Update on vasculitis


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Update on vasculitis

  1. 1. Update on vasculitis บุญธร ตันวรเศรษฐี 10 july 2009
  2. 2. Outline  Definition  Classification  Pathogenesis  Clinical features  Treatment  focus on vasculitic syndromes more likely to be presented to allergist/immunologist in outpatient setting
  3. 3. Definition  inflammation of the blood vessels  Pathology:destruction of the vessel wall  Histology:fibrinoid necrosis  necrotizing vasculitis
  4. 4. Classification Dominant vessel Primary Secondary involved Large arteries Giant cell arteritis Aortitis associated with RA Takayasu arteritis Infection (e.g. syphilis, tuberculosis) Medium arteries Classical PAN HBV-associated PAN Kawasaki disease Small vessels and Wegener’s granulomatosis Vasculitis secondary to RA, SLE, medium arteries Churg–Strauss syndrome Sjogren’s syndrome Microscopic polyangiitis Drugs (PTU,hydralazine) Infection (e.g. HIV) Small vessels Henoch–Schonlein purpura Drugs (sulfa,penicillin,thiazide) (leukocytoclastic) Cutaneous leucocytoclastic Angitis Infection Mixed essential cryoglobulinaemia HCV-induced cryoglobulinaemia Best Practice & Research Clinical Rheumatology 23 (2009) 429–443
  5. 5. Classification Size of dominant vessel Granulomatous Non-Granulomatous affected Large Giant cell arteritis Takayasu arteritis Medium Classical PAN Kawasaki disease Small Wegener’s granulomatosis Microscopic polyangiitis Churg–Strauss syndrome Henoch–Schonlein purpura Cutaneous leucocytoclastic Angitis Mixed essential cryoglobulinaemia Lancet 1997; 349: 553-58
  6. 6. Classification Best Practice & Research Clinical Rheumatology Vol. 15, No. 2, pp. 259±279, 2001
  7. 7. Classification  Antibody mediated  CSS  MPA  WG  Immune complex mediated  CV  Drug-induced vasculitis  HSP  Hepatitis B–associated PAN  Pathogenic T-cell response mediated  CSS  GCA  TAK  WG J ALLERGY CLIN IMMUNOL JUNE 2009
  8. 8. Classification Dominant vessel Corticosteroids Cyclophosphamide Other treatments alone and corticosteroids Large arteries +++ - + Medium arteries + ++ ++ Small vessels and + +++ + medium arteries Small vessels + +/- ++ Best Practice & Research Clinical Rheumatology 23 (2009) 429–443
  9. 9. Mechanisms of vascular inflammation and remodelling 2009 British Society for Immunology, Clinical and Experimental Immunology, 156: 395–404
  10. 10. (a) Viable endothelial cells express P-selectin after activation. P-selectin recognition prompts leucocyte tethering and rolling,resulting in integrin activation with firm adhesion and eventual trans-endothelial migration. (b) Injured endothelial cells fail to express the signals required for leucocyte migration. Recruited platelets express P-selectin and, besides limiting bleeding, substitute endothelial cells in delivering signals to flowing inflammatory leucocytes. (c) A neutrophil can be identified easily on an atherosclerotic lesion in a damaged human vessel, based on nuclear characteristics (blue colour, Hoechst) and on the expression of the CD66b (red). Endothelial cells and activated platelets express P-selectin (pink). The prototypic tissue pentraxin PTX3 (green) is expressed within the lesion at extracellular sites. 2009 British Society for Immunology, Clinical and Experimental Immunology, 156: 395–404
  11. 11. (a) (b) (c) The interaction between activated platelets and flowing leucocytes yields heteroaggregates in the (d) circulating blood, which are typical of several inflammatory diseases.(a,b,c) Confocal images of platelet–neutrophil hetero- aggregates in whole blood samples from a patient with acute myocardial infarction. Glycoprotein Ib expression (red) reveals platelets, the CD66b marker (green) neutrophils. Hoechst (blue) was used to counterstain nuclei. (d) Electron microscopy of the interaction between neutrophil and platelet membranes. 2009 British Society for Immunology, Clinical and Experimental Immunology, 156: 395–404
