Evaluating severity and status in rheumatoid arthritis.

There is general agreement regarding the most appropriate examinations and methods to use to evaluate change in status in randomized controlled trials (RCT). However, no guidelines exist to aid in determining and evaluating actual status rather than change in status, particularly when applied to individual patients with rheumatoid arthritis (RA). In addition, methods appropriate for clinical trials may not be useful in evaluating individual patients because of time constraints.

Etanercept for the treatment of human immunodeficiency virus-associated psoriatic arthritis.

Etanercept may play an important role in modulating the inflammatory activity and progression of human immunodeficiency virus (HIV)-associated psoriasis and psoriatic arthritis. We report the case of a 45-year-old homosexual man with a CD4 cell count of less than 0.05 x 10(9)/L and an HIV viral load of 4200 copies/mL (while receiving highly active antiretroviral therapy) who developed extensive psoriatic plaques, 4.

VH usage and somatic hypermutation in peripheral blood B cells of patients with rheumatoid arthritis (RA).

The human antibody repertoire has been demonstrated to have a marked V-gene-dependent bias that is conserved between individuals. In RA patients, certain heavy chain V genes (VH) have been found to be preferentially used for encoding autoantibodies. To determine if such preferential use of VH genes in autoantibodies is associated with a general distortion of the V gene repertoire in RA patients, the VH composition of peripheral blood B cells was analysed among four RA patients and four age- and sex-matched healthy controls.

Development of an ELISA to detect anti-BP180 autoantibodies in bullous pemphigoid and herpes gestationis.

Autoantibodies associated with the subepidermal blistering disorders bullous pemphigoid and herpes gestationis react with a 180-kD transmembrane hemidesmosomal protein, designated BP180. The BP180 ectodomain is composed of a series of interrupted collagen triple helical domains. Located on one of the noncollagenous extracellular segments of this protein is an immunodominant epitope, designated MCW-1, recognized by patient autoantibodies.

Erosive rheumatoid factor negative and positive rheumatoid arthritis are immunogenetically similar.

Objective: The relationship between rheumatoid factor positive (RF+) and rheumatoid factor negative (RF-) rheumatoid arthritis (RA) is controversial. We sought to determine whether the HLA genes conferring susceptibility for erosive RF+RA are also prevalent in patients with erosive RF-RA.

Methods: DNA-based HLA typing for DRB1, DQB1, and DPB1 was performed on 16 consistently RF--patients with erosive RA.

Inverting the therapeutic pyramid: observations and recommendations on new directions in rheumatoid arthritis therapy based on the author's experience.

In evaluating current therapy for rheumatoid arthritis (RA), it is increasingly being recognized that sequential single-drug treatment, as exemplified by the traditional therapeutic pyramid, is often too little, too late, and ineffective in preventing disease progression or joint damage in patients with "at-risk," aggressive synovitis or what might be called type 2 RA. Designation of drugs as either antiinflammatory or disease-modifying is not supported by the author's experience. Evidence exists that prevention of joint damage correlates best with control of clinical and laboratory measures of inflammation, regardless of the medication used.

Approaches to the management of rheumatoid arthritis: rationale for early combination therapy.

In evaluating current therapy of RA, it is becoming recognized that sequential single drug treatment, as exemplified by the traditional therapeutic pyramid, is often too little and too late in patients with aggressive 'at risk' synovitis. Evidence exists that prevention of joint damage correlates best with control of clinical and laboratory measures of inflammation, regardless of the medication used. Until a major breakthrough occurs in this disease, it is recommended that patients with 'at risk' RA be treated aggressively to achieve early control of inflammation, and then 'bridge down' to a simplified maintenance programme.

The need for aggressive therapy of rheumatoid arthritis.

We are on the threshold of a new era in the treatment of RA if we learn from the experience of the past and utilize new techniques and therapeutic modalities that the future will bring. New strategies and treatment of RA in the future will need to include earlier recognition of progressive disease, earlier interventions, new preparations for use in therapeutic armamentarium, combinations of agents, and monitoring of long-term outcomes to assess results over 5 to 10 years. There is always concern about new therapies and strategies.

Case report: thrombotic thrombocytopenic purpura in a patient with polymyositis: therapeutic importance of early recognition and discussion of pathogenic mechanisms.

