Winston Sequeira

Raynaud's phenomenon

Raynauds phenomenon is characterised by episodic vasospasm of the fingers and toes typically precipitated by exposure to cold. Mild Raynauds 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 Raynauds. 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.

Disease-Specific Patient Reported Outcome Tools for Systemic Lupus Erythematosus

PURPOSE Systemic lupus erythematosus (SLE) can significantly affect both health and non-health-related quality of life (HRQOL and non-HRQOL). However, of the existent published patient-reported outcome (PRO) tools, none were developed from US patients, an ethnically diverse population. Furthermore, these tools do not address men with SLE or assess non-HRQOL issues. Herein, we present the development and validation of the Lupus Patient-Reported Outcome tool (LupusPRO) and discuss its clinical utility and research value compared with other PRO tools currently available for SLE. METHODS Beginning with a conceptual framework, items for LupusPRO were generated using feedback from women and men with SLE. The tool underwent iterations based on patient feedback and clinimetric and psychometric analyses. Validity (content, construct, and criterion) and reliability (internal consistency and test-retest) for the 44-item LupusPRO tool are presented. RESULTS Consistent with the conceptual framework, items were identified that were related to HRQOL and non-HRQOL constructs. HRQOL domains included (1) lupus symptoms; (2) physical health (physical function, role physical); (3) pain-vitality; (4) emotional health (emotional function and role emotional); (5) body image; (6) cognition; (7) procreation; and (8) lupus medications. Non-HRQOL domains were (1) available social support and coping; (2) desires-goals; and (3) satisfaction with medical care. Internal consistency reliability (0.68-0.94), test-retest reliability (0.55-0.92), content, construct (r > 0.50 with SF-36), and criterion (r > -0.35 with disease activity) validity were fair to good. CONCLUSIONS LupusPRO is a valid and reliable disease-targeted patient-reported health outcome tool that is generalizable to SLE patients in the United States of varied ethnic backgrounds and either gender.

Serum free light chains as biomarkers for systemic lupus erythematosus disease activity

To evaluate serum free light chains (FLC) as a putative biomarker of systemic lupus erythematosus (SLE) activity.

Safety of Etanercept in Patients at High Risk for Mycobacterial Tuberculosis Infections

Objective. The magnitude of the risk of reactivation of tuberculosis (TB) on use of etanercept, especially in patients with positive purified protein derivative (PPD) test, has not been assessed. We evaluated the risk of developing active TB among PPD-positive patients treated with etanercept. Methods. All patients with a positive PPD test, as defined by American Thoracic Society guidelines, who received etanercept at Cook County Hospital from 2001 to 2008 were retrospectively reviewed. The primary endpoint was the development of active TB either while receiving or after completing etanercept therapy. Results. Four hundred eighty-seven patients received etanercept, of whom 84 were PPD-positive and constituted the primary cohort. The cohort was composed largely of patients who were at high risk for development of active TB: born in endemic area (80%), ethnic/racial minorities (51 Hispanic, 16 African American, and 8 Asian), and low socioeconomic status (66, 78.57%). Overall etanercept exposure was a mean of 24.6 months (range 3 to 60 mo), with 196 patient-years of etanercept exposure in PPD-positive individuals. Indications for etanercept use included rheumatoid arthritis 58 (69%), ankylosing spondylitis 11 (13%), psoriatic arthritis 13 (15.5%), juvenile inflammatory arthritis 1 (1.2%), and vasculitis 1 (1.2%). Of the 80 subjects, 74 received treatment for latent TB infection (LTBI) prior to initiating etanercept. A comprehensive review of these patients’ medical records failed to reveal any active TB infection. Conclusion. This systematic analysis suggests that the risk of reactivation of LTBI during etanercept therapy is low in appropriately treated individuals.

