves were obtained based on these various models. RESULTS: In all, there were 134 patients from the PsA clinic, 123 with psoriasis, 118 from dermatology, 135 from rheumatology and 178 from family medicine. A simplified discriminatory score based on the skin, joint and nail domains gave results comparable to other methods with an observed overall sensitivity and specificity, based on a single cut point, of 86.8% and 93.1%. When the patients with PsA were compared with each of the other four patient groups individually, the sensitivity and specificity of the ToPAS were: psoriasis 89.1%, 86.3%; dermatology 91.9%, 95.2%; rheumatology 92.6%, 85.7%; and family medicine 90.4%, 100%. CONCLUSION: Our simplified index is very good at classifying those who are not diagnosed with PsA and those who are diagnosed with PsA.

Cardiovascular morbidity in psoriatic arthritis.

BACKGROUND: Increasing evidence for cardiovascular mortality among patients with psoriasis and psoriatic arthritis (PsA) has accumulated, together with evidence for increased prevalence of risk factors for cardiovascular disease (CVD). OBJECTIVES: To describe cardiovascular morbidity in PsA, determine its prevalence and identify risk factors for its development. METHODS: At the University of Toronto, patients were followed up prospectively according to a standard protocol, including disease-related features and comorbidities. Patients with CVD, including myocardial infarction (MI), angina, hypertension and cerebrovascular accident (CVA), were identified. The prevalence of CVD morbidities in these patients was compared with data from the Canadian Community Health Survey through standardised prevalence ratios (SPRs). Cox relative risk regression analysis was used to analyse risk factors. RESULTS: At the time of analysis, 648 patients were registered in the database. After clinic entry, 122 developed hypertension, 38 had an MI and 5, 21 and 11 had CVA, angina and congestive heart failure (CHF), respectively. 155 patients had at least one of these conditions. The SPRs for MI (2.57; 95% CI 1.73 to 3.80), angina (1.97; 95% CI 1.24 to 3.12) and hypertension (1.90; 95% CI 1.59 to 2.27) were statistically significant, whereas the SPRs for CHF (1.19; 95% CI 0.50 to 2.86) and CVA (0.91; 95% CI 0.34 to 2.43) were not. Factors associated with CVD included diabetes, hyperlipidaemia and high Psoriasis Area and Severity Index scores. CONCLUSION: Patients with PsA are at increased risk of cardiovascular morbidities compared with the general population. In addition to known risk factors for CVD, severe psoriasis is an important predictor in patients with PsA.

Occurrence and correlates of fatigue in psoriatic arthritis.

OBJECTIVE: To determine the relationship between fatigue and disease-related and psychosocial variables in psoriatic arthritis (PsA). METHOD: 499 patients attending the University of Toronto PsA Clinic were administered the modified fatigue severity scale (mFSS). At the time of mFSS administration, clinical and laboratory measures of disease activity and damage were recorded. Linear regression models were used to examine the cross-sectional relationship between disease-related and psychosocial variables and mFSS scores. RESULTS: At least moderate fatigue occurred in 49.5% of patients and severe fatigue in 28.7%. Univariately the vast majority of variables were significantly associated with mFSS scores. The final multivariate model was composed of female sex, the medical outcome survey short form 36 (SF-36) pain and mental health scales, the number of fibromyalgia tender points, the health assessment questionnaire (HAQ) and "ever used" methotrexate, and explained 54.5% of the variation in mFSS scores. The SF-36 mental health scale played the largest role in the multivariate model, uniquely accounting for 6.6% of the variation in the fatigue severity scale. The disease-related factors significant at the univariate level did not achieve statistical significance in the context of HAQ and pain measures. CONCLUSION: Fatigue is a common symptom in PsA, and is associated, in a multivariate model, with pain, female sex, physical functional disability, medication status and psychological distress. Fatigue appears to provide some information that does not overlap with the core set of outcome domains in PsA.

Familial aggregation of psoriatic arthritis.

