Ultrasound in Rheumatoid Arthritis: Association Between the Polymorphism -308 A/G of Tumor Necrosis Factor and the Severity of Bone Erosive Damage

Annamaria Iagnocco¹, Fulvia Ceccarelli¹, Carlo Perricone¹, Martina Fabris², Cristiano Alessandri¹, Cinzia Fabro², Elena Pontarini², Salvatore De Vita² and Guido Valesini¹

Affiliations: ¹Dipartimento di Medicina Interna e Specialità Mediche, Division of Reumatologia, Sapienza Università di Roma, Rome and ²Cattedra di
Reumatologia, DPMSC, Università degli Studi di Udine, Udine, Italy

Correspondence: Annamaria Iagnocco, MD, Dipartimento di Medicina Interna e Specialità Mediche, Rheumatology, Sapienza Università di Roma, Viale del Policlinico 155, 00161, Rome, Italy. Tel.: +39 0649974631; Fax: +39 0649974642; e-mail: annamaria.iagnocco@uniroma1.it

ABSTRACT

INTRODUCTION

Rheumatoid arthritis (RA) is an autoimmune disease characterized by erosive bone damage. The tumor necrosis factor (TNF) -308A/G polymorphism was associated with erosive radiographic progression. Musculoskeletal ultrasound (US) was found superior to radiography to identify bone erosions within small joints (metacarpophalangeal [MCP], hand proximal interphalangeal [PIP], metatarsophalangeal [MTP]) in patients affected with RA.

OBJECTIVES

To evaluate the association of TNF -308G/A with bone erosions assessed with an ultrasound.

STUDY DESIGN

Fifty-two patients affected by RA criteria were genotyped for TNF -308G/A. Disease activity was measured with the disease activity score in 28-joints (DAS28) and the clinical response was evaluated according to the European League Against Rheumatism (EULAR) response criteria. Rheumatoid factor (RF) and anticitrullinated protein/peptides antibodies (ACPA) were detected. The analysis of the TNF -308G/A polymorphism was made by polymerase chain reaction amplification. An ultrasound was performed to assess bone surfaces of metacarpophalengeal (MCP), proximal interphalangeal (PIP), and metatarsophalangeal (MTP) joints by multiplanar scans. According to the number of erosions per joint, a semiquantitative score (range 0–3) was applied. A score in each anatomical district was calculated obtaining MCP-total erosion score (TES), PIP-TES, and MTP-TES, ranging from 0 to 30, and a global TES-patient from the sum of these scores (range 0–90).

RESULTS

TNF -308GG genotype was present in 43 patients while TNF -308AG/AA was present in 9 patients. No significant differences within the two groups were observed for mean age (56±13.8 vs 56.8±16.1 years), disease duration (141.6±117.6 vs 140.4±72.3 months), rheumatoid factor (33/76.7 vs 8/88.8 [N/%]), ACPA (38/88.4 vs 8/88.8 [N/%]), ESR (32.4±26.9 vs 29.4±19.9 mm/h), DAS28 (5.5±1.0 vs 4.6±1.3), HAQ (1.5±.9 vs 1.1±.7). A significant association was found between TNF -308AG/AA genotypes and higher TES patient (28.5±23.7 vs 38.1±17.1 [P<.05]), MCP TES (11.2±8.2 vs 18±8.4 [P=.027]), MTP TES (8.2±8 vs 11.2±6 [P<.05]), and no differences for PIP TES (8.7±8.9 vs 8.9±6.2).

CONCLUSION

This study showed an association between the TNF -308 A allele, linked to higher TNF expression, and bone erosive damage evaluated by ultrasound in patients with RA. This preliminary result confirms previous radiographic studies.

