Rheumatoid arthritis (RA) is an autoimmune disease, in which the body’s immune system mistakenly attacks its own tissues. In rheumatoid arthritis, the joints are primarily affected though it can affect other parts of the body.
Seronegative rheumatoid arthritis is a type of rheumatoid arthritis in which certain antibodies are not present in the blood. Most cases of RA are seropositive, in which antibodies are present in the blood.
Two blood tests used to diagnose rheumatoid arthritis include the rheumatoid factor (RF) assay and anti-cyclic citrullinated peptides (anti-CCP). When a patient has symptoms consistent with RA but tests negative for RF and anti-CCP antibodies, they are diagnosed with seronegative rheumatoid arthritis. These patients may have these antibodies in their blood, but at extremely low levels that are undetectable by the blood tests. Seronegative patients may develop antibodies later in the course of their illness.
What Are the Signs and Symptoms of Seronegative Rheumatoid Arthritis?
Patients who have seronegative rheumatoid arthritis patients must experience a specific set of symptoms and signs in order to be diagnosed because the lack of antibodies in the blood makes it more difficult to reach a rheumatoid arthritis diagnosis.
Specific symptoms and signs used to diagnose seronegative rheumatoid arthritis include the following:
- Joint pain and stiffness
- Specifically in the hands, but also in the knees, elbows, hips, feet, and ankles
- Joint swelling and redness
- Joint tenderness
- Symptoms occur on both sides of the body (symmetrical) and in multiple joints
- Chronic inflammation
- Stiffness in the morning that lasts more than 30 minutes
- Fatigue
- Eye redness
Patients with seronegative rheumatoid arthritis may have other symptoms as well, but the above symptoms must be present in order for a diagnosis of seronegative rheumatoid arthritis to be made.
What Causes Seronegative Rheumatoid Arthritis?
It is unknown what causes rheumatoid arthritis but it is thought that susceptibility factors and initiating factors may affect a person's risk of developing the condition:
Susceptibility factors increase a person’s susceptibility to developing rheumatoid arthritis when exposed to risk factors that initiate the inflammatory process. Susceptibility factors include:
- Age: middle-aged or older
- Female sex: twice as likely as men to develop RA
- Genetics: people with a relative who has RA have an increased risk of developing the condition
Initiating factors (triggers) increase the chances a susceptible person will develop the disease, such as:
- Infection: bacteria in the gut or mouth and gums infection (periodontitis) in particular are risk factors
- Smoking
- Stress
How Do Doctors Diagnose Seronegative Rheumatoid Arthritis?
Rheumatoid arthritis is diagnosed with a combination of clinical, laboratory, and imaging information. Patients with seronegative arthritis must present with a particular set of symptoms as outlined above, along with testing negative for RF and anti-CCP antibodies.
The following laboratory studies are used to diagnose rheumatoid arthritis:
- Rheumatoid factor (RF) assay
- This test will be negative in seronegative RA
- Anti-cyclic citrullinated peptide (anti-CCP) and anti−mutated citrullinated vimentin assays
- This test will be negative in seronegative RA
- Erythrocyte sedimentation rate (ESR)
- C-reactive protein (CRP) level
- Complete blood count
- Antinuclear antibody assay (ANA)
- HLA tissue typing
- Lyme disease, to rule out Lyme as a cause for the symptoms
- Uric acid, to rule out gout
Imaging studies used to diagnose rheumatoid arthritis include the following:
- X-rays (first choice): Hands, wrists, knees, feet, elbows, shoulders, hips, cervical spine, and other joints as indicated
- When patients test negative for RF and anti-CCP antibodies, X-rays may show bone and cartilage erosion and damage, which can aid in a seronegative RA diagnosis
- Magnetic resonance imaging (MRI): Primarily the cervical spine
- Ultrasound of joints: Joints, as well as tendon sheaths, changes and degree of vascularization of the synovial membrane, and even erosions
Joint aspiration and analysis of synovial fluid may be indicated in some cases.
What Is the Treatment for Seronegative Rheumatoid Arthritis?
Treatment for seronegative rheumatoid arthritis is the same as for seropositive rheumatoid arthritis.
The following medications are used to treat rheumatoid arthritis:
- Nonbiologic disease-modifying antirheumatic drugs (DMARDs)
- Azathioprine (Imuran)
- Cyclosporine (Gengraf, Neoral)
- Gold salts
- Hydroxychloroquine (Plaquenil)
- Leflunomide (Arava)
- Methotrexate (Rheumatrex, Trexall, Otrexup)
- Minocycline (Dynacin, Minocin)
- Penicillamine (Cuprimine, Depen)
- Sulfasalazine (Azulfidine)
- Biologic tumor necrosis factor (TNF)–inhibiting DMARDs
- Adalimumab (Amjevita, Cyltezo, Humira, Hadlima, Hyrimoz, Adalimumab-atto, Adalimumab-adbm, Adalimumab-bwwd, Adalimumab-adaz)
- Certolizumab (Cimzia)
- Etanercept (Enbrel, Erelzi, etanercept-szzs)
- Golimumab (Simponi, Simponi Aria)
- Infliximab (Remicade, Inflectra, infliximab-dyyb, Renflexis, infliximab-abda, Ixifi, infliximab-qbtx)
- Biologic non-TNF DMARDs
- Abatacept (Orencia)
- Anakinra (Kineret)
- Baricitinib (Olumiant)
- Rituximab (Rituxan)
- Sarilumab (Kevzara)
- Tocilizumab (Actemra)
- Tofacitinib (Xeljanz, Xeljanz XR)
- Upadacitinib (Rinvoq)
Other medicines used to treat rheumatoid arthritis include the following:
- Corticosteroids
- Methylprednisolone (Depo-Medrol, Medrol, Solu-Medrol)
- Prednisolone (Orapred ODT, Pediapred)
- Prednisone (Prednisone Intensol, Rayos)
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Pain relievers (analgesics)
- Topical skin products
- Diclofenac topical (Voltaren)
The following are surgical treatments for rheumatoid arthritis:
- Synovectomy
- Tenosynovectomy
- Tendon realignment
- Reconstructive surgery or arthroplasty
- Arthrodesis
Other therapies for rheumatoid arthritis include the following:
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Freeman, Jennifer. "Seronegative RA: What are the Symptoms of Seronegative RA?" RheumatoidArthritis.org. Oct. 27, 2018. <https://www.rheumatoidarthritis.org/ra/types/seronegative/>.
Smith, H. "Rheumatoid Arthritis (RA)." Medscape.com. Jan. 31, 2022.<https://emedicine.medscape.com/article/331715-overview>.
Venables, P.J.W. "Patient education: Rheumatoid arthritis treatment (Beyond the Basics)." UpToDate.com. Feb. 20, 2020. <https://www.uptodate.com/contents/rheumatoid-arthritis-treatment-beyond-the-basics?search=rheumatoid%20arthritis&topicRef=512&source=see_link>.