Demographics, clinical disease characteristics, and quality of life in a large cohort of psoriasis patients with and without psoriatic arthritis.

INNOVATION: What is already known about the topic: psoriasis (PsO) is a common skin disease with major impact on quality of life (QoL). Patient-reported data on QoL from large number of PsO patients with and without psoriatic arthritis (PsA) are limited. WHAT THIS STUDY ADDS: In a large cohort referred to a university psoriasis center, patients with PsO and concomitant PsA (~30% in this group) had greater degrees of skin and nail involvement and experienced greater negative impacts on QoL. Despite large numbers of patients with moderate-to-severe disease, use of systemic therapy by community practitioners was uncommon. BACKGROUND: PsO and PsA are common diseases that have marked adverse impacts on QoL. The disease features and patient-reported QoL data comparing PsO and PsA patients are limited. OBJECTIVE: To identify and compare demographics, clinical disease characteristics, and QoL scores in a large cohort of PsO patients with and without PsA. METHODS: All PsO patients seen in a psoriasis specialty clinic, named the Center of Excellence for Psoriasis and Psoriatic Arthritis, were enrolled in an observational cohort. Demographic, QoL, and clinical data were collected from patient-reported questionnaires and from physical examinations performed by Center of Excellence for Psoriasis and Psoriatic Arthritis dermatologists and a rheumatologists. Cross sectional descriptive data were collected and comparisons between patients with PsO alone and those with concomitant PsA are presented. RESULTS: A total of 568 patients were enrolled in the database. Mean age of PsO onset was 28 years and mean disease duration was 18 years. Those with family history had an earlier onset of PsO by ~7 years. Mean body surface area involvement with PsO was 14%. Mean body mass index was 30.7. Prevalence of PsA was 29.8%. PsA patients had a higher mean body surface area compared to patients with PsO alone (16.7% vs 13.4%, P<0.05), higher prevalence of psoriatic nail changes (54.4% vs 36%, P<0.0002), and worse QoL scores as assessed by the Short Form-12 (67 vs 52, P<0.00001), Psoriasis Quality of Life-12 questionnaire (62 vs 71, P<0.01), and Routine Assessment of Patient Index Data 3 (2.3 vs 4.7, P<0.01). Strikingly, 49% of patients with PsO had never received any systemic therapy. CONCLUSION: These data highlight that PsO has marked negative impacts on QoL, while those patients with concomitant PsA are affected to a much greater degree. Despite large numbers of patients presenting with moderate-to-severe disease, use of systemic therapy for both PsO and PsA was uncommon.

A novel, short, and simple screening questionnaire can suggest presence of psoriatic arthritis in psoriasis patients in a dermatology clinic.

Delaying diagnosis of psoriatic arthritis (PsA) can lead to poor quality of life and disability. The purpose of this study is to identify simple questions for dermatologists to screen psoriasis patients for psoriatic arthritis. Data regarding psoriasis and arthritis were prospectively collected by a questionnaire from all psoriasis patients. Patients with joint-related symptoms were assessed by a rheumatologist for the presence of PsA. Retrospectively, the sensitivity and specificity, positive and negative predictive values, likelihood ratios, and posttest probabilities of various screening questions were calculated to identify the best combination of parameters. Of 517 patients seen in dermatology clinic, 117 (22.63 %) were found to have PsA. Four screening questions ("Do you have a history of joint pain or swelling?" "Do you have stiffness in the morning?" "Have you had X-rays taken of your joints?" "Do you have PsA?") with psoriatic nail changes demonstrated high sensitivity and specificity for predicting PsA. A cutoff of three out of these five parameters correctly classified patients with and without PsA with 86.9 % sensitivity, 71.3 % specificity, 53 % positive predictive value (PPV), 93.6 % negative predictive value (NPV), and area under the curve (AUC) of 0.87. Likelihood ratios for individual parameters varied between1.6 and 3.7, and with a combination of certain parameters, the posttest probability of PsA was 76 %. This is a preliminary data on a potential screening questionnaire which can help dermatologists quickly screen for PsA. All patients not having evaluated by a rheumatologist could have led to underdiagnosis of PsA and potential misclassification. Psoriasis patients seen at a specialty clinic may introduce a referral bias.

Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA).

OBJECTIVES: To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-PsA (NCT01087788), an ongoing Phase 3 trial in patients with psoriatic arthritis (PsA). METHODS: Patients were randomised 1:1:1 to placebo, 200 mg CZP every 2 weeks (Q2W) or 400 mg CZP every 4 weeks (Q4W). Patients could have had exposure to one previous tumour necrosis factor (TNF) inhibitor therapy. Primary endpoints were American College of Rheumatology 20% (ACR20) response at week 12 and modified Total Sharp Score change from baseline at week 24. Secondary endpoints included; Psoriatic Arthritis Response Criteria (PsARC) score, Health Assessment Questionnaire Disability Index (HAQ-DI), Psoriasis Area and Severity Index, Leeds Enthesitis Index, Leeds Dactylitis Index, and Modified Nail Psoriasis Severity Index. RESULTS: Of 409 patients randomised, 368 completed 24 weeks of treatment. ACR20 response was significantly greater in CZP 200 mg Q2W and 400 mg Q4W-treated patients than placebo (58.0% and 51.9% vs 24.3% (p<0.001)) at week 12, with improvements observed by week 1. There was a statistically significant improvement in physical function from baseline, measured by HAQ-DI in CZP patients compared with placebo (-0.50 vs -0.19, p<0.001) and more patients treated with CZP 200 mg Q2W and CZP 400 mg achieved an improvement in PsARC at week 24 than placebo (78.3% and 77.0% vs 33.1% (p<0.001)). Sustained improvements were observed in psoriatic skin involvement, enthesitis, dactylitis and nail disease. Higher ACR20 response with CZP was independent of prior TNF inhibitor exposure. No new safety signals were observed. CONCLUSIONS: Rapid improvements in the signs and symptoms of PsA, including joints, skin, enthesitis, dactylitis and nail disease were observed across both CZP dosing regimens.

A six-month randomized controlled trial of exercise and pyridostigmine in the treatment of fibromyalgia.

OBJECTIVE: A subset of fibromyalgia (FM) patients have a dysfunctional hypothalamic-pituitary-insulin-like growth factor 1 (IGF-1) axis, as evidenced by low serum levels of IGF-1 and a reduced growth hormone (GH) response to physiologic stimuli. There is evidence that pyridostigmine (PYD) improves the acute response of GH to exercise in FM patients. The purpose of this study was to evaluate the clinical effectiveness of 6 months of PYD and group exercise on FM symptoms. METHODS: FM patients were randomized to 1 of the following 4 groups: PYD plus exercise, PYD plus diet recall but no exercise, placebo plus exercise, and placebo plus diet recall but no exercise. The primary outcome measures were the visual analog scale (VAS) score for pain, tender point count, and total myalgic score. Secondary outcome measures were the total score on the Fibromyalgia Impact Questionnaire (FIQ) and FIQ VAS scores for individual symptoms (fatigue, poor sleep, stiffness, and anxiety), as well as quality of life (QOL) and physical fitness (lower body strength/endurance, upper and lower body flexibility, balance, and time on the treadmill). RESULTS: A total of 165 FM patients completed baseline measurements; 154 (93.3%) completed the study. The combination of PYD and exercise did not improve pain scores. PYD groups showed a significant improvement in sleep and anxiety in those who completed the study and in QOL in those who complied with the therapeutic regimen as compared with the placebo groups. Compared with the nonexercise groups, the 2 exercise groups demonstrated improvement in fatigue and fitness. PYD was generally well tolerated. CONCLUSION: Neither the combination of PYD plus supervised exercise nor either treatment alone yielded improvement in most FM symptoms. However, PYD did improve anxiety and sleep, and exercise improved fatigue and fitness. We speculate that PYD may have improved vagal tone, thus benefiting sleep and anxiety; this notion warrants further study.