  12. 12. Pathogenesis of AASV NEPHROLOGY 2009; 14, 26–32
  13. 13. Schematic representation of the neutrophil responses that are putatively involved in the pathogenesis of ANCA-associated small vessel vasculitis. (A) Proinflammatory (A) cytokines and chemokines (e.g. tumor necrosis factor) that are released as a result of local or systemic infection cause upregulation of the expression of endothelial adhesion molecules (e.g. selectins, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), and prime neutrophils. (B) Neutrophil priming causes upregulation of the expression of neutrophil adhesion molecules (CD11b) and translocation of the ANCA antigens from their lysosomal compartments to the cell surface. (C) Engagement of dimers of the (C) antigen-binding portion of ANCA with ANCA antigens on the cell surface, and interaction of the Fc part of the antibody with Fc receptors, activates eutrophils and causes increased transmigration and adherence of neutrophils to vessel walls. (D) ANCA- (D) mediated neutrophil activation also triggers production of reactive oxygen radicals and possibly causes neutrophil degranulation. The consequent release of proteolytic enzymes leads to vasculitis. KALLENBERG ET AL. NATURE CLINICAL PRACTICE RHEUMATOLOGY DECEMBER 2006 VOL 2 NO 12
  14. 14. The role of ANCA and cytokines in the pathogenesis of neutrophil- mediatedvascular injury. Infection or other inflammatory stimulus leads to production of proinflammatory cytokines (i.e., IL-1, TNF-a, and IL-8), which induce resting neutrophils to express proteinase-3 on their cell surface. IL-1 and TNF-a also induce neutrophils and endothelial cells to increase their expression of adhesion molecules, leading to adhesion of activated neutrophils to the vascular endothelium. Circulating ANCA binds to membrane- associated proteinase-3 and the FcyRlla receptor inducing neutrophil degranulation and generation of oxygen radicals, which results in endothelial cell injury and inflammation Medical Clinics Of North America Volume 81 Number 1 January 1997
  15. 15. Best Practice & Research Clinical Rheumatology Vol. 15, No. 2, pp. 259±279, 2001
  16. 16. Gateway–receptor interaction model. 1. In Wegener’s granulomatosis (WG), expression of PR3 in the extracellular space is increased. PR3 stimulates the expression of PAR-2 on DC. 2. PR3 activates PAR-2 resulting in maturation of DC, as indicated by expression of CD80, CD83, CD86, and HLA-DR. 3. These PR3-maturated DCs stimulate CD4+ T cells to generate increasedexpression of IFN-γ. 4. increasedexpression Expression of IFN-γ favors the development of a granulomatous inflammation as seen in WG. 5 Hypothetically, chronic T cell activation by PR3-maturated DCs may finally promote the development of B-cells towards ANCA-producing plasma cells. Clinic Rev Allerg Immunol (2008) 34:300–306
  17. 17. Adhesion Molecules Best Practice & Research Clinical Rheumatology Vol. 15, No. 2, pp. 259-279, 2001
  18. 18. Chemokine and receptors Best Practice & Research Clinical Rheumatology Vol. 15, No. 2, pp. 259-279, 2001
  19. 19. Cytokine Cytokine Abbreviatio Cellular Source Biologic Effects n Interferon- IFN T cells, NK cells Increases expression of MHC class I and II molecules;macrophage activation; antiviral a gamma ctivity Interleukin-I IL-1 Macrophages,neutrophils, Acts as costimulant for T and B cell proliferation, activates endothelial cells, T and B endothelial cells, induces cells NK cells,fibroblasts, hepatic synthesis of acute smooth muscle cells phase proteins, endogenous pyrogen activity, increases adhesion molecule expression on endothelial cells Interleukin-2 IL-2 T cells Induces proliferation and differentiation of T cells and B cells; stimulates cytotoxicity of NK cells Interleukin-6 IL-6 T cells, endothelial cells, Promote growth and differentiation of T and B cell;induce hepatic synthesis of acute macrophages, phase protein,endogenous pyrogen activity fibroblasts
