Introduction

Rheumatoid vasculitis (RV) is an autoimmune disease characterised by inflammation of the blood vessels with subsequent narrowing and damage to them. In this article, we will explore what RV is, the mechanisms contributing to the disease’s development, its symptoms and potential treatments.

What does rheumatoid vasculitis mean?

As with other medical terminology, we can break down the disease name rheumatoid vasculitis into its Greek/Latin root words to gain insight into what it is. Firstly “rheum” which means “flow” or “flow throughout the body”, vascular from “vascularis” relating to vessels and tubes and “itis” which is used in medical terminology to indicate an inflammation in the body. Hence, it means inflammation of blood vessels throughout the body.

Risk factors for rheumatoid vasculitis

Vasculitis refers to a group of conditions in which inflammation of the blood vessels occurs. There are a number of vasculitis subtypes, including polyarteritis nodosa, eosinophilic granulomatosis with polyangiitis (EGPA), polymyalgia rheumatica and rheumatoid vasculitis (RV). 

RV occurs in 1-5% of people already living with rheumatoid arthritis (RA) and most commonly affects the skin, fingers and toes but can occur anywhere throughout the body.¹ Studies have shown that there is a higher incidence of RV in patients assigned male at birth (AMAB) than those assigned female at birth (AFAB).

Longstanding, severe rheumatoid arthritis has been established as a risk factor. Patients living with RA for over 10 years are predisposed to developing RV and often present with painful, inflamed joints and stiffness. 

High levels of rheumatoid factor, an antibody, which once produced, will begin to act against the body's healthy cells and tissue, have been found in both RA and RV patients. This can be used in a test to identify the presence of autoimmune conditions.

Smoking has been found to be linked to the occurrence of RV. The chemicals in smoke can irritate blood vessels, causing inflammation and weakening them, leaving them more susceptible to other harm. If you do smoke and suspect you might have RV, it is strongly recommended you stop smoking, seeking professional advice to help you do so. 

Causes of rheumatoid vasculitis

RV is a multifactorial disease with no single defined cause. Little is understood about the mechanisms involved in its pathogenesis (the process which leads to the development of a disease); however, research has revealed details about processes that could be involved.

Rheumatoid vasculitis is an example of an autoimmune disease – diseases in which your body's defences, the immune system, begins to attack your body’s own cells and tissues, causing harm and impairing bodily functions. The exact cause of this remains unknown and is a highly researched topic, though the following have been identified as potential triggers:

• Trauma
• Infections
• Hormonal imbalances
• Dietary factors
• Environmental factors
• Exposure to chemicals

The systemic vasculitis associated with RV has been found to be connected to endothelial cell activation.² Endothelial cells form a layer which lines the inside of circulatory/blood vessels. They control vascular tone – the level of relaxation/dilation or contraction/constriction of the blood vessel – and thus have a valuable role in ensuring the distribution of an appropriate blood supply throughout the body. 

Endothelial cell activation is an important part of the immune response but can lead to deleterious effects in the body.

When the immune system is activated, for example when we are exposed to pathogens such as viruses, it firstly works to identify their microbial antigens and then it clears the substance from the body. In order to do this, the immune system initiates a release of small proteins known as cytokines, which send signals to other components of the immune system to tell your immune cells how to fight threats and repair injuries and are key modulators of inflammation. There are two types of cytokines; pro and anti-inflammatory, both of which are crucial to immune system function but have very different roles.

When microbial antigens are detected by the body, the immune system launches an attack against the invading substances by initiating the release of pro-inflammatory cytokines from immune cells such as macrophages and dendritic cells. Examples of pro-inflammatory cytokines include TNF-α, IL-6 and IL-1, which, when secreted in turn, activate further macrophages and other immune cells, directing them to the site of inflammation.³ It is these cytokines which activate the endothelial cells, leading to changes in their cell morphology (cell shape, structure, form and size) and causing barrier dysfunction, i.e. they cease to prevent the contents of the blood vessel from leaking through its walls.⁴ As a result, vascular integrity is compromised, which can lead to vessel leakage and collapse.

Symptoms of rheumatoid vasculitis

Rheumatoid vasculitis can be systemic, affecting the whole body or system, or localized – occurring in one particular location or organ. Because of this, symptoms vary widely and occur with differing severity between individual sufferers. However, the clinical presentation of signs and symptoms often includes:

• Rashes and skin ulcerations
• Neuropathy (nerve damage)
• Pericarditis, which is inflammation of the thin membrane surrounding the heart, it is rare but can occur in more severe cases of RV
• Chest pain
• Reddening of the eyes
• Tingling and loss of sensation in the hands and fingers
• Scleritis - Inflammation of the sclera or white part of the eye.

