1 / 37

Cutaneous and Urticarial Vasculitis

Cutaneous and Urticarial Vasculitis. Roger W. Fox, M.D. Professor of Medicine/Pediatrics University of South Florida Division of Allergy and Immunology. Cutaneous Vasculitis. Rare, or uncommon clinical diagnosis

oihane
Download Presentation

Cutaneous and Urticarial Vasculitis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Cutaneous and Urticarial Vasculitis Roger W. Fox, M.D. Professor of Medicine/Pediatrics University of South Florida Division of Allergy and Immunology

  2. Cutaneous Vasculitis • Rare, or uncommon clinical diagnosis • Spectrum of presentation: clinical characteristics of cutaneousvasculitis may overlap with urticaria • Systemic diseases with cutaneousvasculitis constitute the majority of cases, but there are cases of cutaneousvasculitis without a systemic disorder • Constitutional symptoms often accompany the rash when associated with a systemic disorder • Laboratory tests and skin biopsy are diagnostic • Allergist/Immunologist most commonly are consulted to evaluate urticarialvasculitis

  3. CutaneousVasculitisPalpable Purpura

  4. UrticarialVasculitis

  5. Urticarial Vasculitis:Clinical Features • Nonpruriticurticarial-like lesions and palpable purpura • Individual lesions persist 24-72 h (chronic urticaria lesions persist < 24 h) • Vasculitis is a rare cause of chronic urticaria (<5%) • Diagnosis: Skin biopsy and laboratory

  6. CutaneousVasculitis

  7. Leukocytoclastic Vasculitis

  8. Cutaneous VasculitisClassified • Small vessels(typical of urticarialvasculitis) and/or medium sized vessels (usual signs of medium size vasculitis are: purpura with necrosis, livedoreticularis, subcutaneous nodules, ulcerations, digital ischemia) • Inflammatory infiltrate on skin biopsy; mostly neutrophils, but eosinophils can be present • Direct immunofluorescencedermopathology assay: IgG, IgM, IgA and C3, fibrin deposition • Laboratory investigation: Complement studies, cryoglobulins, anti-neutrophil cytoplasmic antibodies (ANCA), ANA, CBC, ESR, serum protein electrophoresis c-ANCA, anti-proteinase 3 (PR3) associated with Wegener’s; p-ANCA, anti-myeloperoxidase (MPO) associated with Churg-Strauss

  9. Vasculitis • Cutaneousvasculitis often presents as palpable purpuric lesions that may be generalized or limited to the lower extremities or other dependent areas. • Urticarial lesions, ulcers, and hemorrahagic blisters also occur. • May involve other organs  liver, kidney, brain, and joints. Abbas K et al. Cellular and molecular immunology.6th Edition.

  10. Direct Immunofluorescence Examination of a Skin-Biopsy Specimen. Kroshinsky D et al. N Engl J Med 2011;365:252-262

  11. CutaneousVasculitis: Histopathology Criteria • Blood vessel damage (post-capillary venule in dermis) • Endothelial swelling • Fibrinoid necrosis • Leukocytoclasis (nuclear fragments) • Extravasation of RBCs • Perivascular inflammation • Complement components (immunoflorecence); immune complexes deposition

  12. Cutaneous Vasculitis • Urticarialvaculitis- small vessels; C3, IgG, IgM* • Lupus vasculitis- small and medium-sized vessels; C3, IgG, IgM* • Cryoglobinemias- both size vessels; IgM+ • Hypersensitivity vasculitis (drug)- small vessel fibrin, C3+ • Polyarteritisnodosa (both, C3, IgG*), granulomatous polyangiitis (both, C3, IgG*) Henoch-Schonleinpurpura (both, IgA+) *perivascular and BMZ +perivascular

  13. UrticarialVasculitis (UV) Differential Diagnosis • Chronic Idiopathic/Autoimmune Urticaria • Idiopathic UV • Systemic Diseases-SLE • Infections- Hepatitis B/C (cryoglobulinemia) • Serum Sickness and Drug Hypersensitivity Vasculitis • HypocomplementemicUrticarialVasculitis Syndrome (HUVS) • Churg-Strauss Syndrome • Schnitzler Syndrome- IgMgammopathy • Malignancies, immunologic and hematologic diseases reported

  14. Serum Sickness • Chief manifestations  1 to 3 weeks after starting use of an offending agent. • Fever • Urticaria • Lymphadenopathy • Arthralgias Middleton’s. Allergy principles and practice. 7th Edition.

