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This was the first vasculitis, originally described in 1852. The term polyarteritis nodosa (PAN) was adopted in 1992. The current definition of PAN was agreed at the 2012 Chapel Hill Conference:
PAN is necrotising arteritis of medium or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules, and not associated with antineutrophil cytoplasmic antibodies (ANCAs).
It can affect any organ but, for unknown reasons, it spares the pulmonary and glomerular arteries.
A less severe form called cutaneous polyarteritis nodosa (CPAN) has also been described. Its features include tender subcutaneous nodules, livedo reticularis, cutaneous ulcers and necrosis. It is often associated with streptococcal infection. Although progress to classical PAN at a later stage has been reported, generally it is thought to be unlikely.
- PAN affects approximately 3.1 per 100,000 people per year.
- It is seen in all ethnic groups and appears to be present throughout the world, although the incidence is higher in areas where hepatitis B is endemic.
- Although it may be triggered by viral infections, it is idiopathic in most cases.
- It can occur from childhood with a peak incidence at around 10 years. In adults, the most commonly affected age group is between the ages of 40 and 50.
- In adults, men are more commonly affected than women; however, children are equally affected.
Some authors state that the incidence is falling, others that it is rising but this may be due to increased recognition.
Diagnosis is not easy, as PAN often presents in a vague manner with symptoms including fever, weight loss, headache and myalgia. There is a spectrum of organ involvement ranging from a single organ to multisystem disease.
- Peripheral nerves and skin are the most frequently affected tissues.
- The skin can demonstrate a range of lesions, including purpura, livedoid, subcutaneous nodules and necrotic ulcers.
- Neurologically, mononeuritis multiplex is the most common presentation.
- Involvement of the gastrointestinal tract, kidneys, heart and central nervous system is associated with a higher mortality.
- If there is renal involvement, patients may present with hypertension or acute kidney inury.
- Gastrointestinal symptoms occur in 14-65% of patients and postprandial abdominal pain from ischaemia is the most common symptom. Bowel necrosis and perforation are associated with a poor prognosis.
- Myalgia is reported in 72% of childhood patients.
- The typical presentation in children is one- or two-organ involvement, with constitutional symptoms, and the diagnosis is often based on pathology.
Historically these have included the American College of Rheumatology (ACR) and Chapel Hill Consensus criteria[2, 12]. The ACR criteria (10 factors) for classifying a patient with vasculitis within a specific disease entity are useful in clinical practice but make no reference to ANCAs. Also, in many cases, their application results in overlapping diagnoses, particularly in patients with small vessel vasculitis and classical PAN. Therefore, an algorithm based on both the Chapel Hill definitions and the ACR criteria has been considered useful for correctly classifying patients[13, 14].
The patient must be at least 16 years old at the time of diagnosis:
- A patient is said to have polyarteritis nodosa if he or she has three of the 10 signs known as the 1990 ACR criteria:
- Weight loss greater than 4 kg.
- Livedo reticularis.
- Testicular pain or tenderness.
- Mononeuropathy or polyneuropathy.
- New-onset diastolic blood pressure greater than 90 mm Hg.
- Elevated kidney blood tests (blood urea greater than 14.3 mmol/L or creatinine greater than 133 µmol/L).
- Evidence of hepatitis B infection.
- Arteriogram showing the arteries that are dilated or constricted by the blood vessel inflammation.
- Presence of granulocyte or mixed leukocyte infiltrate in an arterial wall biopsy.
Classification of childhood PAN requires a systemic inflammatory disease with evidence of necrotising vasculitis or angiographic abnormalities of medium- or small-sized arteries (mandatory criterion) plus one of five criteria:
- Skin involvement
- Myalgia/muscle tenderness
- Peripheral neuropathy
- Renal involvement
As PAN presents with nonspecific symptoms, numerous alternative diagnoses must be considered:
- Fever caused by viral, bacterial and parasitic infections.
- Ulceration due to pyoderma gangrenosum must be excluded (particularly in children).
- Crohn's disease.
- Connective tissue diseases including systemic lupus erythematosis, rheumatoid arthritis, allergic granulomatosis.
- Vasculitides including giant cell arteritis, Henoch-Schönlein purpura, granulomatosis with polyangiitis, Churg-Strauss syndrome and Kawasaki disease.
- Hepatitis B surface antigen is positive in 30%.
- The p-ANCA test is usually negative in PAN.
- There is a prominent acute phase response but this is nonspecific.
- FBC shows leukocytosis with raised neutrophils.
- Hypergammaglobulinaemia occurs in 30%.
- Biopsy of small arteries will show evidence of necrotising inflammation. However, skin or muscle biopsies are preferred as they are safer and have a higher diagnostic yield.
- Arteriography shows microaneurysms in the small-sized and medium-sized arteries of the kidneys and abdominal viscera. Selective renal angiography shows aneurysms in 40% of children.
Hepatitis B-associated PAN is a form of classical PAN. The pathogenesis is attributed to immune-complex deposition with antigen excess.
- The mainstay of treatment for PAN is corticosteroid therapy:
- If patients relapse despite steroid therapy, the addition of cyclophosphamide has been shown to reduce relapse rate further.