It is important to note there are a number of other medical conditions which cause similar symptoms, including polyarteritis nodosa, atherosclerosis and diabetes mellitus. Therefore, consultation with a medical professional is essential to receive an accurate diagnosis and the best medical treatment.

Diagnosis of rheumatoid vasculitis

Due to its nature and its production of symptoms, which are common in other diseases, such as diabetes mellitus, diagnosis requires careful investigation into the patient's medical history and thorough examination to rule out other conditions. Depending on the area involved, a number of types of imaging could be used, including: 

• Echocardiogram
• X-Rays 
• Abdominal ultrasounds
• Angiogram
• CT scan⁵

Analysis of blood samples and other laboratory tests can also be used to test for:

• C-reactive protein (CRP), which is released due to pro-inflammatory cytokines, is a marker of inflammation and can be used to test for chronic inflammatory conditions such as RA.
• Higher levels of antibodies in the blood of patients, such as rheumatoid factor
• Biopsies – to identify necrosis (death of cells) in tissues caused by reduced blood flow due to occluded (blocked) blood vessels 

Many of the tests mentioned above cannot be used in isolation but in conjunction with other diagnostic, methods can be used to determine whether a person has rheumatoid vasculitis. 

Treatment of rheumatoid vasculitis

Effective management of prior rheumatoid arthritis (RA) has been shown to greatly improve rheumatoid vasculitis (RV). Many of the treatments which are currently recommended for the treatment of RV are those already used to treat RA and include steroids such as corticosteroids and immunosuppressant drugs. 

Methotrexate, an immunosuppressant drug which can also be used to treat cancer, has been shown to reduce pain and joint stiffness.⁶ However, there is a movement toward other treatments including anti-TNF and Rituximab, which are designed to reduce immune system activity and as a result decrease inflammation, and the more that is known about the mechanisms involved in RV the more treatments we will see similar to these biologically active compounds.

Other treatments and recommendations include:

• Topical applications such as antibiotic cream
• Maintaining a healthy, balanced diet may also help to alleviate symptoms. Vitamin C, in particular, is frequently reported as helping cardiovascular disease, and studies have revealed it also strengthens endothelial integrity during inflammation.
• Pain reduction medication treatment
• Stopping smoking is essential

FAQs

Who is most at risk of developing rheumatoid vasculitis?

Rheumatoid vasculitis is a relatively rare condition and affects a small subset of people who are already living with rheumatoid arthritis. People who have long-standing and more severe RA are most at risk. People with RA who smoke have been identified as a particularly high-risk group.

What causes RV?

The root cause remains unknown. RV is an autoimmune disease in which the immune system is stimulated in a way which causes it to attack its own tissues. There are many triggers which are linked to autoimmune disease onset, but at present, no clear causal pathway has been identified. However, pro-inflammatory cytokines involved in the immune response have been shown to induce blood vessel damage through endothelial activation.

Are there any preventative measures I can take?

If you have been diagnosed with RA, the best thing you can do is take the appropriate treatment prescribed to manage the condition. The better the control of RA, the less at risk a person is of developing RV. Ensuring you consume a balanced diet and avoiding smoking or electronic cigarettes is also recommended.

What treatments are available?

Steroids and immunosuppressant drugs are usually prescribed for the treatment of RV by reducing inflammation. For less severe RV, which may affect the skin and fingers, topical applications such as antibiotic cream can be used. Pain medication, such as ibuprofen, can be used to help minimise symptoms and make RV patients more comfortable. 

Summary 

Rheumatoid vasculitis is a rare but serious disease occurring in a small percentage of patients living with rheumatoid arthritis. The condition can cause a range of different symptoms depending on its severity. No definitive cause explains why the immune system begins to attack its own healthy cells and tissues, but research has already revealed pathways and modes involved in the development of RV. There are a number of effective treatments available, including steroids, immunosuppressants and anti-inflammatory pain treatments, which have had positive results and helped to alleviate symptoms. Good management of RA with suitable treatment can also help to prevent RV, as it often arises with a worsening of the rheumatoid arthritis disease. With improving treatment for RA and a subsequent fall in case numbers, the decrease in the number of people with rheumatoid vasculitis has also been documented and is forecast to continue to diminish further.