Predominately medium-sized vessel

Childhood Polyarteritisnodosa (PAN)

  • What is it?
    • Childhood Polyarteritisnodosa, or PAN for short, is a rare type of inflammation or swelling that occurs during childhood and typically targets medium-sized arteries. Arteries are tubes in the body that bring blood and nutrients to the organs and tissues. When they are swollen, the tubes cannot bring as much food to the organs and tissues as they need, causing problems.
    • PAN and a disease called Kawasaki disease (KD) are both common to develop during childhood and have many similar symptoms, so accurate diagnoses are important.
    • It is not contagious, so it will not spread through contact with a patient with PAN. PAN is also not a heritable disorder, so parents usually do not pass it onto their children.
    • Patients with PAN should have regular check-ups to monitor the disease activity and treatment.
    • Different types of PAN include Systemic PAN and Cutaneous PAN (CPAN)
  • Systemic or Classic Polyarteritisnodosa (or just PAN)
    • It is a type of swelling of the blood vessels or tubes that cause general symptoms like fever, malaise and weight loss, and it affects many systems of the body.
  • Cutaneous Polyarteritisnodosa (CPAN)
    • It is a subcategory of polyarteritisnodosa that is rarer, more limited and affects only the skin, muscles and bones, not the internal organs like the heart or liver.
    • Different from PAN, CPAN develops in more girls on the lower part of their legs, producing small swelling reactions, and has a positive prognosis. Another difference is that the structure of the internal elastic lamina, which is a type of tissue of the artery walls that lets it expand and contract as blood is pumped, is maintained in CPAN, but not in PAN.
    • It is hard to tell apart CPAN and PAN based only on skin outbreaks.
    • As of now, there is no official characterization of CPAN but studies of children with PAN and their lab test results show that it is a special form of inflammation with a chance to develop into the systemic form, so follow-ups are suggested.
  • The cause of PAN is actually unknown up to date. Evidence from studies show that the immune system is the key player, making it an autoimmune disease.  The immune system has cells that protect the body by fighting infections, but when they do not work properly in PAN, they can attack and damage the body’s blood vessels.
  • One possible cause may be due to chronic hepatitis B virus infection.
  • PAN is observed about equally in boys and girls.
  • It occurs more often in adults than in children.
  • The diagnosis of PAN generally involves looking through medical histories to find symptoms, physical examinations, laboratory tests such as a tissue biopsy or urinalysis, and imaging tests for example arteriograms, CT or MRI scans, used to detect abnormalities in blood vessels and internal organs.
  • Click here for more detailed information on classifying and diagnosing PAN.
  • Treatment of PAN varies as different factors need to be taken into consideration. For instance, how severe it is and if there is also the presence of CPAN or viral hepatitis.
  • Glucocorticoids are steroids that decrease inflammation. It can be taken on its own or together with medications called immunosuppressants that weaken the body’s immune system.
    • Click here for more detailed information on suggested treatment protocols.

Cabral, David, and Kimberly Morishita. “Vasculitis in Children: Classification and Incidence.” UpToDate. Ed. Robert Sundel and Elizabeth TePas. N.p., Mar. 2016.

Merkel, Peter A. “Treatment and Prognosis of Polyarteritis Nodosa.” UpToDate. Ed. Gene G. Hunder, Eric L. Matteson, and Curtis Ramirez   Monica. N.p., Nov. 2015.

Kermani, T. A., Warrington, K. J., (2012) Vasculitis Foundation. N.p., Sept. 2012.

Khanna, G., Sargar, K., Baszis, K. W., (2015), Pediatric vasculitis: recognizing multisystemic manifestations at body imaging. RadioGraphics, 35(3), 849-865. doi: 10.1148/rg.2015140076

“Polyarteritis Nodosa (PAN).” Cleveland Clinic. N.p., 2014. Web.

“Polyarteritis Nodosa (PAN).” Vasculitis Clinical Research Consortium. Rare Clinical Diseases Research Network, n.d. Web.

