Rheumatoid Arthritis Clinical Presentation

/Home/Complications of Arthritis/Arthritis and Scleritis/Arthritis & Scleritis Symptoms

Rheumatoid Arthritis Clinical Presentation
www.hopkinsmedicine.org


by Alan K. Matsumoto, M.D.

Rheumatoid arthritis is a highly inflammatory polyarthritis often leading to joint destruction, deformity and loss of function. Additive, symmetric swelling of peripheral joints is the hallmark of the disease. Extra-articular features and systemic symptoms can commonly occur and may antedate the onset of joint symptoms. Chronic pain, disability and excess mortality are unfortunate sequelae.

Epidemiology

Rheumatoid arthritis has a worldwide distribution with an estimated prevalence of 1 to 2%. Prevalence increases with age, approaching 5% in women over age 55. The average annual incidence in the United States is about 70 per 100,000 annually. Both incidence and prevalence of rheumatoid arthritis are two to three times greater in women than in men. Although rheumatoid arthritis may present at any age, patients most commonly are first affected in the third to sixth decades.

(top of page)

History

The typical case of rheumatoid arthritis begins insidiously, with the slow development of signs and symptoms over weeks to months. Often the patient first notices stiffness (see below) in one or more joints, usually accompanied by pain on movement and by tenderness in the joint. The number of joints involved is highly variable, but almost always the process is eventually polyarticular, involving five or more joints. Rheumatoid arthritis is an additive polyarthritis, with the sequential addition of involved joints, in contrast to the migratory or evanescent arthritis of systemic lupus erythematosus or the episodic arthritis of gout. Occasionally, patients experience an explosive polyarticular onset occurring over 24 to 48 hours. (see ACR Guidelines)

The joints involved most often are the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints of the hands, the wrists (particularly at the ulnar-styloid articulation), shoulders, elbows, knees, ankles, and metatarsophalangeal (MTP) joints. The distal interphalangeal (DIP) joints are generally spared. The spine except the atlanto-axial articulation in late disease is never affected.

Morning stiffness, persisting more than one hour but often lasting several hours, may be a feature of any inflammatory arthritis but is especially characteristic of rheumatoid arthritis. Its duration is a useful gauge of the inflammatory activity of the disease. Similar stiffness can occur after long periods of sitting or inactivity (gel phenomenon). In contrast, patients with degenerative arthritis complain of stiffness lasting but a few minutes.

Nonspecific systemic symptoms primarily fatigue, malaise, and depression, may commonly precede other symptoms of the disease by weeks to months. Patients complain of severe fatigue 4 to 6 hours after wakening. Fever occasionally occurs and is almost always low grade (37° to 38°C; 99° to 100°F). A higher fever suggests another illness, and infectious causes must be considered.

It is typical of patients with rheumatoid arthritis that their symptoms wax and wane often making diagnosis and treatment decisions difficult. Atypical presentations include intermittent joint inflammation that can be confused with gout or pseudogout, proximal muscle pain and tenderness mimicking polymyalgia rheumatica or diffuse musculoskeletal pain seen in fibromyalgia.

(top of page)

Physical Examination

Symmetric joint swelling, although not invariable, is characteristic of rheumatoid arthritis. Careful palpation of the joints can help to distinguish the swelling of joint inflammation from the bony enlargement seen in osteoarthritis. Fusiform swelling of the PIP joints of the hands is a common early finding. (pictured below) MCP, wrists, elbows, knees, ankles and MTP are other joints commonly affected where swelling is easily detected. In contrast to gout or septic arthritis, redness of affected joints is not a prominent feature of rheumatoid arthritis. Pain on passive motion is the most sensitive test for joint inflammation. Occasionally inflamed joints will feel warm to the touch. Inflammation, structural deformity, or both may limit the range of motion of the joint. To institute proper therapy (see below), it is important to determine which of these processes is the major factor limiting joint function.

Permanent deformity is an unwanted result of the inflammatory process. Persistent tenosynovitis and synovitis leads to the formation of synovial cysts and to displaced or ruptured tendons. Extensor tendon rupture at the dorsum of the hand is a common and disabling problem.