Treatment with Parathyroid Hormone (PTH) for Osteoporosis: Novel Methods and Benefits

John P. Bilezikian

Affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA

Correspondence: John P. Bilezikian, MD, Department of Medicine, College of Physicians and Surgeons, 630 W 168th Street, New York, NY 10032, USA. Tel: +(212) 305 6238; Fax: +(212) 305 6486; e-mail: jpb2@columbia.edu

ABSTRACT

The osteoanabolic era for the treatment of osteoporosis was ushered in by the advent of teriparatide [hPTH(1-34)] and then the full-length molecule, PTH(1–84). The mechanism of anabolic skeletal therapy differs fundamentally from the antiresorptives in that they directly stimulate processes associated with bone formation. The improvements in skeletal microstructure and other bone qualities distinguish these drugs from other available ones. They effectively increase bone density, bone turnover markers, and reduce fracture incidence. Their safety profile is excellent. Over the past decade, the use of anabolic therapy has been studied both as monotherapy and in various combinations. While combination therapy with an antiresorptive has theoretical attractiveness, no approach has clearly shown advantages over therapy with PTH alone. Following treatment for the recommended 18–24 months, it is necessary to follow osteoanabolic therapy with an antiresorptive to maintain the gains achieved during the treatment period. On the horizon are new forms of PTH and delivery systems that may prove to have utility.

Management of Vertebral Body Fractures

Bernd Wiedenhöfer¹, Michael Tanner¹, Carl Hans Fürstenberg¹, Michael Akbar¹, Peter Nawroth^1,2 and Christian Kasperk^1,2

Affiliations: ¹Department of Orthopedics, Trauma Surgery and Spinal Cord Injury Center, Schlierbacher Landstraße, 69118 Heidelberg, Germany and ²Department of Internal Medicine I and Clinical Chemistry, Division of Osteology, University of Heidelberg, INF 410, 69120 Heidelberg, Germany

Correspondence: Christian Kasperk MD PhD, Department of Medicine, Division of Osteology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Tel: +49 6221 56 86 05; Fax: +49 6221 56 57 93; e-mail: christian.kasperk@med.uni-heidelberg.de

B. Wiedenhöfer and M. Tanner contributed equally.

ABSTRACT

Vertebral compression fractures (VCFs) are the most frequent osteoporotic fracture type throughout the Western societies with millions of affected women and men. These fractures severely impair the quality of life and are associated with an increased mortality, thus stating a major health and socioeconomic burden on the societies.

Vertebral compression fractures may be due to trauma, primary osteoporosis, or secondary osteoporosis as a consequence of metabolic-, endocrine-, malassimilation-, medication-, or malignancy-associated disorders of bone metabolism. Therefore an interdisciplinary approach for the proper treatment of the underlying cause and of the mechanical consequences of VCF is required. Many VCFs cause immediate or chronic pain and immobility that also needs the interdisciplinary evaluation whether conservative management, osteoplastic procedures, or major spine surgical approaches are required to improve the patient's situation. Osteoplastic procedures provide an alternative approach between conservative VCF management and reconstructive spine surgery offering the advantages of a minimally invasive procedure with a rapid pain relief, an immediate stabilization of the VCF, and a possible reheightening of an acutely compressed vertebral body. Therefore if technically feasible, osteoplastic procedures in patients with painful VCF are an option to rapidly improve quality of life and simultaneously decrease mortality—which are the ultimate goals of all medical treatment and interventions.

The Long-Term Effectiveness and Safety of Abatacept in Rheumatoid Arthritis

Rene Westhovens

Affiliation: Rheumatology, Department of Musculoskeletal Sciences, K.U.Leuven, Belgium

Correspondence: Rene Westhovens, MD, PhD, Department of Musculoskeletal Sciences, K.U. Leuven, Belgium. Tel: +32 16 34 25 42 and +32 16 34 25 43. e-mail: rene.westhovens@uz.kuleuven.ac.be

ABSTRACT

Several biological drugs with a mode of action different from TNF blockade are currently available for the treatment of rheumatoid arthritis (RA). Since there are no data in literature to compare the different biologicals head-to-head, rheumatologists currently base their treatment decisions on literature reviews and registry data. One of these drugs is Abatacept, a costimulation modulator. A careful analysis of the different extension trials of Abatacept provides interesting insights in the specific efficacy and safety profile that might contribute to the understanding and the appropriate use of this latter drug. Long-term attrition on the drug in these extensions, increasing clinical and X-ray improvements over time, important and stable responses over years, particular improvements in patient-centered outcomes, but also long-term safety, and easy administration with low rates of perfusion reactions will be discussed.