OBJECTIVES: The aim of this study was to determine the recurrence risk of psoriatic arthritis (PsA) and uncomplicated psoriasis in first-degree relatives (FDRs) of patients with PsA. METHODS: All available FDRs (full siblings, parents and children) of 100 consecutive consenting patients attending a PsA clinic were evaluated for the presence of psoriasis and PsA using a standard protocol. The protocol included a screening questionnaire, physical examination by a rheumatologist, and radiographic and laboratory assessment. The prevalence of PsA and psoriasis in FDRs of the index cases was determined, and the recurrence risk ratio (lambda) was calculated, assuming a population prevalence of PsA of 0.25%, and a population prevalence of psoriasis of 2%. RESULTS: The 100 probands had 533 relatives. Eighty-four of them were deceased and 53 were unavailable (age <16 years). Of the remaining 396 FDRs, 107 did not participate (living too far away/did not consent). Thus, 289/396 (73%) of the available FDRs participated in the study. There were 130 siblings, 108 parents and 51 children. The prevalence of PsA and psoriasis among FDRs was 7.6% and 15.2%, respectively. The lambda(1 )was 30.4 for PsA and 7.6 for psoriasis. The prevalence of PsA and psoriasis in siblings was 7.7% and 17.7%, respectively. The lambda(S) was 30.8 for PsA and 8.8 for psoriasis. CONCLUSIONS: The recurrence risk ratio for both PsA and psoriasis is high in FDRs and siblings of patients with PsA. These results confirm that both PsA and psoriasis have a strong heritable component.

Clinical and radiological damage in psoriatic arthritis.

BACKGROUND: Psoriatic arthritis may progress to joint damage. Joint damage may be assessed clinically, by identifying deformed, fused, or flail joints, or radiologically, by recording erosions, joint space narrowing, ankylosis, lysis, or surgery. The relation between clinical and radiological damage is unclear. OBJECTIVE: To study the ordering of clinical and radiological damage detection, and the clinical features associated with the type of damage detected first. METHODS: The University of Toronto psoriatic arthritis database was used to relate clinical and radiological damage in the hand joints in 655 patients followed prospectively between 1978 and 2003. Generalised estimating equations were used to fit logistic regression models to identify factors that predict classification of damage by radiographic assessment first. RESULTS: The majority of the joints were not informative, as they either had evidence of damage by both methods at entry, or remained undamaged. Of the remainder, 81% of the joints showed radiological damage first and 19% had clinical damage first. Development of radiological damage first was related to previous detection of swollen joints, and was inversely related to duration of arthritis. CONCLUSIONS: Radiological damage is often detected before clinical damage is observed. Clinical inflammation often precedes the detection of radiological damage.

Autoantibodies in biological agent naive patients with psoriatic arthritis.

BACKGROUND: Anti-tumour necrosis factor alpha (anti-TNFalpha) treatment may be associated with the production of autoantibodies, including lupus-specific autoantibodies. OBJECTIVE: To investigate the prevalence of autoantibodies in biological agent naive patients with psoriatic arthritis (PsA). METHODS: 94 consecutive, prospectively collected, biological agent naive patients with PsA at the University of Toronto PsA clinic underwent clinical and laboratory assessment. Disease activity was assessed by the number of actively inflamed joints, and the Psoriasis Activity and Severity Index (PASI) score. Antinuclear antibodies (ANA), rheumatoid factor (RF), double stranded DNA (dsDNA), Ro, La, Smith, and RNP were tested. Descriptive statistics and non-parametric tests were used to analyse the data. RESULTS: 44/94 (47%) patients with PsA were ANA positive (>/=1/40); 13/94 (14%) had a clinically significant titre of >/=1/80. Three per cent had dsDNA antibodies, 2% had RF and anti-Ro antibodies, 1% had anti-RNP antibodies, and none had anti-La or anti-Smith antibodies. CONCLUSIONS: The background prevalence of ANA >/=1/80 in patients with PsA was 14%, with very few patients having specific lupus antibodies. This should serve as a baseline figure for the frequency of autoantibodies in biological agent naive patients with PsA for studies of the use of anti-TNFalpha agents.

Dactylitis in psoriatic arthritis: a marker for disease severity?