Reactive arthritis following culture-confirmed infections with bacterial enteric pathogens in Minnesota and Oregon: a population-based study.

OBJECTIVE: To describe the epidemiology and clinical spectrum of reactive arthritis (ReA) following culture-confirmed infection with bacterial enteric pathogens in a population-based study in the USA. METHODS: We conducted telephone interviews of persons age>1 year with culture confirmed Campylobacter, Escherichia coli O157, Salmonella, Shigella and Yersinia infections reported to FoodNet (http://www.cdc.gov/FoodNet/) in Minnesota, USA and Oregon, USA between 2002 and 2004. SUBJECTS: with new onset joint pain, joint swelling, back pain, heel pain and morning stiffness lasting >or=3 days within 8 weeks of culture (possible ReA) were invited to complete a detailed questionnaire and physical examination. RESULTS: A total of 6379 culture-confirmed infections were reported; 70% completed screening interviews. Of these, 575 (13%) developed possible ReA; incidence was highest following Campylobacter (2.1/100,000) and Salmonella (1.4/100,000) infections. Risk was greater for females (relative risk (RR) 1.5, 95% CI, 1.3 to 1.7), adults (RR 2.5, 95% CI, 2.0 to 3.1) and subjects with severe acute illness (eg, fever, chills, headache, persistent diarrhoea). Risk was not associated with antibiotic use or human leukocyte antigen (HLA)-B27. A total of 54 (66%) of 82 subjects examined had confirmed ReA. Enthesitis was the most frequent finding; arthritis was less common. The estimated incidence of ReA following culture-confirmed Campylobacter, E coli O157, Salmonella, Shigella and Yersinia infections in Oregon was 0.6-3.1 cases/100,000. CONCLUSIONS: This is the first population-based study of ReA following infections due to bacterial enteric pathogens in the USA. These data will help determine the burden of illness due to these pathogens and inform clinicians about potential sequelae of these infections.

Hand bone densitometry in rheumatoid arthritis, a five year longitudinal study: an outcome measure and a prognostic marker.

OBJECTIVE: To investigate whether hand bone mineral content (BMC) measurement is an outcome measure for RA and whether the early changes in hand BMC predict functional disability. METHODS: Tender and swollen joints in hands and body, HAQ score, Larsen score on hand radiographs, serum CRP, and hand BMC measurement by DXA were studied every six months for five years in 40 patients with early RA. At the final visit, patients completed the SF-36 and Duruoz hand function questionnaires. RESULTS: All patients completed two years and 29 completed five years' follow up. Hand BMC worsened over the first three years (percentage loss from baseline: mean (SD) -5.5 (7.2), -7.5 (8.4), -9.8 (9.4)) and stabilised over last two years (-9.9 (8.8), -10 (7.8)). Baseline disease activity and function correlated with hand BMC loss at five years (swollen joints in hands: r=-0.38, p=0.043; swollen joints in body: r=-0.47, p=0.01; HAQ: r=-0.52, p=0.004). Percentage change in hand BMC over five years correlated with SF-36 physical function (r=0.61, p<0.01), hand function (r=-0.64, p<0.01), HAQ score (r=-0.63, p<0.01) at five years. Relative risk of bad hand functional outcome at five years was significantly higher for patients with hand BMC loss of >/=1.17 g (smallest detectable difference) than for patients with less bone loss within the first six months (OR=6.9, 95% CI 1.3 to 34.5, p<0.02). CONCLUSION: Early loss of hand BMC in patients with RA is a composite marker of disease activity and functional status and can predict poor functional outcome.

Bone changes in early rheumatoid arthritis.