  20. 20. Cytokine Cytokine Abbreviatio Cellular Source Biologic Effects n Interleukin-8 IL-8 T cells, NK cells Increases expression of MHC class I and II molecules;macrophage activation; antiviral a ctivity Tumor TNF-α Macrophages,neutrophils, Acts as costimulant for T and B necroti factor cell proliferation, activates endothelial cells, T and B endothelial cells, induces alpha cells NK cells,fibroblasts, hepatic synthesis of acute smooth muscle cells phase proteins, endogenous pyrogen activity, increases adhesion molecule expression on endothelial cells Platelet- PDGF T cells Induces proliferation and derived differentiation of T cells and B cells; stimulates cytotoxicity of growth factor NK cells T cells, endothelial cells, Promote growth and differentiation of T and B cell;induce hepatic synthesis of acute macrophages, phase protein,endogenous pyrogen activity fibroblasts
  21. 21. Clinical signs ( primary systemic vasculitis )  Fever of unknown origin  Unexplained migratory polyarthritis  Mononeuritis multiplex  Rapidly progressive glomerulonephritis  Palpable purpura  Diffuse alveolar hemorrhage  Unexplained infarction in multiple vascular territories  Unexplained multisystem disease J ALLERGY CLIN IMMUNOL JUNE 2009
  22. 22. Giant cell arteritis  “Temporal arteritis”  Granulomatous large-vessel vasculitis  Older than 50 years  Headache ( ‘‘sinus’’ headache )  Fever, jaw or tongue claudication, and scalp tenderness  Polymyalgia rheumatica ( 40-50%)  Blindness from optic nerve ischemia (15- 20%) ,diplopia and ptosis  Life-threatening aortic rupture or dissection J ALLERGY CLIN IMMUNOL JUNE 2009
  23. 23. Giant cell arteritis  Nodularity, tenderness or absent pulsations of the temporal arteries and other involved vessels  Bruits, and asymmetric extremity blood pressure measurements  ESR usually increased ,ncnc anemia, thrombocytosis, and increased alk. phosphatase levels.  Temporal artery biopsy (TAB) : granulomatous inflammation of the media and adventitia, with histio cytes and mononuclear cells, giant cells, irregular fra gmentation of the internal elastic lamina, neointimal p roliferation, and sometimes luminal thrombosis (25% ). positive 60-80%  Contralateral TAB if first biopsy negative J ALLERGY CLIN IMMUNOL JUNE 2009
  24. 24. Giant cell arteritis  Prednisone at 40 to 60 mg/d  Immediate symptomatic benefit and reduction in the risk of blindness (1%)  IV methylprednisolone (1 g for 3 days) in patients with acute vision loss ( protect unaffected eye )  Baby aspirin prevent ischemic complications  MTX and Infliximab not shown benefit  Relapse > 75%  40-50% unable to taper prednisone  Acute mortality is uncommon  Late mortality :rupture or dissection of aortic aneurysms J ALLERGY CLIN IMMUNOL JUNE 2009
  25. 25. Takayasu arteritis  Granulomatous large-vessel vasculitis  Affects aorta, its main branches, and pulmonary a.  Predominantly in young women  Headaches and dizziness  Vascular hypoperfusion :limb claudication, double vision or rapid decrease in VA,chest pain,CHF,TIAor stroke  HT , bruits (carotid or subclavian) diminished pulses, asymmetric BP, AR, and arterial tenderness  Glucocorticoids ,once-weekly MTX ,surgical revascularization (while clinically inactive) J ALLERGY CLIN IMMUNOL JUNE 2009
  26. 26. Takayasu arteritis FIG 1. Magnetic resonance angiography in a patient with TAK sho wing multiple stenoses at the origin of both common carotid arteries and the l eft subclavian artery. J ALLERGY CLIN IMMUNOL JUNE 2009
  27. 27. Wegener granulomatosis  Granulomatous, necrotizing, small and medium vessel  Involves upper,lower airways, and kidneys  Any age (40-55 yrs.) Men and women equally  Frequency of 3 per 100,000 persons  Upper airways symptoms (recurrent or nonresolving sinusitis, nosebleeds, nasal crusting  Sinus pain, epistaxis, persistent otitis media with effusion or decreased hearing, and cartilage ischemia with nasal septal perforation (saddle nose deformity) subglottic stenosis.  Single or multiple cavitating/noncavitating nodules or diffuse alveolar hemorrhage J ALLERGY CLIN IMMUNOL JUNE 2009
