Oral steroids in rheumatoid arthritis. Helpful but not remittive

Although low-dose oral corticosteroid therapy cannot be considered remittive, it has earned a place in the therapeutic armamentarium for rheumatoid arthritis. Major clinical trials of a group using corticosteroid compared with a control group have not been done since the 1950s. One of these three large trials showed some slowing of the destructive joint changes of rheumatoid arthritis with use of low doses of corticosteroid. However, these agents have well-known side effects, especially when used long-term. Elderly patients or those who have features of the disease that indicate progression (eg, multiple joint involvement, elevated ESR, early evidence of erosion on x-ray films) are likely to benefit from carefully controlled doses of a corticosteroid. Because these drugs diminish bone formation and arthritis itself accelerates osteoporosis, supplemental calcium and vitamin D are useful adjuncts. A remittive agent and aspirin-like drug should be prescribed along with the corticosteroid. Abrupt withdrawal of even a very low dose of corticosteroids in rheumatoid arthritis patients causes a flare.     

Diagnosis and management of rheumatoid arthritis

Rheumatoid arthritis is the most commonly diagnosed systemic inflammatory arthritis. Women, smokers, and those with a family history of the disease are most often affected. Criteria for diagnosis include having at least one joint with definite swelling that is not explained by another disease. The likelihood of a rheumatoid arthritis diagnosis increases with the number of small joints involved. In a patient with inflammatory arthritis, the presence of a rheumatoid factor or anti-citrullinated protein antibody, or elevated C-reactive protein level or erythrocyte sedimentation rate suggests a diagnosis of rheumatoid arthritis. Initial laboratory evaluation should also include complete blood count with differential and assessment of renal and hepatic function. Patients taking biologic agents should be tested for hepatitis B, hepatitis C, and tuberculosis. Earlier diagnosis of rheumatoid arthritis allows for earlier treatment with disease-modifying antirheumatic agents. Combinations of medications are often used to control the disease. Methotrexate is typically the first-line drug for rheumatoid arthritis. Biologic agents, such as tumor necrosis factor inhibitors, are generally considered second-line agents or can be added for dual therapy. The goals of treatment include minimization of joint pain and swelling, prevention of radiographic damage and visible deformity, and continuation of work and personal activities. Joint replacement is indicated for patients with severe joint damage whose symptoms are poorly controlled by medical management.     

Role of biological agents in immune-mediated inflammatory diseases

A new era in the treatment of immune-mediated inflammatory disorders has begun with the clinical availability of anticytokine therapy. Biological agents that are currently available include 3 agents that decrease the activity of tumor necrosis factor-alpha (infliximab, adalimumab, etanercept) and an interleukin-1 receptor antagonist (anakinra), with many more in development. Those extraordinarily effective medications are an important addition to our therapeutic armamentarium, and, although originally developed for rheumatoid arthritis and Crohn disease, have been found to be efficacious in the treatment of seronegative spondyloarthropathies (psoriatic arthritis, ankylosing spondylitis) and juvenile rheumatoid arthritis. Their role is currently being defined in other autoimmune disorders such as uveitis, sarcoidosis, interstitial lung disease, vasculitis, inflammatory myopathies, graft-versus-host disease, and Sj?gren syndrome.     

Polyarticular pseudosepsis in rheumatoid arthritis.

Three patients with longstanding seropositive rheumatoid arthritis had fever and marked synovial fluid leukocytosis in multiple joints. No infectious agents were found in synovial fluid or blood, and the patients recovered uneventfully without prolonged antibiotic therapy. Acute, severe exacerbations of synovitis in patients with rheumatoid arthritis may simulate a septic process and involve multiple joints.     

Old and new drugs used in rheumatoid arthritis: a historical perspective. Part 2: the newer drugs and drug strategies

After a 20-year hiatus, drug development for rheumatoid arthritis resumed in the early 1980s with cyclosporine, continuing in the 1990s with minocycline, leflunomide, and the tumor necrosis factor-alpha antagonists, infliximab and etanercept. Unlike the older disease-modifying antirheumatic drugs (apart from the cytotoxics), the newer drugs were designed with strict reference to proven pathophysiology in rheumatoid arthritis and, apart from minocycline, the intended action of these agents is highly likely the explanation for the observed efficacy. The evidence for the evolution of more rational drug development in rheumatoid arthritis has not altered the fact that efficacy versus toxicity still remains the major determinant in the practical use of these agents, as well as in the use of other, experimental agents briefly discussed. Action, efficacy, and toxicity also determine the rational chronologic use of these drugs alone and, in particular, in combination.     

