Seminars in Arthritis and Rheumatism

Seminars in Arthritis and Rheumatism Enters a New Decade

Marc C. Hochberg — 2010-02-01

I am writing as the new Editor-in-Chief of Seminars in Arthritis and Rheumatism, taking over the journal's leadership from the well-known and experienced team of Roy Altman, MD, and Norman Gottlieb, MD. Drs. Altman and Gottlieb, working in the past with the late John Talbott, MD, and David Howell, MD, established Seminars as one of the top journals in the subspecialty of rheumatology. Both Drs. Altman and Gottlieb graciously have agreed to remain on as “Editors Emeritus” and I know the journal and I will continue to benefit from their dedication and expertise in manuscript review and journal publishing. In addition, I will be aided by a new group of Associate Editors including Drs. Jack Cush, Nancy Lane, Joachim Sieper, Nora Singer, Virginia Steen, and Michael Weisman, each of whom has their own area of clinical and research expertise. They will work with me not only in the processing of manuscripts but also in the solicitation of invited review articles.

Lupus Registries: Evolution and Challenges

Liang-Jing Lu, Daniel J. Wallace, Sandra V. Navarra, Michael H. Weisman — 2008-11-11

Objectives: To review the current status of lupus registries, highlight the importance and evolution of registries in clinical lupus research, discuss substantial advances in the understanding of lupus through the use of registries, and discuss the future role of registries in terms of opportunities and challenges.Methods: The literature reviewed originated from the PubMed database and was limited to adult disease in articles published before June 01, 2008. Keywords used in the PubMed search included the following terms: systemic lupus erythematosus, registry, cohort, and database. All articles were sorted and analyzed according to a template devised by the authors describing the different types of registries.Results: The most important features of a lupus registry are that they contain a large number of subjects and reflect a relatively real world environment for lupus patients. Data obtained from the lupus registries are essential for planning, designing, and conducting clinical lupus studies, especially those difficult, inappropriate, or even unethical to study in randomized controlled trials. Up to now, some well-conducted registries have received recognition for their contributions to lupus research through their focus on different goals: epidemiology, genetics, ethnic diversity, clinical features, or outcomes. Although they have evolved in design and study emphasis steadily, there are still many issues left to resolve. Apart from the development and future direction of the lupus registry, attention needs to be applied to normalizing the ethical and legal rules involving a lupus registry.Conclusions: Lupus registries have demonstrated high standards and achieved much success through decades of effort, but they are still in an active state of evolution as they address more questions with greater clarity and sophistication.

Transverse Myelitis Affecting More Than 4 Spinal Segments Associated with Systemic Lupus Erythematosus: Clinical, Immunological, and Radiological Characteristics of 22 Patients

2008-11-20

Objective: To analyze the clinical and laboratory characteristics and outcomes of patients with transverse myelitis affecting more than 4 spinal segments secondary to systemic lupus erythematosus (SLE).Methods: A computer-assisted (PubMed) search of the literature was performed to identify all cases of transverse myelitis affecting more than 4 spinal segments secondary to SLE from 1966 to April 2008. In addition, we present 2 previously unreported cases of SLE patients with transverse myelitis affecting more than 4 spinal segments.Results: Twenty-two SLE patients with transverse myelitis affecting more than 4 spinal segments were finally reviewed. There were 17 (77%) females and the mean age at the diagnosis of myelitis was 29.3 ± 9.4 years (range, 12-53 years). It was the first manifestation of SLE in 5 (23%) patients. The most frequent clinical manifestations were sensory deficit in 20 (91%) patients, variable motor deficit in 19 (86%), and urinary sphincter dysfunction in 15 (83%) patients. On magnetic resonance imaging, all patients showed increased T2 signal intensity of the spinal cord, most frequently in the cervical to mid-lower thoracic spinal segments. Most patients received a combination of therapies; corticosteroids and cyclophosphamide was the most common (45%). Three patients (14%) had complete resolution of symptoms and 14 (59%) had partial recovery.Conclusions: Transverse myelitis affecting more than 4 spinal segments is a rare complication in patients with SLE but may be the first clinical manifestation of the disease in some patients. A high proportion of affected patients have variable degrees of disability after treatment.