According to the EULAR/PRINTO/PRES criteria for classification of childhood PAN, abnormalities in a small- or medium-sized artery must be found from a biopsy or from an angiogram that shows aneurysms (the bulging of arteries due to the weakened wall), stenosis (narrowing) or occlusions (blockage of the artery), that are not as the result of fibromuscular dysplasia (unusual growth in artery walls), in addition to at least of the 5 systemic features listed below:

  1. Skin involvement (livedo reticularis, tender subcutaneous nodules, superficial or deep skin infarctions)
  2. Myalgia or muscle tenderness
  3. Hypertension
  4. Peripheral neuropathy (sensory peripheral neuropathy or motor mononeuritis multiplex)
  5. Renal involvement (proteinuria, hematuria, or red blood cell casts, or glomerular filtration rate of less than 50% the normal value for age)
    • To reach an accurate diagnosis, it is important to consider a combination of clinical features, laboratory tests, along with biopsy. For more details view the diagnostic algorithm for PAN.
    • Below is a table of symptoms of PAN patients in various studies. The most common symptoms displayed by PAN patients are usually caused by damage to the digestive tract, kidneys, skin, joints, muscle, heart, and the nervous system. Some symptoms include weakness, joint and muscle aches, abdominal pain, decreased appetite, fatigue, fever and weight loss.
      • It is important to remember that not all of the symptoms listed below are displayed by every patient as it varies case by case.
    • Patients with PAN can experience some or all of the following:
  • Type of Symptom Symptoms
    Constitutional/General Malaise, fatigue
    Fever
    Weight loss, decreased appetite
    Cutaneous Skin rash, sores
    Livedo reticularis (network of purple discolouration on skin)
    Tender nodules under the skin
    Superficial or deep skin infarctions
    Renal Abnormal urinalysis results
    Proteinuria (proteins leaking into urine)
    Hematuria (blood in urine)
    Red blood cell casts
    Impaired glomerular filtration
    Pulmonary/Respiratory Hard time breathing
    Abnormal lung function test results
    Chest pain
    Gastrointestinal Abdominal pain
    Chronic nausea
    Vomiting
    Diarrhea or blood in bowel movements
    Musculoskeletal Myalgia (Muscle and joint pain/tenderness)
    Arthritis (joint inflammation)
    Nervous System Numbness
    Pain
    Weakness
    Cardiovascular High blood pressure
  • Inflammatory markers
    • C-reactive protein (CRP) – Has a higher sensitivity and specificity than the ESR to indicate the acute phase of inflammation
    • Erythrocyte sedimentation rate (ESR) – usually considered if CRP is unavailable
  • Tissue biopsy
  • Urinalysis (UA) – hematuria, proteinuria, and red blood cell casts. It tests how well the kidney is working.
  • Additional tests to exclude other diagnoses
    • Complete blood count (CBC) – rules out infection
    • Antineutrophil cytoplasmic antibodies (ANCA) – rules out ANCA-associated vasculitis
    • Hepatitis B surface antigen – rules out related chronic hepatitis
    • Antinuclear antibody (ANA) – rules out diseases of connective tissue
    • Antiglomerular basement membrane antibodies – rules out antiglomerular basement membrane disease (anti-GBM), disease of the kidney that affects the removal of wastes from blood
  • Imaging plays a big role in the diagnosis of PAN.
  • Possible imaging tools used in assessing PAN:
    • Arteriogram/ Angiogram
      • An arteriogram is like an X-ray of the arteries and can be used to help determine the condition of an artery by injecting a special dye into the patient’s blood stream to create a visual image. It will show if there is narrowing or blockage of the artery.
      • It is one of the most useful tools to diagnose PAN because the most valuable finding is the discovery of aneurysms, the bulging of arteries due to the weakening of its wall.
    • Magnetic Resonance (MR) Imaging
      • A technique that uses magnetic fields and radio waves to produce 3D images.
      • Patients will need to be in a big tube-like machine for a period of time.
      • However, there is a tendency of MR imaging to fail to spot smaller aneurysms and overestimating the degree of artery narrowing.
    • Computed Tomography (CT)
      • CT scan findings can be nonspecific, but they include bowel wall thickening; vascular engorgement; ureteral dilatation; renal, hepatic, and splenic infarctions; and perinephric hematoma
      • CT angiography performs similarly to MR angiography, but at the expense of high ionising radiation exposure.
    • Light micrograph
  • A biopsy of an affected region can be used to confirm whether or not the tissue is inflamed.

