Validation of the LupusPRO version 1.8: an update to a disease-specific patient-reported outcome tool for systemic lupus erythematosus.

Objectives LupusPRO has shown good measurement properties as a disease-specific patient-reported outcome tool in systemic lupus erythematosus (SLE). For the purpose of clinical trials, the version 1.7 (v1.7) domain of Pain-Vitality was separated into distinct Pain, Vitality and Sleep domains in v1.8, and the psychometric properties examined. Methods A total of 131 consecutive SLE patients were self-administered surveys assessing fatigue (FACIT, SF-36), pain (Pain Inventory, SF-36), insomnia (Insomnia Severity Index), emotional health (PHQ-9, SF-36) and quality of life (SF-36, LupusPRO) at routine care visits. Internal consistency reliability (ICR) for each domain was obtained using Cronbach's alpha. The convergent construct validity of LupusPRO domains with corresponding SF-36 domains or tools were tested using Spearman correlation. Varimax rotations were conducted to assess factor structures of the LupusPRO v1.8. Results Mean (SD) age was 40.04 (14.10) years. Scores from the LupusPRO-Sleep domain strongly correlated with insomnia scores, while LupusPRO-Vitality correlated strongly with fatigue (FACIT) and SF-36 vitality. The LupusPRO-Pain domain correlated strongly with pain (SF36 Bodily-Pain, Pain Inventory) scores. Similarly, the LupusPRO domains of Physical and Emotional Health had significant correlations with corresponding SF-36 domains. The ICR for HRQoL and non-HRQoL were 0.96 and 0.81. LupusPRO (domains HRQoL and QoL) scores correlated with disease activity. Principal component analysis included seven factor loadings presenting for the HRQOL subscales (combined Sleep, Vitality, and Pain), and three factors for the NHRQoL (Combined Coping and Social Support). Conclusions LupusPRO v1.8 (including its Sleep, Vitality, and Pain domains) has acceptable reliability and validity. Use of LupusPRO as an outcome measure in clinical trials would facilitate responsiveness assessment.

Practice patterns in longitudinal lupus care provision: patient and physician perspectives.

Background/purpose To plan a quality improvement project, we need to understand the practice patterns of physicians. We undertook an online survey of systemic lupus erythematosus (SLE) patients and physicians providing care to SLE patients to determine the patterns of medical care provided to SLE patients. Materials and methods Two self-report surveys were developed. A 12-item survey for the patients and a 13-item survey for physicians enquired about longitudinal care for SLE. Surveys were administered online to physicians providing care to SLE patients, and to patients who self-identified as having SLE, through the Lupus Society of Illinois. Patient and physician data were analyzed for physician practice patterns for SLE care, using chi square tests and t tests. A P value of 0.05 or less was considered significant on two-tailed tests. Results A total of 283 patients completed the survey. Mean (SD) age and disease duration of patients were 45.9 (13.2) and 12.7 (9.7) years. Half of the participants were being seen at 3-4-month intervals. More than 70% of patients reported being tested for antinuclear antibody (ANA), and 20-30% anti-ENA antibody and Sjögren's (SSA/SSB) antibodies, respectively, at each follow-up visit. Eighty-six rheumatologists completed the surveys. Mean (SD) age was 55 (12) years and 56% were men. More than half (54%) provided care only in a private practice setting. More than 80% of physicians reported seeing their SLE patients at 3-4-month interval. Only 2% reported performing ANA tests at each visit, while 4-5% performed anti-ENA and anti-SSA/SSB antibody tests at each visit for their SLE patients. More than 75% of physicians in private practice also ordered sedimentation rate at each visit for their SLE patients. Conclusions Unnecessary laboratory investigations may be being ordered routinely for patients at every visit. These results indicate a need for physician education on indications and utility of some of the laboratory tests such as ANA.

Serum free light chains, interferon-alpha, and interleukins in systemic lupus erythematosus.

