Manifestations Of Rheumatic Diseases Research Articles

The treatment of recurrent uveitis with TNFα inhibitors

Uveitis is a severe manifestation of rheumatic diseases since it can lead to visual impairment and even blindness. Ocular involvement is frequently a clinical challenge because its occurrence often requires changes of the therapeutic strategy. There are growing evidence that tumor necrosis factor alpha (TNFalpha) inhibitors may be an effective treatment of refractory uveitis. Purpose of this study was to evaluate the efficacy and safety of TNFalpha blocking agents in patients with seronegative spondylo-arthropathies (SNSA) and Behcet disease (BD) associated relapsing uveitis. Five consecutive patients with chronic or relapsing uveitis were prospectively studied. Two patients with SNSA had recurrent anterior uveitis and three patients had BD associated uveitis (one anterior, two posterior uveitis). All of the patients were taking systemic and topical corticosteroids and three of them were also treated with DMARDs (methotrexate, cyclosporine, sulphasalazine) without clinical benefit. Four patients received infliximab, an anti-TNFalpha monoclonal antibody, at a dosage of 5 mg/kg body weight and one patient was treated with etanercept, a TNFalpha receptor p75-Fc fusion protein, at a dosage of 25 mg twice weekly. Both infliximab and etanercept induced a marked improvement in uveitis and none relapse was observed throughout all the study. Systemic corticosteroids were progressively tapered and stopped in all patients. Also methotrexate and sulphasalazine were discontinued, while cyclosporine dose has been reduced by 30%. No side effects were observed. Therapy with TNFalpha blockers, infliximab and etanercept, was effective and safe in the treatment of rheumatic disease associated uveitis. A complete remission was achieved even in patients with severe steroid resistant uveitis. Further controlled studies on larger number of patients are needed to better define the different forms of ocular involvement that can benefit from the therapy with TNFalpha inhibitors.

Introduction from Editor-in-Chief

Welcome to 2011 from the editorial staff of Current Rheumatology Reports! As Henry David Thoreau eloquently stated, “Could a greater miracle take place than for us to look through each others eyes for an instant?” While the eyes are a fascinating window into the systemic manifestations of rheumatic diseases, a surprising lack of awareness of the ocular manifestations of rheumatic diseases exists. In this issue of the journal, we attempt to correct this discrepancy by presenting several expertly written articles on the topic. I am sure that the readership will find great practical value in these wonderful articles and I invite you to provide any comments or vignettes that come to mind. In the second part of this issue, we present thought provoking articles about issues that come up in the treatment of rheumatoid arthritis with biologic agents. The issue of whether biologic agents increase the risks for cancer and infection has been debated since the advent of the biologic era. While no consensus has been achieved on these topics, Drs. Bongartz and Finckh provide us with an uptodate review of the literature. Dr. De Keyser tackles the question of failure of a TNF blocker and provides expert guidance in this often encountered clinical scenario. We look forward to your continued readership.

Otolaryngological manifestations of rheumatic diseases in children

Rheumatic diseases represent a group of autoimmune conditions which primarily affect the musculo-skeletal system but can also involve other internal organs such as the auditory and the respiratory systems. Among the rheumatic diseases of children those which present an otolaryngological involvement at disease onset or during their course are essentially juvenile idiopathic arthritis (JIA), Cogan syndrome (CS), relapsing polycondritis (RPC) and Wegener granulomatosis (WG). In this section, we will review the main characteristics of these conditions with the attempt to propose a few elements for an easy differential diagnosis which might help for an early diagnosis and a more appropriate treatment.

Nineteen Episodes of Recurrent Myelitis in a Woman With Neuromyelitis Optica and Systemic Lupus Erythematosus

To describe the case of a patient with systemic lupus erythematosus (SLE) and neuromyelitis optica (NMO) who experienced 19 recurrent attacks of myelitis. Case report. An outpatient neurorheumatology clinic at the Johns Hopkins Hospital devoted to care of patients with neurological manifestation of rheumatic diseases. Patient A woman with NMO and SLE. Intervention Rituximab therapy. Clinical and neuroimaging features of relapsing disease. Recurrent and increasingly severe myelitis attacks still occurred after treatment with rituximab. It may be progressively more difficult to prevent relapses and commensurate disability in patients with later stages of relapsing NMO. Recognition of NMO as a distinct diagnostic entity in patients with SLE and other rheumatic diseases is crucial, in that institution of earlier targeted immunosuppressant treatment may be more effective than later targeted immunosuppression. The cellular arm of the immune system may be recruited by pathogenic B cells and may explain why relapses may occur after treatment with B cell-depleting therapy.