In this image, you can see the diagnostic algorithm for PAN by following the diagram from the “INDICATIONS FOR TESTING” box (at the top) to the first box on the right for “Polyarteritis Nodosa…”

Retrieved from: https://arupconsult.com/content/takayasu-arteritis/?tab=tab_item-1This is the website for ARUP Consult, whose disclaimer and policies outline that the “content at this website may be freely downloaded and used for non-commercial purposes.”

Cabral, David, and Kimberly Morishita. “Vasculitis in Children: Classification and Incidence.” UpToDate. Ed. Robert Sundel and Elizabeth TePas. N.p., Mar. 2016.

Kermani, T. A., Warrington, K. J., (2012) Vasculitis Foundation . N.p., Sept. 2012.

Khanna, G., Sargar, K., Baszis, K. W., (2015), Pediatric vasculitis: recognizing multisystemic manifestations at body imaging. RadioGraphics, 35(3), 849-865. doi: 10.1148/rg.2015140076

“Polyarteritis Nodosa.” Ed. Gordon A. Starkebaum, David Zieve, and Isla Ogilvie. MedlinePlus Medical Encyclopedia, 2016. Web.

“Five Things Physicians and Patients Should Question.” American Society for Clinical Pathology, Feb. 2015.Web.

Khan, A. N., and Macdonald, S., “Imaging in Polyarteritis Nodosa.” Emedicine.medscape. Medscape, Sept. 2016. Web.

“Polyarteritis Nodosa – PAN.” ARUP Consult. N.p., Oct. 2016. Web.

Steroids
In many cases, the patient will be given medicine to suppress his/her immune system. One treatment of PAN is to use high doses of glucocorticoids that get reduced gradually.

  • Corticosteroids
  • Oral glucocorticoid monotherapy
    • Usually meant for patients with mild PAN

Immunosuppressants

  • Immunosuppressants that weaken the body’s immune system are often prescribed with steroids. It is important to know that different combinations of medications produce different effects.
  • In mild cases, patients who are resistant to or intolerant of the dose of glucocorticoids required for disease control, the addition of azathioprine or methotrexate is suggested. Such patients include those who do not respond to glucocorticoids alone, whose glucocorticoid dose cannot be tapered to an acceptable level without facing a relapse of disease, who are at high risk of adverse effects for the expected treatment course with glucocorticoids, or in whom the adverse effects of continued glucocorticoids in the dose being used are unacceptable.
  • For patients with mild PAN and confirmation of infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), it is suggested for them to be initially treated with antivirals only, rather than also treating with immunosuppressive medications. Patients with severe manifestations of hepatitis virus-associated PAN may benefit from short-term treatment with glucocorticoids and plasma exchange until antiviral therapy becomes effective.
  • Patients with moderate to severe PAN, or if there is any sign of decreased kidney function, significant proteinuria, gastrointestinal, cardiac, or neurologic involvement, who have ongoing worsening of the disease that is not controlled by treatment with glucocorticoids and CYC within two to three months, should be treated with pulse glucocorticoids, followed by prednisone, and switch from CYC to a different immunosuppressive agent.
  • Although the best route, dose, and length of CYC treatment for PAN is uncertain, and there are no trials comparing intravenous and oral routes of therapy, intravenous CYC still has been used extensively.
    • Methotrexate (MTX)
    • Azathioprine (AZA)
    • Mycophenolate mofetil (MMF)
    • Cyclophosphamide (CYC)
  • The reported relapse rates in PAN have ranged from 10-30%.
  • Even though the fraction of PAN patients with only a single occurrence of disease is much higher than that in several other forms of inflammation, especially the antineutrophil cytoplasmic antibody (ANCA)-associated diseases, the relapse rate in PAN is still significant.

Below you can find downloadable PDF files of suggested treatment protocols for patients with Polyarteritis Nodosa.

Suggested Treatment Protocols:

  1. (These numbers depend on the types of treatment protocols provided for Polyarteritis Nodosa)
  2. (These numbers depend on the types of treatment protocols provided for Polyarteritis Nodosa)
  3. (These numbers depend on the types of treatment protocols provided for Polyarteritis Nodosa)

Merkel, Peter A. “Treatment and Prognosis of Polyarteritis Nodosa.” UpToDate. Ed. Gene G. Hunder, Eric L. Matteson, and Curtis Ramirez Monica. N.p., Nov. 2015.

“Polyarteritis Nodosa (PAN).” Vasculitis Clinical Research Consortium. Rare Clinical Diseases Research Network, n.d. Web