Current Rheumatology Reviews - Volume 6, Issue 1, 2010

Welcome to a new year and new volume of the CRR! As in past years, we promise to provide high quality, thought provoking articles of current interest to the general rheumatologist in the forthcoming issues. The purpose of this journal is to provide a forum for thought leaders to disseminate useful insights to general rheumatologists, and to publish worthy reviews from expert phsyicians. In pursuing this goal, we are proud to publish reviews of organ involvement in the antiphospholipid syndrome (APS) by Dr. Cervera and his colleagues. Dr. Cervera and his European colleagues have contributed greatly to the field of APS research through the publication of prospective data on morbidity and mortality associated with the APS [1]. Thus, there is no one better to guest edit a hot topic issue on APS than Dr. Cervera and indeed you will find great pleasure in reading these review articles and discovering valuable insights about APS from the luminaries in this field. Dr. Cervera and colleagues lay the foundation for understanding the diverse organ manifestations of this syndrome, which would be of interest to any rheumatologist, but also have significance to other subspecialists such as ophthalmologists, dermatologists, pulmonologists, neurologists, endocrinologists etc. In addition to the hot topic issue, we publish an excellent review of psoriatic arthritis treatments, a field where there are several new treatment options available. Lastly, we publish two thoughtful review articles from our orthopedic colleagues about ankle and foot involvment in RA and isolated cartilage lesions in knee. We welcome your comments about the articles and hope that these articles will lead to a healthy debate about some of the thoughts presented.

The antiphospholipid syndrome (APS) is defined by the occurrence of venous and arterial thromboses, often multiple, and pregnancy morbidity (abortions, fetal deaths, premature births), in the presence of antiphospholipid antibodies, namely lupus anticoagulant, anticardiolipin antibodies, or anti-β2 glycoprotein-I antibodies [1]. The APS can be found in patients having neither clinical nor laboratory evidence of another definable condition (primary APS) or it may be associated with other diseases, mainly systemic lupus erythematosus (SLE), but occasionally with other autoimmune conditions, infections, drugs and malignancies [2]. Rapid chronological occlusive events, occuring over days to weeks, have been termed the catastrophic APS [3]. Other postulated APS subsets include the microangiopathic [4] and the seronegative APS [5]. In the 25 years since the original description of this syndrome [6], advances in recognition of both the clinical as well as the underlying aspects of the condition have been notable. Single vessel involvement or multiple vascular occlusions may give rise to a wide variety of presentations in the APS. Any combination of vascular occlusive events may occur in the same individual and the time interval between them also varies considerably from weeks to months or even years. The study of 1,000 European APS patients (“Euro-Phospholipid project”) [7] has provided accurate information on the prevalence of the majority of clinical manifestations of this syndrome and it is now recognised as a major cause of common conditions, including deep vein thrombosis, stroke, heart attack, miscarriage, epilepsy and memory loss. As a consequence, the APS is, at last, gaining recognition in all branches of medicine, from obstetrics to cardiology, from psychiatry to orthopedics. This volume highlights the most common clinical manifestations of this syndrome according to the involved organ. It also brings together many of the internationally known experts in this field. Although the APS is a relatively “young” syndrome, it seems to “replace” SLE in its diversity of manifestations, number of clinical and scientific publications and number of medical meetings. There is still a lot to be unrevealed to explain the involvement of so many different organs, tissues and systems. This book is dedicated to the current revelations systems.

Antiphospholipid syndrome is an autoimmune disorder characterized by the presence of antiphospholipid antibodies, hypercoagulability leading to vascular thrombosis, and recurrent fetal loss. Since its recognition, a great number of cardiac manifestations have been reported in association with these antibodies: valvular disease, coronary artery disease, cardiomyopathy and intracardiac thrombosis. Pulmonary manifestations may be associated with this syndrome in both the primary and secondary forms including pulmonary embolism and infarction, pulmonary hypertension, acute respiratory distress syndrome, intraalveolar hemorrhage, primary thrombosis of lung vessels, both large and small, as well as pulmonary capillaritis. In the present chapter we shall focus on the main cardiac and pulmonary features related to the presence of aPL which may be of interest to clinicians.

