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classic polyarteritis nodosa (PAN)

Classic form described in 1866 by Kussmaul & Maier. Etiology: - associated diseases: a) hepatitis B infection - hepatitis B surface antigen (HBSAg) positive (20-50%) b) hepatitis C (5%) c) hairy cell leukemia d) rheumatoid arthritis e) Sjogren's syndrome Epidemiology: 1) mean age of onset: 48 years 2) male:female ratio 1.6:1 3) uncommon: incidence 4.6-9/million 4) all racial groups affected Pathology: 1) multisystem necrotizing vasculitis 2) necrotizing inflammation of small & medium sized muscular arteries 3) lesions are transmural, segmental & occur at bifurcations 4) neutrophils & monocytes invading the vessel walls 5) fibrinoid necrosis of vessels 6) thrombosis of necrosed vessels with infarction of affected tissue 7) renal artery vasculitis & mesenteric artery vasculitis characteristic 8) kidney disease but no glomerulonephritis 9) no granulomas 10) no eosinophilia 11) pathology may be initiated by immune complexes Genetics: - associated with mutations in CECR1 Clinical manifestations: 1) general: a) fever b) weight loss c) malaise d) weakness e) night sweats f) hypertension g) symptoms develop over days to months 2) central nervous system: (23%) a) headache b) stroke c) seizure d) delirium 3) peripheral nervous system: (50%) a) peripheral neuropathy (asymmetric) 1] distal weakness 2] numbness in stocking glove pattern b) mononeuritis multiplex 4) gastrointestinal: (44%) a) mesenteric artery vasculitis b) nausea/vomiting, abdominal pain c) intestinal infarction, intestinal perforation d) hepatic infarction e) pancreatitis, pancreatic infarction f) cholecystitis g) appendicitis h) GI bleed 5) renal: (60%) a) proteinuria (rarely in nephrotic range) b) hypertension c) acute renal failure is rare d) no glomerulonephritis e) renal artery vasculitis [3] f) flank pain 6) cardiac: (36%) a) cardiomyopathy 1] myocarditis 2] congestive heart failure (CHF) b) myocardial infarction (MI) c) pericarditis 7) musculoskeletal: (64%) a) myalgias b) arthralgias c) arthritis 8) genitourinary: (25%) a) testicular pain, orchitis b) epididymal pain c) ovarian pain d) renal disease resulting from ischemia rather than glomerulonephritis [3] 9) skin: (43%) a) rash b) palpable purpura [3] c) painful subcutaneous nodules [3] d) cutaneous infarcts, ulceration e) livedo reticularis f) Raynaud's phenomenon 10) eye: scleritis 11) respiratory tract rarely involved [3] 12) sensorineural hearing loss [3] 13) pulmonary disease & eosinophila are not features Laboratory: 1) complete blood count (CBC): - leukocytosis, anemia, thrombocytosis [3] - no eosinophilia 2) elevated erythrocyte sedimentation rate (ESR) & serum C-reactive protein 3) liver function tests 4) hepatitis B panel (30% positive for HBSAg) 5) hepatitis C serology 6) anti neutrophil cytoplasmic antibody (ANCA) may be positive a) p or peripheral type (pANCA) in polyarteritis nodosa - MKSAP19 makes no mention of this [3] b) c or central type (cANCA) in Wegener's granulomatosis 7) serum complement levels are normal [3] 8) biopsy a) skin biopsy (skin nodule)* b) painful testes c) muscle biopsy d) nerve biopsy (sural nerve)* e) microscopy of medium sized muscular arteries for diagnosis (see Pathology:) 9) urinalysis: - proteinuria (rarely nephrotic range), hematuria, no erythrocyte casts [3] 10) see ARUP consult [5] * gold standards for diagnosis [3] Radiology: - abdominal CT angiography may demonstrate microaneurysms, stenosis, occlusion, & beading in small & medium sized arteries, especially of the renal arteries & mesenteric arteries - MKSAP19 suggests MRI angiography diagnostic test of choice Differential diagnosis: - microscopic polyangiitis - eosinophilic granulomatosis with polyangiitis - pulmonary disease & eosinophilia Complications: - see clinical manifestations Management: 1) many patients respond to high-dose glucocorticoids - prednisone 1 mg/kg/day 1) combination therapy a) prednisone 1 mg/kg PO QD + cyclophosphamide 2 mg/kg PO QD b) recommended initial therapy [14] c) cyclophosphamide formerly reserved for patients without hepatitis B who do not respond to prednisone or have significant renal, gastrointestinal, cardiac or neurologic manifestations [3] d) prednisone + azathioprine or methotrexate controversial [14] e) 90% long term remission after discontinuation of therapy 2) HBSAg+ polyarteritis nodosa a) antiviral therapy 1] lamivudine or entecavir [3,7] 2] vidarabine 3] interferon alpha b) prednisone for 2 weeks, followed by plasmapheresis, then antiviral therapy - apparently outdated recommendation [3] c) patients generally respond to therapy, but become chronic carriers of hepatitis B & may later die of cirrhosis or variceal bleeding 3) control of hypertension reduces renal, cardiac & CNS complications 4) prognosis a) prognosis of untreated polyarteritis nodosa is poor 1] fulminant deterioration 2] slow progression with intermittent exacerbations 3] 5 year survival is 13% if untreated b) predictors of poor prognosis with treatment 1] renal, gastrointestinal, CNS or cardiac involvement 2] 5 year survival is 65% with any of these predictors & 90% without [3] 5) hepatitis B vaccine reduces incidence of polyarteritis nodosa [3]