  28. 28. Wegener granulomatosis  Microscopic hematuria, proteinuria, and rapidly progressive RF  Skin rash, migratory arthritis  Ocular involvement (scleritis, corneal ulceration,orbital dis.)  Mononeuritis multiplex or CNS involvement with or without pachymeningitis  Risk of venous thrombosis (DVT,PE) mechanism unclear  ANCA (180pt., 96%with severe dis.,83%with limited dis.)  Lung biopsy yield 91% of cases  Upper airway biopsy yield only 21%of cases  Renal biopsy:focal, segmental necrotizing, crescentic glomerulonephritis with few to no immune complexes J ALLERGY CLIN IMMUNOL JUNE 2009
  31. 31. Wegener granulomatosis  Active severe organ- or life-threatening (2 mkd CYC and 1 mkd prednisone) 91% improvement ,75% complete remission, and 80%survival  Fulminant disease (1 g/d iv methylprednisolone 3d and 3 to 4 mg/kg/d iv or oral CYC 3 d,reduced to 2 mg/kg/d after 4 weeks, if improvement, tape prednisone 6-9 mo.  Maintainance at least 2 yrs.(MTX 15-25mg/wk,AZA 2 mkd),MMF,leflunomide (small data )  Nonsevere (weekly MTX+daily prrednisolone)=> higher of relapse rate  TMP-SMZ reduce only relapses upper airways , prophylaxis for Pneumocystis jiroveci infection J ALLERGY CLIN IMMUNOL JUNE 2009
  32. 32. Wegener granulomatosis  Plasma exchange additional in severe renal vasculitis (Cr>5.8mg/dl) reduced risk of progression to ESRD by 24% over 1 year  Etanercept (no benefit)  Infliximab (absence of randomized control trial )  Rithuximab (being studied) J ALLERGY CLIN IMMUNOL JUNE 2009
  33. 33. Wegener granulomatosis FIG 2. WG involving the lungs with pulmonary nodules. J ALLERGY CLIN IMMUNOL JUNE 2009
  34. 34. Wegener granulomatosis FIG 3. WG involving the lungs with diffuse alveolar hemorrhage and pulmonary nodules J ALLERGY CLIN IMMUNOL JUNE 2009
  35. 35. Wegener granulomatosis FIG 4. WG involving the right orbit and paranasal sinuses, resulting in an orbital mass and enophthalmos J ALLERGY CLIN IMMUNOL JUNE 2009
  36. 36. Microscopic polyangiitis  Nongranulomatous necrotizing small-vessel vasculitis,few or no immune deposits  More common in male , average age of onset is 50 years  Persistent cough with or without hemoptysis  Kidneys (79%), lungs (12- 29%), joints (65- 72%), skin (44- 58%), GI tract (32- 58%), peripheral nerves (14- 36%)  Pulmonary pathology shows capillaritis and absence of linear IF, differentiating from goodpasture syndrome  Renal histology is similar to WG  Severe disease (lung, kidney, or nerve) 2 mkd oral CYC and 1 mkd prednisone 3- 6 mo., Followed by weekly MTX or daily AZA J ALLERGY CLIN IMMUNOL JUNE 2009
  37. 37. Churg-Strauss syndrome  asthma, fever, hypereosinophilia, systemic vasculitis  Prevalence 3 per million , all ages but rare in children and adolescents and occurs equally between sexes  recurrent allergic rhinitis, difficult-to-treat asthma, nonresolving ‘‘pneumonia’’/pulmonary infiltrates, or persistent eosinophilia  most common presentation =>1.asthma 2. mononeuritis  3 phases: prodromal phase (AR and asthma), eosinophilia and eosinophilic tissue infiltrates, vasculitic phase with visceral involvement  Pulmonary imaging: subpleural ground-glass opacities, lobular consolidation,centrilobular nodules, bronchial wall thickening, mediastinal or hilar lymphadenopathy, and pleural or pericardial effusion J ALLERGY CLIN IMMUNOL JUNE 2009
  38. 38. Churg-Strauss syndrome Different presentation forms in Churg-Strauss syndrome. (A) Chest X-ray of a 22-year-old man who presented with asthma, allergic rhinitis, eosinophilia and recurrent pulmonary infiltrates for 2 years until he developed cutaneous lesions which led to diagnosis. (B) A 48- year-old man who had asthma and recurrent sinusitis for 12 years abruptly presented with abdominal angina, eosinophilia and severe mononeuritis multiplex. Sural nerve biopsy revealed necrotizing vasculitis. The picture shows remaining right cubital and median palsy several months after diagnosis. Best Practice & Research Clinical Rheumatology Vol. 15, No. 2, pp. 259±279, 2001
