Vasculitides classification by blood vessel size
2012 International Chapel Hill Consensus Conference
PAN1866 periarteritis nodosa used to describe any form of systemic vasculitis.Vasculitis predominantly affecting medium arteries defined as the main visceral arteries and their branches. Polyarteritis nodosa (PAN) = Necrotizing arteritis of medium or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules, and not associated with antineutrophil cytoplasmic antibodies (ANCAs).
Epidemiology Incidence: 2 - 9 per million in Europe and the US (ACR criteria)16 per million (by CHCC definition) in Kuwait77 per million described in an Alaskan population endemic for HBV (based on only 13 actual cases of HBV PAN study before ACR criteria or CHCC definitions) Changed since vaccination for HBV: incidence of HBV-related PAN follows HBV infection rates: 7% to 38.5% of patients dg with PANPAN develops in 1% to 5% of patients with HBV infection, confers an approximately 1000-fold increase in risk compared with the background population
Watts RA et al. Epidemiology of vasculitis. In Bridges L, Ball G, editors: Vasculitis, Oxford, UK, 2008, Oxford University Press, pp 722.; el-Reshaid K et al: The spectrum of renal disease associated with microscopic polyangiitis and classic polyarteri- tis nodosa in Kuwait, Nephrol Dial Transplant 12:18741882, 1997. McMahon BJ et al. Hepatitis B-associated polyarteritis nodosa in Alaskan Eskimos: clinical and epidemiologic features and long-term follow-up, Hepatology 9:97101, 1989.
Pathogenesis in HBV- PANDirect vessel injury by replicating virus or deposition of immune complexes leads to activation of the complement cascade, resulting in an inflammatory response and subsequent endothelial damage. The vasculitis typically occurs within the first few months following HBV infection and may be the first presenting feature Mechanism supported by treatment strategy to eradicate HBV with antiviral therapy and removal of immune complexes by plasmapheresis without the need for long-term immunosuppression.
Pathogenesis for idiopathic PANPAN responds to immunosuppressive therapy suggests an immunologic mechanism. Evidence of endothelial dysfunction, an increase in inflammatory cytokines, and an increase in expression of adhesion molecules.Propensity for the inflammatory lesions to occur at the sites of bifurcation in vessels, where there is most likely to be turbulent flow. Following the inciting event, there is focal and segmental necrotizing inflammation of medium- and small-sized arteries. This leads to intimal proliferation with subsequent thrombosis, resulting in ischemia or infarction of the organ or tissue supplied by these arteries.
Clinical presentation PAN
Clinical featureAge 40-60 years; no gender preference
Cutaneous PANImplies a separate entity from PAN limited to the skin, but there is some uncertainty as to whether these are actually just early cases of PAN and whether progression to PAN will occur. Pathologically the findings on skin biopsy are indistinguishable In a retrospective review of cutaneous PAN patients from a Japanese group, 22 patients with histologically proven cutaneous vasculitis were followed: 32% had a peripheral neuropathy, and 27% had myalgia, suggesting a need to revise the current criteria to differentiate between the two entities of cutaneous PAN and PANHCV infection has been associated with cutaneous PAN-31/161 (19%) dg with PANFurukawa F. Cutaneous PAN: an update. Ann Vasc Dis. 2012;5 (3) 282-8Saadon D et al. Hepatitis C ssociated PAN. Arthritis Care Res (Hoboken). 2011 Mar;63(3):427-35
Labs that support the diagnosis of PANTESTSupport diagnosisElevated ESR/ CRP+Elevated Creatinine (w/out hematuria, proteinuria, cell casts)+/- (suggest renal ischemia)Abnormal liver test+ (suggest HBV/ liver ischemia)Anemia + (chronic inflammation/ blood loss)CPK+ (normal/slightly elevated despite muscle involvement )
Labs that are against PANTESTAgainst the diagnosisANCA+ (GPA/ MPA)Blood Cultures+ (endocarditis/ infectious vasculitis)HCV+ (HCV associated cryoglobulinemia)RF, CCP+ RFANA, dsDNA+ SLE/CTDHIV+
ImagingAngiogram = imaging of choice shows multiple small aneurysms, vessel ectasia, and focal occlusive lesions in medium-sized vessels, typically in the renal and mesenteric arteries. Sensitivity -89% and specificity 90% MR/ CT angiography are less invasive but are much less sensitive in demonstrating microaneurysms.Doppler ultrasound can identify renal and hepatic aneurysms CXR excludes other vasculitides that may affect the lungs and also to exclude infection
Hekali P, et al: Diagnostic significance of angiographically observed visceral aneurysms with regard to polyarteritis nodosa, Acta Radiol 32:143148, 1991. Ozaki K, et al: Renal involvement of polyarteritis nodosa: CT and MR findings, Abdom Imaging 34:265270, 2009. Ozcakar ZB, et al: Polyarteritis nodosa: successful diagnostic imaging utilizing pulsed and color Doppler ultrasonography and computed tomography angiography, Eur J Pediatr 165:120123, 2006.