Interactions

disease interactions

General

arteritis autoimmune disease

References

  1. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1671-2
  2. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 1912-14
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18,19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Khasnis A and Langford CA. Update on vasculitis. J Allergy Clin Immunol 2009 Jun; 123:1226. PMID: 19501230
  5. ARUP Consult: Polyarteritis Nodosa - PAN The Physician's Guide to Laboratory Test Selection & Interpretation https://arupconsult.com/content/polyarteritis-nodosa
  6. Henegar C, Pagnoux C, Puachal X et al A paradigm of diagnostic criteria for polyarteritis nodosa: analysis of a series of 949 patients with vasculitides. Arthritis Rheum. 2008 May;58(5):1528-38. PMID: 18438816
  7. 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 Sep;84(5):313-22. PMID: 16148731
  8. Pagnoux C, Seror R, Henegar C et al 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. 2010 Feb;62(2):616 PMID: 20112401
  9. Ebert EC, Hagspiel KD, Nagar M, Schlesinger N Gastrointestinal involvement in polyarteritis nodosa. Clin Gastroenterol Hepatol. 2008 Sep;6(9):960-6 PMID: 18585977
  10. de Menthon M, Mahr A. Treating polyarteritis nodosa: current state of the art. Clin Exp Rheumatol. 2011 Jan-Feb;29(1 Suppl 64):S110-6. PMID: 21586205
  11. De Virgilio A, Greco A, Magliulo G et al Polyarteritis nodosa: A contemporary overview. Autoimmun Rev. 2016 Jun;15(6):564-70. Review. PMID: 26884100
  12. Forbess L, Bannykh S. Polyarteritis nodosa. Rheum Dis Clin North Am. 2015;41(1):33-46, vii. Review. PMID: 25399938
  13. Alibaz-Oner F, Koster MJ, Crowson CS Clinical Spectrum of Medium-Sized Vessel Vasculitis. Arthritis Care Res (Hoboken). 2017 Jun;69(6):884-891. PMID: 27564269 Free Article
  14. Chung SA, Gorelik M, Langford CA et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of polyarteritis nodosa. Arthritis Rheumatol 2021 Aug; 73:1061-1070. PMID: 34235889 https://onlinelibrary.wiley.com/doi/10.1002/acr.24633