  39. 39. Churg-Strauss syndrome  Peripheral eosinophilia (absolute eosinophil usually>1500)  Increased ESR,CRP, and IgE level  ANCA positive 50% of cases (predominantly MPO-pANCA)  Histology: eosinophilic tissue infiltrates, extravascular ‘‘allergic’’ granulomas, and small-vessel necrotizing vasculitis  Association between LTAs and CSS remains unclear  62 pts. CSS take LTAs, 57 had CSS within first year  Prednisone (1 mkd) alone is effective  Life-threatening :glucocorticoids and oral CYC (2 mkd)  IVIG, MTX, IFN-a (uncontrolled studies)  Cardiac involvement:main cause of death J ALLERGY CLIN IMMUNOL JUNE 2009
  40. 40. Potential targets for biologicals interfering with lymphoid neoformation in WG-granulomata as key to self-perpetuating inflammation, autoimmunity and ANCAinduced vasculitis in WG: After hypothetical barrier dysfunction and potential exogenous triggers (e.g., S. aureus), PR3 is released from neutrophil granulocytes. PR3 induces DC maturation via the protease-activated receptor (PAR)-2. PR3 also enhances proinflammatory IL-32 action.39 Dendritic cells (DCs) and other antigen-presenting cells (APCs) induce a Th1-type effector memory T-cell (TEM) response via cytokines such as IL-15 (?) and PR3-specific T cells. Subsequent granuloma formation might provide the necessary “proinflammatory environment” for the break of tolerance. In this environment the antiapoptotic capacity of IL-15 may counteract the mechanisms supporting self-tolerance. Lymphoid-like tissue neoformation in WG-granulomata could sustain autoimmunity to PR3. PR3-ANCA formation results in PR3-ANCA–associated vasculitis, giving rise to further inflammatory lesions. Genetic factors predispose to granulomatous inflammation (HLA- DPB1∗0401) and PR3-ANCA seropositivity (PTPN22∗620W), thereby determining disease progression.40 Anti-TNF- treatment may interfere with TNF--induced APC activation in granuloma formation, endothelial cell activation, and priming of neutrophils in vasculitis induction.B cell depletion by anti-CD20 antibodies could interfere with PR3-ANCA production and other B cell functions (cytokine production, interaction with T cells, APC function). ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
  41. 41. Expert Opin. Investig. Drugs (2007) 16(5)
  42. 42. Expert Opin. Investig. Drugs (2007) 16(5)
  43. 43. Polyarteritis nodosa  medium-vessel disease  Incidence 2- 9 per million annually  Men = women  constitutional symptoms, HT,musculoskeletal symptoms, symptoms from vasculitic involvement of nerves, GI tract , skin, heart, and nonglomerular renal vessels  suspected immunologic disease  Biopsy specimens : necrotizing inflammation involving medium-sized or small arteries,with abundant neutrophils, fibrinoid changes, disruption of the internal elastic lamina  Angiographic changes : microaneurysms ,stenoses, occlusion, beaded pattern J ALLERGY CLIN IMMUNOL JUNE 2009
  44. 44. Polyarteritis nodosa  severe life-threatening disease ( GI tract, heart, or CNS system): 2 mkd oral CYC and glucocorticoids  non–life or non–organ-threatening : glucocorticoids alone  Plasma exchange in severe cases  5-year survival rate with treatment 80%  Relapses are infrequent (8- 19%)  PAN-like vasculitis ass. with viral inf. eg. HBV,HCV , HIV  Rx with glucocorticoids , antiviral treatment , and plasma exchange induced remission 81% , relapse 10%  If clinical improvement , immunosuppression should be withdrawn while continuing antiviral treatment J ALLERGY CLIN IMMUNOL JUNE 2009
  45. 45. Clinics in Dermatology (2006) 24, 414– 429