Respiratory Tract Manifestations of Rheumatic Diseases in Children

Frequency and type of respiratory manifestations differ among individual rheumatic diseases in childhood as well as among children and adults. It is important to recognise respiratory complications of established diseases like juvenile systemic lupus erythematosus or dermatomyositis early enough to prevent serious disease outcomes. Nevertheless, it is of the same importance to reveal unusual characteristics of respiratory symptoms which rheumatic disease may present with, like in Wegeners granulomatosis. Therefore high degree of suspicion and good access to specialised paediatric care including paediatric rheumatology and intensive care units are often of vital importance. In this review respiratory symptoms are summarised firstly by anatomical location of affected area and secondly by individual rheumatic diseases. Where applicable, differences between paediatric and adult disease are shown and main diagnostic and therapeutic principles overviewed. Disease spectrum covers juvenile idiopathic arthritis, juvenile systemic lupus erythematosus and dermatomyositis, systemic scleroderma and primary systemic vasculitides. Keywords: Paediatric rheumatology, systemic disease, respiratory involvement

High prevalence of rheumatoid factor associated with clinical manifestations of rheumatic disease in Kaingang and Guarani Indians from Southern Brazil

The aim of the present study was to perform a screening for rheumatoid factor (RF) and anti-nuclear antibody in Kaingang, Guarani and Mestizos individuals from Mangueirinha Reservation, State of Paraná, Brazil, and associate it with demographic and clinical data. Serum samples from 321 aborigines (125 male and 196 female; 4-86 years old) and 180 non-Indians healthy individuals were analysed (62 male and 118 female; 2-81 years old). Antinuclear antibody (ANA) was tested by indirect immunofluorescence, and RF by agglutination in latex and turbidimetry. RF was higher in Kaingang when compared to Guarani (P = 0.009), Mestizos (P = 0.061) and non-Indians (P = 0.010). A significant increase of RF was observed in Kaingang women versus Kaingang men (P = 0.002) and, among the women, in Kaingang when compared to Mestizos and Guarani (P <or= 0.008). The positivity for ANA did not show significant differences between the groups. Clinical evaluation of RF positive individuals (n = 6) confirmed rheumatoid arthritis in two Kaingang Indians. Other two individuals (RF positive) will be under medical observation, as well as two Mestizos. The differences observed among the investigated groups, suggest the influence of genetic and hormonal factors in the development of auto antibodies in these populations.

Pediatric Rheumatology for the Adult Rheumatologist

Although many manifestations of rheumatic diseases in children are similar to those in adults, there exist important differences. These include variations in presentation and complications, differential diagnoses to consider, medication side effects, impact on growth, and psychosocial issues. As there is a US and worldwide shortage of pediatric rheumatologists, many children with rheumatic illnesses are cared for by other physicians, especially by adult rheumatologists. This article is aimed toward educating the adult rheumatologist in 4 key areas of childhood rheumatic disease: juvenile idiopathic arthritis, other rheumatic and inflammatory illnesses seen primarily in the pediatric population, differences in rheumatic diseases common to both adults and children, and psychosocial issues.