Thrombotic thrombocytopenic purpura (TTP) is characterized by the pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurologic symptoms, and renal dysfunction. Thrombotic thrombocytopenic purpura has recently been reported in association with rheumatic diseases (RDs). The authors present a patient with TTP and polymyositis and speculate on the pathophysiology linking these two conditions.

Challenging the therapeutic pyramid: a new look at treatment strategies for rheumatoid arthritis.

Traditional therapy of rheumatoid arthritis (RA) has been dominated by the therapeutic pyramid. This approach is not working. The designation of drugs as either antiinflammatory or disease modifying is not borne out by experience.

Reforming the pyramid. A plan for treating rheumatoid arthritis in the 1990s.

Standard treatment of rheumatoid arthritis as illustrated by the pyramid does not prevent joint damage in most patients. The concept that slow-acting drugs are uniquely disease modifying is not supported by experience. Disease modification correlates best with control of inflammation and this has been demonstrated with prednisone.

Remodeling the pyramid--a concept whose time has come.

It is clear that the traditional treatment program, as illustrated by the pyramid, does not suppress inflammation in most patients with RA to an extent sufficient to prevent joint damage. There is no basis for the concept that slow acting drugs are uniquely disease modifying. Disease modification correlates best with control of inflammation.

Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease.

Study Objective: To determine whether methotrexate has anti-inflammatory activity in refractory inflammatory bowel disease.

Design: Nonrandomized, open-label, preliminary trial of methotrexate along with standard medications for 12 weeks.

Setting: Referral-based gastroenterology practice.

HLA genes associated with rheumatoid arthritis. Identification of susceptibility alleles using specific oligonucleotide probes.

We examined the association of individual HLA genes with rheumatoid arthritis (RA), using oligonucleotide probes that identified both DR4-associated and non-DR4-associated genes. Two distinct HLA-DR beta alleles (Dw4 and Dw14) were found in DR4+ RA patients compared with controls (Dw4 50% versus 17%; Dw14 35% versus 5%; total DR4 73% versus 30%), indicating that these 2 alleles are independent susceptibility genes. Remarkably, the majority of the DR4- RA patients also demonstrated a linear DNA sequence, apparently "shuffled" between different susceptibility alleles, identified with an oligonucleotide probe to a key portion of the Dw14 gene.

Identification of HLA-Dw14 genes in DR4+ rheumatoid arthritis.

Genes of the major histocompatibility complex, HLA, are associated with susceptibility to rheumatoid arthritis (RA), but the aetiology of this chronic inflammatory disease is not known. Synthetic oligonucleotide DNA probes were constructed to distinguish between two closely related but distinct alleles encoding the HLA-DR4 specificity in patients with RA. With these allele-specific oligonucleotide probes an uncommon DR4 genetic variant, Dw14, was identified in 6 of 7 RA patients homozygous for HLA-DR4.

Association between giant cell (temporal) arteritis and HLA-Cw3.

Thirty-five Caucasian patients with giant cell (temporal) arteritis were typed for HLA class I and II antigens. A significant increase was found for A31, B40, Cw3, and DR4. HLA-Cw3 was the most frequent antigen observed (57%) and had the highest relative risk (5.

Polymyalgia rheumatica and giant cell arteritis. The dilemma of therapy.

Polymyalgia rheumatica, next to rheumatoid arthritis the most common inflammatory rheumatic disorder of the elderly, is a nonspecific clinical syndrome involving pain in the shoulder and pelvic girdles. Giant cell arteritis appears to localize in elastin-containing arteries and can cause similar myalgias. A relationship exists between the two diseases, as evidenced by their frequent coexistence in the same patient.

Polymyalgia rheumatica and giant cell arteritis.

Polymyalgia rheumatica is a relatively common syndrome of older patients, mostly white, manifested by aching and morning stiffness of the pelvic and shoulder girdles and accompanied by a rapid erythrocyte sedimentation rate. The symptoms are due to a synovitis, which is mild, nondestructive and very responsive to low-dose steroid treatment, which may need to be continued for several years. Temporal arteritis, which may accompany polymyalgia, can present as headache, loss of vision, diplopia or jaw claudication.