2What is Vasculitis?Disease characterized by inflammation of blood vessel walls, leading to altered blood flow through obstructed walls. This causes ischemia and tissue damage.In addition there is an intense inflammatory rxn causing further systemic signs and symptomsCan be fatal
5Polymyalgia Rheumatica (PMR) Most ‘benign‘ of the groupCommon: 50/100,000, age > 50, average age 75. Highest prevalence in northern European ancestry, females>>malesCause unknown
6PMR Clinical Presentation Usually abrupt onsetIntense morning stiffness and pain that can last all day involving the shoulders and hip girdle areaNo small joint involvementMuscle strength normalFatigue and anorexia commonElevated CRP and ESR; anemia of chronic disease, elevated platelets15% get GCA (more later)
7PMR Treatment Low Dose Steroids (10-20 mg/day) The only drug that worksLook to normalize the CRP and ESR; if they continue to be elevated, rethink the dx (?paraneoplastic syndrome or GCA)Usually self-limited: 65% of patients able to taper off Prednisone by 1 year, >85% in 2 yearsDisease flares not uncommon as prednisone is tapered and may require dose adjustments
8Giant Cell Arteritis Can occur exclusively but often seen with PMR Rare: 15/100,000Age >50Cause unknownInvolves the medium/large blood vessels of the head and neck including the blood vessels that supply the optic nerve
9GCA PathophysiologyUnknown trigger causes inflammatory response with the release of IL-1 and IL-6.This leads to systemic symptoms and the infiltration of inflammatory cells into the adventitia of the temporal and other involved arteriesTypical histologic pattern: Giant Cells
13GCA Diagnostic Studies Temporal Artery Biopsy is the gold standardElevated ESR and CRP, usually levels higher than in PMRAnemiaElevated LFTs not uncommon
14Treatment of GCAHigh dose Steroids (60 mg/day) is the only drug that worksSlow taper over time usually 1-2 years. Some patients require low dose (<10 mg/day) chronically
15GCA Complications Blindness Scalp Necrosis Lingual Infarction Aortic Dissection/AneurysmComplications from high dose steroids: osteoporosis, cataracts, elevated blood sugars, wt. gain etc.
16Wegener’s Granulomatosis (WG) Potentially fatal vasculitis involving small vesselsRare: 3-14/million, more common in whites, any age but rare in childrenPathology shows necrotizing granulomas usually in upper airways, lungs and kidneys
17WG PathophysiologyComplex immunopathogenic events in which the production and activity of ANCAs (usually c-ANCA) play a central role. These autoantibodies interact with primed neutrophils to cause vascular injury and necrosis.Histologic lesions show granulomas
18WG Clinical Presentation Variable, multisystem involvementOrgans:Eyes: episcleritis/scleritis, proptosis due retro-orbital massCNS: rare mass lesionUpper airway: otitis media, nasal chondritis, sinusitis with purulent drainage and epistaxis, ulcerations, subglottic stenosisKidney: neprotic syndrome, proteinuria, renal failureSkin: palpable purpura due to leukocytoclastic vasculitis, pyoderma gangrenosum, panniculitisLung: cough, hemoptysis, hemorrhage, resp failureCardiac: pericarditis, conduction abnormalitiesSystemic: fever, night sweats, wt loss, fatigue
22WG Diagnostic StudiesPresence of c-ANCA (cytoplasmic staining pattern antineutrophil cytoplasmic antibodies + clinical picture is often enough to make the diagnosis. It is % of generalized WG.If the c-ANCA is -, tissue biopsy of lung or kidney is recommended.“Limited” refers to disease limited to the airways; c-ANCA often is -.
23Additional labs Elevated CRP and ESR Anemia, leukocytosis, & thrombocytosisElevated CrActive urine sediment with red cell casts, hematuria and proteinuria
24WG Clinical Course/Progression Prior to immunosuppression therapies, WG was uniformly fatal. Now survival rates almost 90% with aggressive treatment.High dose steroids and Cyclophosphamide are cornerstone of therapy. Methotrexate or Azathioprine sometimes used as steroid sparing agents.
25Polyarteritis Nodosa (PAN) Medium vessel vasculitisCan be caused by Hep B5/million casesPeak incidence 50’s & 60’s, slightly more common in males
26PAN PathophysiologyIn Hep B assoc cases immune complexes play significant roleIn non Hep B cases, the pathophysiology is less understood
27PAN Clinical Presentation Systemic: fever, fatigue, wt lossAbdominal pain due to mesenteric angina/ischemiaMononeuritis multiplexMyalgias/arthalgias/mild arthritisHypertensionSkin: livedo reticularis, palpable purpura, fingertip ulceration, subcutaneous nodulesTesticular pain or tenderness
35PAN Treatment High dose steroids and Cyclophosphamide Methotrexate or Azathioprine is used as steroid sparing agents later once the disease is controlledTreatment for Hep B with antivirals. Sometimes plasma exchange is used to remove immune complexes