boards’ fodder Vasculitides Anna Chacon, MD

Diagnosis Epidemiology Pathogenesis Clinical Diagnostic Pathology Therapy Complications/ Features Approach Associations SMALL VESSEL Cutaneous small vessel vasculitis [(CSVV), cutaneous leukocytoclastic vasculitis (LCV)/angiitis, angiitis, allergic vasculitis, cutaneous necrotizing venulitis] Henoch- Most common IgA-dominant immune 1 - Intermittent Palpable Necrotizing Self-limited, supportive. Renal vasculitis Schönlein purpura in children < 10 deposits in small palpable purpura on (required) w/ vasculitis. Dapsone & colchicine often mild but can (anaphylactoid yrs; associated w/ blood vessel walls. extensor extremities at least 1 of the Immunoreactants may decrease duration be chronic. May purpura, purpura preceding respiratory Dx supported by IgA & buttocks following: arthritis/ deposited in of skin lesions. Systemic be associated rheumatica, infection- 75% by predominance in the 2 – arthralgias, arthralgia, diffuse skin are IgA. steroids: Rx for arthritis w/underlying CSVV secondary GAS. May be seen correct clinical setting. arthritis abdominal pain, renal DIF: perivascular & abdominal pain. malignancy in to circulating in adults. Slight male 3 - abdominal pain/ involvement, bx w/IgA IgA, C3 & fibrin Nephrology referral w/ adults. IgA immune predominance. melena; bowel deposition. deposits. renal involvement. complexes) angina/ischemia 4 – renal involvement (hematuria & RBC casts). Acute Seen primarily in Unknown. 75%: Benign clinical Routine labs: LCV involving Spontaneous resolution Extracutaneous hemorrhagic children 4-24 months associated w/infxn, course. Annular, nonspecific. Dx based capillaries & within 1-3 weeks. involvement rare. edema of infancy of age. Child is well drug exposure, circular, or targetoid on clinicopathologic postcapillary Antihistamines for Two-thirds of pts (Finkelstein’s appearing. or immunization. purpuric plaques on correlation. venules of upper symptomatic relief. have infectious dz, Seidlmayer Thought to involve face & extremities. Characteristic: age & mid-dermis. DIF: prodrome. syndrome, Tender, non-pitting onset < 2 yrs., IgA deposits in purpura en deposition edema of acral disease confined to vascular pattern in cocarde responding to sites. skin, brief duration. 1/3 – 1/4 of cases. avec edema, antigenic trigger. postinfectious cockade purpura) Urticarial Uncommon. Peak Complement Painful/burning Lab: ESR, CRP, SPEP, Typically hive Difficult. Try: Many pts have vasculitis (chronic incidence: 5th decade. activation triggers urticarial lesions ANA, autoantibodies w/edema but antihistamines, dapsone, persisting urticaria as a 60-80% female. mast cell release lasting >24 hrs; (anti-SS-A/Ro, also w/LCV. A NSAIDS, antimalarials. >24 hrs, but few manifestation of Hypocomplementemic of inflammatory resolve leaving anti-SS-B/La), perivascular Unresponsive/ have urticarial venulitis, urticaria form: almost mediators. Idiopathic behind hemosiderin, complement levels lymphocytic systemic: steroids & vasculitis w/signs & arthralgia w/ exclusively in women. or associated with causing red- (CH50, C3, C4). infiltrate is not perhaps additional & sxs. Systemic: necrotizing SLE, Sjӧgren’s, brown maculae/ Further evaluation can enough for dx. immunosuppressants. arthritis, nephritis, angiitis) , postinflammatory include: CXR, PFTs, abdominal or Wegener’s hyperpigmentation. RFTs. distress. Lung granulomatosis. involvement can be fatal. Erythema Uncommon, rare. Suspicion that Symmetrical, slowly Skin biopsy. LCV w/thickening Limited: intralesional Association with elevatum diutinum Can develop at any streptococci are developing red- Serum protein of vessel walls; or high-potency topical IgA monoclonal (extracellular age. No racial/gender trigger for chronic brown papules & electrophoresis later – fibrosis, steroids. Widespread/ gammopathy cholesterosis) predilection. immune complex nodules favoring (SPEP). granulomatous resistant: dapsone. or even multiple reaction. Occurs backs of hands, inflammation, Nicotinamide & myeloma. Earlier in HIV/AIDS, over digital joints, occasional tetracycline may help. onset more often unclear if result of knees, & elbows. cholesterol in HIV setting. other factors vs. Rarely more deposits. immunosuppression. widespread. Usually asymptomatic. Secondary causes of CSSV: Drugs; infections; malignancies, most often hematologic SMALL & MEDIUM-SIZED VESSEL VASCULITIS (“MIXED”) Cryoglobulinemia Frequency varies Circulating Ig Type I: thrombosis, Blood must be Papular lesions Avoid cold. Treat Peripheral [types I, II, III; w/geography, may complexes that livedo, Raynaud transported to lab show LCV, while underlying disease. neuropathy & types II & III: reflect prevalence precipitate when syndrome, ulcers. at 37°C then cooled necrotic or If HCV involvement: glomerulonephritis “mixed”); “Types 2 differences in HCV. incubated at <4° C. Types II-III: chronic to < 4° C; cryocrit ulcerated lesions interferon + ribavirin. can develop. & 3, LCV” Higher prevalence in Compositions: I – immune complex is then determined may demonstrate Progressive: MTX or Types II-III: most Southern Europe. monoclonal IgG or vasculitis, skin & & protein selectively medium-sized cyclophosphamide + commonly in the IgM; II – monoclonal kidneys. analyzed. Reactive vessel vasculitis. systemic steroids, +/- setting of HCV IgM + polyclonal IgG; hypocomplementemia. DIF: granular plasma exchange. infection, 80%. III – polyclonal IgG. deposits w/IgM & C3 in vascular pattern in papillary dermis.