Rheumatic Diseases Presenting as Sports-Related Injuries

Most individuals seeking consultation at sports medicine clinics are young, healthy athletes with injuries related to a specific activity. However, these athletes may have other systemic pathologies, such as rheumatic diseases, that may initially mimic sports-related injuries. As rheumatic diseases often affect the musculoskeletal system, they may masquerade as traumatic or mechanical conditions. A systematic review of the literature found numerous case reports of athletes who presented with apparent mechanical low back pain, sciatica pain, hip pain, meniscal tear, ankle sprain, rotator cuff syndrome and stress fractures and who, on further investigation, were found to have manifestations of rheumatic diseases. Common systemic, inflammatory causes of these musculoskeletal complaints include ankylosing spondylitis (AS), gout, chondrocalcinosis, psoriatic enthesopathy and early rheumatoid arthritis (RA). Low back pain is often mechanical among athletes, but cases have been described where spondyloarthritis, especially AS, has been diagnosed. Neck pain, another common mechanical symptom in athletes, can be an atypical presentation of AS or early RA. Hip or groin pain is frequently related to injuries in the hip joint and its surrounding structures. However, differential diagnosis should be made with AS, RA, gout, psudeogout, and less often with haemochromatosis and synovial chondochromatosis. In athletes presenting with peripheral arthropathy, it is mandatory to investigate autoimmune arthritis (AS, RA, juvenile idiopathic arthritis and systemic lupus erythematosus), crystal-induced arthritis, Lyme disease and pigmented villonodular synovitis. Musculoskeletal soft tissue disorders (bursitis, tendinopathies, enthesitis and carpal tunnel syndrome) are a frequent cause of pain and disability in both competitive and recreational athletes, and are related to acute injuries or overuse. However, these disorders may occasionally be a manifestation of RA, spondyloarthritis, gout and pseudogout. Effective management of athletes presenting with musculoskeletal complaints requires a structured history, physical examination, and definitive diagnosis to distinguish soft tissue problems from joint problems and an inflammatory syndrome from a non-inflammatory syndrome. Clues to a systemic inflammatory aetiology may include constitutional symptoms, morning stiffness, elevated acute-phase reactants and progressive symptoms despite modification of physical activity. The mechanism of injury or lack thereof is also a clue to any underlying disease. In these circumstances, more complete workup is reasonable, including radiographs, magnetic resonance imaging and laboratory testing for autoantibodies.

Rheumatologic complications of HIV infection

The pandemic caused by the human immunodeficiency virus (HIV) has entered its second quarter-century, with 40 million people now affected worldwide – particularly in Africa, where the impact has been most devastating. A complex array of rheumatic disease manifestations has been described, including diseases specific to HIV infection such as HIV-associated arthritis and the diffuse infiltrative lymphocytosis syndrome; other conditions which occur prominently in HIV-positive individuals include vasculitis, reactive and psoriatic arthritis and HIV-associated polymyositis, opportunistic musculoskeletal infections, and finally disorders that were originally ameliorated by HIV infection, such as rheumatoid arthritis and lupus. Effective antiretroviral treatment ameliorates many of these disorders; however, the introduction of highly active antiretroviral treatment (HAART) has introduced a new spectrum of disorders and new challenges confronting the clinician, including osteonecrosis, rhabdomyolysis, and, with immune reconstitution, the appearance de novo of a variety of autoimmune disorders and phenomena.

Macrophage activation syndrome as the presenting manifestation of rheumatic diseases in childhood

We describe 3 patients who presented with features of macrophage activation syndrome (MAS) at the time of presentation of systemic lupus erythematosus (SLE), systemic juvenile idiopathic arthritis, and Kawasaki disease. Immunohistochemical studies in the patient with SLE demonstrated extensive expression of CD163 on hemophagocytic macrophages, suggesting a possible role as a marker of MAS.

Cognitive dysfunction in the patient with antiphospholipid antibodies: Considerations for cause and treatment

The evidence supporting a causal relationship between antiphospholipid (aPL) antibodies and cognitive dysfunction is very limited despite a general impression that one exists. Patients with aPL antibodies may complain of cognitive difficulties in their everyday lives, forcing the clinician to examine this issue. As with other non-thrombotic antiphospholipid syndrome (APS) manifestations, cognitive dysfunction in this population should be approached as a diagnosis of exclusion. The complexity in diagnosing and treating various manifestations of rheumatic disease holds true for identifying and addressing cognitive decline in these patients.

The cardiovascular manifestations of rheumatic diseases

To review the cardiovascular manifestations of several more common rheumatic conditions in the light of the recent reported literature. Evidence that chronic inflammation is associated with the occurrence of cardiac events in people both with and without chronic inflammatory joint disease is emerging. Both atherosclerosis and rheumatic diseases, however, have a complicated cause, and it is likely that inflammation contributes to other environmental and host risk factors in these patients. Treatments used to suppress inflammation in many rheumatic conditions have the potential to reduce cardiovascular disease morbidity as well as improve musculoskeletal function. Cardiovascular morbidity and mortality have been found to be increased in association with many of the rheumatic diseases. In particular, coronary heart disease seems to be associated with inflammatory rheumatic conditions. Whilst it is likely that chronic systemic inflammation promotes accelerated atherosclerosis in these patients, the mechanisms by which this occurs are complex and the effects of treatment and other cardiovascular risk factors need to be considered.

