What is Seronegative Rheumatoid Arthritis?

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  • Written By: Maggie J. Hall
  • Edited By: Susan Barwick
  • Last Modified Date: 13 September 2019
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The autoimmune disease, seronegative rheumatoid arthritis, may produce the same symptoms as rheumatoid arthritis (RA), although blood samples typically do not show the rheumatoid factor (RF) commonly associated with the disorder. Up to 20 percent of the patients suffering from this chronic inflammatory disease do not initially exhibit the RF, although some eventually convert to seropositive, producing the factor as the disease progresses. Joint inflammation, pain and damage usually occur in advanced cases, and other body systems might also become involved. Health care providers generally treat seronegative rheumatoid arthritis based on symptoms and disease progression.

Seronegative rheumatoid arthritis begins with cellular and humoral immune responses in the body. White blood cells from the bone marrow and the thymus begin making antibodies. These white blood cells, and the chemicals they produce, invade body tissue, especially joints. The first seronegative rheumatoid arthritis symptoms usually occur months before joint involvement and generally include depression, fatigue and malaise, which may be accompanied by a low-grade fever. After two or three months, patients experience inflammation, pain and tenderness in one joint.


As the disease progresses more extremity joints become involved. Morning stiffness and joint pain continue for a period of hours, a symptom which usually differentiates RA from other types of arthritis. Seronegative rheumatoid arthritis typically produces joint swelling and tenderness along with warmth and pain on movement. These symptoms occur because the autoimmune response causes tendon inflammation that may lead to cyst formation and eventual connective tissue ruptures. Usually within two years of onset, the loss of connective tissue causes bone cell erosion and proliferation, which results in joint deformities.

The swelling and inflammation commonly associated with seronegative rheumatoid arthritis might also compress sensitive nerve tissue, causing nerve pain. Patients may also experience symptoms related to muscle involvement. The autoimmune response may progress and eventually involve the cardiac and pulmonary systems, causing inflammation, fluid accumulation, and tissue fibrosis. Some develop a condition known as Sjogren’s syndrome, in which white blood cells infiltrate lacrimal, salivary, and exocrine glands, inhibiting the normal flow of body fluids.

Definitive diagnosis of seronegative rheumatoid arthritis often presents a challenge in the early stages. Not only do patients not exhibit RF in blood samples, the symptoms can come and go. Individuals might experience an exacerbation of symptoms for 24 to 48 hours followed by complete resolution. Some people have complete remission within six months from onset of initial symptoms. Development of the anti-cyclic citrullinated protein (anti-CPP) antibody blood test has helped to identify the disease in some patients who do not typically produce RF.

Health care providers generally prescribe seronegative rheumatoid arthritis medications that correlate with symptoms. Non-steroidal anti-inflammatory and corticosteroid medications generally help reduce inflammation and swelling. If x-rays indicate joint space narrowing, physicians can administer disease modifying anti-rheumatoid drugs, also referred to as DMARDS, to reduce the risk of joint damage and deformity.


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