Polyarteritis Nodosa Diagnosis And Treatment

Overview

Polyarteritis Nodosa (PAN) is a rare disease leading to inflammation and narrowing of the blood vessels. This inflammation, known as vasculitis, can cause organ damage, particularly to the kidneys due to a lack of oxygen. PAN’s symptoms are similar to some more common illnesses so, understanding PAN is crucial for an appropriate diagnosis. A strong knowledge base about PAN creates an understanding of the potential complications and the importance of early detection. This helps in preventing serious and lasting damage. Further information on PAN will be explored below, alongside its diagnosis and treatment.

Understanding polyarteritis nodosa

What is vasculitis?

Vasculitis is an autoimmune disease that causes inflammation in the blood vessels. Generally, inflammation is the immune system’s response to an infection. In vasculitis, the immune system attacks healthy blood vessels, narrowing the blood vessels and damaging them. Under the umbrella condition of ‘vasculitis’, several rare diseases exist with different symptoms, causes, and risk factors. Some types of vasculitis affect smaller blood vessels while others target large vessels. In small blood vessel vasculitis, diagnosis usually entails looking for a protein, specifically an antibody.¹ This antibody, known as antineutrophil cytoplasmic antibody (ANCA) attacks the body’s neutrophils, a white blood cell involved in fighting infections. However, vasculitis in larger blood vessels is not diagnosed with the ANCA test.²

What Is polyarteritis nodosa?

Polyarteritis Nodosa (PAN) is a type of vasculitis that usually targets medium-sized blood vessels but rarely affects smaller vessels.² In this case, testing for ANCA is not effective, so we need to explore other options. A less common form of PAN may only affect the skin (cutaneous PAN or CPAN).² When medium-sized vessels are affected, this can cause organ damage, especially in the major organs such as the kidneys, gut, and nerves. Compared to other forms of vasculitis, PAN does not affect the lungs.³ Individuals can have a sudden onset of PAN, or it can be a secondary form of illness occurring after a particular infection or cancer, most commonly with hepatitis B, hepatitis C, or hairy cell leukaemia.² 

Rare diseases affect fewer than 200,000 cases (United States) or fewer than 5 cases per 10,000 cases in the European Union.⁴ PAN has fewer than 5,000 cases in the United States and thus is a rare disease. This statistic shows how important it is for healthcare teams to be aware of rare diseases and the difficulty that may occur when attempting to make a diagnosis 

The importance of blood vessels

Blood vessels are important components of the circulatory system because they deliver blood to and from the heart to other parts of the body. Vessels are classified into three categories: arteries, veins, or capillaries.:

• Arteries - carry oxygenated blood from the heart to other parts of the body; one exception is the pulmonary artery (which carries deoxygenated blood from the heart to the lungs).
• Veins -carry deoxygenated blood towards the heart;  with the exception of the pulmonary vein (which carries oxygenated blood from the lungs to the heart)
• Capillaries -smaller blood vessels responsible for the exchange of materials between blood cells and the body tissues  

In individuals with PAN, inflamed arteries cannot function as usual. Since the main function of arteries is to carry oxygenated blood this can lead to serious problems. A lack of oxygenated blood in major organs can lead to cell death and dysfunction.² Additionally, inflammation can weaken the vessel walls leading to bulges in the vessel walls known as aneurysms. These aneurysms can rupture, releasing blood into the surrounding tissue. This increases blood pressure and causes further damage because blood is no longer flowing to its intended organ (also known as ischemia).^2,5 

Causes and risk factors

Current understandings of PAN

Most cases of PAN are sudden (primary PAN) and the cause is unknown. In rare cases, PAN can be a secondary complication of an infection.² For example, a 2005  report ( looking back over the prior 30 years) found a correlation between hepatitis B and PAN (hepatitis B Virus-Associated PAN or HBV-PAN).⁶ Individuals with HBV-PAN were treated with antiviral medications for hepatitis B. This treatment led to a decrease in PAN-associated symptoms.⁶ These findings were supported after the development of the hepatitis B vaccine which significantly decreased the PAN cases. 

Other factors associated with PAN include hepatitis C⁷ and hairy-cell leukaemia.⁸ It is currently impossible to determine how PAN develops based on the existing treatment history or the limited number of individuals available for evaluation. There is currently no hepatitis C vaccine so prevention is the best tactic to lower the risk of Hepatitis C.

