Bailliere's clinical rheumatology最新文献

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease characterized by the deposition of autoantibodies and immune complexes, leading to tissue damage. The immunopathogenesis of SLE is like a jigsaw puzzle, some pieces of which are missing or have not fallen into place. In predisposed individuals, the initial stimulus is likely to be one or more of the environmental agents interacting with susceptibility genes.

Once the critical threshold is breached there is a failure of the immune system to downregulate the ensuing abnormal immune response, involving polyclonal B cell activation and hyperactive T cell help. Key questions include, what are the processes behind the availability of autoantigens and the breakdown of tolerance that give rise to the pathogenic autoantibodies? Current areas of research also involve the roles played by cytokines, adhesion molecules, co-stimulatory molecules and apoptosis.

The antiphospholipid syndrome, initially described in systemic lupus erythematosus (SLE), occurs in 20–35% of patients with this condition. Its clinical manifestations may precede, be concurrent with, or follow clinical featurs of SLE. There are no major differences between the primary antiphospholipid syndrome and the secondary form that associates with SLE. Several studies suggest that the presence of an antiphospholipid syndrome in patients with SLE conveys a worse prognosis. To prevent recurrence of thrombotic events (particularly arterial events), oral anticoagulation with an international normalized ratio (INR) close to 3 is recommended. Treatment of recurrent fetal loss is with aspirin, or with aspirin plus heparin. Controlled studies are underway to determine optimal treatment in patients with cerebral ischaemia as well as the optimal treatment in women with recurrent pregnancy loss.

All aspects of the role of renal biopsy in systemic lupus erythematosus may not be defined and accepted, but there is increasing agreement as to the information that can be obtained from biopsy. Awareness of the importance of clinical (non-biopsy) predictors has permitted a clearer understanding of the ability of renal biopsy to confirm and to add information to a determination of prognosis based on clinical data. New techniques for scoring the patterns of injury detectable on renal biopsy have provided important insights into prognosis, pathogenesis and treatment of lupus nephritis. Watchful waiting is often an unwise course for the management of lupus nephritis. Thus, renal biopsy is increasingly seen as an important tool in the timely determination of prognosis.

Over the past decade, cytotoxic drugs have come to assume an increasingly important role in the management of systemic lupus erythematosus. Intravenous cyclophosphamide has become the standard treatment for lupus affecting major organs, in particular lupus nephritis. Cytotoxics with less potential for adverse side effects such as azathioprine and methotrexate are widely used in the management of non-major organ lupus and as an adjunct to reduce corticosteroid requirements. Recent clinical experience in lupus with newer cytotoxic drugs such as cyclosporin A, adenosine analogues, and mycophenolate mofetil appear promising and may offer improvements in lupus management in the future.

Pain is a major symptom in chronic inflammatory arthropathies such as rheumatoid arthritis and affects the health status of arthritis patients negatively. There has been much debate about the role of pain in juvenile chronic arthritis and this review deals with the controversies about this subject. Pain in children is best understood as a multifactorial concept in which pain is the result of somatosensory, behavioural and environmental factors. The role of the different factors contributing to pain will be assessed with special reference to mechanisms relevant to children with chronic pain, the various instruments to measure pain, such as visual analogue scales and algometry, and the treatment of chronic pain in juvenile chronic arthritis. For a true understanding of chronic pain in children, these multidimensional assessments should be integrated into a biobehavioural model, by means of which a better understanding should lead to new therapeutic interventions for one of the most common symptoms of rheumatic diseases in childhood: pain.

Rheumatoid paediatric diseases are a leading cause of uveitis in childhood. Juvenile chronic arthritis (JCA), juvenile onset spondyloarthropathies as well as sarcoidosis and other systemic diseases with arthritis may include ocular manifestations that can threaten vision, and especially so in juvenile chronic arthritis. Special risk factors concerning the eye have to be considered for JCA. The diagnosis, detection, follow-up studies and treatment in children may differ significantly from adult rheumatoid diseases because of the young age of the patients and the specific features and signs of ocular involvement. Medical and surgical treatment of such ocular manifestations may be challenging. Special attention to children's ophthalmic complications must be undertaken by paediatricians and ophthalmologists.

Juvenile arthritis (JA) is a term that covers a number of different disease entities, of which only three present with significant Human Leukocyte Antigen (HLA) associations. (1) Pauciarticular JA with late onset and a strong male proponderance is associated with HLA-B27 and represents the group of juvenile spondyloarthropathies related to adult ankylosing spondylitis. (2) Early onset pauciarticular JA with a preponderance of females and a frequent occurance of chronic iridocyclitis and the frequent presence of anti-nuclear antibodies is associated with alleles from three different regions of the HLA system: HLA-A2, which shows a very strong correlation with early age of onset; DR8, DR11 and DR12 as well as DQA1*0401, *0501, *0601 and finally DPB1*0201. These alleles show no linkage disequilibrium in the control population. (3) Rheumatoid factor positive polyarticular JA is associated, as is adult rheumatoid arthritis, with DR4.

Concerning the possible mechanisms of the immunopathogenesis, it is speculated that the normal function of HLA molecules, namely the presentation of antigenic peptides, plays a major role. Data collected on HLA associations in early onset pauciarticular JA have been interpreted as indicating that alleles of the DQA1 locus (*0401, *0501, *0601) are probably responsible for presenting the hypothetical arthritogenic peptides. It is speculated that the pathogenic process includes the presentation of HLA-A2 or HLA-DPB1*0201 derived peptides presented by DQ molecules.

It is clearly stated that typing for HLA alleles has very little or no importance for clinical diagnosis and prognosis.

The concept of spondyloarthropathies in childhood is emerging. It should now be more easily recognized since more specific diagnostic criteria are available for young patients. It probably accounts for about 20% of the whole group of chronic arthritides seen in paediatric rheumatology clinics. Juvenile ankylosing spondylitis stricto sensu is very rare in childhood. Most children who present with peripheral arthritis at onset meet the diagnostic criteria of undifferentiated spondyloarthropathies such as those of the SEA syndrome, or those of the ESSG or Amor criteria. At follow-up, quite a large proportion of children may develop axial involvement. Psoriatic arthritis differs from the other spondyloarthropathies with a different sex ratio, and an earlier onset. The role of immunogenetic, environmental and ethnic factors are important for a better understanding of these diseases.

Chronic childhood arthritis impairs joint function and may result in severe physical handicap. Joint pain and inflammation trigger a vicious cycle that often ends in joint damage and fixed deformities.

A comprehensive rehabilitation programme must start early to restore loss of function and prevent permanent handicap. It is dominated by a physiotherapeutic regimen consisting of pain relief, movement expansion, training of muscular coordination and finally re-integration of a physiological movement pattern. The approaches of occupational therapy become integrated into the treatment programme, concentrating on joint protection and self-care training. Additional aids support the aim of joint restoration. They include individual splinting, adapted footwear and walking aids.

Depending on the child's age and developmental status different aspects of rehabilitation dominate. Small children need adequate mobility to promote their psychosocial development. In later years integration into school life and the peer group becomes important. Adolescents require help for an adequate vocational training and self-care support.

Last but not least, parental education and integration of the whole family into the rehabilitation programme markedly improve the patient's prognosis.

The classification of chronic childhood arthritis has challenged physicians for a century. Currently used classifications are all based on clinical characteristics and because they are frequently used imprecisely, communication of scientific data has been difficult. The new classification of the International League of Associations of Rheumatologists (ILAR) represents the results of an international effort to clarify the classification of this group of diseases based on identification of clinically homogeneous groups. This classification process is ongoing, and will reflect the results of scientifically based studies as they become available.