Cutaneous vasculitis

Shaimaa Elkoly, M.D. Cairo University

Cutaneous vasculitis

Shaimaa Elkholy, M.D.Cairo University, Egypt


Agenda Introduction.AetiologyPathogenesis. Common features.Histopathology.Special entity of vasculitis. Treatment .


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.


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.

• There are no clinical, histologic, or laboratory criteria that differentiate between vasculitides of the skin and systemic vasculitides.


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‘’


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‘’


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)


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)


ANCA associated


Pathogenesis

The development of the different types of vasculitis is affected by many factors.

1. 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.


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, suchas lactoferrin.


Common Features

Petechiae Palpable purpura Hemorrhagic bullae Macules Subcutaneous nodules Ulceration or digital necrosis Livedo reticularis and livedo racemosa Urticaria


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


Common Features

Palpable purpura Palpable purpura are very

common manifestation of small vessel vasculitis

Leukocytoclastic vasculitis


Henoch-Schonlein purpura


Common Features

Hemorrhagic bullae (vesicles) : Small vessel involvement throughout the dermis can result in necrosis of overlying tissue and extravasation of red blood cells.



Common Features

Macules

Cryoglobulinemic vasculitis.Acute hemorrhagic edema of enfancy


Common Features

Hemorrhagic bullae (vesicles) : Small vessel involvement throughout the dermis can result in necrosis of overlying tissue and extravasation of red blood cells.



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


Common Features

Ulceration or digital necrosis – Ulceration and tissue necrosis occur when vasculitis results in reduced vascular perfusion in the skin



Cryoglobulinemic vasculitis.


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


Urticarial vasculitis. UV typically presents with erythematous macules


Nodules Urticaria Vesicles Papules Purpura

+ ++ ++ ++ ++++ Cutaneous small-vessel vasculitis

++ +++ ++ +++ Urticarial vasculitis

+++ ++++ Henoch–Scho¨nlein purpura

++ ++++ Cryoglobulinemic vasculitis

++++ +++ Polyarteritis nodosa

++ ++++ Wegener granulomatosis

++ + +++ Churg–Strauss syndrome


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.


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


Fibrinoid necrosis of the vascular wall


Leukocytoclastic vasculitis: leukocytoclasis, extravasation of red blood cells


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.


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



• 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 )



Infections+ Bacterial• = Streptococcus• = Staphylococcus• = Meningococcus• = Gonococcus• = Pseudomonas• = Treponema pallidum• = Mycobacterium leprae• = Mycobacterium tuberculosis (?)+ Viral (most common)• = Hepatitis B• = Influenza ( most common)• = Cytomegalovirus+ Parasitic• = Plasmodium



Infections+ Bacterial• = Streptococcus• = Staphylococcus• = Meningococcus• = Gonococcus• = Pseudomonas• = Treponema pallidum• = Mycobacterium leprae• = Mycobacterium• tuberculosis (?)+ Viral• = Hepatitis B• = Influenza• = Cytomegalovirus+ Parasitic• = Plasmodium



Drugs (7- 10 days)• + Penicillins• + Tetracyclines• + Sulfonamides• + Erythromycin• + Griseofulvin• + Anti-inflammatory agents (aspirin, phenacetin)• + Thiazides• + Loop diuretics• + Propylthiouracil (p-ANCA)• + Penicillamine• + Phenothiazines• + Quinidine



Associated with chronic persistent disorders• + Systemic lupus erythematosus• + Rheumatoid arthritis• + Sjogren syndrome• --- Inflammatory bowel diseaseso + Ulcerative colitiso + Crohn disease• --- Mixed cryoglobulinemia• --- Hypergammaglobulinemic



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


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



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.



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.


• REFERENCES• Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides

. Proposal of an international consensus conference. Arthritis Rheum 1994; 37:187.• Carlson JA. The histological assessment of cutaneous vasculitis. Histopathology 2010; 56:3.• Gonzalez-Gay MA, Garcia-Porrua C, Pujol RM. Clinical approach to cutaneous vasculitis. Curr Opin Rheumatol 2005; 17:56.• Jennette JC, Falk RJ. The role of pathology in the diagnosis of systemic vasculitis. Clin Exp Rheumatol 2007; 25:S52.• Nagai Y, Hasegawa M, Igarashi N, et al. Cutaneous manifestations and histological features of microscopic polyangiitis. Eur J Dermatol 2009; 19:57.• Carlson JA, Ng BT, Chen KR. Cutaneous vasculitis

update: diagnostic criteria, classification, epidemiology, etiology, pathogenesis, evaluation and prognosis. Am J Dermatopathol 2005; 27:504.• Gross RL, Brucker J, Bahce-Altuntas A, et al. A novel cutaneous vasculitis syndrome induced by levamisole-contaminated cocaine. Clin Rheumatol

2011; 30:1385.• Chung C, Tumeh PC, Birnbaum R, et al. Characteristic purpura of the ears, vasculitis, and neutropenia

--a potential public health epidemic associated with levamisole-adulterated cocaine. J Am Acad Dermatol 2011; 65:722.• Ullrich K, Koval R, Koval E, et al. Five consecutive cases of a cutaneous vasculopathy in users of levamisole-adulterated cocaine. J Clin Rheumatol

2011; 17:193.• Xu LY, Esparza EM, Anadkat MJ, et al. Cutaneous manifestations of vasculitis. Semin Arthritis Rheum 2009; 38:348.• Dhadly M, Dean SM, Eberhardt RT. Cutaneous changes in peripheral vascular arterial disease. In: Fitzpatrick's Dermatology in General Medicine, 7th

ed, Wolff K, Goldsmith LA, Katz SI. (Eds), McGraw-Hill, 2008. Vol 2, p.1667.• Chen KR, Carlson JA. Clinical approach to cutaneous vasculitis. Am J Clin Dermatol 2008; 9:71.• Chung L, Kea B, Fiorentino DF. Cutaneous vasculitis. In: Dermatology, 2nd ed., Bolognia JL, Jorizzo, JL, et al. (Eds), Elsevier Limited, Spain 2008. Vol 1,

p.347.• Piette W. Purpura: mechanisms and differential diagnosis. In: Dermatology, 2nd ed, Bolognia JL, Jorizzo JL, Rapini RP, et al. (Eds), Elsevier Limited,

Spain 2008. Vol 1, p.321.• Minz RW, Chhabra S, Singh S, et al. Direct immunofluorescence of skin biopsy: perspective of an immunopathologist. Indian J Dermatol Venereol

Leprol 2010; 76:150.• Hung SP, Yang YH, Lin YT, et al. Clinical manifestations and outcomes of Henoch-Schönlein purpura: comparison between adults and children. Pediatr

Neonatol 2009; 50:162.• Savige J, Pollock W, Trevisin M. What do antineutrophil cytoplasmic antibodies (ANCA) tell us? Best Pract Res Clin Rheumatol 2005; 19:263.• Grau RG. Churg-Strauss syndrome: 2005-2008 update. Curr Rheumatol Rep 2008; 10:453.• Grotz W, Baba HA, Becker JU, Baumgärtel MW. Hypocomplementemic urticarial vasculitis syndrome: an interdisciplinary challenge. Dtsch Arztebl Int

2009; 106:756.• Davis MD, Brewer JD. Urticarial vasculitis and hypocomplementemic urticarial vasculitis syndrome. Immunol Allergy Clin North Am 2004; 24:183.

Cutaneous vasculitis

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