  47. 47. Cutaneous vasculitis  most commonly vasculitic manifestation in clinical practice  presumed drug allergy or chronic urticaria  palpable purpura, necrotic papules, cutaneous infarcts, urticaria, hemorrhagic vesicles, indurated erythema, or ulcerative lesions  Histology: dermal small-vessel inflammation , often with leukocytoclasis  idiopathic or occur because of medications, infections, allergies,malignancies, CNT dis., or primary vasculitis  Diagnosis of exclusion  Rx: observation and measures such as leg elevation. J ALLERGY CLIN IMMUNOL JUNE 2009
  48. 48. Cutaneous vasculitis  Glucocorticoids (no optimal regimen)  Other medications : NSAIDs, dapsone, colchicine , antihistamines , and pentoxifylline  severe idiopathic cutaneous vasculitis : MTX or AZA J ALLERGY CLIN IMMUNOL JUNE 2009
  49. 49. Cryoglobulinemic vasculitis Mixed cryoglobulinaemia may manifest with recurrent purpura and arthralgia only, as shown in(A), or may produce severe ischaemic lesions and organ dysfunction as displayed in (B) where necrotic toes and peroneal palsy can be clearly appreciated Best Practice & Research Clinical Rheumatology Vol. 15, No. 2, pp. 259±279, 2001
  50. 50. Cryoglobulinemic vasculitis  Cryoglobulins : mono or polyclonal Ig precipitate at temp. < 37º C and redissolve on warming  lymphoid neoplasms, chronic infections, and inflammatory and autoimmune diseases  Hepatitis C infection is leading cause of cryoglobulinemia  Small vessel vasculitis caused by deposition of circulating immune complexes (cryoglobulins and complement)  drug-induced or other allergy-related skin rash  clinical triad : recurrent palpable purpura (100%), polyarthralgias (73%), and renal disease (55%)  Pathology of glomeruli :deposition of IgG, IgM, and complement, with coexistent renal arteritis J ALLERGY CLIN IMMUNOL JUNE 2009
  51. 51. Cryoglobulinemic vasculitis  Patients with HCV–associated CV, antiviral Rx=> first line  Severe case (eg. Vasculitis )=> glucocorticoids, CYC, or AZA  Plasma exchange serves to remove immune complexes  Rituximab used for resistant CV or setting of B-cell lymphoproliferative disorders  Rituximab,with interferon and ribavirin : favorable results in management of HCV–associated CV. J ALLERGY CLIN IMMUNOL JUNE 2009
  52. 52. Kawasaki disease  Acute vasculitis that affects children  Primary cause of acquired heart disease in children from the united states and japan  80% of cases occur < 5 yrs. , Boys >1.5 times than girls  Incidence in japan 112/100,000 among children <5 years old  In US asian 32.5/100,000 , in white 9.1/100,000  Fever at least 5 days, rash, conjunctival injection, and oral mucosal changes. Extremity changes, including brawny induration, followed by desquamation; cervical adenopathy  Coronary artery abnormalities can be diagnosed  Cardiac involvement is most of morbidity and mortality J ALLERGY CLIN IMMUNOL JUNE 2009
  53. 53. Kawasaki disease  IVIG (2 g/kg) single infusion prevent coronary aneurysm formation (appear 1-4wks after onset,15-25% of untreated ), lessen fever, and reduce myocardial inflammation  Aspirin (80-100 mkd) concurrently with IVIG, but not affect coronary artery aneurysm formation  refractory case : anecdotal experience with glucocorticoids, pentoxifylline, plasma exchange, ulinastatin, abciximab (for large aneurysms), infliximab, and CYC  Echocardiogram recommended at baseline and at 2, 6, and 8 weeks after onset of the disease  MRI/MRA, ultrafast CT, stress test, myocardial perfusion studies, and conventional angiography J ALLERGY CLIN IMMUNOL JUNE 2009
  54. 54. Kawasaki disease  aneurysms resolve within 1-2 yrs. depend on size, age of onset of disease, shape of the aneurysm (fusiform more likely than saccular), and location (distal more likely than proximal )  Children with multiple aneurysms, giant aneurysms, or coronary artery obstruction require close follow-up and possible long-term anticoagulation J ALLERGY CLIN IMMUNOL JUNE 2009