- Azathioprine can also be used as maintenance therapy and seems to be effective and well tolerated with fewer long-term side-effects than cyclophosphamide.
- Other immunosuppressants tend to be reserved for patients with the most severe disease and poor prognostic factors.
- In patients with active hepatitis B, antivirals and plasma exchanges prevent the development of long-term hepatic complications of hepatitis B viral infection.
- Intravenous immunoglobulin (IV-Ig) and aspirin are effective in childhood PAN but, in resistant cases, either steroid or infliximab has a role.
- Mild cases may require only non-steroidal anti-inflammatory drugs (NSAIDs) or colchicine.
- Prednisolone 30 mg daily or less is often effective in more severe cases but a dosage of 1 mg/kg/day may be required. Unfortunately, exacerbations occur with the tapering of the corticosteroids and adverse effects limit their long-term use.
- Immunosuppressive agents are frequently effective in CPAN resistant to high-dose corticosteroids and should be reserved for these severe relentless forms.
Without treatment, hypertension-induced acute kidney injury is a cause of great morbidity and mortality. The patient should also be monitored for:
- Cerebrovascular events
- Peripheral neuropathy
- Older age group.
- Renal, CNS or cardiac involvement.
Avoidance of hepatitis B (by lifestyle choices and hepatitis B immunisation) may reduce the incidence of hepatitis B-associated PAN but it will not eradicate PAN altogether.
Further reading and references
Cutaneous polyarteritis nodosa; DermNet NZ
Sunderkotter C, Sindrilaru A; Clinical classification of vasculitis. Eur J Dermatol. 2006 Mar-Apr16(2):114-24.
Jennette JC, Falk RJ, Bacon PA, et al; 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan65(1):1-11. doi: 10.1002/art.37715.
Howard T, Ahmad K, Swanson JA, et al; Polyarteritis nodosa. Tech Vasc Interv Radiol. 2014 Dec17(4):247-51. doi: 10.1053/j.tvir.2014.11.005. Epub 2014 Nov 13.
Morgan AJ, Schwartz RA; Cutaneous polyarteritis nodosa: a comprehensive review. Int J Dermatol. 2010 Jul49(7):750-6.
Nakamura T, Kanazawa N, Ikeda T, et al; Cutaneous polyarteritis nodosa: revisiting its definition and diagnostic criteria. Arch Dermatol Res. 2008 Sep 19.
Mohammad AJ, Jacobsson LT, Mahr AD, et al; Prevalence of Wegener's granulomatosis, microscopic polyangiitis, polyarteritis nodosa and Churg-Strauss syndrome within a defined population in southern Sweden. Rheumatology (Oxford). 2007 Aug46(8):1329-37. Epub 2007 Jun 6.
Hernandez-Rodriguez J, Alba MA, Prieto-Gonzalez S, et al; Diagnosis and classification of polyarteritis nodosa. J Autoimmun. 2014 Feb-Mar48-49:84-9. doi: 10.1016/j.jaut.2014.01.029. Epub 2014 Jan 28.
Lane SE, Scott DG, Heaton A, et al; Primary renal vasculitis in Norfolk - increasing incidence or increasing recognition? Nephrol Dial Transplant. 2000 Jan15(1):23-7.
Ebert EC, Hagspiel KD, Nagar M, et al; Gastrointestinal involvement in polyarteritis nodosa. Clin Gastroenterol Hepatol. 2008 Sep6(9):960-6. Epub 2008 Jun 27.
Ozen S, Pistorio A, Iusan SM, et al; EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010 May69(5):798-806.
Ozen S; Juvenile polyarteritis: is it a different disease? J Rheumatol. 2004 Apr31(4):831-2.
Lightfoot RW Jr, Michel BA, Bloch DA, et al; The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rheum. 1990 Aug33(8):1088-93.
Watts R, Lane S, Hanslik T, et al; Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis. 2007 Feb66(2):222-7. Epub 2006 Aug 10.
Kallenberg CG; The last classification of vasculitis. Clin Rev Allergy Immunol. 2008 Oct35(1-2):5-10.
Stanson AW, Friese JL, Johnson CM, et al; Polyarteritis nodosa: spectrum of angiographic findings. Radiographics. 2001 Jan-Feb21(1):151-9.
Brogan PA, Davies R, Gordon I, et al; Renal angiography in children with polyarteritis nodosa. Pediatr Nephrol. 2002 Apr17(4):277-83.
Guillevin L, Mahr A, Callard P, et al; Hepatitis B virus-associated polyarteritis nodosa: clinical characteristics, outcome, and impact of treatment in 115 patients. Medicine (Baltimore). 2005 Sep84(5):313-22.
Guillevin L, Pagnoux C; When should immunosuppressants be prescribed to treat systemic vasculitides? Intern Med. 2003 Apr42(4):313-7.
Dillon MJ, Eleftheriou D, Brogan PA; Medium-size-vessel vasculitis. Pediatr Nephrol. 2010 Sep25(9):1641-52. Epub 2009 Nov 28.
Bourgarit A, Le Toumelin P, Pagnoux C, et al; Deaths occurring during the first year after treatment onset for polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: a retrospective analysis of causes and factors predictive of mortality based on 595 patients. Medicine (Baltimore). 2005 Sep84(5):323-30.