What Is Rheumatoid Arthritis;Symptoms,Causes And Therapy

Rheumatoid arthritis is a systemic disease of unknown cause. The frequency of extra-articular manifestations justifies the concept of “rheumatoid disease,” but in the majority of patients clinical and pathologic findings and disability are the result of chronic inflammation of synovial membranes. There is striking heterogeneity among patients regarding mode of onset, pattern of joint involvement, frequency of extra-articular manifestations, and clinical course. There is a tendency for symmetrical involvement of hands, wrists, and feet. Spontaneous remissions and exacerbations are characteristic. Ten to 20 per cent of patients have complete remissions, whereas the remainder have sustained fluctuating activity. Joint injury results from formation of chronic granulation tissue (pannus), products of proliferative and exudative synovitis; this is capable of altering articular and periarticular structures.

What Is Rheumatoid Arthritis;Symptoms,Causes And Tharapy

Incidence and Epidemiology of Rheumatoid Arthritis.

The frequency of rheumatoid arthritis, based on limited population surveys in Europe and North America, is in the range of 1 to 3 per cent. It is two to three times more common in females. The onset is most frequent in the fourth and fifth decades of life, but it may occur at any age There are no consistent trends relating prevalence to geography, climate, or culture. The apparent relative rarity in tropical climates may reflect the age of indigenous populations and the level of available medical care. Multiple family members in selected kindreds may be affected; but in general, familial patterns (even in monozygotic twins) are not striking.

Pathology. The pathologic elements of chronic synovitis include exudation, cellular infiltration, and the proliferation of granulation tissue. Although polymorphonuclear leukocytes predominate in synovial fluid, the principal infiltrating cells in synovial membranes are lymphocytes. These are often arranged in nodular aggregates. occasionally as true lymphoid follicles with germinal centers. Rarely, the majority of infiltrating cells are plasmacytes. Multinucleated giant cells may be seen. None of the aforementioned histologic feat ures are diagnostic of rheumatoid arthritis.

Pannus. presumably by its content of hydrolytic enzymes. is capable of eroding articular cartilage, subchondral bone, ligaments, and tendons. Products of exudation seen. None of the aforementioned histologic features are diagnostic of rheumatoid arthritis.

Rheumatoid Arthritis Extra articular manifestations.

although clinically evident in a minority of patient*, may give rise to widespread pathologic features of rheumatoid arthritis Many of these appear to result from focal perivascular inflammation Ten to 20 per cent of patients with rheumatoid arthritis form subcutaneous or periosteal nodules over pressure or friction points The histologic appearance of nodules (central areas of necrosis surrounded by palisading connective tissue cells and an envelope of granulation tissue) is characteristic. In rare instances, the same granulomatous process can occur in multiple organs. More commonly i probably in the range of 50 per cent of cases’ there is a mild perivascular infiltration of mononuclear cells in muscle ami peripheral nerves An uncommon but significant complication of the disease is the development of diffuse necrotizing arteritis with visceral involvement indistinguishable from polyarteritis nndosa Milder forms of vasculitis, manifested by peripheral neuropathy and chronic skin ulcers of the lower extremities. are much more frequent In such patients chronic inflammation of the sclera is common.


The role of inflammation in the production of iirticular. periarticular, and extrn-urticular injury is evident. A variety of lysosomal enzymes, neutral protoases, and synovial collagenase are capable of hydrolyzing constituents of connective tissue, and the role of such enzymes in the induction of tissue injury seems explicit. A more basic question, however, is: What initiates and perpetuates the inflammatory response? In this regard, immunologic theories predominate.

Immunologic Features of Rheumatoid Arthritis

Synovial tissue in rheumatoid arthritis often displays histologic features characteristic of lymphoid organs, with prominent collections of lymphocytes and plasma cells (sometimes in the form of germinal centers Immunoglobulin synthesis has been demonstrated in rheumatoid synovial t issue by immuno-histologic and tissue culture studies. There is evidence for a role of immune complexes in the induction of inflammation. Synovial fluid exudate cells and synovial lining cells contain deposits of immunoglobulin and complement Complement levels 111 synovial fluid are reduced in a pattern consistent with immune activation, and complexes of immunoglobulins are detectable in joint fluid. Detailed characterization of these has not been accomplished, but in part they consist of rheumatoid factors.

Rheumatoid Arthritis Symptoms.

Pain, the dominant symptom, corresponds to the pattern and intensity of joint involvement, whereas stiffness is more generalized and is characteristically maximal after periods of physical inactivity. Morning stiffness is an almost invariable feature: its intensity and duration can guide one in assessment of disease activity.

