Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects 1% of the U.S. population. It is mainly characterized by inflammation of small and large joints resulting in significant pain, swelling, loss of function, deformities and structural joint damage. In about 40% of patients, rheumatoid arthritis affects other organs such as the eyes, nerves heart, lungs and blood vessels.
Rheumatoid vasculitis is a serious complication of long standing RA in which inflammation spreads to involve small to medium sized and rarely, large blood vessels in the body. When inflamed, blood vessel walls become thickened and their lumen narrows down, often to the point of complete blockage. This compromises blood supply to the affected organ. Multiple organs may be affected including the skin, nerves, eye, heart, lung, brain, gastrointestinal tract or kidney. It can be life threatening in some circumstances where appropriate treatment is not initiated promptly. Research shows that since the advent of effective drug therapy for RA, fewer people are developing rheumatoid vasculitis in recent years.
The exact etiology of rheumatoid vasculitis is unknown. It is thought that an abnormally active immune system, starts acting against the patient’s own body, targeting blood vessels and causing vascular inflammation. Patients with rheumatoid vasculitis may have high levels of rheumatoid factor in their blood and abnormal proteins called immune complexes. Sometimes, blood measurements show that proteins called ‘complements’ are low when there is a lot of inflammation. Under the microscope, the inflamed blood vessels show a prominence of inflammatory cells.
Rheumatoid vasculitis most often develops in patients with long-standing RA, generally more than 10-years duration. It generally develops in patients with severe RA joint disease. For reasons that are unknown, rheumatoid vasculitis is more common in males. Up to 1 in 9 males with rheumatoid arthritis may develop vasculitis at some point in their lifetime. Research has shown that smokers are more likely to develop rheumatoid vasculitis. Some individuals with RA are genetically predisposed to developing vasculitis. Patients with RA who have high amounts of rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies in their blood are more likely to develop rheumatoid vasculitis, as are individuals with an enlarged spleen and low white cell count in their blood, known by a condition termed ‘Felty’s syndrome.’
Depending on the size of blood vessel and organ involved, rheumatoid vasculitis has many different clinical presentations.
When inflammation involves small to medium sized blood vessels (arteries and veins) supplying the skin of the fingertips and around nails, it can lead to formation of small painful sores at the fingertips that can progress to ulcers. These are predisposed to developing infection, which can lead to gangrene or necessitate amputation. Similar ulcers can develop when skin over the legs are affected.
Vasculitis that involves blood vessels supplying the nerves can cause sensations of numbness, tingling, pain, weakness or loss of function of hands and/or feet. Inflammation of small blood vessels of the eye can lead to a condition called ‘scleritis’ that is characterized by a focal area of redness on the sclera (white of the eye), pain and light sensitivity. When severe, it can result in melting away of the sclera and permanent damage to the eye.
Small blood vessels can also be inflamed in the lining of the heart (‘pericarditis’) or lung (‘pleuritis’) causing persistent cough, chest pain and shortness of breath.
Rarely, blood vessels in the brain, heart or abdomen can be involved to the point of narrowing or complete blockage leading to stroke, heart attack, severe abdominal pain or gastrointestinal bleeding.
Rheumatoid vasculitis is often accompanied by constitutional symptoms like fevers, chills, night sweats, weight loss, fatigue and lack of energy with a general sense of feeling unwell.
There is no definitive laboratory test for rheumatoid vasculitis. The diagnosis of rheumatoid vasculitis is made by a physician in a patient with RA using a combination of patient medical history and symptoms, physical examination, pertinent laboratory investigations, some specialized tests (nerve conduction tests) and sometimes a tissue biopsy from the organ affected.
Most patients have elevation in their erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), which can signify the presence of inflammation. Some patients have another abnormal protein called anti-neutrophil cytoplasmic antibody (ANCA) that is seen in other forms of vasculitis as well.
Specialized tests depend on the organ affected and may include other blood or urine tests, chest x-ray, EKG, CT or MRI scans (of brain, chest or abdomen), angiography (to see vessel wall thickening or blockage), endoscopy (upper or lower) and nerve conduction tests. Tissue biopsy is helpful is demonstrating inflammation in the blood vessels and confirms presence of vasculitis. It is commonly taken from the edge of a skin ulcer, a nerve and/or muscle.
Treatment of RV is based on the organ affected and severity of organ involvement.
In mild cases like fingertip sores, pain control with local protection and prevention of infection in the goal. Optimizing RA treatment is definitely necessary. This can be done by addition of immunosuppressant medications such as methotrexate, leflunomide or biologic response modifiers such as tumor necrosis factor inhibitors, rituximab, abatacept, and others that help control inflammation not only in the joints but the blood vessels as well.
In general, corticosteroids (such as prednisone) are first line therapy for rheumatoid vasculitis and can be given orally or by vein. Dose and duration of corticosteroid treatment will vary based on your doctor’s judgment and expertise.
When there are signs of impending organ damage to major organs and with large vessel vasculitis stronger immunosuppression is achieved by using cyclophosphamide in addition to steroids.
Close monitoring of laboratory tests during treatment and regular follow up with your doctor is critical is achieving good outcomes.
Active ongoing management of RA is critical to prevent flares, improve quality of life and increase life expectancy. Just like RA, there is no cure for rheumatoid vasculitis, but with early diagnosis and treatment, symptoms can be controlled and damage can be prevented. Relapses can occur. Patients must contact their physician at the earliest sign of suspected recurrence.
Rheumatoid vasculitis is one of the most serious complications of RA, substantially contributing to the disease burden suffered by patients with RA. The rarity of rheumatoid vasculitis, and the variability in clinical presentation and lack of a standard definition for rheumatoid vasculitis have always created challenges in conducting research studies and developing standard approaches to therapy. Fortunately, it is becoming less common with the use of newer treatments for RA.
Though the new class of drugs (biologics) offers a broader array of potential therapeutic options, no controlled studies exist to guide treatment. Moreover, a concern has risen with several small studies implicating biologics in causing RV. Research is being conducted at leading medical centers throughout the world to better understand the cause, and biology of, and treatment options for rheumatoid vasculitis.
Revision: September 2012
The Vasculitis Foundation gratefully acknowledges Dr. Ashima Makol from the Mayo Clinic, Rochester, MN, for her expertise and contribution in compiling this information.