How to Use Synovial Immunohistology as a Tool for the Better Understanding of the Clinical Use of Different Antirheumatic Treatments

Petra Neregård and Anca Irinel Catrina

Affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institute and University Hospital, Solna, Stockholm, Sweden

Correspondence: Anca Irinel Catrina, Rheumatology Department, Karolinska University Hospital and Institute, D2:01, Solna, Stockholm, S-17176, Sweden. Tel: +46 8 5177 2475; Fax: +46 8 5177 3080.

ABSTRACT

Arthroscopy is a safe and reliable technique to obtain synovial biopsies for studies of the local inflammatory process in joint diseases such as rheumatoid arthritis. In this review we aimed to provide an overview on the use of this particular research tool in studies concerning mechanisms of action of distinct antirheumatic drugs. These studies contribute to identification of both new therapeutic targets and synovial biomarkers for prediction of disease outcome and therapy response. We conclude that further development and standardization as well as efforts to organize large synovial tissue biobanks are warranted.

The Epidemiological and Pathogenic Association of Rheumatoid Arthritis With Atherosclerotic Cardiovascular Disease

Mandana Nikpour^1,2, Sharmayne RE Brady³ and Danny Liew¹

Affiliations: ¹The University of Melbourne Department of Medicine, St. Vincent’s Hospital Melbourne, Victoria, Australia; ²Department of Rheumatology, St. Vincent’s Hospital Melbourne, Victoria, Australia and ³Alfred Hospital, Melbourne, Victoria, Australia

Correspondence: Mandana Nikpour, The University of Melbourne Department of Medicine, St. Vincent’s Hospital, 41 Victoria Parade Fitzroy, Victoria 3065, Australia. Tel: +61 3 9288 2211; Fax: +61 3 9288 3652; e-mail: mnikpour@medstv.unimelb.edu.au

ABSTRACT

Rheumatoid arthritis (RA) is associated with an approximately twofold increased risk of atherosclerotic cardiovascular disease (CVD) including myocardial infarction and stroke. The increased risk of CVD in RA is due to an interplay between traditional risk factors such as hyperlipidemia, hypertension, and smoking and disease-related variables such as the presence of rheumatoid factor and anticyclic citrullinated peptide antibodies, high erythrocyte sedimentation rate, and joint swelling. Systemic inflammation and immune mechanisms form a pathogenic link between synovitis and atherosclerosis in RA. Indeed, high levels of C-reactive protein, an inflammatory marker, predict cardiovascular mortality in RA. Furthermore, the risk of CVD is greatly diminished among patients who respond to disease modifying antirheumatic drugs and biological therapies such as tumor necrosis factor (TNF) alpha antagonists. Through adverse effects on lipid profile and blood glucose level, long-term use of high-dose glucocorticoids in RA also increases cardiovascular risk. However, through control of active disease, glucocorticoids may also indirectly attenuate cardiovascular risk. Through their lipid-lowering and immunomodulatory effects, statins may have a dual benefit in the treatment of patients with RA. However, data on cardiovascular risk reduction in RA through management of traditional risk factors remain scant. Current research efforts are directed toward elucidating the risk factors for CVD in RA and developing strategies to minimize this risk.