Scintigraphy in rheumatic diseases

The aim of this review is to summarise the clinical role of nuclear medicine in rheumatology taking into consideration the most specific diagnostic applications and other worthwhile therapeutic contributions. Traditional bone scintigraphy and recent inflammation-targeting radiopharmaceuticals, such as radiolabelled leucocytes and immunoscintigraphy, now allow us to obtain highly sensitive total-body and tomographical imaging information that can be used for the diagnosis of osteoarticular disease. The most common extra-articular manifestations of rheumatic diseases due to digestive, central nervous, respiratory and cardiovascular system involvement can be diagnosed by specific scintigraphic methods. Radiosynovectomy plays an important role in providing effective treatment for some joint diseases that are resistant to pharmacological therapy. Diagnostic and therapeutic applications of nuclear medicine show the highest efficacy in the early phase of rheumatic diseases. In more advanced stages, scintigraphical techniques play a complementary role to radiographical investigations in the assessment of prognosis and therapy efficacy.

Skin manifestations of systemic autoimmune connective tissue disease: diagnostics and therapeutics.

Skin disease can significantly affect the quality of life of patients suffering from rheumatic diseases. In addition, important relationships exist between the cutaneous and systemic manifestations of rheumatic disease. It is thus important for practicing rheumatologists to have a solid working understanding of the subject of rheumatic skin disease. Unfortunately, it is not possible within the scope of this chapter to provide a comprehensive overview of the recognition and management of all of the cutaneous manifestations of lupus erythematosus (LE), much less those of dermatomyositis (DM)/polymyositis and scleroderma/systemic sclerosis (SSc) as well. As can be seen in in the text, the cutaneous manifestations of polygenic autoimmune disorders such as LE can be as heterogeneous clinically as are its systemic manifestations. This discussion will therefore focus on recent key developments concerning the diagnosis and management of the more common skin changes that the practicing rheumatologist is likely to encountered in the three major rheumatic diseases: LE, DM and SSc.

KONSUPREN IN THETHERAPY OF RHEUMATIC DISEASES

Summary Aim: to assess the efficacy and tolerability of Consupren (Galena, Chekia ) in some rheumatic diseases. Material and methods. Three months’ therapy by Consupren was studied in 12 patients: 4 with SLE, 4 with Behcet’s disease, 2 with rheumatoid arthritis with systemic manifestations, 2 with juvenile rheumatoid arthritis. Sandimmune therapy was changed for Consupren in 9 patients. All patients were controlled for the level of serum creatinine and AD and had consultations with ophtalmologist. Results. 3 SLE patients treated by Consupren demonstrated decreasing of proteinuria, disease activity by SLAM and SLEDA1, the fourth patient demonstrated fading of diskoid rash and normalizing of temperature. Patients with Behcet’s disease had no episodes of ulcerous stomatitis and uveitis exacerbation, in one patient stable nodular erythema disappeared. Patients with JRA improved articular syndrome, normalized temperature, reduced acute phase indices. Both patients continue taking Consupren, RA patients had long term of onset of the disease and 111-IV radiological stage , thus the effect on the articular syndrome was not so demonstrative but the activity of the disease reduced. Conclusion: consupren is effective and well tolerable drug for patients with systemic manifestations of rheumatic diseases. No side effects were noticed.

