Cutaneous vasculitis

Cutaneous involvement is very common in the different types of vasculitis. Skin lesions may be the only manifestation or may occur in the context of systemic disease

1. Cutaneous vasculitis Shaimaa Elkholy , M.D. Cairo University, Egypt Shaimaa Elkoly, M.D. Cairo University

2. Agenda Introduction. Aetiology Pathogenesis. Common features. Histopathology. Special entity of vasculitis . Treatment . Shaimaa Elkoly, M.D. Cairo University

3. Introduction Vasculitis is a term that refers to the inflammation and necrosis of blood vessels irrespective of the type of vessel involved (veins, arteries, or both), the etiology of the process , or the organ affected. Vasculitis may be idiopathic or secondary to infection, drugs, neoplastic disease, or systemic inflammatory disease. Shaimaa Elkoly, M.D. Cairo University

4. Introduction Cutaneous involvement is very common in the different types of vasculitis . Skin lesions may be the only manifestation or may occur in the context of systemic disease. T here are no clinical, histologic , or laboratory criteria that differentiate between vasculitides of the skin and systemic vasculitides . Shaimaa Elkoly, M.D. Cairo University

5. Aetiology Cutaneous vasculitis results from inflammation of the small or medium-sized blood vessels in the skin. Small blood vessels (<50 µm) are capillaries, post-capillary venules , and non-muscular arterioles in the superficial papillary dermis. Henoch–Schönlein purpura (HSP) urticarial vasculitis (UV) cryoglobulinemic vasculitis (CV), cutaneous small vessel vasculitis (CSVV),commonly referred to as ‘’ cutaneous leukocytoclastic angiitis ‘’ Shaimaa Elkoly, M.D. Cairo University

6. Aetiology Cutaneous vasculitis results from inflammation of the small or medium-sized blood vessels in the skin. Small blood vessels (<50 µm) are capillaries, post-capillary venules , and non-muscular arterioles in the superficial papillary dermis. Henoch–Schönlein purpura (HSP) urticarial vasculitis (UV) cryoglobulinemic vasculitis (CV), cutaneous small vessel vasculitis (CSVV),commonly referred to as ‘’ cutaneous leukocytoclastic angiitis ‘’ Shaimaa Elkoly, M.D. Cairo University

7. Aetiology Medium sized blood vessels (50 - 150 µm) arterioles with smooth muscle walls that are found within the deeper dermis near the junction of the dermis and subcutis . Includes : Poly arteritis nodosa PAN Kawasaki disease (KD) Shaimaa Elkoly, M.D. Cairo University

8. Aetiology Mixed-vessel vasculitis can involve both small and medium vessels and often present with more diverse cutaneous findings than observed in either small-or medium vessel vasculitis alone include: Microscopic polyangiitis (MPA) Wegener granulomatosis (WG) Churg –Strauss syndrome (CSS) Shaimaa Elkoly, M.D. Cairo University

9. ANCA associated Shaimaa Elkoly, M.D. Cairo University

10. Pathogenesis The development of the different types of vasculitis is affected by many factors . Deposition of circulating immune complexes within vessel walls ( hypersensitivity vasculitis ). Potential antigens include drugs and chemicals as well as infectious agents such as viruses or bacteria. Interacting with the complement system, the immune complex deposition stimulates the production of chemotactic factors, vasoactive amines (histamine), and proinflammatory cytokines ( interleukin [IL ] 1, tumor necrosis factor. Shaimaa Elkoly, M.D. Cairo University

11. Pathogenesis 2. Antineutrophil cytoplasmic antibodies (ANCA) also play a role in the development of vasculitis . ANCA are autoantibodies directed primarily against the cytoplasmic protein antigens proteinase 3 (PR3) and myeloperoxidase . It is either perinuclear (p-ANCA), cytoplasmic ( c-ANCA ), or atypical. The atypical pattern (x-ANCA or a-ANCA) includes features common to both . Although most c-ANCA recognize PR3 and most p-ANCA recognize myeloperoxidase , a percentage of p-ANCA are directed against other components of primary cytoplasmic granules, such as elastase and cathepsin , or components of the secondary granules, such as lactoferrin . Shaimaa Elkoly, M.D. Cairo University

12. Common Features Petechiae Palpable purpura Hemorrhagic bullae Macules Subcutaneous nodules Ulceration or digital necrosis Livedo reticularis and livedo racemosa Urticaria   Shaimaa Elkoly, M.D. Cairo University