Reprinted from the Clinical Slide Collection on the Rheumatic Diseases, copyright 1991, 1995, 1997. Used by permission of the American College of Rheumatology.

As evident in the picture below, bony erosions seen at the margins of the joint, at the attachment of the synovium, are the hallmark of rheumatoid arthritis.



Reprinted from the Clinical Slide Collection on the Rheumatic Diseases, copyright 1991, 1995, 1997. Used by permission of the American College of Rheumatology.

Erosions, clearly seen in the x-ray below, occur rapidly within the first 2 years of the disease. These anatomic changes result in limitations in range of motion, flexion contractures, and subluxation (incomplete dislocation) of articulating bones.



Reprinted from the Clinical Slide Collection on the Rheumatic Diseases, copyright 1991, 1995, 1997. Used by permission of the American College of Rheumatology.


Typical visible changes (shown below) include ulnar deviation of the fingers at the MCP joints, hyperextension or hyperflexion of the MCP and PIP joints, flexion contractures of the elbows, and subluxation of the carpal bones and toes (cocked -up).




Reprinted from the Clinical Slide Collection on the Rheumatic Diseases, copyright 1991, 1995, 1997. Used by permission of the American College of Rheumatology.

(top of page)

Laboratory Tests

Chemistries Hematology Serology Radiology

Initial Laboratory work-up

Complete blood count
Comprehensive metabolic panel
Urinalysis
Sedimentation Rate
Rheumatoid Factor
Anti-nuclear Antibody
Chemistries
Chemistries are normal in rheumatoid arthritis with the exception of a slight decrease in albumin and increase in total protein reflecting the chronic inflammatory process. Renal and liver function should be checked prior to instituting therapy.

(top of section)

Hematology
A mild anemia with hematocrit values in the range of 30 - 34% occurs in approximately 25 to 35% of patients with rheumatoid arthritis. In most cases, the reduced red cell mass is caused by the anemia of chronic disease, a normocytic-normochromic process characterized by a low concentration of serum iron, a low serum iron-binding capacity, and a normal or increased serum ferritin concentration. However, occasionally true iron deficiency anemia can develop secondary to intercurrent blood loss often from gastrointestinal (GI) bleeding due to NSAIDS. The inflammation of rheumatoid arthritis inhibits erythropoiesis, making it difficult to differentiate anemia secondary to chronic blood loss, from the anemia of chronic disease, without an iron stain of the bone marrow. Patients should be monitored closely for symptoms of GI bleeding and consideration must also be given to other causes of GI blood loss such as colonic lesions.

The white cell count is usually normal in patients with rheumatoid arthritis, but can be mildly elevated secondary to inflammation. Similarly, the platelet count is usually normal but thrombocytosis occurs in response to inflammation. Drug reactions and Felty's syndrome are rare causes of leukopenia or thrombocytopenia (see below).

The erythrocyte sedimentation rate (ESR) is usually elevated in patients with rheumatoid arthritis and in some patients is a helpful adjunct in following the activity of the disease.

(top of section)

Serology
Rheumatoid factors are antibodies directed against the Fc portion of immunoglobulin G (IgG). A positive test for rheumatoid factor is by no means pathognomonic of rheumatoid arthritis, but is present in 70 to 90% of patients with the disease. The titer does not correlate with the activity of disease, but patients with a high titer rheumatoid factor are more likely to have erosive joint disease, extra-articular manifestations, and greater functional disability. In contrast, generally, rheumatoid factor negative patients exhibit a milder disease course. Rheumatoid factors are also detectable in non-rheumatoid patients who have chronic antigenic stimulation, such as prolonged infection (bacterial endocarditis, tuberculosis, cytomegalovirus, human immunodeficiency virus (HIV), collagen vascular disease, or dysproteinemia). Low titers of rheumatoid factors may be detected in the serum of apparently normal people, especially over the age of 70, where its prevalence is anywhere from 10 - 25%. The anti-nuclear antibody (ANA) is positive in 20-30% of patients with rheumatoid arthritis and is more common in patients with extra-articular manifestations.