Microscopic Estimated incidence Unknown. May Palpable purpura, Presence of P-ANCA. Segmental 2 phases: More severe polyangiitis 3-24/million. Men > be associated erythematous Additional testing: necrotizing 1) Remission – renal vasculitis (microscopic women. Mean age w/infectious macules & CXR, EMG/nerve vasculitis of initially steroids, favors older pts. polyarteritis, of onset = 57 years, endocarditis. patches, splinter conduction studies, smallest blood cyclophosphamide or ANCA persistence microscopic peak 65-75 yrs. Medications/ hemorrhages & lung/nerve/kidney bx. vessels & less rituximab for significant despite remission polyarteritis malignancy may be ulcers. Constitutional often of small/ organ involvement. – increased risk of nodosa) a trigger. ANCA is sxs, crescentic medium-sized 2) Maintenance: MTX, relapse. thought to play a role. necrotizing arteries. Absence azathioprine, MMF, IVIg. glomerulonephritis of granuloma Plasma exchange may be & alveolar formation. beneficial. Anna Chacon, MD, is hemorrhage. Wegener’s Incidence = Unknown. Infections, Stages - 1st: general Tissue dx: usually Triad: necrotizing Fauci regimen: Frequency of a preliminary resident granulomatosis 0.3/100,000 annually; including S. aureus, signs & sxs – fever, airway/renal bx, LCV, necrosis, prednisone & organ involvement: (granulomatosis USA: prevalence are suspected malaise, upper sometimes skin helps. granuloma cyclophosphamide. lungs 95%, upper at Orlando Regional with polyangiitis) 1/25,000. Most triggers. airway problems. Investigate: upper formation. Unresponsive: agents airway 90%, Medical Center. She often in Caucasians. 2nd: lower airway: airways, kidneys, Granulomas can be increased. kidneys 85%, joints Slight female cough, dyspnea, lungs. can be in vessel If + response, 70%, eyes 60%, will be a dermatology predominance. hemoptysis, pleurisy. C-ANCA positive walls or adjacent; taper steroid. Other ears 60%, skin 3rd stage: in 50% during early palisading, or immunosuppressants 45%, nerves 20%, resident at the generalized phase, >90% when rich in giant cells. under investigation: heart 10%. involvement generalized. Irregular necrosis – Cyclophosphamide University of Maryland ANCA-Associated Vasculitides incl. skin. Skin: “geographic.” induction followed Medical Center polymorphic by MTX. Recurrence/ beginning July 2014. picture including localized: co-trimoxazole. LCV, urticarial vasculitis, necrotizing pyodermas, panniculitis. Oral ulcers, recurrent epistaxis, nasal septal perforation irinections D­Residency p. 4 • Summer 2014 boards’ fodder Vasculitides (cont.) Anna Chacon, MD