Bone disease in rheumatoid arthritis affects the peri-articular and axial skeleton and is a major cause of disability. Recent studies have shown that pro-inflammatory cytokines stimulate the expression of osteoprotegerin ligand, a transmembrane protein of the tumour necrosis factor ligand superfamily, on synoviocytes and activated T cells. Osteoprotegerin ligand stimulates osteoclast formation and activation, membrane-bound and soluble osteoprotegerin ligand leading to osteoporosis as well as erosions. Bone densitometry using dual energy X-ray absorptiometry is an objective and precise method for monitoring this bone disease. Bone loss is more rapid in patients with early rheumatoid arthritis and correlates well with measures of inflammation and function. Data are emerging that monitoring bone loss of the hands in early rheumatoid arthritis could be an outcome measure and a prognostic indicator of future functional disability. Suppressing inflammation effectively and the use of bone active agents can reduce the rate of loss. In animal models, osteoprotegerin-a decoy receptor of osteoprotegerin ligand-blocks osteoporosis and erosions without affecting inflammation. The use of new biological agents could in future effectively prevent and treat rheumatoid bone disease.

Longitudinal involvement of the spinal cord in a patient with lupus related transverse myelitis.

Transverse myelitis is a rare and serious complication of systemic lupus erythematosus (SLE). Magnetic resonance imaging is the investigation of choice for diagnosis and followup. This typically shows T1 and T2 signal prolongation, cord widening, and contrast enhancement over several spinal segments. We describe a 21-year-old woman with SLE who developed very extensive SLE related transverse myelitis with longitudinal involvement of the spinal cord from C3 to T2 and from T7 to the conus medullaris. Clinically, this was manifest as leg weakness, bladder dysfunction, severe low back pain, and patchy lower limb sensory loss. She responded to treatment with pulse cyclophosphamide and high dose corticosteroids with complete recovery in 3 months. To our knowledge, this is the first case report of such an extensive "longitudinal" myelitis.

Bone mass measurement and bone metabolism in rheumatoid arthritis: a review.

The involvement of bone in rheumatoid arthritis (RA) is well recognized, and hand bone densitometry appears to be a promising new technique to monitor disease progression by assessing serial changes in hand bone mass in patients with RA. New biochemical markers of bone formation (i.e. osteocalcin) show contradictory results in different studies, although markers of bone resorption (i.e. urinary collagen cross-links) have shown significant increase in patients with RA. Bone histomorphometric studies suggest that the periarticular osteopenia in RA could be related to increased bone turnover locally, whereas generalized osteoporosis could be due to a global negative remodelling balance. The important factors implicated in the pathogenesis of the bone loss are circulating cytokines [e.g. tumour necrosis factor alpha (TNF alpha), interleukin (IL) 1 and IL6] produced by the inflammatory process, use of oral corticosteroids (in the dose of > or = 5 mg) and reduced mobility due to functional impairment. Apart from this underlying osteoporosis, patients with RA have an increased risk of falls secondary to functional impairment and there is an increased risk of fractures in patients with RA. Very few studies are presently available looking at the therapeutic measures to prevent osteoporosis in RA. Future drug trials on the treatment of RA should include bone mass measurement, especially of the hand, as one of the outcome measures.

Longitudinal study of hand bone densitometry in rheumatoid arthritis.

OBJECTIVE: To measure hand bone mineral content (BMC) by dual x-ray absorptiometry and to seek clinical correlates in patients with rheumatoid arthritis (RA), in a prospective, longitudinal study. METHODS: Eighty-one patients with non-steroid-treated RA were assessed at baseline and at month 12, for hand BMC and for disease activity and severity. Hand BMC in patients was compared with that in a control group of 95 normal volunteers, and rate of loss was compared with that in 37 controls. RESULTS: At the initial assessment, male and female patients with RA had lower hand BMC than controls, after correction for age, height, and weight (mean reduction 7.5% in men [P = 0.003] and 7.8% in women [P = 0.01]). After 1 year, there was a further loss of hand BMC in patients (median loss 3.25% in men [P = 0.001] and 1.46% in women [P = 0.05]), but normal controls did not have significant changes in their hand BMC. In patients with disease duration of < 2 years at study entry, the parameters of disease activity improved over 1 year, but they lost significant amounts of hand BMC. Hand BMC loss correlated with baseline C-reactive protein levels. In those with RA of > 2 years duration at entry, the Health Assessment Questionnaire scores and Larsen scores had worsened after 1 year, but there was no significant loss of hand BMC. CONCLUSION: Patients with RA had low hand BMC compared with normal controls, even within 2 years of disease onset. The rate of loss was highest in patients with early disease and correlated with measures of initial disease activity. This loss continued despite clinical improvement.