Neurologic disorders are among the most comum and important clinical manifestations associated with the antiphospholipid syndrome (APS), mainly those that affects the central nervous system (CNS). These include sroke, transient ischemic attack, Sneddon's syndrome, convulsions/epilepsy, dementia, cognitive deficits, headaches/migraine, chorea, multiple sclerosis-like, transverse myelitis, ocular symptoms and Guillain-Barre syndrome. On the other hand, only one study investigated the occurrence of peripheral neuropathy and showed alterations in 35 ' of PAPS patients. The proposed mechanisms of nervous system involvement in APS are: thrombosis, and antiphospholipid antibodiesbinding CNS, leading to deregulation of its functions. This article updates the data regarding the clinical aspects related to major neurologic manifestations associated to antiphospholipid syndrome.

Antiphospholipid syndrome (APS) in pregnancy is characterized by the presence of autoantibodies in association with recurrent early miscarriages, fetal losses or severe obstetric complications such as prematurity, intrauterine growth restriction and uteroplacental insufficiency. Several mechanisms are hypothesized to explain the pathogenesis of pregnancy failures including decidual thrombosis or placental vasculopathy and antiphospholipid antibodies (aPL) direct effect on the utero-placental unit. According to the Sapporo criteria, APS is present in patients with three or more unexplained consecutive spontaneous abortions before the 10th week of gestation, after exclusion of maternal anatomic or hormonal abnormalities, or one or more losses starting in the fetal period (from 10th week of gestation). In the last years, several studies were performed for identifying the predictors of pregnancy outcome in APS patients. The uterine artery Doppler is a useful method for the study of patients at higher risk of preeclampsia and small for gestational age infants. A multidisciplinary team (obstetricians, rheumatologists and neonatologists) is important to achieve a good obstetric outcome and to reduce the possible consequences of premature delivery.

Osteonecrosis (ON) or avascular necrosis of bone is a well recognised complication in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). The pathogenesis of ON is probably multifactorial, of which abnormal hemostatic state such as the presence of antiphospholipid antibodies (aPL) may play an important role. In patients with aPL, bilateral involvement of femoral head is often found, but some patients follow an asymptomatic course. Atypical site ON (talus, vertebral, carpal lunate) and/or multiple ON (more than three bones affected) are not uncommon in patients with APS. HIV patients positive for aPL had also a higher risk for the development of ON. By definition, frank and sustained arthritis are not usually seen in patients with Primary APS. On the other hand, arthralgias are not uncommon. Other anecdotal features such as stress fractures have been reported to be associated with aPL. The management of patient with aPL and ON without venous or arterial thrombosis is still controversial. A high diagnostic suspicion is crucial in order to prevent the onset of ON in new territories and to avoid the need of joint replacement.

The eye involvement in the antiphospholipid syndrome (APS) is particularly frequent and includes a number of annexes and anterior and/or posterior segment lesions. There is a high prevalence of transient visual mono- or binocular disturbances related to autoimmune-mediated inflammatory responses and ischemia. The posterior ocular pole is usually the most affected and the one with more severe functional damage. Particularly, the advanced chorioretinal and optic nerve involvement is associated with central nervous system involvement and may have important visual and vital prognostic implications. A new term, the so-called “APS chorioretinopathy”, is presented, as well as a clinical classification for this particular vaso-occlusive ocular disease. On the other hand, sensorineural hearing loss is the most common otological disorder in the APS and can be the first clinical manifestation of the syndrome.

Skin manifestations are very frequent in the antiphospholipid syndrome (APS) and may be the presenting symptom of the disease. Taking into account the impact of early diagnosis on APS outcome, recognition and interpretation of these skin manifestations is paramount. Most skin lesions are the result of blood-flow impairment in the skin microvascular system. Livedo reticularis, livedo racemosa, retiform purpura and livedoid vasculopathy are frequent manifestations of the disease. Although all these terms are used to describe net-like-pattern vascular lesions, their clinical distinction is important because of the different clinical implications of each. APS may present skin lesions very similar to those of Degos' disease; however, it remains unclear how many patients with this rare vasooclusive disease present antiphospholipid antibodies (aPL). Although numerous case reports have emphasized the strong association between primary anetoderma, which is characterized by the loss of the dermal elastic fibers, and aPL, this condition seems to be a rare finding in APS. Nonetheless, many authors consider it mandatory to seek underlying aPL in patients presenting with primary anetoderma. Patients with APS may also present unspecific skin manifestations, such as superficial thrombophlebitis and post-phlebitic ulcers, due to the involvement of the venous territory. Thrombocytopenic purpura has been detected in some cases and seems to be more frequent in the SLE-related APS subset. Dermographism and chronic urticaria have been related to APS, with suspicion of an autoimmune origin. However, the potential relationship between chronic autoimmune urticaria and APS needs further confirmation and should be specifically analyzed in future studies on skin manifestations in APS.

