Polyarteritis Nodosa



Polyarteritis Nodosa


Surya V. Seshan, MD





Key Facts


Terminology



  • Necrotizing inflammation of medium-sized or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules


Clinical Issues



  • HBV association in ˜ 36% of PAN cases


  • Up to 77/million in endemic areas for hepatitis B viral infection


  • Adult: Peak at 5th to 7th decade


  • Multisystemic involvement


  • Rarely, ANCA positive


  • Kidney frequently involved (70-80%)


  • New onset hypertension, sometimes malignant range


  • Cyclophosphamide and steroids for severe cases, remission in 90%


Image Findings



  • Angiography localizes microaneurysms


Microscopic Pathology



  • Intralobar, arcuate, and, rarely, interlobular arteries affected (medium-sized vessels)


  • Characteristic features are fibrinoid necrosis and transmural and periarterial inflammation


  • Late arterial lesions include aneurysms and stenosis


Top Differential Diagnoses



  • Kawasaki disease


  • ANCA-related small vessel vasculitides


  • Systemic lupus erythematosus


  • Fibromuscular dysplasia







Kidney biopsy in polyarteritis nodosa (PAN) shows circumferential, transmural fibrinoid necrosis and active inflammatory infiltrate composed of neutrophils and lymphocytes.






Trichrome-stained kidney section shows a healing PAN of a medium-sized vessel with focal thrombosis and early microaneurysm formation. It is common to have both active and healed lesions in PAN.


TERMINOLOGY


Abbreviations



  • Polyarteritis nodosa (PAN)


Synonyms



  • Macroscopic polyarteritis


  • Classic polyarteritis nodosa


  • Kussmaul and Maier periarteritis nodosa


Definitions



  • Chapel Hill Consensus Conference criteria



    • Necrotizing inflammation of medium-sized or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules


  • American College of Rheumatology criteria



    • Weight loss ≥ 4 kg, livedo reticularis, testicular pain or tenderness, myalgias, weakness or leg tenderness, mono- or polyneuropathy, diastolic BP > 90 mmHg, elevated BUN or creatinine, hepatitis B virus, biopsy diagnosis of small or medium-sized arteries, arteriography with aneurysms or occlusions in visceral arteries


    • 3 or more of the above criteria have high sensitivity and specificity for diagnosis


  • EULAR/PRINTO/PRES criteria for childhood PAN



    • Necrotizing vasculitis, angiographic abnormalities, and either skin involvement, myalgia/muscle tenderness, hypertension, peripheral neuropathy, or renal involvement


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • Hepatitis B virus (HBV)



    • Accounts for ˜ 36% of PAN cases


  • Possibly other bacterial and viral infections



    • Hepatitis C virus (HCV)


    • Rarely HIV, Epstein-Barr virus


Other



  • HBV immunization


  • Exposure to silica-containing compounds


  • In majority, etiology is unknown


Pathogenesis



  • Immunologically mediated



    • Believed to be chronic immune-complex mediated disease



      • Resembles chronic serum sickness model


    • Probably a T-cell-mediated immune component


    • Antigen unknown


    • May be microbial or autoantigen in vessel wall


  • Participation of neutrophilic and mononuclear inflammatory infiltrate (T cells and macrophages)



    • Weakness in vessel wall leads to thrombosis or fibrosis and microaneurysm formation


  • Chronic, cyclic insults support presence of different stages of vasculitis


CLINICAL ISSUES


Epidemiology



  • Incidence



    • 2-31/1,000,000 in Europe and USA



      • Some studies have included cases now classified as microscopic polyangiitis


    • Up to 77/1,000,000 in endemic areas for hepatitis B viral infection


  • Age



    • Adults: Peak at 5th to 7th decade


    • Children: 7-11 years



      • However, less common in children


  • Gender



    • Male predilection (M:F = 2:1)


  • Ethnicity



    • 2x higher prevalence in Europeans vs. others


    • Specific HLA haplotypes


    • Involves all ethnic groups



Presentation



  • Multisystemic involvement


  • Clinical symptoms related to ischemia and are dependent on organ involved and disease severity


  • Constitutional symptoms: Fever, malaise, weight loss, myalgia, abdominal pain


  • Renal



    • Kidney frequently involved (70-80%)



      • Focal renal infarction (˜ 30%)


      • Microaneurysms (˜ 65%)


      • Hematuria, proteinuria (˜ 20%)


      • Loin pain


      • Acute renal failure


    • New onset hypertension, sometimes malignant range


    • Rare: Rupture of kidney with perirenal hematoma


    • Massive retroperitoneal and peritoneal hemorrhage following rupture of arterial aneurysm


  • Heart



    • Ischemic heart disease


  • Neurologic (10%)



    • Focal defects, hemiplegia, visual loss, mononeuritis multiplex


  • Skin



    • Varied lesions: Palpable purpura, necrotic with peripheral gangrene, livedo reticularis, ulcers


    • Subcutaneous nodules


  • Skeletal muscle and mesentery (30%)


  • Gastrointestinal, peripheral nerves, skin (50%)


Laboratory Tests



  • Anemia, leukocytosis, thrombocytosis


  • Elevation of ESR and C-reactive protein


  • Positive hepatitis B serology in some cases


  • No specific serologic tests


  • No significant association with ANCA


  • Rarely, ANCA positive (usually perinuclear) by indirect IF only, when overlap with microscopic polyangiitis


Treatment



  • Steroid therapy is 1st line of therapy; remission in 50% of patients


  • Cyclophosphamide and steroids for severe cases; remission in 90%


  • Plasma exchange/plasmapheresis in refractory cases


  • HBV-associated PAN needs antiviral therapy


Prognosis



  • Fulminant disease with < 5-year survival


  • 40% of patients have relapse


  • 5 factor score (FFS) estimates prognosis



    • Scores renal (Cr > 1.6 mg/dL, proteinuria > 1 gm/24 hr), GI, cardiac, and CNS involvement


    • Lower score correlates with better 5-year survival


IMAGE FINDINGS


Ultrasonographic Findings



  • Pulsed and color Doppler ultrasonography



    • Localization of microaneurysm (seen in 50-60%)


Computed Tomography Angiography



  • Microaneurysms often seen at artery bifurcations


  • Tc-99m DMSA uptake scanning detects patchy renal parenchymal disease


MICROSCOPIC PATHOLOGY


Histologic Features



  • Glomeruli



    • Mostly varying degrees of ischemic collapse associated with vessel involvement


    • Global glomerulosclerosis with tubular atrophy in healed cortical scars


    • Normal histology of glomeruli located away from vasculitis


    • Rarely, focal crescentic glomerulonephritis (pauci-immune type)



      • Suggests overlap of PAN and microscopic polyangiitis


      • Rarely, positive ANCA reported


  • Tubules and interstitium




    • Acute ischemic infarction in distribution of affected artery


    • Tubular simplification, atrophy, and mild interstitial fibrosis


    • Active &/or chronic interstitial and periarterial inflammation


  • Arteries

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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Polyarteritis Nodosa

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