The majority of patients experience constitutional symptoms such as weakness, increased fatigability, and diminished appetite. Temperature elevation in excess of 37.8*0 is uncommon. Higher temperatures should prompt search for superimposed infection, but occasionally temperatures as high as 40″ C have no other explanation than active rheumatoid arthritis. Many patients complain of coldness and hypesthesias and paresthesias in the hands and feet (in the absence of signs of nerve entrapment).

Physical Signs. The physical signs of rheumatoid arthritis vary enormously according to anatomic patterns, severity, and stage of disease. The “classic” articular and extra-articular expressions are features of chronic rheumatoid arthritis.

Differential Diagnosis of Rheumatoid Arthritis.

Differential considerations are numerous and vary according to the pattern of disease. There is seldom confusion in identifying “classic” rheumatoid arthritis, but symmetrical involvement of hand and wrist joints can be a feature of other syndromes (see below). Differentiation is more difficult and complex in patients with early acute polyarthritis or in those with arthritis limited to one or a few joints.

Chronic Polyarthritis.

The most common form of chronic arthropathy, degenerative joint disease, is usually quite distinct from rheumatoid arthritis. Minimal inflammatory signs, absence of constitutional symptoms. ESR determinations in the range of normal, and the characteristic radiographic findings usually serve to identify degenerative joint disease. A clinical pattern of degenerative joint disease which has been termed “primary generalized osteoarthritis” (see Ch. 98) may be mistaken for rheumatoid arthritis, especially when there is symmetrical enlargement of interphalangeal joints in the hands. Bouchard’s nodes, the bony enlargement of proximal interphalangeal joints of the hand (see Fig. 4B) are rather frequently misinterpreted as signs of rheumatoid arthritis.

Other Antirheumatic Therapy.

For the patient whose response to salicylate therapy has not been adequate, several other anti-inflammatory agents can be employed. These include indomethacin, phenylbutazone (and oxvphenbutazone), antimalarial drugs (chloroquine and hydroxychloroquine), and gold compounds. At the time of this writing, several other nonsteroidal antiinflammatory agents are under evaluation but are not yet licensed for use in the United States. The adrenocor-ticosteroid drugs are the most potent anti-inflammatory medications available, but their value, for reasons stated below, is limited. Unfortunately all medications employed for the treatment of rheumatoid arthritis, except gold compounds, have in common the property of promoting peptic ulceration.

Among those who specialize in the management of rheumatic disease, there is no uniformity of habit regarding the employment of agents listed above, although the majority, at some time, will institute gold therapy for the patient with sustained rheumatoid arthritis. Codeine and related analgesics may be required on a temporary basis, but their chronic use should Ik discouraged.

(Cytotoxic) Therapy.

Several drugs initially developed for cancer chemotherapy have been applied in the treatment of rheumatoid arthritis. The categories of compounds include alkylating agents, purine and pyrimidine antagonists, and folic acid analogues. There is no basis for concluding that one compound is superior to another in immunosuppressive and anti-inflammatory properties, but the best data with regard to the treatment of rheumatoid arthritis derive from a controlled study of cyclophosphamide therapy. Patients receiving up to 150 mg daily of cyclophosphamide sustained significantly fewer new bone erosions over the period of study. In spite of these observations, the use of immunosuppressive agents is to be viewed as experimental therapy. Acute toxicity, especially myelo-suppression, is potentially fatal and, as well, there is concern that immunosuppressive therapy may foster the emergence of primary malignant tumors.

Other Experimental Drugs. Penicillamine, in a well-controlled study in England, had moderate efficacy in the suppression of severe chronic rheumatoid arthritis and resulted in reductions of rheumatoid factor titers. As an antirheumatic agent, penicillamine remains in the experimental category, primarily because of potentially serious toxicity (agranulocytosis and nephropathy).

Orthopedic Surgery.

Orthopedic surgeons are playing an increasingly important role in the management of rheumatoid arthritis. The value of reconstructive surgery in the rehabilitation of selected subjects is well established. Techniques of arthroplasty and prosthetic joint replacement have improved dramatically during the past decade. The rationale for synovectomy is sound, i.e., the removal of chronic pannus and its destructive potential, but proof of its efficacy is lacking. Disease frequently recurs in regenerated synovium, but the intensity of recurrent inflammation tends to be less. On the basis of current experience, synovectomy is probably warranted for patients with sustained (several months or more) proliferative synovitis affecting knee, hand, and wrist joints.


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