难治性类风湿关节炎的治疗

简述了难治性类风湿关节炎 (RRA)的定义 ,分析了难治的可能原因 ,详述了RRA的用药策略。如加大病情改善药(DMARD)用量 ,联合用DMARD如甲氨蝶呤、柳氮磺吡啶与羟氯喹联用 ,加用皮质激素 ,用新型免疫抑制剂来氟米特 ,生物制剂如肿瘤坏死因子阻滞剂等。     

Current treatment strategies for rheumatoid arthritis

The management of rheumatoid arthritis has changed considerably during the past 15 years. Current strategies emphasize the need for early diagnosis and therapeutic intervention based on the use of disease-modifying antirheumatic drugs. The advent of agents that are more tailored to inhibit the specific disease processes will profoundly affect management. Immunogenetic studies may eventually assist in identifying subgroups of patients with rheumatoid arthritis who have more aggressive disease and who require a more aggressive treatment approach.     

Rethinking the therapeutic pyramid for rheumatoid arthritis. When are NSAIDs alone not enough?

A large number of agents that compare quite favorably to nonsteroidal anti-inflammatory drugs in terms of toxicity and efficacy are available to physicians for the treatment of rheumatoid arthritis. Primary care physicians need to familiarize themselves with the use of these drugs and consider prescribing them early in the course of the disease, when they may be of greatest benefit.     

The rheumatoid vasculitis and malignant rheumatoid arthritis(MRA)

The inflammatory process characteristic of rheumatoid arthritis is typically targeted to the synovial membrane. In a subset of patients, rheumatoid disease is complicated by an inflammatory destruction of blood vessels, rheumatoid vasculitis. Rheumatoid vasculitis has been understood to be the result of severe disease extending beyond the joint, possibly caused by immune complex deposition. However, in Japan malignant rheumatoid arthritis(MRA) is designated as rheumatoid arthritis with vasculitis. Rheumatoid arthritis patients can be separated into two groups: individuals with synovial disease and individuals with synovial plus extra-articular disease, MRA. The model is supported by immunogenetic analysis describing an accumulation of vasculitis patients with rheumatoid arthritis among HLA-DRB10401 homozygotes. Therapy depends upon the clinical manifestation of rheumatoid vasculitis. Then, MRA is usually treated with steroid, and steroid pulse therapy and immunosuppressants are useful for severe MRA.     

Focus on biological agents in rheumatoid arthritis: newer treatments and therapeutic strategies

Tumour necrosis factor (TNF)-alpha and interleukin (IL)-1 are major regulators of inflammation. TNFalpha inhibitors have been shown to be effective in treating some inflammatory diseases such as rheumatoid arthritis. TNFalpha inhibitors include soluble receptor antagonists (etanercept) and monoclonal antibodies (infliximab, adalimumab). IL-1 inhibitors (anakinra) were also developed, used in therapeutics and licensed in France. TNFalpha inhibitors can be added to background regimens of methotrexate in second-line treatments. Etanercept and adalimumab can be administered alone, especially to patients who have experienced methotrexate toxicity or who do not show clinical and/or radiological improvement. The use of these new agents may optimise rheumatoid arthritis treatment and delay disease progression, particularly when first-line treatments are disappointing. This paper reviews recent data on biological therapies for rheumatoid arthritis: tolerance and their ability to modify the course of disease and prevent radiological damage.     

Rheumatoid arthritis. Practical use of medications

The treatment of rheumatoid arthritis is undergoing steady change as new medications are approved and new regimens are attempted. Once the diagnosis is ensured, therapy should include appropriate rest, physical and occupational therapy, involvement of the family or a supportive caregiver, and, most important, participation of the patient. If the disease is not terribly aggressive, therapy with nonsteroidal anti-inflammatory drugs is appropriate initially. If no response is obtained within 2 to 3 weeks, a new dose or different nonsteroidal agent is recommended. In many patients, aspirin, particularly if enteric-coated, is successful and very cost-effective. Disease-modifying antirheumatic drugs (DMARDs) are sometimes being used earlier in disease than previously. Hydroxychloroquine sulfate (Plaquenil Sulfate), auranofin (Ridaura), or sulfasalazine (Azulfidine, S.A.S.-500) is sometimes effective for early rheumatoid arthritis. For patients with more aggressive disease, intramuscular gold is the drug of first choice, and it is the only one that has been shown to decrease the rate of formation of new erosions. Significant toxic reactions occur in 30% to 40% of patients, however. D-penicillamine (Cuprimine, Depen) and azathioprine (Imuran) can be used if intramuscular gold is unsuccessful. Methotrexate (Rheumatrex Dose Pack) is the newest DMARD approved for treatment of rheumatoid arthritis. Its onset of action is rapid, and it is an effective anti-inflammatory agent. Its toxicity in patients with rheumatoid arthritis is not yet fully understood, however. Combination therapy with DMARDs is in its infancy, but such treatment is likely to become more prevalent in the future.     

Damage control in rheumatoid arthritis. Hard-hitting, early treatment is crucial to curbing joint destruction

Right from the onset, rheumatoid arthritis is an aggressive disease that can quickly alter joint structure and integrity. Such rapid pathogenesis requires that the diagnosis be established early and aggressive therapy initiated swiftly. In this article, Drs Issa and Ruderman describe what is known about the cause, progression, and outcomes of rheumatoid arthritis. They review the steps toward its diagnosis and urge that treatment be started promptly--to both contain disease and reduce joint destruction as soon as possible.     

