What is PAN?

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Patient Presentation
An 18-year-old female came to clinic for her health supervision visit before leaving for college in another state.

Her past medical history showed she had had cutaneous polyarteritis nodosa (PAN) diagnosed at age 14 when she had some fever, myalgia and subcutaneous erythematous nodules along her bilateral shins. She had been managed by rheumatology with steroid medication and had achieved and remained in remission after being weaned off her medication.

The pertinent physical exam revealed a healthy female with normal vital signs and stable growth parameters.

The diagnosis of a healthy female in remission for cutaneous PAN was made. Her next rheumatology appointment was in 2 months. “You can always call your rheumatologist if you have any concerns while you are at college, but it probably is also good to have another rheumatologist already picked out if you need someone. I’m also here to help you so you can call me too,” the pediatrician explained.

Discussion
Vasculitis is an inflammation of the blood vessels. Often, the term implies the arterial vessels, but venous and capillary vessels can be affected. The nomenclature to describe vasculitis and its classification have varied over time. Arterial vessel size is one method and some more common entities include:

  • Small vessel, mainly
    • Granulomatous – granulomatosis with polyangiitis (aka Wegener’s granulomatosis), eosinophilic granulomatosis with polyangiitis (aka Churg Strauss syndrome)
    • Nongranulomatous – Henoch-Schonlein purpura (HSP), microscopic polyangiitis
  • Medium vessel, mainly
    • Childhood systematic polyarteritis nodosa
    • Cutaneous polyarteritis nodosa
    • Kawasaki disease (KD)
  • Large vessel, mainly
    • Takayasu arteritis
  • Other
    • Bechet disease
    • Secondary due to infection, drug, and malignancy including Hepatitis-B-associated polyarteritis nodosa
    • Central nervous system vasculitis, isolated
    • Connective tissue disease associated vasculitis

Management and treatment can involve multiple specialists because of potential complications. Mainstays of treatment are glucocorticoids and anti-inflammatory medications.

Learning Point
Polyarteritis nodosa was first described in 1866 and “…is a necrotizing vasculitis associated with aneurysmal nodules along the walls of medium-sized muscular arteries…” It can also occur in small vessels. It is the third most common childhood systemic vasculitis after HSP and KD, but overall is relatively rare. Diagnosis is with evidence of necrotizing vasculitis in small or medium sized arteries on biopsy or abnormal angiographic findings such as aneurysm, occlusion or stenosis, plus other findings such as myalgia, hypertension or renal involvement or peripheral neuropathy. Clinical features can include:

  • Systemic – fever, malaise, pain (e.g. abdominal pain, arthralgia myalgia) and rash
  • Dermatological – variable – livido reticularis (net-like, red-blue skin discoloration to the skin that is relatively well demarcated), subcutaneous nodules (particularly in lower legs)
  • Gastrointestinal – peritoneal or retroperitoneal bleeding
  • Organic pain – ischemic heart pain, testicular pain
  • Neurological – focal defects, hemiplegia, visual loss, psychosis
  • Renal – hematuria, proteinuria, hypertension

The differential diagnosis includes HSP, KD, other vasculitides, connective tissue diseases, infections (e.g. subacute bacterial endocarditis) and malignancies. Antineutrophil cytoplasmic antibodies (ANCA) are negative and this helps to differentiate it from other vasculitides.

Cutaneous PAN is a necrotizing vasculitis of small and medium sized arteries but is limited to the skin. It can have systemic involvement such as fever, arthralgia, and myalgia but skin lesions predominate. Skin findings can include livido reticularis, and usually painful, subcutaneous non-purpuric lesions. The lower extremities are a common location. In children cutaneous PAN is associated with streptococcal infections and may recur with them. Cutaneous PAN has a high remission rate.

PAN and cutaneous PAN can be seen both in childhood and adults but adults are more common overall. One relatively large, registry study in France consisting of 21 children (<18 years) and 84 adults studied patients’ characteristics and outcomes. Children were slightly less likely to have systemic disease than adults but most comparisons were not statistically significant. Children also had shorter relapses than adults, but children were more likely than adults to have at least 1 flare than adults. Cumulative body damage and deaths were similar between the two groups.

Children with cutaneous PAN were statistically less likely to have myalgias and purpura, but were more likely to have skin nodules but this was not statically significant (92% versus 59%, p=0.06). Children with cutaneous PAN had the same relapse rates, and deaths as adults.

Questions for Further Discussion
1. What are the characteristics of HSP? A review can be found here
2. What are the characteristics of KD? A review can be found here
3. What are the characteristics of Bechet’s Disease? A review can be found here

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Vasculitis

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Dillon MJ, Eleftheriou D, Brogan PA. Medium-size-vessel vasculitis. Pediatr Nephrol. 2010;25(9):1641-1652. doi:10.1007/s00467-009-1336-1

Ozen S. The changing face of polyarteritis nodosa and necrotizing vasculitis. Nat Rev Rheumatol. 2017;13(6):381-386. doi:10.1038/nrrheum.2017.68

Iudici M, Quartier P, Pagnoux C, et al. Childhood- versus Adult-Onset Polyarteritis Nodosa Results from the French Vasculitis Study Group Registry. Autoimmunity Reviews. 2018;17(10):984-989. doi:10.1016/j.autrev.2018.08.001

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Published