Ntatsaki E, Carruthers D, Chakravarty K, et al; BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis. Rheumatology (Oxford). 2014 Dec;53(12):2306-9. doi: 10.1093/rheumatology/ket445. Epub 2014 Apr 11. PubMed PMID: 24729399.
Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan;65(1):1-11. doi: 10.1002/art.37715. PubMed PMID: 23045170.
Mukhtyar C, Guillevin L, Cid MC, et al; European Vasculitis Study Group. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2009 Mar;68(3):310-7. doi: 10.1136/ard.2008.088096. Epub 2008 Apr 15. PubMed PMID: 18413444.
Polyarteritis nodosa (PAN) is a necrotizing antineutrophil cytoplasmic antibody (ANCA)-negative vasculitis involving medium and small arteries. It can be distinguished from other vasculitides (mainly from microscopic polyangiitis) by the absence of pulmonary involvement, features of glomerulonephritis, or involvement of arterioles, capillaries, or venules. PAN is strongly associated with hepatitis B virus (HBV) infection (10%-80% of patients, according to various sources). A cutaneous form of PAN may also be associated with hepatitis C virus (HCV) infection. PAN usually affects patients aged 40 to 60 years and is more frequent in men than in women.
Clinical Features and Natural HistoryTop
The onset of PAN is usually associated with general symptoms (fatigue, myalgia, arthralgia, weight loss, fever), which may persist for several months. Later signs and symptoms include:
1) Cutaneous manifestations: Palpable purpura (most frequent), livedo reticularis, ulcerations (on fingers, ankles, the anterior aspect of lower legs), subcutaneous nodules <2 cm in diameter (usually on the anterior aspect of lower extremities and dorsal aspect of feet).
2) Nervous system manifestations: Most frequently mononeuritis multiplex (usually fibular nerve palsy [foot drop]), less often symmetric peripheral neuropathy.
3) Renal manifestations: Hypertension related to extraglomerular vessel inflammation, features of renal failure. Rarely, it can lead to renal infarction (acute severe lumbar pain).
4) Gastrointestinal manifestations: Abdominal pain, most frequently due to intestinal ischemia from visceral vessel involvement (intestinal necrosis and perforation is rare).
Untreated disease has a fatal course and leads to death within 1 to 2 years. The cutaneous form (without internal organ involvement) has a mild course and may resolve spontaneously but frequently recurs.
Diagnosis is based on clinical manifestations and histologic findings from biopsies of the involved organs.
Laboratory test results often reveal elevations in the erythrocyte sedimentation rate and C-reactive protein levels as well as anemia (usually normocytic). In patients with renal involvement there can be elevated serum creatinine levels and rarely moderate proteinuria and microscopic hematuria. Angiography of the visceral arteries reveals dilations (microaneurysms) of medium arteries, for instance, kidney, liver, or intestinal arteries.
Other vasculitides, in particular granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). ANCA testing is useful to help in the differentiation, as ANCA is negative in PAN.
Remission induction is recommended with a combination of cyclophosphamide (intravenous or oral) and glucocorticoids.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Guillevin L, Jarrousse B, Lok C, et al. Longterm followup after treatment of polyarteritis nodosa and Churg-Strauss angiitis with comparison of steroids, plasma exchange and cyclophosphamide to steroids and plasma exchange. A prospective randomized trial of 71 patients. The Cooperative Study Group for Polyarteritis Nodosa. J Rheumatol. 1991 Apr;18(4):567-74. PubMed PMID: 1676753. Guillevin L, Lhote F, Cohen P, et al. Corticosteroids plus pulse cyclophosphamide and plasma exchanges versus corticosteroids plus pulse cyclophosphamide alone in the treatment of polyarteritis nodosa and Churg-Strauss syndrome patients with factors predicting poor prognosis. A prospective, randomized trial in sixty-two patients. Arthritis Rheum. 1995 Nov;38(11):1638-45. PubMed PMID: 7488285. Dosing is the same as in granulomatosis with polyangiitis.
In PAN associated with HBV infection, initial high-dose glucocorticoids (without cyclophosphamide) may be effective with tapering of the dose over 2 weeks. At the same time, the use of plasmapheresis followed by antiviral treatment may be of benefit.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the presence of small observational studies with no patient-important outcomes, imprecision, indirectness, and risk of bias. Guillevin L, Mahr A, Callard P, et al; French Vasculitis Study Group. Hepatitis B virus-associated polyarteritis nodosa: clinical characteristics, outcome, and impact of treatment in 115 patients. Medicine (Baltimore). 2005 Sep;84(5):313-22. PubMed PMID: 16148731. In the cutaneous form of PAN, oral glucocorticoids alone may be of benefit. Hypertension requires aggressive antihypertensive treatment. As patients may have impaired renal arterial perfusion, angiotensin-converting enzyme inhibitors should be used with caution.
In treated patients, 5-year survival rates are ≤80%. In the cutaneous form of PAN, the prognosis is good with only rare progression to systemic disease.