AIM: To describe dactylitis in a large cohort of patients with psoriatic arthritis followed prospectively in a specialist clinic, and identify whether it is associated with a worse prognosis. METHODS: Between 1979 and 1999, 537 patients were registered in the psoriatic arthritis clinic and entered onto a longitudinal database. Patients were followed prospectively at six to 12 month intervals according to a standard protocol, and all information was entered onto a database. The database was searched for patients with dactylitis. Descriptive statistics were used to describe the population and chi(2) tests to relate dactylitis to radiographic changes. RESULTS: Dactylitis was documented in 260 patients (48%); 69% of the episodes were recorded at presentation to the clinic. Dactylitis affected feet only in 65% of cases, hands only in 24%, and both hands and feet in 12%. Recurrent dactylitis occurred in 44% of the patients. Increased radiological progression was noted in digits showing dactylitis compared with those without dactylitis (50% v 38%, respectively; p<0.0001). CONCLUSIONS: Dactylitis is common among patients with psoriatic arthritis. It most often affects the feet, in an asymmetrical distribution. It is associated with a greater degree of radiological damage than occurs in digits not affected by dactylitis.

Treatment of refractory psoriatic arthritis with infliximab: a 12 month observational study of 16 patients.

OBJECTIVE: To evaluate the effectiveness and toxicity of infliximab in patients with recalcitrant psoriatic arthritis (PsA). METHODS: Patients with treatment resistant PsA and at least six actively inflamed joints, who had failed to respond to at least two disease modifying agents, were included. Infliximab (5 mg/kg) was given at weeks 0, 2, 6, and every 6-8 weeks pending response. Clinical and laboratory measures included actively inflamed joint count (AJC), swollen joint count (SJC), psoriasis severity (PASI), HAQ, and SF-36. Response was defined as at least a 30% reduction in AJC and PASI. Differences from baseline were analysed using the signed rank test. RESULTS: Sixteen patients (12 male, 4 female), mean age 48 and disease duration 14 years, were included. At baseline the mean AJC was 22.5 and mean PASI 4.5. Eleven patients continued receiving methotrexate. The AJC did not show a statistically significant response. SJC improved significantly at week 54 (p = 0.01). The PASI improved significantly at weeks 14 (p = 0.001) and 30 (p = 0.002) and CRP was reduced significantly at week 30 (p = 0.02). The HAQ score improved at week 30 (p = 0.02). Six patients became positive for dsDNA without clinical features of a connective tissue disease. Six patients discontinued treatment owing to lack of efficacy (1) and toxicity (5). Other serious adverse events included: urticaria (3); thrombocytopenia (1); lower gastrointestinal bleeding (2); severe diarrhoea (2); serious infections (6). Raised transaminases, at least 1.5x normal, occurred in four patients. CONCLUSION: In refractory PsA, infliximab led to a marked improvement in psoriasis but modest response in joint disease. Toxicity and rate of treatment termination was high.

CARD15: a pleiotropic autoimmune gene that confers susceptibility to psoriatic arthritis.

A recent genomewide scan in psoriatic arthritis (PsA) revealed a susceptibility locus at 16q. This region overlaps CARD15, a susceptibility gene in Crohn disease. The possibility of a common susceptibility gene between PsA and Crohn disease is further supported by epidemiological studies that note an increased incidence of psoriasis in subjects with Crohn. We screened 187 patients with PsA and 136 healthy controls, all from Newfoundland, for the three common, independent sequence variants of CARD15 (R702W, leu1007fsinsC, and G908R), which were detected by polymerase chain reaction by use of allele-specific primers and visualized through gel electrophoresis. In total, 53/187 (28.3%) probands with PsA had at least one variant of the CARD15 gene, compared with 16/136 (11.8%) controls (odds ratio 2.97; 95% confidence interval 1.61-5.47; P=.0005). Allele frequencies of R702W, leu1007fsinsC, and G908R were 10.43%, 3.21%, and 1.61%, respectively, in patients with PsA, compared with 3.31%, 2.57%, and 0.37%, respectively, in the control patients. CARD15 conferred susceptibility to PsA independent of HLA-Cw*0602. Thus, CARD15 represents a pleiotropic autoimmune gene and is the first non-MHC gene to be associated with PsA.

HLA-DRB1*04 alleles in psoriatic arthritis: comparison with rheumatoid arthritis and healthy controls.