OBJECTIVE: Interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-alpha (IFN-α), and free light chains (FLCs: lambda, kappa) have all been noted to be of importance in systemic lupus erythematosus (SLE). Herein, we quantified and explored the relationship between these inflammatory mediators and disease activity in SLE; and stratified by their current anti-dsDNA antibody status. METHODS: Seventy-seven SLE patients underwent assessment of disease activity using the SLE disease activity index (SLEDAI). Serum FLC (lambda, kappa, and total), IL-6, IL-10, and IFN-α were quantified. Demographics of disease characteristics were determined by chart reviews. Statistical analyses included Mann-Whitney test, chi square, and linear regression analyses. RESULTS: Mean (SD) age of the patients was 44.9 ± 12.7 years; SLEDAI (mean ± SD) was 3.4 ± 4.0. Serum lambda FLC levels had a moderate correlation (r = 0.46 with physician global assessment, 0.44 with SLEDAI) and the strongest correlation with disease activity as compared with other inflammatory mediators including current dsDNA antibody status. After adjusting for prednisone use, the correlation of lambda FLC with PGA (r = 0.48) and SLEDAI (r = 0.52) was better than of current dsDNA antibody status with PGA (r = 0.33) and adjusted SLEDAI (r = 0.24), respectively. IL-10 and IFN-α activity did not correlate with disease activity. Serum FLC and IL-6 levels could differentiate between active and inactive SLE patients. Serum lambda FLC and IL-6 levels differed significantly among patients with and without current dsDNA antibodies. Serum lambda FLC levels accounted for 31% of variance in SLEDAI scores. CONCLUSION: Serum FLC and IL-6 are potentially useful biomarkers of disease activity in SLE. Further studies, with larger study sample and longitudinal design, are indicated.

Etanercept therapy in patients with a positive tuberculin skin test.

INTRODUCTION: Etanercept (Enbrel), a tumor necrosis factor-alpha (TNF-alpha) antagonist, is commonly used for the treatment of a variety of rheumatic diseases. Tuberculosis (TB) infections have been associated with chronic TNF-alpha blocking therapy, and there is concern that such therapy may predispose patients to TB reactivation. In this study, we attempted to evaluate the frequency of latent TB reactivation among patients treated with etanercept. METHODS: All patients with either a positive purified protein derivative (PPD) for TB or a previous history of therapy for latent TB infection (LTBI) who were prescribed etanercept in the division of rheumatology at John H. Stroger Jr Hospital of Cook County prior to November 2005 were enrolled in this study. A retrospective chart review was performed looking for evidence of active TB infection during etanercept treatment. RESULTS: Forty-eight patients with a positive PPD were treated with etanercept, and followed for an aggregate of 818 patient-months of etanercept exposure, with a mean follow-up period of 17 months (range 5 to 48 months); all patients had at least one follow-up visit. Forty-four patients (92%) were fully or partially treated with LTBI therapy prior to initiation of etanercept. Chest roentgenograms were available for review in 43 patients, ten of which had evidence of old granulomatous disease. No cases of active TB were described during the study period. CONCLUSIONS: In this small retrospective analysis, none of the 48 patients with positive PPDs who were treated with etanercept for average of 17 months developed active TB.

Genetic analysis of the claret locus of Drosophila melanogaster.

The claret (ca) locus of Drosophila melanogaster comprises two separately mutable domains, one responsible for eye color and one responsible for proper disjunction of chromosomes in meiosis and early cleavage divisions. Previously isolated alleles are of three types: (1) alleles of the claret (ca) type that affect eye color only, (2) alleles of the claret-nondisjunctional (cand) type that affect eye color and chromosome behavior, and (3) a meiotic mutation, non-claret disjunctional (ncd), that affects chromosome behavior only. In order to investigate the genetic structure of the claret locus, we have isolated 19 radiation-induced alleles of claret on the basis of the eye color phenotype. Two of these 19 new alleles are of the cand type, while 17 are of the ca type, demonstrating that the two domains do not often act as a single target for mutagenesis. This suggests that the two separately mutable functions are likely to be encoded by separate or overlapping genes rather than by a single gene. One of the new alleles of the cand type is a chromosome rearrangement with a breakpoint at the position of the claret locus. If this breakpoint is the cause of the mutant phenotype and there are no other mutations associated with the rearrangement, the two functions must be encoded by overlapping genes.

Serum angiotensin-converting enzyme levels in sarcoid arthritis.

The serum angiotensin-converting enzyme (SACE) level is elevated in 75% of patients with sarcoidosis and often is associated with disease activity. In an attempt to correlate the SACE level with sarcoid arthritis, we did a retrospective chart review of 116 patients with sarcoidosis. Of the 24 patients who complained of arthritis, five were excluded from the study because they were receiving corticosteroids, SACE levels were not determined, or another cause for their arthritis was found. The mean SACE levels were 65 units/mL for the patients with acute arthritis and 51 units/mL for the patients with chronic arthritis. Levels of SACE may be helpful in the differential diagnosis of patients with "seronegative polyarthritis."