  55. 55. Henoch-SchÖnlein purpura  small-vessel vasculitis  predominantly affects children  suspected drug allergy or immunologic condition  Purpura (100%), arthritis (82%), abdominal pain (63%), GI bleeding (33%), and nephritis (40%)  Uncommon : bullous skin lesions, testicular involvement , seizures, intestinal obstruction  Complication : intussusception , ESRD ( 2- 5%)  Recurrence occurs in up to 40% ( mostly first 3 months)  tissue Bx : leukocytoclastic vasculitis with IgA deposition in blood vessel walls J ALLERGY CLIN IMMUNOL JUNE 2009
  56. 56. Henoch-SchÖnlein purpura  Typically self-limited  Glucocorticoids might lessen tissue edema, arthritis, and abdominal discomfort and decrease risk of intussusception , not prevent recurrence of abdominal symptoms, skin involvement, or renal disease and not shorten duration or lessen relapse  Active glomerulonephritis and progressive renal insufficiency : glucocorticoids combined cytotoxic agent  Outcome usually excellent in children, in adults more severe  Predictors of progression to ESRD: proteinuria (>1 g/d) , HT , renal impairment at presentation, age < 30 years, male sex , crescents < 50% of glomeruli, and TI fibrosis on renal Bx J ALLERGY CLIN IMMUNOL JUNE 2009
  57. 57. Urticarial vasculitis  Resembling urticaria  Skin biopsy : inflammation of dermal capillaries and postcapillary venules  Chronic or subacute urticaria  Urticaria (usually >24 hours), violaceous color ,burning pain more frequent than pruritus, and residual pigmentation after resolution  Involve GI, musculoskeletal ,renal , and pulmonary (particularly COPD) , less commonly in ocular and central nervous systems  Confirmed by skin biopsy ( LCV, Ig, complement, fibrin deposition at dermalepidermal junction and around blood vessels J ALLERGY CLIN IMMUNOL JUNE 2009
  58. 58. Urticarial vasculitis  classified as normo- or hypocomplementemic UV  normocomplementemic UVare idiopathic(most), remainder ass. With monoclonal gammopathy, neoplasia, UV light sensitivity, or repeated cold exposure.  Hypocomplementemic UV due to SLE,SjÖgren syndrome, serum sickness reaction, or neoplasia or HUVS  HUVS : specific autoimmune disorder involves >6 mo. of UV with hypocomplementenia in presence of angioedema , moderate-to-severe COPD(occurs in 50%), ocular inflammation (uveitis occurs in 30%), and glomerulonephritis.  C3, C4, C1q levels are low , anti-C1q antibody levels (C1q precipitins) are detectable J ALLERGY CLIN IMMUNOL JUNE 2009
  59. 59. Urticarial vasculitis  Treatment based on the severity and underlying disease  skin : antihistamines+/- short course of glucocorticoids , colchicine, dapsone, hydroxychloroquine, pentoxifylline,and indomethacin  montelukast, cyclosporine A, and AZA used in combinations as sequential treatment if patients had suboptimal response to treatment with cinnarizine and glucocorticoids for 6 months  HUVS or systemic disease : require initial glucocorticoid therapy J ALLERGY CLIN IMMUNOL JUNE 2009
  60. 60. Semin Arthritis Rheum 38:348-360
  61. 61. Semin Arthritis Rheum 38:348-360
  62. 62. Presentations of vasculitic syndromes to the allergist/immunologist Vasculitic syndrome Presentation to allergist/immunologist GCA ‘‘Sinus’’ headache TAK Headache WG Recurrent sinusitis, nosebleed and nasal crusting, otitis media, cough, hoarseness, nonresolving ‘‘pneumonia’’/ pulmonary infiltrates MPA cough +/- hemoptysis, nonresolving ‘‘pneumonia’’/pulmonary infiltrates CSS Allergic rhinitis, nasal polyposis, asthma, nonresolving ‘‘pneumonia’’/pulmonary infiltrates, eosinophilia PAN Suspected immunologic disease, postprandial abdominal pain with suspected food allergy KD Skin rash, soft tissue edema Cutaneous Skin lesions in which an allergy or drug reaction might be suspected vasculitis CV Skin lesions in which an allergy or drug reaction might be suspected HSP Purpura, soft tissue edema, or both in which an allergy might be suspected; food enterocolitis UV Chronic or subacute urticaria, angioedema J ALLERGY CLIN IMMUNOL JUNE 2009