Adalimumab for rheumatoid arthritis

In the last few years significant advances have been made in our understanding of the molecular mechanisms underlying rheumatoid arthritis pathogenesis. Pro-inflammatory cytokines, such as TNF-alpha, play a pivotal role in its pathogenesis. Anti-TNF-alpha biological agents are considered a major advance in the treatment of rheumatoid arthritis. Adalimumab is a fully human monoclonal antibody that binds specifically to TNF-alpha, thereby neutralising its activity. It had significant efficacy in well-designed, placebo-controlled trials in patients suffering from rheumatoid arthritis, both as monotherapy and in combination with various disease-modifying antirheumatic drugs, including methotrexate. Adalimumab was generally well tolerated during both concomitant therapy with methotrexate or standard antirheumatic therapy and monotherapy. In addition, the radiographic progression of structural joint damage was significantly inhibited by adalimumab and improved quality of life. This review summarises the recent available data.     

TNF-alpha antagonist induced lupus on three different agents

Tumor necrosis factor alpha (TNF alpha) antagonists are biologic agents used in the management of inflammatory conditions such as rheumatoid arthritis, seronegative spondyloarthropathies and inflammatory bowel disease. These agents have been recently shown to cause a syndrome called anti-TNF induced lupus (ATIL), a rare condition which has similar clinical manifestations to idiopathic systemic lupus erythematosus (SLE). Given that extra-intestinal manifestations of inflammatory bowel disease include arthritis, it can be difficult to separate arthritis due to underlying disease from drug-induced arthritis. We present a case of a 28-year-old female with Crohn’s disease, who developed disabling arthritis as a clinical manifestation of ATIL following treatment with three anti-TNF agents, namely infliximab, adalimumab and certolizumab.     

Adalimumab for rheumatoid arthritis

In the last few years significant advances have been made in our understanding of the molecular mechanisms underlying rheumatoid arthritis pathogenesis. Pro-inflammatory cytokines, such as TNF-α, play a pivotal role in its pathogenesis. Anti-TNF-α biological agents are considered a major advance in the treatment of rheumatoid arthritis. Adalimumab is a fully human monoclonal antibody that binds specifically to TNF-α, thereby neutralising its activity. It had significant efficacy in well-designed, placebo-controlled trials in patients suffering from rheumatoid arthritis, both as monotherapy and in combination with various disease-modifying antirheumatic drugs, including methotrexate. Adalimumab was generally well tolerated during both concomitant therapy with methotrexate or standard antirheumatic therapy and monotherapy. In addition, the radiographic progression of structural joint damage was significantly inhibited by adalimumab and improved quality of life. This review summarises the recent available data.     

B Lymphocytes in Rheumatoid Arthritis and the Effects of Anti–TNF-α Agents on B Lymphocytes: A Review of the Literature

Purpose

The aim of this article was to review published research related to B lymphocytes in rheumatoid arthritis, their role in the pathogenesis of the disease, the effects of tumor necrosis factor (TNF)-α inhibitors on B lymphocytes, the risk for infection, and responses to vaccines.

Lyme arthritis

Infection with B. burgdorferi can cause a large joint inflammatory arthritis in patients who have not been treated for early Lyme disease; the knee is the most common joint affected. The diagnosis depends on a history of known exposure to the spirochete, characteristic clinical features, and serologic studies (ELISA and Western blot) confirming exposure to the spirochete. In most patients, antibiotic therapy is curative, but in a smaller percentage of patients, the presence of the HLA-DR beta 1*0401 haplotype can trigger treatment-resistant arthritis, in which antibiotic therapy is ineffective; in these instances, remittive agents, such as hydroxychloroquine and methotrexate, are indicated. Arthroscopic synovectomy may be considered when antibiotic therapy is not curative. Fibromyalgia can follow infection with B. burgdorferi but is unresponsive to antibiotic therapy; it is treated with tricyclic antidepressants and an exercise program. Lyme arthritis is the only chronic inflammatory arthritis in which the specific cause is known and can be cured. As such, it serves as an excellent model with which to study the pathogenesis of more common inflammatory arthritides, such as rheumatoid arthritis.     

类风湿关节炎的生物制剂治疗

类风湿关节炎（rheum atoid arthritis,RA）是一种常见的致残性疾病,严重影响患者的生活质量。传统的RA药物治疗主要包括非甾体抗炎药、糖皮质激素以及慢作用药物,然而这些药物常常不能满意控制那些难治性RA患者的病情,最终导致关节进行性破坏。近年,由于多种生物制剂的出现,为治疗难治性RA带来了希望,这些生物制剂在控制风湿病情和改善生活质量方面发挥了重要作用。