(top of section)

Radiology
Radiological findings early in the disease may show nothing other than soft tissue swelling. Thereafter, periarticular osteopenia may develop. With progression of their disease, narrowing of the joint space is caused by loss of cartilage, and juxta-articular erosions appear, generally at the point of attachment of the synovium. In end-stage disease, large cystic erosions of bone may be seen. Bony proliferation may occur because of degenerative changes that follow inflammation. In the picture below, erosive changes at the carpal bones can be seen.






Reprinted from the Clinical Slide Collection on the Rheumatic Diseases, copyright 1991, 1995, 1997. Used by permission of the American College of Rheumatology.

(top of section)
(top of page)

Extra-Articular Disease

Rheumatoid Nodules Cardiopulmonary Disease Ocular Disease Neurologic Disease Felty's Syndrome Rheumatoid Vasculitis Sjogren's Syndrome

Although the joints are almost always the principal focus of the rheumatoid arthritis, other organ systems may also be involved. Extra-articular manifestations of rheumatoid arthritis occur most often in seropositive patients with more severe joint disease. Interestingly, extra-articular manifestations can occur in later stages of the disease when there is little active synovitis ("burnt-out" disease). In contrast to the predilection of rheumatoid arthritis for women, extra-articular manifestations of the disease are more common in men.

Rheumatoid Nodules
The subcutaneous nodule is the most characteristic extra-articular lesion of the disease. Nodules occur in 20 to 30% of cases, almost exclusively in seropositive patients. They are located most commonly on the extensor surfaces of the arms and elbows (shown below) but are also prone to develop at pressure points on the feet and knees.


Reprinted from the Clinical Slide Collection on the Rheumatic Diseases, copyright 1991, 1995, 1997. Used by permission of the American College of Rheumatology.

Rarely, nodules may arise in visceral organs, such as the lungs, the heart, or the sclera of the eye. (learn more about rheumatoid nodules in case report #6)

(top of section)

Cardiopulmonary Disease
There are several pulmonary manifestations of rheumatoid arthritis, including pleurisy with or without effusion, intrapulmonary nodules, rheumatoid pneumoconiosis (Caplan's syndrome), diffuse interstitial fibrosis, and rarely, bronchiolitis obliterans pneumothorax. On pulmonary function testing, there commonly is a restrictive ventilatory defect with reduced lung volumes and a decreased diffusing capacity for carbon monoxide. Although mostly asymptomatic, of greatest concern is distinguishing these manifestations from infection and tumor. Pericarditis is the most common cardiac manifestation. (learn more about pulmonary complications in rheumatoid arthritis in case report #6)

(top of section)

Ocular Disease
Keratoconjunctivitis of Sjogren's syndrome is the most common ocular manifestation of rheumatoid arthritis. Sicca (dry eyes) is a common complaint. Episcleritis occurs occasionally and is manifested by mild pain and intense redness of the affected eye. Scleritis and corneal ulcerations are rare but more serious problems.

(top of section)

Neurologic Disease
The most common neurologic manifestation of rheumatoid arthritis is a mild, primarily sensory peripheral neuropathy, usually more marked in the lower extremities. Entrapment neuropathies (e.g., carpal tunnel syndrome and tarsal tunnel syndrome) sometimes occur in patients with rheumatoid arthritis because of compression of a peripheral nerve by inflamed edematous tissue. Cervical myelopathy secondary to atlantoaxial subluxation is an uncommon but particularly worrisome complication potentially causing permanent, even fatal neurologic damage.

(top of section)

Felty's Syndrome
Felty's syndrome is nowadays a rare complication of rheumatoid arthritis and is characterized by splenomegaly, and leukopenia - predominantly granulocytopenia. Recurrent bacterial infections and chronic refractory leg ulcers are the major complications.

(top of section)

Rheumatoid Vasculitis
The most common clinical manifestations of vasculitis are small digital infarcts along the nailbeds. (see picture below) The abrupt onset of an ischemic mononeuropathy (mononeuritis multiplex) or progressive scleritis is typical of rheumatoid vasculitis. The syndrome ordinarily emerges after years of seropositive, persistently active rheumatoid arthritis; however, vasculitis may occur when joints are inactive.