  15. Serum Sickness

  16. HypocomplementicUrticarialVasculitis Syndrome (HUVS) • Urticariavasculitis • Arthralgias/arthritis • Abdominal pain • Angioedema • Uveitis, scleritis, conjuncitivitis (unusual in SLE) • Proliferative glomerulonephritis (resembles SLE) • COPD, pleuritis(unusual in SLE) • Rarely, cardiovascular involvement: pericarditis, valvular disease • CNS involvement: aseptic meningitis, neuropathies

  17. HUVS: Lung Transplant for COPD

  18. Clinical Photographs of the Patient. Kroshinsky D et al. N Engl J Med 2011;365:252-262

  19. Skin-Biopsy Specimen from a Lesion (Hematoxylin and Eosin). Kroshinsky D et al. N Engl J Med 2011;365:252-262 neutophilic infiltration and leukocytoclasis

  20. Immunoflorescence: HUVS C3, C1q and IgG

  21. HUVS vs SLE • Granular deposition of immunoreactants along basement-membrane zone (characteristic of cutaneous lupus) • However, in conjunction with perivascularimmunoreactivity, suggests HUVS • Urticarial vasculitis and low complement levels are commonly associated with extra-cutaneous involvement as in SLE. HUVS has profoundly low complement levels

  22. Vasculitis: Henoch-SchonleinPurpura • Small vessel vasculitis with IgA immune complexes • Classic triad of palpable purpura, arthritis, colicky abdominal pain. • Monitor for chronic nephritis • Usual course 4-6 weeks

  23. CutaneousVasculitis • Drugs may be implicated in cutaneousvasculitis Direct immunofluorescent changes in these lesions suggest immune-complex deposition. • Drugs implicated: Allopurinol, thiazides, sulfonamides, other antimicrobials, several NSAIDs, interferons and anti-TNF α; metformin and sulfonylurea antidiabetic drugs. • The presence of eosinophils in the perivascular infiltrate of skin biopsy may indicate a higher probability of a drug etiology.  http://emedicine.medscape.com/article/1049474-overview

  24. Hypersensitivity SyndromeDrug-induced

  25. Churg-Strauss Syndrome • “Allergic angiitis and granulomatosis” • Almost exclusively in individuals with asthma and allergic rhinitis; systemic vasculitis with eosinophilia, associated with fever, malaise, weight loss. • The pulmonary involvement dominates the clinical picture. Asthma is a defining feature and precedes the onset of vasculitis. Skin, heart, peripheral nervous system, GI tract and kidney can be involved.

  26. CutaneousVasculitis:Laboratory • CBC with differential • Sedimentation rate • C-reactive protein • Complement studies • Autoantibody profiles • Liver and renal function • Serum protein electrophoresis

  27. Treatments for CutaneousVasculitis • Corticosteroids • Hydroxychloroquine • Dapsone • Immunomodulating drugs

  28. Schnitzler Syndrome

  29. Chronic urticaria with daily fevers X 6 mos

  30. Schnitzler Syndrome • Onset as an adult (acquired disorder), although recently a gain of function mutation has been found in the NLRP3/CIAS-1 gene (1 patient) • Characterized by: • Recurring fevers • Neutrophilic urticaria • Monoclonal IgM gammopathy • Joint/bone pain • Similar presentation to MWS (no hearing loss) • May evolve into IgM multiple myeloma or Waldenstrom’s macroglobulinemia

  31. NeutrophilicUrticaria

  32. Autoinflammatory Syndromes • Past 10 years • Newly identified classification of disease • Dysregulation of innate immunity • Recurrent fevers is common feature • Innate immunity recognize “danger" • Uncontrolled cytokine-mediated inflammation (IL-1B)

  33. Muckle-Wells Syndrome (MWS) Moderate in severity of inflammation - more intense and long-lasting inflammation flares Characterized byurticarial rash with onset at birth, deafness and amyloidosis Sensorineural hearing loss Amyloidosis caused by build up of serum amyloid A (SAA) protein in kidneys which can lead to kidney failure Urticarial-like skin eruption in MWS Reprinted from Arth Rheum 2004 Feb; 50(2)607-612, Hawkins RN, et al. “Spectrum of Clinical Features of Muckle-Wells Syndrome and Response to Anakinra” with permission from Wiley InterScience. 33 Shinkai K, et al. Clin Exper Derm 2007;33:1-9.

  34. NLRP3 Inflammasome pathway NLRP3 Inflammasome • The inflammasome is a large complex of proteins, the most important of which is NLRP31 • Mutations in the NLRP3 gene (a.k.a. CIAS1), which encode the cryopyrin (NALP3) protein, cause “autoinflammatory” diseases with a spectrum of onset and severity (MWS, FCAS)2,3 • Symptoms and pathology result from overexpression of Interleukin-13 *Ilaris is not FDA approved for NOMID NOMID = Neonatal Onset Multisystem Inflammatory Disease; MWS = Muckle Wells Syndrome; FCAS = Familial Cold Auto-Inflammatory Syndrome NLRP3= Nucleotide-binding oligomerization domain, leucine-rich-repeat family, pyrin domain containing 3 NALP3=NACHT leucine-rich repeat protein; CIAS1=Cold Induced Autoinflammatory Syndrome 1 34 1Neven B, et al. Nat Clin Pract Rheum 2008;4(9):481-489. 2Hoffman HM, et al. Arthr Rheum 2008;58(8):2443-2452. 3ChurchLD, et al. Nat Clin Pract Rheum 2008;4(1):34-42.

  35. Urticarial lesions on trunk (A). Within 24 hours of commencing anakinra, these lesion had resolved (B). Schnitzler Syndrome J Allergy Clin Immunol 2008;121:261

  36. Characteristics of Autoinflammatory Disorders • Periodic fevers • Associated with a constellation of other symptoms and physical exam findings • Arthralgias/arthritis • Malaise • Lymphadenopathy • Rashes or urticaria • Markers of autoimmunity are negative (e.g. ANA, an expression of adaptive immunity)

More Related