Ophthalmologic manifestations of rheumatic diseases

Objectives: Detailed review of the manifestations of eye involvement in the context of rheumatic diseases. Methods: An OVID Medline search of the rheumatology and ophthalmology English literature related to the eye manifestations of human rheumatic diseases from 1966 to the present was conducted by the authors. Results: Analysis of 300 recent and consecutive rheumatology consultations from a large Veterans Administration Healthcare System shows that 4% are referred for eye manifestations of suspected rheumatic diseases, most commonly, anterior uveitis and keratoconjunctivitis sicca (KCS). Ocular involvement is common in the rheumatic diseases but varies among the different disorders. A literature review indicated that the most common ocular manifestations of rheumatic diseases include keratoconjunctivitis sicca, anterior uveitis, and scleritis. The most serious eye complications of the inherited connective tissue disorders are lens involvement with cataract formation or subluxation. The most significant side effects of the drugs used to treat rheumatic diseases are the maculopathy associated with anti-malarial agents and cataracts and glaucoma associated with corticosteroid use. Although many of the eye manifestations are easily recognizable, consultation with an ophthalmologist is usually necessary for optimal treatment and prevention of complications. Conclusions: The rheumatologist, in coordination with the ophthalmologist, can play a major role in detecting and managing the eye involvement in his patients to save this important sense. Understanding the varied manifestations of eye disease will permit the rheumatologist to better evaluate the activity of the rheumatic disease. Semin Arthritis Rheum 30:217-241. Copyright © 2001 by W.B. Saunders Company

Autoantibody recognition of distinctly modified forms of the U1-70-kd antigen is associated with different clinical disease manifestations.

To examine whether autoantibody recognition of modified forms of the U1-70-kd RNP antigen correlates with manifestations of rheumatic disease. Blinded to clinical disease manifestations, sera from 27 rheumatic disease patients with U1-70-kd antibodies were used to immunoblot control, apoptotic, and oxidatively modified HeLa cell lysates. Using densitometry, recognition of antigen fragments was quantitated. The presence or absence of 1) lupus skin disease and 2) Raynaud's phenomenon (RP) was determined for each patient by chart review. The ability of patient sera to recognize the different fragments was compared for patients with and without skin disease and with and without RP. Patients with lupus skin disease had higher recognition of apoptotic U1-70 kd than did patients without skin disease (mean +/- SD fragment recognition index [FRI] 1.35 +/- 0.57 versus 0.95 +/- 0.25; P < 0.024, by Student's t-test). Patients with RP had higher recognition of oxidatively modified U1-70 kd than did patients without RP (mean +/- SD FRI 0.95 +/- 0.80 versus 0.24 +/- 0.22; P < 0.048). Recognition of apoptotically and oxidatively modified forms of the U1-70-kd autoantigen are associated with distinct clinical rheumatic disease manifestations. This finding provides in vivo evidence for the hypothesis that immune recognition of modified forms of self antigens may be relevant to the pathogenesis of systemic rheumatic diseases. Understanding the antigenic modifications to which patients react may help predict the expression of rheumatic syndromes.

Pulmonary alveolar hemorrhage in patients with rheumatic diseases in Korea. Clinical presentation, treatment, survival, and outcome

Pulmonary alveolar hemorrhage (PAH) is a rare and often fatal presenting feature of rheumatic diseases, with high mortality rate ranging from 40% to 90%. This study was undertaken to review the clinical manifestations, disease course, prognosis, and treatment of PAH in rheumatic diseases in Korea. A retrospective analysis was performed from October 1995 to March 1999 at the Samsung Medical Center. Ten cases were diagnosed as having pulmonary hemorrhage with rheumatic diseases that comprised the following: 6 systemic lupus erythematosus (SLE), 3 microscopic polyangiitis (MPA), and 1 mixed connective tissue disease (MCTD). In 80% of the patients in the present series, PAH was the first clinical manifestation of rheumatic diseases. The most consistent systemic manifestation occurring in conjunction with PAH was renal involvement (80%). The overall patient mortality rate was 50% (5/10) in the current series. Our study suggests that PAH often occurs as the first clinical manifestation of rheumatic diseases and needs urgent medical treatment including plasmapheresis in addition to cyclophosphamide and methylprednisolone.

Radiographic Manifestations of Rheumatic Diseases Affecting The Foot and Ankle

Radiographic Manifestations of Rheumatic Diseases Affecting The Foot and Ankle

Ocular manifestations in rheumatic diseases

全身性疾患である膠原病では多彩な病態を示す眼病変がしばしばみられる. 本領域では視力予後にもかかわる重要な病変であるぶどう膜炎・血管病変の頻度が高い. またシェーグレン症候群をしばしば合併し乾燥性角結膜炎が問題となる. 一方, ステロイド剤の副作用の影響もあり白内障・緑内障が多くみられる. 膠原病の診療においては内科医と眼科医の連係が重要である.