Endocrine manifestations of the antiphospholipid syndrome (APS) are very rare. Adrenal insufficiency, surprisingly usually due to venous infarction, is the most common. It can even be the presenting manifestation of APS, occur in patients with transient antiphospholipid antibodies or even in a neonate through transplacental transfer of maternal antiphospholipid antibodies. The presentation, differential diagnosis, and treatment of adrenal involvement due to APS will be reviewed. Other even rarer endocrine manifestations will also be briefly discussed.

The antiphospholipid syndrome is characterized by arterial/venous thrombosis and recurrent pregnancy loss in the presence of antiphospholipid antibodies in laboratory tests. There are well-documented additional associations between antiphospholipid antibodies and several abnormalities of specific cellular components of the blood, such as thrombocytopenia, hemolytic anemia, and, less frequently, leukopenia. The main hematological manifestations seen in patients with antiphospholipid antibodies are thrombocytopenia, usually mild, and hemolytic anemia with positive Coombs test. In the present chapter we first discuss the relationship between antiphospholipid antibodies and platelets, the proposed mechanisms causing thrombocytopenia in the antiphospholipid syndrome, and the treatment of thrombocytopenia in patients with antiphospholipid antibodies. In the second place, we comment on the relationship between antiphospholipid antibodies and erythrocytes focusing on both the positive Coombs test hemolytic anemia and the microangiopathic hemolytic anemia as part of thrombotic microangiopathic syndromes. Finally, we review leukocyte abnormalities referred to be related to antiphospholipid antibodies, mainly leukopenia and lymphopenia.

Psoriatic arthritis (PsA) is a chronic systemic disease with inflammatory arthritis which occurs in patients who are currently or have been affected by psoriasis. PsA may result in significant functional impairment and reduced quality of life. Evidence now exists documenting the central role of TNF-α in both PsA and psoriasis. Genetic, environmental, and immunologic factors play an interrelated role which provides us with a better insight in disease pathogenesis and options for treatment. Although the cause of PsA is unknown, research has shown the transformations occurring in the skin, synovium, enthesium, and bone in PsA. Both features of this disease similar to, and distinct from, other forms of SpA were revealed. Psoriatic arthritis develops into a disorder of peripheral joints, spine and entheses associated with psoriasis. Over the past two decades it has become clear that PsA is more aggressive than previously thought. About 20% of the patients develop a destructive form of arthritis. The presence of radiologic changes early in the course of psoriatic arthritis suggests an aggressive form of disease. The treatment of psoriatic arthritis is directed at controlling the inflammatory process and preventing damage to joints. Treatment of PsA should be individualized, balancing risk associated with active disease and likelihood of progression in peripheral joints, spine, enthesis, skin and the impact on physical function and quality of life (QoL). There is now great interest for clinicians with regard to PsA with the novel treatments and therapeutic strategies. Based on greater understanding of immunology and on the pathogenesis of the disease along with progress in biopharmaceutical development, a completely new concept of the treatment of PsA has emerged. Much data focus on anti-TNF-alpha. Results of 3 Phase III randomized controlled trials with infliximab, etanercept, and adalimumab have been published. All three agents and more recently a fully humanized antibody against TNFα - Golimumab - were approved for use in PsA by the United States Food and Drug Administration (FDA). The introduction of biologic therapies has changed the management of psoriatic arthritis and more and more trials are done to find better and safer treatments.

Articular cartilage defects have poor healing capacity and can lead to osteoarthritis. Treatment strategies for isolated cartilage lesions of the knee are discussed with a special focus on natural history and evidence of the effectiveness of procedures. Many approaches have been undertaken during the last two decades to find treatments for biological repair of the cartilage surface. Surgical techniques include debridement, stimulation by microfracture, mosaicplasty, autologous chondrocyte implantation (ACI) and autologous matrix-induced chondrogenesis (AMIC). Although these treatments are promising and scientifically interesting, there is no evidence for a breakthrough in cartilage repair. The evidence justifies cartilage repair procedures in patients with symptomatic full-thickness lesions and in patients with large defects in the weightbearing surface of the knee joint.

Rheumatoid arthritis is a common and disabling condition which can be effectively managed through a multidisciplinary approach. A review of the etiology, pathophysiology, clinical presentation, diagnosis and treatment is presented, followed by a discussion focused on the disease presentation and management in the foot and ankle. Conservative care options, perioperative considerations and surgical treatment options for rheumatoid deformity in the foot and ankle are discussed.