Systemic Lupus Erythematosus, Immunosuppression, and Vaccinations: Focus on Human Papillomavirus Vaccination

Noortje Groot, Marloes W. Heijstek and Nico M. Wulffraat

Affiliation: Department of Pediatric Immunology, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, The Netherlands

Correspondence: N. M. Wulffraat, associate professor pediatric immunology, Department of Pediatric Immunology, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, Room number KC 03.063.0, PO BOX 85090, 3508 AB, Utrecht, The Netherlands. Tel: +31-(0)887554003; Fax: +31-(0)887555350; e-mail: n.wulffraat@umcutrecht.nl

ABSTRACT

Patients with systemic lupus erythematosus (SLE) may be at higher risk of infections, due to the underlying disease or immunosuppressive treatment. Vaccinations against several pathogens may prevent these infections. The vaccine against human papillomavirus (HPV) serotype 16 and 18 has been developed to prevent chronic HPV infections, one of the causative agents for cervical cancer and its premalignant lesions. The purpose of this study is to review the safety and efficacy of vaccination in SLE patients, especially the pneumococcal and influenza vaccines. In addition, we wanted to assess whether vaccination against HPV in women with SLE prevents cervical cancer and premalignant lesions. A literature search in Medline (PubMed) was performed. We pound that nonlive vaccines can be used safely in SLE, but several drugs used for control of the disease can reduce the immunogenicity. Cervical cancer and premalignant lesions are more prevalent in patients with SLE. This underlines the necessity of prevention of chronic HPV infections in these patients. The HPV vaccine has proven to be immunogenic and safe in the general population, although long-term efficacy in preventing cancer is still unknown. No studies have been performed on HPV vaccination in SLE patients. Circumstantial evidence in favor of HPV vaccination is that most nonlive composite vaccines appear to be immunogenic and safe in patients with quiescent SLE in conclusion. Vaccination of SLE patients with the HPV vaccine may be recommended. Studies on short-term safety and immunogenicity of the HPV vaccine in SLE patients are necessary. Subsequently, a long-term cohort study has to prove whether the HPV vaccine actually reduces the incidence of cervical cancer and premalignant lesions in patients with SLE.

Review: Surfactant Protein D and KL-6 in Scleroderma-Related Interstitial Lung Disease

Faye N. Hant and Richard M. Silver

Affiliation: Department of Medicine, Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC, USA

Correspondence: Faye N. Hant, Medical University of South Carolina, Department of Medicine, Division of Rheumatology and Immunology, 96 Jonathan Lucas Street, Suite 912, Charleston, SC 29425, USA. Tel: (843) 792-1991; Fax: (843) 792-7121; e-mail: hant@musc.edu

ABSTRACT

This article will review the clinical background and significance of two promising serum biomarkers that have been studied in relation to systemic sclerosis (scleroderma, SSc). Systemic sclerosis is a rare and difficult to treat connective tissue disease, with pulmonary involvement being the leading cause of mortality. The most common pulmonary manifestation in SSc is interstitial lung disease (SSc-ILD), and noninvasive serum markers to evaluate and monitor patients and their lung disease are being sought. Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) are glycoproteins secreted by type II pneumocytes. Serum levels of KL-6 and SP-D have been shown in several studies to correlate with the presence of interstitial lung disease in patients with a variety of lung conditions including SSc-ILD. In this article, we will examine the background and significance of these glycoproteins and assess their role to this point as biomarkers of SSc-ILD.

New Insights in Fibromyalgia: A Review

Ralph Nisell¹ and Eva Kosek²

Affiliations: ¹Department of Rheumatology, Karolinska University Hospital, S-171 76 Stockholm, SWEDEN and ²Institute of Clinical Neuroscience, Karolinska Institute, Stockholm, SWEDEN

Correspondence: Ralph Nisell, Department of Rheumatology, Karolinska University Hospital, S-171 76 Stockholm, SWEDEN. Tel: +46 73 978 91 37; Fax: +46 8 517 730 80; e-mail: ralph.nisell@karolinska.se

ABSTRACT

When Mrs. Blomberg, a 52-year-old fibromyalgia patient, meets her health care providers such as a physician, nurse, or physiotherapist, she asks many questions: What kind of a disease is this? What is the cause and is it common? What can be done regarding treatment and what is the prognosis?

The present review article summarizes up-to-date evidence-based facts in order to provide answers to these questions and to have a good scientific basis when discussing fibromyalgia with the patient as well as with health care colleagues, researchers, and others.