Neutrophilic dermatosis (Sweet's syndrome). Association with a hydralazine-induced lupus syndrome.

Neutrophilic dermatosis (Sweet's syndrome) is a condition that presents with arthritis and a skin rash. A case report is presented, and an association with hydralazine and lupus is described.

Coronary artery disease in systemic lupus erythematosus: A review of the literature.

CONTEXT: Coronary artery occlusive disease is a common though underappreciated complication of systemic lupus erythematosus (SLE), typically a disease of young women. A case of a premenopausal patient with SLE and an acute myocardial infarction is presented, and the etiology and management of coronary artery disease in SLE reviewed. OBJECTIVES: To review the incidence, risk factors, pathology and treatment of coronary artery disease in systemic lupus erythematosus. DATA SOURCES: MEDLINE search of articles in English-language journals from 1980 to 2000. The index words "systemic lupus erythematosus" and the following co-indexing terms were used: "coronary artery disease," "atherosclerosis," "vasculitis," "anticardiolipin antibodies," "antiphospholipid syndrome." SELECTION SYNTHESIS AND ABSTRACTION: Papers identified were reviewed and abstracted by the authors with a presentation of a summary. RESULTS: The prevalence of coronary artery disease among women with SLE between the ages of 35 and 44 years is at least 50-fold greater than among age-matched control subjects. Of these, coronary atherosclerosis accounts for the vast majority of cases; vasculitis of the coronary arteries and other causes generally believed to be more typical of SLE are comparatively rare. CONCLUSIONS: The evidence suggests that SLE is a significant risk factor for coronary atherosclerosis independent of the classic risk factors of hypertension, tobacco use, and hyperlipidemia.

The neuropathic joint.

Neuropathic arthritis is a destructive arthropathy frequently associated with loss of proprioception. A third of patients, however, may have no demonstrable neurological deficit. Patients with diabetes, syphilis, syringomyelia and other neuropathies are particularly prone to developing this joint disease. The diagnosis of Charcot's joints should be considered in anyone who develops what appears to be a severe osteoarthritis or a transverse fracture of the tibia or fibula after minor trauma. Scoliosis with particularly destructive changes on radiography should prompt a search for syringomyelia or syphilis. The most common radiographic abnormalities are those of distension in 3D (Dislocation, Destruction and Degeneration). An atrophic form with resorption of the proximal humerus, most frequently described in syringomyelia, has been observed in diabetes. Loss of the distal end of the clavicle has not been described before in the neuropathies. These changes coupled with speckled calcification or shards of bone in the periarticular soft tissue confirm the diagnosis. Infection and CPPD crystal disease can be difficult to exclude. The joint fluid may be inflammatory and infection may be a complication. Treatment includes anti-inflammatories and splinting. Indications for surgery are limited.

Rhabdomyolysis in a patient taking simvastatin after addition of cyclosporine therapy.

Medications inhibiting 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase are commonly used as lipid-lowering therapy. Myopathy has been reported as a rare adverse effect in up to 0.2% of patients; however, this complication appears to be more common in patients who are concurrently receiving cyclosporin A(CsA). We present a case of a 74-year-old woman tolerating a stable dose of simvastatin 80 mg daily for hyperlipidemia. After the addition of CsA for a corneal stem limbal cell transplant, the patient experienced a cholesterol-lowering agent myopathy syndrome (CLAMS), with creatine phosphokinase values up to 78,472 U/L. We explore the interaction between simvastatin and CsA, including effects on hepatic microsomal metabolism via the cytochrome P-450 pathway, cholestasis, and myoblast histology, with a review of previous literature regarding HMG-CoA reductase inhibitors (HMGRIs) and rhabdomyolysis. Caution should be exercised in patients receiving concomitant simvastatin and CsA, and a reduced dose of simvastatin is suggested. Inhibition of HMG-CoA reductase is an accepted therapy for hyperlipidemias. The development of a CLAMS is a known potential adverse effect (1), with an increased incidence during coadministration of lovastatin and CsA, first reported by Norman et al. and East et al. in 1988 (2, 3). The interaction between the HMGRIs and CsA, which leads to this muscle toxicity, appears to be related to altered clearance of the HMGRIs with resultant increased tissue exposure (4). The majority of experience with rhabdomyolysis has been in cardiac and renal transplant patients requiring lovastatin and CsA. Theoretically, however, any of the HMGRIs may predispose a patient requiring CsA to develop myositis. In particular, there is a suggestion of an increased sensitivity of myoblasts to both lovastatin and simvastatin (5). We present a case of rhabdomyolysis in a corneal stem cell transplant patient receiving simvastatin and CsA, with a review of the literature.