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis usually seronegative for rheumatoid factor. An increased frequency of HLA-DR4 has been noted in PsA, particularly among patients with a rheumatoid arthritis like (RA) arthritis. The aim of the current investigation was to compare HLA-DRB1*04 alleles in patients with PsA, patients with RA, and healthy controls. Sample size calculations based on the frequency of HLA-DR4 suggested that 90 individuals in each patient group would be sufficient to address our question. Therefore, 90 HLA-DRB1*04 positive patients from each patient group underwent high resolution molecular typing and were included in this study. Although HLA-DRB1*0401 was the most frequent allele in all groups, its frequency among the PsA patients was lower than that of RA patients and controls. HLA-DRB1*0402 was higher among patients with PsA. Patients with RA were more likely to have more than one shared epitope allele than either PsA or the healthy control group. HLA-DQB1 alleles did not contribute further information. We suggest that the differences in the class II HLA epitope(s) may also be related to interaction specificity with another molecule functioning in the immune response to a putative arthritogenic antigen and result in differences in disease expression.

Comparison of radiological severity in psoriatic arthritis and rheumatoid arthritis.

OBJECTIVE: To compare the radiological severity of patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: Patients were identified from the University of Toronto PsA and RA databases. Using the earliest available radiographs, each RA patient was matched to a single PsA patient on the basis of sex, age, and disease duration. Two rheumatologists blinded to the patient's diagnosis scored the radiographs using the modified Steinbrocker method. RESULTS: PsA and RA groups were similar with respect to demographics as well as the use of disease modifying antirheumatic medications. No significant difference in Steinbrocker score for the hands and feet or the hands only was noted. Patients with RA had a higher radiological score in the feet. The 2 groups were similar in the number of joints with significant radiological damage (Steinbrocker 3 and 4). CONCLUSION; Overall the radiological severity in the hands and feet of patients with PsA was comparable to that of patients with RA.

Remission in psoriatic arthritis.

OBJECTIVE: To determine the frequency of remission in psoriatic arthritis (PsA), to describe the characteristics of remission in PsA, and to identify features associated with remission in PsA. METHODS: Patients with PsA are followed prospectively according to a standard protocol. Only patients with > or =3 visits and those with peripheral arthritis were included in this study. Patients who sustained remission, defined as no actively inflamed joints on at least 3 consecutive visits, were compared to patients with persistent inflammation throughout the followup period (nonremission). RESULTS: Among 391 patients with peripheral arthritis and > or =3 visits, 69 patients sustained remission and 178 had persistent inflammatory activity. The frequency of remission was thus 17.6%. The average duration of remission was 2.6 years. However, 52% of the patients experienced flare after a mean of 1.8 years. Univariate analyses revealed that male sex, fewer actively inflamed and damaged joints, and better functional class at presentation to clinic were associated with remission. CONCLUSION: Remission does occur in PsA and may be prolonged. There are clinical characteristics of patients at their first clinic visit that are associated with future remission.

The long-term use of azathioprine in patients with psoriatic arthritis.

Despite the widespread use of methotrexate in the treatment of psoriatic arthritis (PsA), there are patients who are either refractory, develop toxicity to, or refuse to take methotrexate. In search of an alternative, we studied long-term tolerability of and clinical response to azathioprine (AZA) in PsA patients in comparison with matched controls and followed them in a longitudinal clinic. Twenty-eight of 485 patients followed prospectively between 1978 and 1998 took AZA during their clinic follow-ups. Eighteen of the 28 took AZA for 12 months and were included in the study. AZA was well tolerated by most patients, even in the long-term. Although there was no statistically significant difference in the reduction in number of actively inflamed joints between AZA-treated patients and controls, and AZA was no better in preventing progression of damage, AZA was still as good as the other medications. Consequently, AZA was often given to individuals who had not responded to other medications in the past. We provide illustrative case reports in which AZA also controlled psoriasis, and we conclude that, whereas AZA is not superior to other medications in the treatment of PsA, it may be safely used and it provides an alternative therapy for patients with PsA.

Comparison of clinical and immunogenetic features in familial versus sporadic psoriatic arthritis.

