VASCULITIS MADE SIMPLE(R) 2016 Richard Wernick, M.D. I.

Generalities & Random Comments    

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II.

When to Consider Vasculitis (those presentations in which the probability of vasculitis is high enough to justify attempts to rule it in - see IV) 1. 2. 3. 4. 5. 6. 7.

III.

Heterogeneous group of disorders all characterized by pathologic inflammation in vessel walls Clinical manifestations secondary to ischemia (2o to stenosis from vessel inflammation) or inflammation, rarely bleeding (from aneurysmal rupture) Clinical sx/signs so diverse, virtually any unexplained illness could be vasculitic - seriously consider vasculitis only in distinct syndromes (e.g. not in older patient with CVA, MI) Pathogenesis poorly understood; etio usually unknown Evidence for immune complexes weak, excepting SLE, mixed cryo, HSP & Hep B PAN ANCA? – in vitro and mouse data suggest possible role Incidence of (non-giant cell) systemic vasculitis  40/million (in UK), ½ ANCA-associated Any age, gender Giant cell arteritis most common

Unexplained multisystem disease (pulm-renal or otherwise) Skin – palpable (can you find them if you close your eyes?) purpura > ulcer, infarct, urticaria (last >24 hr in contrast to usual ones) Mononeuritis multiplex (wrist &/or foot drop) Glomerulonephritis (esp rapidly progressive, i.e. RPGN) FUO Specific vasculitic syndromes (e.g. GCA - see below) Weird ischemia (too young, multiple arterial beds)

Types of Vasculitis Vessel Size* Small

Medium

ANCA-Associated Wegener’s (GPA) Microscopic polyangiitis (MPA) Churg-Strauss (EGPA) Drug-induced -

Not ANCA-Associated “Leukocytoclastic”

Polyarteritis nodosa Kawasaki Large Giant cell arteritis (med-large) Takayasu *Uncommonly, vasculitis of each of the 3 categories can affect any size artery.

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Note many cases overlap vessel size categories; there are numerous classification schemes published, none perfect, most by size of vessel involved most commonly. To clinician, it's most important to 1) determine if vasculitis present; 2) determine extent and severity of disease – the type is far less important.

A.

Small Vessel - "leukocytoclastic vasculitis"/ANCA-negative  Formerly called hypersensitivity or allergic but usually it's not!  Usually presents as palpable purpura (non-palpable would suggest platelet deficiency or dysf'n, or vessel problem - e.g. scurvy) of lower legs palpability 2o to inflammation  Do punch bx to confirm - histo shows vessel damage and either neutrophil or monocyte inflammation + neutrophil disruption ("leukocytoclastic").  Question #1 - Is the vasculitis limited to skin? (usually is) Do good H&P, chem & U/A, ? CXR, ? CBC  Question #2 - What is underlying cause of this syndrome? Diff Dx 1) Idiopathic in 50% 2) Drug hypersensitivity 10-15% - D/C any new Rx 3) ID ? 10% - N. meningitidis was #1, now hep C; but almost any infection can - G+& - bact, Rickettsia, herpes, syphilis, HIV, Hep B, SBE, Tb 4) Connective tissue/inflammatory disease 10-20% SLE, RA, Sjogren's - rarely the presenting sign Behcet's (oral & genital ulcers, uveitis) Henoch-Schonlein purpura (HSP) - IgA dominant immune deposits in small vessels of skin, gut, glomerulus & jts; kids mostly 5) Mixed cryoglobulinemia - frequent GN, arthritis, liver involvement; characterized by cryoprecipitable immune complexes of polyclonal IgG and monoclonal IgM rheumatoid factor (RF) (Type II) or polyclonal IgM RF (Type III) evidence for Hep C infection in most pts (positive Ab and HCV RNA) Dx by assay for serum cryo; RF usually high, complement low 6) Malignancy 1-3%, usually hematologic NOTE: "vasculitis" may represent nonrheumatic disease such as infection, malignancy, or iatrogenic

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B.

Initial lab workup depends on clinical setting, answer to question #1; could include ANA, ANCA, RF, cryo, Hep B & C serology, complement, cultures, HIV Ab

Small vessel – ANCA-associated (GPA/Wegener’s, microscopic polyangiitis (MPA), EGPA/Churg-Strauss, drug-induced)  Most common 1 systemic small-medium vessel vasculitis in adults (esp 50-70 y/o)  Differences: Wegener’s – granuloma, no asthma Churg-Strauss – granuloma, eos, asthma renal uncommon Micro polyangiitis – no granuloma, no asthma  Lack of deposition of immunoglobulin/complement (“pauci-immune”) in involved tissue  C-ANCA (anti-proteinase 3) in 80-90% Weg (spec 98%)  Anti-myeloperoxidase (MPO) in  75% MPA, 40% C-S ( if GN) – gives p-ANCA pattern,but so do other unrelated antibodies.(p-ANCA present in 60% ulc colitis, 30% Crohn’s, ? 5% nls, 25% SLE, 10% RA)  #1 cause of pulmonary-renal syndrome  Death secondary to bowel infarction, infection (secondary to Rx and  in older pts) most commonly  20% with ANCA-associated vasculitis progress to end-stage renal failure  Drug-induced: hydralazine, PTU, minocycline, levamisole-laced cocaine; MPO-ANCA 1.

2.

Wegener’s (granulomatosis with polyangiitis)  Small-medium size vessels  2 of triad of upper & lower resp, renal; but can present oddly (e.g. hearing loss)  Prevalence 3/100K in US  85% lung (nodules, diffuse infiltrates on cxr), 95% ENT (epistaxis, sinusitis), 40% skin,