Understanding the Epidemiology and Progression of Systemic Lupus Erythematosus

2009-01-12

Objectives: This review examines the burden and patterns of disease in systemic lupus erythematosus (SLE) and the influence and interactions of gender, ethnicity, age, and psychosocial attributes with respect to disease progression, focusing on issues relevant to clinical practice and research.Methods: PubMed literature search complemented by review of bibliographies listed in identified articles.Results: An increased risk among reproductive age women is clearly seen in African Americans in the United States. However, in other populations, a different pattern is generally seen, with the highest age-specific incidence rates occurring in women after age 40 years. The disease is 2 to 4 times more frequent, and more severe, among nonwhite populations around the world and tends to be more severe in men and in pediatric and late-onset lupus. SLE patients now experience a higher than 90% survival rate at 5 years. The less favorable survival experience of ethnic minorities is possibly related to socioeconomic status rather than to ethnicity per se, and adequate social support has been shown to be a protective factor, in general, in SLE patients. Discordance between physician and patient ratings of disease activity may affect quality of care.Conclusions: Our understanding of ways to improve outcomes in SLE patients could benefit from patient-oriented research focusing on many dimensions of disease burden. Promising research initiatives include the inclusion of community-based patients in longitudinal studies, use of self-assessment tools for rating disease damage and activity, and a focus on self-perceived disease activity and treatment compliance.

Determinants of Morbidity and Mortality of Systemic Sclerosis in Canada

Firas F. Al-Dhaher, Janet E. Pope, Janine M. Ouimet — 2008-08-15

Objectives: To describe the morbidity and mortality in Canadian scleroderma (SSc) patients focusing on gender, SSc type, and organ-specific prognosis in a cohort of patients seen from 1994 to 2004 in a Southwestern Ontario SSc clinic. We also compared this cohort to data from the literature, which showed that mean survival in recent studies has risen to 72 months versus 48 months in earlier studies.Methods: This was a cohort study of all SSc patients followed at 1 rheumatology center. Data were abstracted by chart review and entered into a database. The demographic and clinical characteristics of SSc patients were compared between those who survived versus those who died over the 10-year follow-up period. Five- and 10-year survival rates were compared between cohort subsets (sex, diffuse/limited disease type, and organ involvement including the following: scleroderma renal crisis, interstitial lung disease (ILD), hypertension, cardiac, gastrointestinal involvement, pulmonary arterial hypertension, and antinuclear antibody positivity).Results: One hundred eighty-five subjects (158 women), 63% with limited cutaneous SSc, were included. The mean disease duration until last visit or death was 9.1 years (7.9 years in diffuse and 9.8 years in limited). Although more women had either subtype, men were more likely to have diffuse cutaneous SSc (dcSSc) than women (67% of men had dcSSc versus 32% of women, P = 0.0009), and to have an earlier mean age of diagnosis (41.3 ± 2.8 years old versus 49.7 ± 1.2 years, P = 0.006). Overall mortality was 23%; 22% of men (n = 6) and 23% of women (n = 36) were deceased. The 5-year survival was 90% (95% for limited and 81% for diffuse) and the 10-year survival was 82% (92% for limited and 65% for diffuse). Deceased persons were more likely to have had dcSSc (P = 0.03), cardiac disease (P < 0.0001), ILD (P = 0.006), gastrointestinal disease (P = 0.01), and systemic hypertension (P = 0.009). Four of 13 patients with scleroderma renal crisis died. Survival analyses demonstrated that persons with dcSSc (P = 0.001), cardiac disease (P < 0.0001), and hypertension (P = 0.01) had worse survival rates than their counterparts without these disorders. The primary cause of death was ascertained for 33 of the 42 deceased individuals and included the following: pulmonary arterial hypertension (n = 5), renal complications (n = 9), ILD (n = 10), and cardiac complications (n = 9). There appears to be a trend toward longer survival of scleroderma patients over the past few decades.Conclusions: We conclude that cardiac involvement, dcSSc, and hypertension are associated with worse survival, and survival of patients with scleroderma is improving compared with older reports in the literature.

Natriuretic Peptides in Systemic Sclerosis-related Pulmonary Arterial Hypertension

2009-06-18

Objectives: Systemic sclerosis-related pulmonary arterial hypertension (SSc PAH) is a major complication of both limited and diffuse systemic sclerosis and leads to substantial morbidity and mortality. Natriuretic peptides (NP) are clinically useful markers of right ventricular dysfunction and pulmonary hypertension. The aim of our review was to examine the evidence for the physiologic, diagnostic, and prognostic role of NP in the context of SSc PAH.Methods: A Medline search for articles published between January 1999 and December 2008 was conducted using the following keywords: natriuretic peptides, systemic sclerosis or scleroderma, and pulmonary arterial hypertension.Results: In patients with SSc PAH, NP levels increase in proportion to the extent of right ventricular dysfunction and correlate significantly with functional capacity and echocardiographic and hemodynamic parameters. NP may also provide prognostic information beyond conventional risk markers but their use has to be considered against the background of the parameters that may influence their concentration.Conclusion: There is growing evidence that NP, along with the traditional assessment modalities such as echocardiography and the 6-minute walking test, may be a suitable marker for SSc PAH in terms of screening, diagnostic evaluation, risk stratification, and response to therapy; this merits prospective evaluation.