Coronary angiogram25-year-old F dg with PAN 3 years earlier and was receiving prednisolone maintenance therapy when she presented with cardiac arrest. Although severe cardiac involvement in polyarteritis nodosa is unusual, it can result in myocardial infarction and confers a poorer prognosis. Despite treatment, the patient died a few months later.
Renal angiogram47-year-old man with abdominal pain, weight loss, and an elevated ESRRight renal arteriogram reveals multiple microaneurysms within the upper pole of the kidney on this selective right renal artery injection (upper pole branch)
ACR criteria 19903/10 criteriaSensitivity 82%; Specificity 86%Did not differentiate PAN from MPA or GPA
PAN and drugsMinocycline (many case reports)Levamisole (antihelmintic, immunomodulator withdrawn from US market in 2003 ) SE agranulocytosis and erythematous painful papules on the skin; ThiabendazoleAbatacept-cutaneous PAN to one armGemcytabine Hep B vaccination (child)Interferon tx for HepC
PAN & drugs - referencesMinocycline-induced polyarteritis nodosa-like vasculitis presenting as brainstem stroke. Klaas JP, Matzke T, Makol A, Fulgham JR. J Clin Neurosci. 2015 May;22(5):904-7. doi: 10.1016/j.jocn.2014.12.003. Epub 2015 Mar 14.Minocycline-induced polyarteritis nodosa-like vasculitis. Agur T, Levy Y, Plotkin E, Benchetrit S.Isr Med Assoc J. 2014 May;16(5):322-3. No abstract available.Eur J Dermatol. 2013 Sep-Oct;23(5):738-9. doi: 10.1684/ejd.2013.2160.Cutaneous polyarteritis nodosa localized to the arm receiving an infusion of abatacept Shibata S1, Asano Y, Sato S.Levamisole-induced vasculitis with ecchymosis and necrosis syndrome from contaminated cocaine. Desai N, Patel M, Desai S, Cerceo E. BMJ Case Rep. 2012 Nov 21;2012. pii: bcr2012007319. doi: 10.1136/bcr-2012-007319. No abstract available. Thiabendazole-induced acute liver failure requiring transplantation and subsequent diagnosis of polyarteritis nodosa. Groh M, Blanche P, Calmus Y, Guillevin L. Clin Exp Rheumatol. 2012 Jan-Feb;30(1 Suppl 70):S107-9. Epub 2012 May 11.Eur J Dermatol. 2009 Jul-Aug;19(4):400-1. doi: 10.1684/ejd.2009.0695. Epub 2009 May 25. Cutaneous polyarteritis nodosa in a child following hepatitis B vaccination. Ventura F, Antunes H, Brito C, Pardal F, Pereira T, Vieira AP.
PAN and Hairy cell leukemia (HCL)There is a well-recognized association between HCL and PAN [Fortin, 1996].Direct evidence linking the two conditions with histopathology showing direct invasion of the vessel wall by leukemic cells [Hasler et al. 1995]. In a literature review of 42 cases of vasculitis associated with HCL, 21 cases were consistent with PAN ( 4 cases showed vessel wall infiltration by the leukemic cells). PAN often occurred after the diagnosis of HCL and splenectomy. Fortin P.R. (1996) Vasculitides associated with malignancy. Curr Opin Rheumatol 8: 3033 Gabriel S.E., Conn D.L., Phyliky R.L., Pittelkow M.R., Scott R.E. (1986) Vasculitis in hairy cell leukemia: Review of literature and consideration of possible pathogenic mechanisms. J Rheumatol 13: 11671172 Hasler P., Kistler H., Gerber H. (1995) Vasculitides in hairy cell leukemia. Semin Arthritis Rheum 25: 134142
PAN and the risk of cancersIn a series of 115 patients with HBV-PAN, 3 patients (2.6%) died from cancer over a mean follow-up of 69 months ( 2 lung, 1 prostate cancer) [Guillevin et al. 2005]. In a prospective, randomized, open-label treatment study that included 58 patients with non-HBV PAN, three PAN patients (5.2%) developed cancer over follow-up [Ribi et al. 2010] (to CS vs azathioprine alone) -- 1 Hodgkin's lymphoma and 2 colon cancer ( The cancers occurred 19 mo, 10 mo and 4 years after inclusion in the study)348 patients with PAN with mean follow up of 68.3 months, there were 5 cancer-related deaths (1.4%): 1 lung, 1 liver, 2 prostate cancers, and 1 myelodysplasia occurring 419 years after PAN diagnosis [Pagnoux et al. 2010].
Pagnoux C.et al. (2010) Clinical features and outcomes in 348 patients with polyarteritis nodosa: A systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Arthritis Rheum 62: 616626Ribi C., et al. (2010) Treatment of polyarteritis nodosa and microscopic polyangiitis without poor-prognosis factors: A prospective randomized study of one hundred twenty-four patients. Arthritis Rheum 62: 11861197 Guillevin L. et al. (2005) Hepatitis B virus-associated polyarteritis nodosa: Clinical characteristics, outcome, and impact of treatment in 115 patients. Medicine (Baltimore) 84: 313322