LupusQoL-US Benchmarks for US Patients with Systemic Lupus Erythematosus

Objective. The LupusQoL-US instrument was recently validated in the US. We studied the benchmarks for a US patient cohort with systemic lupus erythematosus (SLE) and relevant demographic and disease correlates. Methods. LupusQoL-US was administered to 185 patients with SLE. Demographic data (age, sex, ethnicity, marital status) and disease features (duration, disease activity and damage) were assessed simultaneously. Descriptive statistics were obtained. LupusQoL-US domain scores were calculated, and compared by sex, ethnicity, and marital status using nonparametric tests. Correlation between LupusQoL-US domains and age, disease duration, disease activity, and disease damage were obtained. Results. Mean age of patients was 42.2 ± 14.5 years; 94% of subjects were women. African American patients comprised 60% of the study cohort. The most affected domains were Fatigue and Physical Health. The least affected was Intimate Relationships. Age correlated with Physical Health, Pain, and Body Image (r = 0.15–0.18). Differences were observed based on sex and marital status, but not by ethnicity; there the LupusQoL-US correlated inversely with disease activity (r = −0.001 to −0.36) and damage (r = −0.003 to −0.40). Conclusion. All domains of the LupusQoL-US based health related quality of life (HRQOL) were affected adversely. HRQOL varied by age, sex, and marital status in our SLE cohort.

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.

Posterior reversible encephalopathy syndrome in systemic lupus erythematosus.

Background/Objective Posterior reversible encephalopathy syndrome (PRES) is an underrecognized and reversible condition in systemic lupus erythematosus (SLE) that could mimic neuropsychiatric lupus. Identification of any distinct clinical patterns is important as one would need to escalate rather than decrease or discontinue immune suppression in neuropsychiatric lupus. Methods We retrospectively identified and described 5 patients with SLE who were hospitalized and diagnosed with PRES from 2008 to 2013 in a tertiary medical center and reviewed relevant literature. Results Posterior reversible encephalopathy syndrome in SLE occurred in young women with age distribution from 19 to 37 years. At the time of presentation, all had hypertension (systolic blood pressures ranging from 150 to 220), moderate to severe disease activity (Systemic Lupus Erythematosus Disease Activity Index scores ranging from 11 to 41), and prototypical magnetic resonance imaging findings of PRES and nephritis (4 of 5 patients had biopsy-proven lupus nephritis). Seizures, headache, and confusion were the most common clinical symptoms. One patient had intracerebral hematoma, and 2 patients had cerebral petechial hemorrhages. All patients improved without any neurological deficits, with a mean hospital stay of 11.2 days. Conclusions Systemic lupus erythematosus should be considered in the differential diagnosis of patients who present with PRES. One should have a low threshold for magnetic resonance imaging especially when neurological symptoms occur in young women with or without an established diagnosis of SLE and especially among those with active SLE, lupus nephritis, renal failure, and/or poorly controlled hypertension. Given the good prognosis of PRES in SLE patients with early supportive treatment, prompt recognition is crucial to institute appropriate management.

The treatment of psoriatic arthritis

Psoriatic arthritis (PsA) is a chronic, autoimmune, seronegative inflammatory arthritis characterized by varying degrees of axial and peripheral arthritis. Here, we review the literature on the pharmacological management of PsA and present a simple treatment algorithm based on the available information. Although PsA management must be individualized to the degree and type of joint pain and inflammation, in general, nonsteroidal antiinflammatory drugs (NSAIDs) still represent first-line treatment of mild PsA. Second-line therapy includes older agents such as gold salts, methotrexate, sulfasalazine, and cyclosporine. The tumor necrosis factor alpha (TNF-alpha) antagonists represent the most recent major advance in the clinical management of PsA.

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.

Scleroderma lung: pathogenesis, evaluation, and current therapy.

Interstitial lung disease (ILD) is now the most common cause of mortality in scleroderma, although its pathogenesis remains poorly understood. Management requires early detection and treatment before the onset of lung fibrosis. In a number of uncontrolled studies, the combination of daily oral cyclophosphamide and low-dose prednisone appears to be effective, although these conclusions have yet to be confirmed.