Reprinted from the Clinical Slide Collection on the Rheumatic Diseases, copyright 1991, 1995, 1997. Used by permission of the American College of Rheumatology.
(top of section)

Sjogren's Syndrome
Approximately 10 to 15% of patients with rheumatoid arthritis, mostly women develop Sjogren's syndrome, a chronic inflammatory disorder characterized by lymphocytic infiltration of lacrimal and salivary glands. This leads to impaired secretion of saliva and tears and results in the sicca complex: dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca).

Patients with Sjogren's syndrome have a variable expression of disease in other exocrine glands. This is manifested clinically as dry skin, decreased perspiration, dry vaginal membranes, or a nonproductive cough. Commonly, there is also a polyclonal lymphoproliferative reaction characterized by lymphadenopathy and splenomegaly. This can mimic and rarely transform into a malignant lymphoma.

(top of section)
(top of page)

Clinical Course

The course of rheumatoid arthritis cannot be predicted in a given patient. Several patterns of activity have been described:

a spontaneous remission particularly in the seronegative patient within the first 6 months of symptoms (less than 10%)
recurrent explosive attacks followed by periods of quiescence most commonly in the early phases
the usual pattern of persistent and progressive disease activity that waxes and wanes in intensity.
Disability is higher among patients with rheumatoid arthritis with 60% being unable to work 10 years after the onset of their disease. Recent studies have demonstrated an increased mortality in rheumatoid patients. Median life expectancy was shortened an average of 7 years for men and 3 years for women compared to control populations. In more than 5000 patients with rheumatoid arthritis from four centers, the mortality rate was two times greater than in the control population. Patients at higher risk for shortened survival are those with systemic extra-articular involvement, low functional capacity, low socioeconomic status, low education, and prednisone use.

(top of page)

References

Sjogren's syndrome. Rheum Dis Clin North Am 16:3, 1992.

Kelly WN, Harris ED Jr, Ruddy S, Sledge CB (eds): Textbook of Rheumatology, 5th ed. Philadelphia, WB Saunders, 1997.

Harris ED Jr.: Rheumatoid Arthritis, Philadelphia, WB Saunders, 1997.

Schumacher HR, Kippel JH, Koopman WJ: Primer on the Rheumatic Diseases, 10th ed. Atlanta, Arthritis Foundation, 1988.

McCarty DJ, Koopman WJ (eds): Arthritis and Allied Conditions, 12th ed. Philadelphia, Lea & Amp; Febiger, 1993.

Arnett FC, Edworthy SM, Bloch DA, et al: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315, 1988.

Harris ED Jr: Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med 322:1277, 1990.

Contact the Johns Hopkins Arthritis Center
Appointments
For more information on appointments with the Johns Hopkins Arthritis Center visit our appointment information page.

Web Site Inquiries
Email Us

Mailing Address
Johns Hopkins Arthritis Center
Attn: Wes Linda
5200 Eastern Ave
Suite 4100
Baltimore, MD 21224


Division of Rheumatology
Welcome to the Division of Rheumatology at Johns Hopkins. The Division of Rheumatology is a thriving clinical and academic center, which concentrates clinically on providing care to patients affected by a variety of common and uncommon rheumatic disorders.

We hope that you will find these pages useful to learn more about our clinical, research and educational programs, and that they will allow you to easily access the information and services that you seek. You will see in these webpages both the form and the spirit of our Division, created by the people who work here. Each person here embraces 3 values that guide our actions and work:

A relentless pursuit of Excellence in everything we do – patient care, teaching, and research
Caring – about patients, about students, about colleagues, about safety, about compliance
Helping – going the extra mile for patients, students, residents, colleagues, and coworkers.
Thank you for visiting us – we hope that we can be of assistance.

Sincerely,

Antony Rosen, MB ChB, BSc(Hons)
Mary Betty Stevens Professor of Medicine,
Professor of Cell Biology and Pathology,
Director, Division of Rheumatology