Diagnosis Epidemiology Pathogenesis Clinical Diagnostic Pathology Therapy Complications/ Features Approach Associations Double dose SMALL & MEDIUM-SIZED VESSEL VASCULITIS (“MIXED”) of Boards’ Churg-Strauss Extremely rare. Unknown. > 80%, Tissue dx: skin or Striking Very steroid Multi-organ syndrome 0.3/100,000 yearly, Speculation: role often presenting lung. Investigate palisading responsive – i.e. involvement: Fodder! (allergic perhaps associated of leukotriene symptom. Later: lungs & other granulomas w/ prednisolone. Reserve mononeuritis granulomatosis w/. antagonists, pulmonary organs based on marked necrosis, immunosuppressants multiplex 60%, In addition to & angiitis, vaccines, rapid D/C infiltrates, signs & sxs. both associated for tx failures or life- kidneys 50%, this issue’s granulomatous of corticosteroids, vasculitis. Transient Labs: elevated ESR, w/vessels & at a threatening dz. heart 40%, vasculitis of desensitization may pulmonary hypereosinophilia, distance. Marked Both IFN-a & IVIg have GI tract 40%. Boards’ Fodder, Churg-Strauss) trigger disorder. eosinophilic elevated IgE, eosinophilia, shown promise. Localized Vasculitides, don’t infiltrates occur. cryglobulins, nuclear dust, granulomas: Granulomatous immune complexes. giant cells. sometimes forget to download inflamxn of Both cANCA & limited to the new Board’s myocardium = pANCA can be skin, mostly leading cause of positive, about 20% associated w/RA, Fodder online death for each. also infections, exclusive from ANCA-Associated Vasculitides Skin: involved in lymphoma, 70% - purpura, idiopathic. www.aad.org/ nodules, urticarial DIR, where a new vasculitis. chart is published

Secondary causes: Infections, Inflammatory disease (e.g., AI-CTD) each quarter. The MEDIUM-SIZED VESSEL VASCULITIS Summer 2014 Polyarteritis Rare. Incidence = Involvement in Fevers, wt loss, Histologic Segmental Systemic steroids; can Thrombosis online Boards’ nodosa [(PAN), 0.5/100,000 yearly. segments. Favors arthralgias. confirmation: involvement start w/pulse therapy. leads to infarcts panarteritis Mostly affects areas where Skin: frequent usually skin or makes it Unresponsive or major & vessel-wall Fodder is nodosa, middle-aged men. branching occurs. involvement; livedo muscle bx. Imaging: hard to find organ involvement: add obliteration. GI phototherapy by Kussmaul-Maier Associations: HBV, Small aneurysms racemosa, digital angiography lesions. Initial cyclophosphamide tract: “intestinal dz) HIV/AIDS; strep frequently develop. gangrene, SQ can reveal inflammatory or other angina,” Rebecca Bialas, nodules, ulcers, microaneurysms in infiltrate is immunosuppressants. ischemic bowel MD. LCV. GI or renal aa. neutrophilic, If HBsAg+: start w/ perforation, Cutaneous PAN: Labs: few changes, later replaced prednisone & plasma mesenteric a. limited to skin; high ESR, anemia, by mononuclear exchanges, followed thrombosis To view, download, benign, chronic thrombocytosis, cells w/intimal by IFN & lamivudine – or rupture. or print every course; nodules microscopic proliferation, hepatology consult. Peripheral & punched-out hematuria. Check finally neuropathy. Boards’ Fodder ulcers usually on HBsAg. ANCA+ granulomas & Kidney: 10%. ever published, legs. <5%. fibrosis. Heart: MI or CHF. CNS: stroke risk, both in print and HTN changes. online, check REFERENCES out the com- 1. Sterry W, Paus R, Burgdorf W: Purpura and Vasculitis. In: Dermatology. edn. New York, NY.: Thieme.; 2006: 245-261. 2. Wolff K, RA Johnson.: The Skin Signs in Immune, Autoimmune, and Rheumatic Disorders. In: Color Atlas & Synopsis of Clinical Dermatology. edn. United States of America: plete archives at McGraw Hill; 2009: 397-410. www.aad.org/ 3. Shinkai K, Fox L: Cutaneous Vasculitis. In: Dermatology. Volume 1. , edn. Edited by Bolognia JL, Jorizzo JL, Schaffer JV: Elsevier.; 2012: 385-409. BFarchives.

irinections www.aad.org/DIR Summer 2014 • p. 5 D­Residency