OBJECTIVE: To compare patients with familial versus sporadic psoriatic arthritis (PsA) with respect to clinical, radiological and immunogenetic features. METHODS: All patients were identified from the University of Toronto Psoriatic Arthritis Clinic. Familial and sporadic PsA were distinguished based on the proband's self-reported history. The probands were compared at presentation to clinic with respect to: demographic information, age of onset of psoriasis and inflammatory arthritis, disease activity, disease damage, laboratory variables, functional class and HLA antigens. The two groups were compared using a univariate analysis. RESULTS: In total 407 patients were included. Thirty-six patients (8.8%) were eliminated as they reported a family history of arthritis in the absence of psoriasis. Of the remaining 371 patients, 150 patients reported a positive family of either PsA or psoriasis. 221 patients (54.2%) had no family history of psoriatic arthritis, psoriasis, or "arthritis". The familial group were younger at presentation to clinic (p = 0.003), had an earlier age of onset of psoriasis (p = 0.001) and inflammatory arthritis (p = 0.001) and were more likely to be receiving treatment (p = 0.001). The mean number of actively inflamed joints was higher in the sporadic group (p = 0.035), along with a higher frequency of rheumatoid factor positivity (p = 0.04). Only the age of onset variables and medication use retained significance after correction for multiple comparisons. CONCLUSIONS: In comparing probands with familial versus sporadic PsA, we noted a marked difference in the age of onset of psoriasis and inflammatory arthritis, along with other differences in several clinical variables. These differences may be helpful in identifying PsA patients with a stronger genetic predisposition.

Hyperuricemia in psoriatic arthritis: prevalence and associated features.

We aimed to assess the prevalence of hyperuricemia in a cohort of patients with psoriatic arthritis (PsA) and to determine the influence of skin involvement on serum uric acid (SUA) levels. Patients followed at the University of Toronto Psoriatic Arthritis clinic from 1991-1997 were studied. Those who developed hyperuricemia (SUA >/= 450 mumol/L for males or >/=360 mumol/L for females) and the next 3 normouricemic PsA patients were studied. Skin involvement was assessed using the Psoriasis Area and Severity Index score. Of 265 patients, 55 (20.7%) had

Excessive paternal transmission in psoriatic arthritis.

OBJECTIVE: The differential expression of a disease according to the sex of the disease-transmitting parent has been demonstrated in several autoimmune disorders. The purpose of the present study was to determine whether there are differences in the transmission and expression of psoriatic arthritis (PsA) that are dependent on the sex of the affected parent. METHODS: All probands (patients with PsA) were identified from among the patients attending the University of Toronto Psoriatic Arthritis Clinic. A self-reported family history of psoriasis or PsA was noted for each proband. Differences in parental and offspring transmission with respect to the proband were evaluated. In addition, the expression of PsA according to the sex of the affected parent was assessed at the time of the proband's presentation to the clinic. RESULTS: Ninety-five probands had affected parents: 62 (65%) had an affected father, and 33 (35%) had an affected mother. Thus, the proportion of paternal transmission (0.65) was significantly greater than was expected (0.5) (P = 0.001). Twelve of 74 offspring from male probands (16.2%) were affected with psoriasis or PsA, as compared with 9 of 108 offspring from female probands (8.3%) (P = 0.10). Probands whose fathers were affected had a higher frequency of skin lesions prior to arthritis (P = 0.047), an erythrocyte sedimentation rate > 15 mm/hour (P = 0.044), and a lower incidence of rheumatoid factor (P = 0.044). No differences were noted with respect to age at the onset of psoriasis or PsA, the severity of the PsA, or the frequency of HLA antigens. CONCLUSION: There appears to be excessive paternal transmission in PsA. Further clinical confirmation and elucidation of its genetic basis is warranted.

Re-examining the concept of severity in traumatic brain injury.

This paper re-examines the theoretical concept of severe brain injury focusing on the duration of coma as a precise indicator of the clinical profile. A retrospective hospital chart study of 361 traumatic brain-injured patients was undertaken to determine the homogeneity of the subsample of the severely brain-injured (defined as 2 or more days of coma) with respect to the probability of four types of impairment: ataxia, contractures, paralysis and speech impairment. The current concept of severity assumes homogeneity among the 'severely brain-injured'. However, our results indicate significant differences in impairment within this population. The authors feel strongly that future studies must describe coma duration in finer gradations, and test for homogeneity within samples before inferences are made. Improvements in life-sustaining technologies have resulted in longer coma durations. The need to use coma days as an indicator of impairment rather than a broad category of severity is emphasized.