Measurement of hand bone mineral content by dual energy x-ray absorptiometry: development of the method, and its application in normal volunteers and in patients with rheumatoid arthritis.

OBJECTIVES--To develop a method of measuring hand bone mineral content (BMC) by dual energy x ray absorptiometry (DXA); to apply this method of measuring hand BMC to normal volunteers to ascertain causes of variability; and to measure hand BMC in patients with rheumatoid arthritis (RA) of varying duration and severity. METHODS--The x ray beam of the Hologic QDR 1000 dual energy x ray absorptiometer was hardened by introducing a perspex-aluminium plate and the analysis software altered to allow for the small tissue bulk of the hand compared with the torso. Ninety five volunteers (46 men age 24-81 and 49 women age 20-83) had scans of both hands. Eight volunteers were assessed repeatedly to establish reproducibility and effect of hand position. Fifty six patients (22 men, 34 women, age range 25-86 years) with RA of differing duration and severity, had hand BMC measurement by DXA. RESULTS--The precision of BMC measurement was 2.3% with no additional variation due to hand position. Hand dominance had no significant effect on BMC. In men, hand BMC correlated with height (r = 0.57, p < 0.0001), weight (r = 0.58, p < 0.0001), forearm span (r = 0.5, p = 0.0006) and hand volume (r = 0.66, p < 0.0001). In women hand BMC correlated with height (r = 0.66, p < 0.0001), weight (r = 0.4, p = 0.003), forearm span (r = 0.3, p = 0.03) and hand volume (r = 0.49, p = 0.0008). After correcting for all these variables, male volunteers had significantly higher hand BMC than female volunteers (p = 0.01) and patients with RA had lower hand BMC than normal volunteers (total hand BMC in male volunteers 90.9 gms, 95% CI 86.9-95, in male patients 81.7 gms, 95% CI 73.7-89.6, p < 0.004, total hand BMC in female volunteers 62.2 gms 95% CI 59.8-64.5, female patients 52.3 gms, 95% CI 48.1-56.5, p < 0.005). In patients with RA, the hand BMC showed an inverse correlation with age (r = -0.44, p = 0.01), disease duration (r = -0.62, p = 0.0003), Larsen's grades (r = -0.62, p = 0.0002) and modified Sharp's method score (r = -0.69, p < 0.0001) in female patients only. CONCLUSIONS--A new, sensitive and reproducible technique of measurement of hand bone mineral content by DXA, has been developed and this method has been applied to normal volunteers and patients with RA. Hand dominance had no significant effect on hand BMC. After correcting for physical size, men have higher hand BMC than women. Hand BMC inversely correlates in women patients with disease duration and other validated methods of assessing radiological outcome in RA. Longitudinal studies are needed to establish its role in monitoring disease progression.

Fluid retention syndrome and fibromyalgia.

Fluid retention syndrome (FRS) or idiopathic oedema is an unusual clinical entity almost exclusively seen in women, which remains under-diagnosed and poorly understood. It can produce a variety of symptoms ranging from headaches and blurring of vision to abdominal pains and diarrhoea [1]. More commonly it presents with symptoms of bloating, fatigue and generalized weakness. We describe four cases of FRS who presented to the rheumatology clinic with signs and symptoms of fibromyalgia. We also discuss the common features of these two conditions and argue that rheumatologists need to be aware of this condition.