Arthritis associated with hidradenitis suppurativa.

OBJECTIVE: To review the presentation and clinical findings of arthritis associated with hidradenitis suppurativa. METHOD: Medical records from the rheumatology clinics of two major teaching hospitals were reviewed for arthritis and hidradenitis suppurativa. The nine patient records fulfilling these criteria were reviewed and compared with 20 previous reports. RESULTS AND CONCLUSION: The arthritis associated with hidradenitis suppurativa is rare and most commonly affects the peripheral joints. The axial skeleton is less frequently involved and is often asymptomatic.

Sparing effect of hemiplegia on scleroderma.

The paretic limb is spared in patients who develop rheumatic diseases after a hemiplegic stroke. This has been described previously in rheumatoid arthritis, gout, and osteoarthritis. A similar presentation in a case of scleroderma is described in this report. Scleroderma skin changes are absent in the completely paretic limb and were markedly reduced in the weak left leg. Inflammation may be modified either by neuropeptides or by an anatomical neurological lesion and this may explain the phenomenon.

Cocaine and scleroderma: is there an association?

Scleroderma is a multisystem disease of unknown etiology. A disease predominantly of women, it is distinctly rare in young men. A case of scleroderma in a young male cocaine user is presented, and the possibility that cocaine may play a part in its etiology is explored.

Raynaud's phenomenon.

Raynaud's phenomenon is characterised by episodic vasospasm of the fingers and toes typically precipitated by exposure to cold. Mild Raynaud's is common and is not usually a harbinger of clinically important disability; its onset, however, can be startling and uncomfortable for patients, and the well recognised association in some cases with systemic rheumatic conditions often precipitates aggressive assessments for underlying diseases. Advances in vascular physiology have shed light on the role of the endothelium as well as endothelium-independent mechanisms in the altered vasoregulation of Raynaud's. We review clinical aspects of the disorder and new insights with respect to pathophysiology, and we discuss potential new therapeutics based on the disease mechanism, such as prostacyclin analogues, serotonin antagonists, and calcitonin gene-related peptides.

Detection of alpha 2-macroglobulin-associated proteases in the plasma of patients with rheumatoid arthritis.

In previous work a polyclonal B cell activator has been detected in the serum of patients with rheumatoid arthritis (RA). This activator is associated with alpha 2-macroglobulin (alpha 2M) and its activity is blocked by low-Mr trypsin inhibitors, which suggests that it may be a protease-alpha 2M complex. Here we determined the possibility of developing a routine clinical chemistry test for detection of this complex in patients' blood. We measured with chromogenic substrates the total proteolytic activity of citrated plasma and of the alpha 2M immunoabsorbed from plasma. Low-Mr substrates containing Arg were degraded much better by plasma from RA patients than by plasma from patients with other arthritides. Low-Mr substrates containing Leu, Lys, or Gly or the large-Mr substrate Azocoll were not degraded by RA patients' plasma. alpha 2M from RA patients' plasma attached to a solid-phase immunoabsorbent degraded an Arg-containing tripeptide much better than did the alpha 2M from normal donors, from patients with systemic lupus erythematosus, or from those with joint inflammation of other, "non-autoimmune" origin. Although the enzyme associated with alpha 2M in the plasma from RA patients appeared to be similar to trypsin, the differences in optimal pH, cation concentration, degradation of Lys-containing substrates, and biological activity suggest otherwise. We speculate that the alpha 2M-protease complexes are generated in the immune system and contribute to the inflammatory and autoimmune phenomena in RA.

Septic arthritis in childhood.

We studied retrospectively the pattern of septic arthritis in childhood at a major municipal hospital during a ten-year period. Hemophilus influenzae was the most common organism in septic arthritis in patients less than two years old and was associated with upper respiratory tract infections in nine of 12 patients (75%). Staphylococcus aureus was seen in seven of eight (87.5%) children above the age of five and was associated with history of trauma. All patients were black. Despite the high incidence of sickle cell disease in our hospital population, not one patient had sickle cell disease.