Genetics and population overview

According to the Johns Hopkins Vasculitis Center, men are 50% more likely to develop PAN than women. The average age at diagnosis is between 40 to 50 years of age although it can occur at any age. A specific gene mutation has been identified in individuals with Georgian Jewish or German ancestry that seems to increase the risk of PAN.⁹ Genes contain DNA that tells cells what to do. The gene, CECR1 (cat eye syndrome critical region protein 1), produces a protein called adenosine deaminase 2 (ADA2).⁹ This genetic mutation is passed from parent to child and could increase the risk of developing PAN.⁹ 

Symptoms and signs

Symptoms of PAN are similar to symptoms seen in other health conditions. Symptoms may occur throughout the body and include: 

• Persistent Fever (defined as a temperature over 100.4^F or 38^C)
• General unwell feeling
• Different types of skin rashes 
• Lumps in the skin (due to inflammation) 
• Stomach aches
• Gastrointestinal bleeding (which may be mistakenly diagnosed as inflammatory bowel disease )
• Weight loss
• Presence of protein in urine (which is a sign of inflammation)
  • Eventually, a small number of individuals may need dialysis
• High blood pressure
• Damage to the heart, brain, nerves, or liver due to inflammation in the arteries
  • A small number of cases may lead to heart attacks or heart failure
• Inflammation of the white of the eye
• Nerve numbness or tingling in the hands, feet, arms, and legs (occurring in 50–70% of individuals)
• In some cases after 2–3 years, lesions may develop in the central nervous system which can lead to decreased alertness and seizures
• Testicular infarction (a loss of blood flow to the testicle causing tissue damage and death)

Diagnosis

Symptoms vary from person to person, making it difficult to diagnose PAN based on symptoms alone. One test that can be used is the erythrocyte sedimentation rate (ESR) test. The test measures the rate at which blood falls to the bottom of a tube. Individuals with autoimmune disorders, inflammation, cancer, or infection will have an elevated result.¹⁰ However, the test is not specific to PAN and only indicates that the individual has inflammation. Urine protein can help identify patients with PAN but only once their kidney function has been affected. 

The best method for diagnosis is a biopsy, but this can be invasive, and potentially dangerous if the affected vessels are near important organs.² Therefore, a biopsy is reserved for skin or muscle involvement cases. Other less invasive procedures may aid in identifying PAN and include angiography (visualisation of the blood vessels through X-rays),² which can show aneurysms in the blood vessels leading to organs. Other imaging services could include Magnetic Resonance Imaging (MRI), or a Computed Tomography scan (CT scan).²

Other blood tests should be done to rule out PAN-associated infections including viral load blood tests for hepatitis B, and an antibody blood test along with PCR (polymerase chain reaction) for hepatitis C.² 

Treatment

The treatment of PAN usually involves steroids (corticosteroids) but can also include medicine to suppress the immune system (immunosuppressants). Treatments will vary depending on the progress of the disease.² In patients with PAN located in significant organs, steroids such as prednisone are used in combination with cyclophosphamide to suppress the immune system.² Cyclophosphamide is also used to treat cancer, but only at high doses. For those with PAN, cyclophosphamide is given at lower doses and only in critical cases. 

Untreated PAN generally leads to a shorter life expectancy, however, timely treatment can significantly improve an individual's condition (prognosis) even in severe cases.² Relapses can occur but vary in symptoms and severity. To minimise the risk of relapse, Cleveland Clinic suggests speaking to a healthcare professional immediately to report any new symptoms.

Summary

Rare diseases like PAN are difficult to diagnose and require a lot of time, thought, and conversation with your healthcare provider. This rare disease leads to the inflammation of medium (and in some cases, small) sized blood vessels. A lack of treatment for the disease can lead to cell death and eventual organ failure. While the majority of PAN cases are sudden, and due to an unknown cause, other cases can stem from infections such as hepatitis B and C or cancer such as hairy cell leukaemia. While PAN associated with hepatitis B infections can be treated specifically with medications targeting the hepatitis B virus, generally the treatment for PAN relies on steroid use and immunosuppressants.