Predominately medium-sized vessel

Cutaneous Polyarteritisnodosa (CPAN)

  • What is it?
    • It is a subcategory of polyarteritisnodosa (PAN) that is a rarer, more limited form of a vasculitis or inflammation in the blood vessels of the body, mostly the 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.
    • It normally affects only the skin, muscles and bones, not the internal organs like the heart or liver.
    • CPAN most often develops on the legs, produce mild inflammatory reactions, and has a favourable prognosis.
  • The cause of PAN is actually unknown up to date, so it may not be surprising that it is the same in the case of CPAN.
  • Evidence from studies has shown that the immune system is the key player, making it an autoimmune disease. Immune cells usually protect the body by fighting infections, but in these cases they do not act properly and attack blood vessels instead, causing swelling.
  • One possible cause may be chronic hepatitis virus infection.
  • CPAN is seen more often in girls than boys, unlike PAN, although it is more common in adults than in children.
  • The diagnosis of CPAN usually involves telling it apart from PAN, but it is not easy to do based only on skin outbreaks.
  • According to the EULAR/PRINTO/PRES criteria, a disease with cutaneous symptoms and at least one extracutaneous symptom with relevant findings in tissues can still be diagnosed as PAN.
  • Also, as of now, there is no official characterization of CPAN but past results show that it is a special form of inflammation of arteries with a small chance to turn into the more severe systemic form, so follow-ups are recommended.
  • Diagnosis by doctors is done by looking through medical histories to find symptoms, physical exams, laboratory tests such as testing a sample of the skin or urine, and using imaging tests to detect anything abnormal.
  • Click here for more detailed information on classifying and diagnosing CPAN.
  • Treatment of CPAN changes depending on how severe it is and if there is the presence of 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.

Furukawa, F. (2012). Cutaneous Polyarteritis Nodosa: An Update. Annals of Vascular Diseases, 5(3), 282–288. http://doi.org/10.3400/avd.ra.12.00061

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

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).” Cleveland Clinic. N.p., 2014. Web.

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

  • In the early 1900s, the characteristics of CPAN were described as 1) findings of vasculitis limited to the skin, 2) histopathological findings of skin biopsy comparable to those of PAN, and 3) absence of internal organ lesions.
  • In CPAN, different from PAN, laboratory examination shows only a small number of abnormalities that are typically mild, for example increases in inflammatory markers and a positive antinuclear antibody titer.
  • Another difference between PAN and CPAN is that the internal elastic lamina, which is a kind of tissue found in the walls of the artery that functions to accommodate the variability of the size of the artery as it expands and contracts as blood is pumped, is histologically maintained in CPAN, whereas in PAN, there are different forms of eruption such as gangrene and bloody bullae.
  • Even when CPAN is suspected based on skin lesions and pathological findings, the possibility that they are pieces of evidence for PAN should constantly be considered.
  • According to the EULAR/PRINTO/PRES criteria for classification of CPAN, the clinical and laboratory features of cutaneous polyarteritis nodosa include:
    1. Subcutaneous nodular, painful, non-purpuric lesions with or without livedo reticularis are present without evidence of systemic involvement (except for myalgia, arthralgia, and non-erosive arthritis).
    2. Tissue biopsy demonstrates necrotizing nongranulomatous vasculitis.
    3. Tests for antineutrophil cytoplasmic antibodies (ANCA) are negative.
    4. There is often a history of a preceding streptococcal infection. Consequently, there may be serological or microbiological evidence of streptococcal infection.
    • To reach an accurate diagnosis, it is important to consider a combination of clinical features, laboratory tests, along with biopsy
  • Like many other inflammation diseases, there is swelling and blockage of blood vessels.
  • Some examples of symptoms include feeling tired and low energy, joint, muscle and abdominal pain, sometimes do not feel like eating, fever and weight loss.
  • Some key cutaneous manifestations that are seen mainly on the legs include dark red, painful lumps underneath the skin, networks of purple discolouration, gangrene or dark-coloured tissue, and ulcers which are open sores.
  • Tender nodules found just beneath the skin on the lower legs is a typical characteristic of CPAN
  • 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 done if CRP unavailable and it is elevated in up to 60% of CPAN patients
  • Skin biopsy
    • Sampling the skin can easily be done and is very helpful for a definite diagnosis. But, the sample needs to be taken from the dermal lower layer to subcutaneous fat tissue, where the damaged blood vessels build up.
    • If ulcer lesions are present, the region in the middle of the ulcer should be tested. When lesions cannot be confirmed, serial sections are prepared, or re-biopsy should be done. In the scar tissue stage, inflammatory cell infiltration is mild, so diagnosis is difficult but the method of staining can confirm the internal elastic lamina.
    • After confirming the presence of vasculitis from the biopsy, the diagnosis of CPAN can only be made after the exclusion of systemic PAN, so the systemic manifestations of PAN must be ruled out.
  • Urinalysis (UA) – hematuria, proteinuria, and red blood cell casts. It tests how well the kidney is working.
  • Additional tests to exclude other diagnoses
    • Measurements of complete blood count, anti-neutrophil cytoplasmic antibody (ANCA), anti-nuclear antibody (ANA), rheumatoid factor, complement levels, liver and kidney function tests can be used to exclude other causes of vasculitis, and to distinguish CPAN from systemic PAN.
    • Complete blood count (CBC) – rules out infection
    • Antineutrophil cytoplasmic antibodies (ANCA) – rules out ANCA-associated vasculitis
    • Hepatitis B surface antigen – rules out concomitant chronic hepatitis
    • Antinuclear antibody (ANA) – rules out connective tissue diseases
    • Antiglomerular basement membrane antibodies – rules out an antiglomerular basement membrane disease (anti-GBM)
    • Liver and kidney tests
  • Imaging plays an effective role in the diagnosis of CPAN.
  • Possible imaging tools used in assessing CPAN:
    • 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.
    • 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 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.