13. Common Features Petechiae : Petechiae are nonblanchable , pinpoint macules (less than a few millimeters in diameter) that result from capillary inflammation and red blood cell extravasation Shaimaa Elkoly, M.D. Cairo University

14. Common Features Palpable purpura Palpable purpura are very common manifestation of small vessel vasculitis Leukocytoclastic vasculitis Shaimaa Elkoly, M.D. Cairo University

15. Henoch-Schonlein purpura Shaimaa Elkoly, M.D. Cairo University

16. Common Features Hemorrhagic bullae (vesicles) : Small vessel involvement throughout the dermis can result in necrosis of overlying tissue and extravasation of red blood cells. Leukocytoclastic vasculitis Shaimaa Elkoly, M.D. Cairo University

17. Common Features Macules Cryoglobulinemic vasculitis . Acute hemorrhagic edema of enfancy Shaimaa Elkoly, M.D. Cairo University

18. Common Features Hemorrhagic bullae (vesicles) : Small vessel involvement throughout the dermis can result in necrosis of overlying tissue and extravasation of red blood cells. Leukocytoclastic vasculitis Shaimaa Elkoly, M.D. Cairo University

19. Common Features Subcutaneous nodules –  Intense inflammation of medium-sized vessels (vessels with muscular walls in the deep dermis and subcutis ) can lead to the formation of nodular lesions Erythematous nodules in polyarteritis nodosa Shaimaa Elkoly, M.D. Cairo University

20. Common Features Ulceration or digital necrosis –  Ulceration and tissue necrosis occur when vasculitis results in reduced vascular perfusion in the skin Leukocytoclastic vasculitis Shaimaa Elkoly, M.D. Cairo University

21. Cryoglobulinemic vasculitis . Shaimaa Elkoly, M.D. Cairo University

22. Common Features Livedo reticularis and livedo racemosa : It results from compromise of blood flow in medium sized vessels, and can occur in the setting of vasculopathy due to vasospasm, hypercoagulable states, thrombosis, increased blood viscosity, or embolic phenomena, as well as in association with vasculitis PAN Shaimaa Elkoly, M.D. Cairo University

23. Urticarial vasculitis . UV typically presents with erythematous macules Shaimaa Elkoly, M.D. Cairo University

24. Nodules Urticaria Vesicles Papules Purpura + ++ ++ ++ ++++ Cutaneous small-vessel vasculitis ++ +++ ++ +++ Urticarial vasculitis +++ ++++ Henoch–Scho¨nlein purpura ++ ++++ Cryoglobulinemic vasculitis ++++ +++ Polyarteritis nodosa ++ ++++ Wegener granulomatosis ++ + +++ Churg –Strauss syndrome Shaimaa Elkoly, M.D. Cairo University

25. Histo pathology BIOPSY  — Biopsy is an important part of the management of patients with cutaneous lesions that are suspicious for vasculitis . The clinical characteristics of skin lesions cannot reliably distinguish between the different types of cutaneous vasculitis . Thus, biopsies should be performed in all patients. Shaimaa Elkoly, M.D. Cairo University

26. Histo pathology Diagnostic criteria  —  Small vessels : require two out of three: Angiocentric and/or angioinvasive inflammatory infiltrates Disruption and/or destruction of vessel walls by the inflammatory infiltrate. Fibrinoid necrosis (fibrin deposition within the vessel wall or lumen; results from the accumulation and conversion of plasma proteins. Medium-sized vessels: require both of the following criteria Inflammatory infiltrate infiltrating the muscular vessel wall Fibrinoid necrosis Shaimaa Elkoly, M.D. Cairo University

27. Fibrinoid necrosis of the vascular wall Shaimaa Elkoly, M.D. Cairo University

28. Leukocytoclastic vasculitis : leukocytoclasis , extravasation of red blood cells Shaimaa Elkoly, M.D. Cairo University

29. Histo pathology Timing  —  Lesions that are between 24 and 48 hours. Type of biopsy  —according to the cutaneous features Cutaneous findings that are suggestive of small vessel ( petechiae , palpable purpura , or urticarial papules or plaques) evaluated with a punch biopsy that is 4 mm in diameter or larger. Cutaneous findings suggestive of medium vessels: ( livedo racemosa , subcutaneous nodules, ulcers) require a large punch biopsy (8 to 10 mm) or wedge biopsy that includes the subcutaneous tissue. Shaimaa Elkoly, M.D. Cairo University