Survival, Causes of Death, and Risk Factors Associated With Mortality in Spanish Systemic Sclerosis Patients: Results From a Single University Hospital

Beatriz E. Joven, Raquel Almodovar, Loreto Carmona, Patricia E. Carreira — 2009-09-27

Objective: To analyze the causes of death, survival, and risk factors for mortality in a large series of Spanish systemic sclerosis (SSc) patients followed over the last 25 years in a tertiary care university hospital.Methods: Demographic, clinical, and outcome data from all SSc patients followed in the rheumatology department were included in a database created in 1989. ANOVA, Kruskal-Wallis, or χ2 tests were used to identify differences among groups; Kaplan-Meier analysis was used to estimate survival, and Cox proportional hazards regression analysis was used to identify factors associated with mortality.Results: A total of 204 patients were included, of whom 182 (89%) were women. Mean age at diagnosis was 49 ± 17 years, and mean follow-up was 8 years. Over 1635 patient-years, 36 of 44 deaths were attributable to SSc: 28 related to cardiorespiratory involvement, 4 to peripheral vascular disease, 3 to gastrointestinal, and 1 to renal involvement. The main SSc-unrelated causes of death were malignancy (3 cases) and infections (2 cases). Survival rates from disease onset were 85, 75, and 55% at 5, 10, and 20 years, respectively, with poorer survival in patients with renal disease and pulmonary hypertension (PH). Independent prognostic factors for mortality were older age at diagnosis, diffuse skin involvement, proteinuria, PH, and elevated erythrocyte sedimentation rate.Conclusions: Ten-year survival is over 70% in Spanish SSc patients. The main causes of death are lung and cardiac involvement, and to a lesser extent, peripheral vascular disease and coexisting malignancy. Diffuse subset, proteinuria, PH, elevated erythrocyte sedimentation rate and older age at diagnosis are the main risk factors for mortality.

Nonsteroidal Anti-Inflammatory Drugs: Adverse Effects and Their Prevention

Harald E. Vonkeman, Mart A.F.J. van de Laar — 2008-09-29

Objectives: To discuss nonsteroidal anti-inflammatory drugs (NSAIDs), their history, development, mode of action, toxicities, strategies for the prevention of toxicity, and future developments.Methods: Medline search for articles published up to 2007, using the keywords acetylsalicylic acid, aspirin, NSAIDs, cyclooxygenase 2, adverse effects, ulcer, and cardiovascular.Results: NSAIDs are 1 of the oldest, most successful drugs known to modern medicine. They are effective for alleviating pain, fever, and inflammation by inhibiting prostaglandin synthesis. Aspirin, by its irreversible inhibition of blood platelet function, is also effective in the prevention of cardiovascular disease. NSAIDs may cause gastrointestinal ulcers, serious cardiovascular events, hypertension, acute renal failure, and worsening of preexisting heart failure. These adverse effects may be prevented by limiting NSAID dosage and duration and by performing individual risk assessments and treating patients accordingly. Those at risk for gastroduodenal ulcers may be treated with concomitant proton-pump inhibitors, misoprostol and/or COX-2 selective NSAIDs. Those at risk for cardiovascular events may be treated with naproxen and a proton-pump inhibitor or misoprostol, but should best avoid NSAID use altogether.Conclusions: Physicians should always prescribe the lowest effective dose for the shortest possible time and must take into account both the gastrointestinal and the cardiovascular risks of individual patients when prescribing NSAIDs.

Sarcoidosis Appearing During Anti-Tumor Necrosis Factor α Therapy: A New “Class Effect” Paradoxical Phenomenon. Two Case Reports and Literature Review

Alfonso Massara, Luigi Cavazzini, Renato La Corte, Francesco Trotta — 2009-01-16

Objectives: To report 2 cases of sarcoidosis that developed during treatment with tumor necrosis factor α (TNFα) antagonists, infliximab and adalimumab, used for inflammatory rheumatic disease and to review previously reported cases.Methods: We describe 2 patients, the first with psoriatic arthritis, the second with rheumatoid arthritis, who developed noncaseating granulomas of the lungs consistent with sarcoidosis while being treated with anti-TNFα drugs. A retrospective review of the literature was performed using the PubMed database.Results: In our patients sarcoidosis developed after 2 years of continuous treatment with infliximab and adalimumab. Both patients presented with low-grade fever, chest pain, and dyspnea. The diagnosis of sarcoidosis was established by the typical well-formed noncaseating granulomas on transbronchial biopsy, after excluding all other granulomatous conditions. Following withdrawal of anti-TNFα agents and a brief course of steroids, the clinical picture resolved. Thirteen additional cases of sarcoidosis that developed after anti-TNFα treatment have been reported, and in 9 of these the causative agent was etanercept.Conclusions: The development of sarcoidosis during treatment with TNFα antagonists represents a rare and paradoxical adverse event. The occurrence of sarcoidosis with all 3 available agents suggests a new “class effect” probably linked to a cytokine disequilibrium in patients receiving anti-TNFα treatment.

2010-02-01

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