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. As noted by Huskisson, however, "In the absence of knowledge about the cause of disease and the mode of action of the drugs, the only way forward is by clinical trials of different preparations. With trial, there is always the risk of error." Our greatest error, however, will be if we ignore lessons from the past, fail to control the inflammatory process early, and continue to spend years writing "doing well" in the charts of patients who become progressively disabled before our eyes.

Polymyalgia rheumatica and seronegative rheumatoid arthritis may be the same entity.

Of 159 patients with either polymyalgia rheumatica, seronegative rheumatoid arthritis (RA) or an undifferentiated syndrome with features of both who were followed for at least 30 months, synovitis recurred in 57. Twenty of the 57 patients had one episode of polymyalgia and another that looked like RA. Recurrences responded to prednisone and no joint destruction was seen. Temporal arteritis was seen with both diagnoses. These observations suggest that a benign symmetric synovitis occurs in older patients and may present as polymyalgia or as a polyarthritis that resembles RA.

Relation of giant cell arteritis to polymyalgia rheumatica.

Polymyalgia rheumatica and temporal arteritis appear to be separate syndromes rather than two manifestations of an underlying giant cell arteritis. Polymyalgia rheumatica is a synovitis that may be persistent or recurrent, while temporal arteritis is almost always a single episode; documented recurrences are rare. The two syndromes frequently occur in the same patient although not necessarily at the same time and they may be separated by a long interval. In some patients with polymyalgia rheumatica, giant cell arteritis is found on biopsy of an asymptomatic temporal artery. The frequency of this concurrence is variable in different populations. It is high in Scandinavia, low in Israel and intermediate between these extremes in other populations that have been studied.

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. We possess a number of drugs, each only partially effective against inflammation, that work by poorly understood mechanisms. Until a major breakthrough appears, it is proposed to treat RA with a combination of these medications early in the disease course, to gain control of the inflammation, and then bridge to a simplified program by withdrawing drugs sequentially.

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. Many medications working by different mechanisms have a partial or temporary effect on inflammation. Following the example of cancer chemotherapy, we propose the step-down bridge, a therapeutic plan in which a combination of drugs is used to control inflammation early in the disease before joints become damaged. Medications are then sequentially discontinued as inflammation remains controlled.

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. Contrary to popular wisdom, this has been best demonstrated with prednisone. The arbitrary concept of a drug being either antiinflammatory or disease modifying serves no useful purpose and should be dropped. Many medications provide incomplete or temporary suppression of inflammation, presumably by differing mechanisms of action. Based on this rationale, a therapeutic program is proposed, employing a combination of drugs to control inflammation in the critical early stages of RA. With this step-down bridge concept, medications are sequentially withdrawn in contrast to the traditional pyramid, in which they have been sequentially added. Our early experience with patients indicates that toxicity is no greater problem with combined drugs than with the same drugs used individually. Time and comparative observations will be needed to show the optimum combination of drugs and whether the step-down bridge concept will achieve the sought-for and presently unobtained goal of early and sustained control of inflammation, improved quality of life, and prevention of bone and joint damage.

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.

Late-onset rheumatoid arthritis vs polymyalgia rheumatica: making the diagnosis.

Differentiating polymyalgia rheumatica from the onset of rheumatoid arthritis in the elderly has been the cause of much unnecessary confusion. Differential diagnosis of these disorders can be straightforward. A strategy is outlined, comprising a complete history, attention to clinical signs, and appropriate use of laboratory diagnostics. The clinical picture of each disorder is discussed, as are common obstacles to diagnosis.