Morgan, A. J. and Schwartz, R. A. (2010), Cutaneous polyarteritis nodosa: a comprehensive review. International Journal of Dermatology, 49: 750–756. doi:10.1111/j.1365-4632.2010.04522.x

“Polyarteritis Nodosa – PAN.” ARUP Consult. N.p., Oct. 2016. Web. “Five Things Physicians and Patients Should Question.” American Society for Clinical Pathology, Feb. 2015.Web.

Rodrigues, M., Amaral, D., Barrerira, J. L., Brito, I. (2014), Childhood polyarteritis nodosa presenting as stroke and arterial hypertension. doi:10.1136/bcr-2014-207866

Steroids

  • CPAN is generally treated similarly to mild systemic PAN, which involves the use of glucocorticoids
  • In many cases, medicine to suppress the immune system will be administered.
  • It should be noted that the initial treatment of CPAN should be less aggressive than that of systemic PAN as some patients may require only nonsteroidal anti-inflammatory drugs (NSAIDs) to show improvement.
    • Corticosteroids

Immunosuppressants

  • Immunosuppressants are often used in combination with steroids. It is important to make note that different combinations of medications used to treat PAN produce altered effects.
  • 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 CPAN 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.
    • Methotrexate (MTX)
    • Azathioprine (AZA)
    • Mycophenolate mofetil (MMF)
    • Cyclophosphamide (CYC)

Non-steroidal anti-inflammatory drugs

  • NSAIDS are administered to patients with mild CPAN and they normally show improvements after.
  • To treat more severe CPAN or patients that show no improvements after taking NSAIDS alone, systemic steroid administration at a moderate dose is prescribed along with NSAIDS.

Treatments that improve circulation

  • For example, anticoagulants (blood thinners), thrombolytic agents that break down blood clots, anti-platelet drugs that prevent blood clots, and vasodilators that allow make blood vessels wider to allow more blood flow are used and can be continuously considered in patients showing noticeably impaired circulation.

Externally used drugs

  • There is no specific treatment to use drugs for external use, but local washing with physiological saline is usually helpful.

Below you can find downloadable PDF files of suggested treatment protocols for patients with Cutaneous Polyarteritisnodosa. These suggested treatment protocols vary depending on the phase of the treatment (induction, maintenance, flare) and on which conditions are presented in patients.

Suggested Treatment Protocols:

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

Furukawa, F. (2012). Cutaneous Polyarteritis Nodosa: An Update. Annals of Vascular Diseases, 5(3), 282–288. http://doi.org/10.3400/avd.ra.12.00061

Merkel, Peter A. “Treatment and Prognosis of Polyarteritis Nodosa.” UpToDate. Ed. Gene G. Hunder, Eric L. Matteson, and Curtis Ramirez Monica. N.p., 30 Nov. 2015.

Morgan, A. J. and Schwartz, R. A. (2010), Cutaneous polyarteritis nodosa: a comprehensive review. International Journal of Dermatology, 49: 750–756. doi:10.1111/j.1365-4632.2010.04522.x