30. Small Vessel Leukocytoclastic Vasculitis It is the most common type of vasculitis encountered in dermatologic practice. It has also been called hypersensitivity vasculitis and cutaneous , necrotizing venulitis . The clinical manifestations are: purpuric lesions (most common) Occasionally: erythematous papules, vesicles, blisters, pustules, or annular plaques; lesions are generally located on the lower limbs or in the dependent areas of the body Shaimaa Elkoly, M.D. Cairo University

31. Small Vessel Leukocytoclastic Vasculitis Extracutaneous symptoms may be present such as arthralgia , fatigue, fever, or anorexia. The specific origin of the condition is never determined in up to 50% of patients, but It may be associated with many factors as : Drugs Infections Auto immune diseases Malignancy Chemical agents ( Insecticides ,Herbicides, Petroleum derivatives ) Shaimaa Elkoly, M.D. Cairo University

32. Small Vessel Leukocytoclastic Vasculitis Infections + Bacterial = Streptococcus = Staphylococcus = Meningococcus = Gonococcus = Pseudomonas = Treponema pallidum = Mycobacterium leprae = Mycobacterium tuberculosis (?) + Viral (most common) = Hepatitis B = Influenza ( most common) = Cytomegalovirus + Parasitic = Plasmodium Shaimaa Elkoly, M.D. Cairo University

33. Small Vessel Leukocytoclastic Vasculitis Infections + Bacterial = Streptococcus = Staphylococcus = Meningococcus = Gonococcus = Pseudomonas = Treponema pallidum = Mycobacterium leprae = Mycobacterium tuberculosis (?) + Viral = Hepatitis B = Influenza = Cytomegalovirus + Parasitic = Plasmodium Shaimaa Elkoly, M.D. Cairo University

34. Small Vessel Leukocytoclastic Vasculitis Drugs (7- 10 days) + Penicillins + Tetracyclines + Sulfonamides + Erythromycin + Griseofulvin + Anti-inflammatory agents (aspirin, phenacetin ) + Thiazides + Loop diuretics + Propylthiouracil (p-ANCA) + Penicillamine + Phenothiazines + Quinidine Shaimaa Elkoly, M.D. Cairo University

35. Small Vessel Leukocytoclastic Vasculitis Associated with chronic persistent disorders + Systemic lupus erythematosus + Rheumatoid arthritis + Sjogren syndrome --- Inflammatory bowel diseases + Ulcerative colitis + Crohn disease --- Mixed cryoglobulinemia --- Hypergammaglobulinemic Shaimaa Elkoly, M.D. Cairo University

36. Small Vessel Leukocytoclastic Vasculitis  The American College of Rheumatology proposed the following for the diagnosis of hypersensitivity vasculitis in a patient with vasculitis ( = or >3): Age >16 Use of a possible offending drug in temporal relation to the symptoms Palpable purpura Maculopapular rash Biopsy of a skin lesion showing neutrophils around an arteriole or venule Shaimaa Elkoly, M.D. Cairo University

37. Small Vessel Leukocytoclastic Vasculitis treatment Stop offending agent if identified Symptomatic treatment of skin lesions with bed rest with elevation of the lower limbs NSAIDs (as long as these are not the cause of the symptoms) or antihistamines are recommended Good results have also been achieved with colchicine83 at a dose of 0.5 mg/8 h and/or dapsone84 at a dose of 50---200 mg/24 h. In cases of severe cutaneous vasculitis characterized by large necrotic or ulcerated areas, treatment with systemic corticosteroids is necessary; prednisone in a regimen starting at a dose of 0.5 mg to 1 mg/kg/d and gradually tapering over 4---6 weeks Shaimaa Elkoly, M.D. Cairo University

38. Small Vessel Leukocytoclastic Vasculitis treatment If clinical relapse occurs when the dose is being reduced, corticosteroid-sparing immunosuppressive agents may be used: for example, azathioprine (50---100 mg/d) or methotrexate (10---25 mg/wk). If there is systemic involvement, initial treatment should include high-dose corticosteroids and/or oral or intravenous cyclophosphamide pulse therapy until remission of symptoms is achieved. Once remission is achieved, a maintenance regimen can be instituted with azathioprine , mycophenolate mofetil , or methotrexate . Shaimaa Elkoly, M.D. Cairo University

39. Small Vessel Leukocytoclastic Vasculitis treatment Intravenous immunoglobulin or plasmapheresis can be useful in selected cases. Drugs such as infliximab and rituximab have shown promising results in the treatment of systemic vasculitis refractory to conventional therapies. Shaimaa Elkoly, M.D. Cairo University

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